BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)...BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.展开更多
BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyro...BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.展开更多
Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance...Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.展开更多
Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally ...Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally prevalent complications among male diabetic patients. There is a need to understand the role of a male reproductive hormone in the etiology of infertility in diabetic patients. Objective: This study aims to determine the effect of diabetes mellitus on the Male reproductive hormone (testosterone) on diabetic patients attending the Urology unit of Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria and the effect of industrial sugar consumption in rats model. Materials and Methods: 30 samples (including repeats, n = 3) were collected from known diabetic patients and 30 (including repeats, n = 3) control-non diabetic healthy individuals. Five millilitres (5 ml) of blood was collected from the antecubital vein of each participant and placed into a plain container for serum testosterone measurement using the enzyme-linked immunoassay technique. Blood was also collected from the same subjects in a fluoride oxalate container for plasma enzymatic glucose estimation using a Randox Glucose oxidase kit. For in vivo rat model, the albino rats were grouped into 2 of five (5) rats. The control group (1) was only given normal rat food and water while the test group (2) was treated with 0.4 g of industrial sugar/mL/body weight in addition to rat food and water via oral intubation for 21 days. Blood samples were collected via ocular puncture into plain tubes for testosterone measurement as described above. Results: There is a significant (p Conclusion: In conclusion, data available from this study suggests that increased plasma glucose levels and excessive industrial sugar consumption are associated with decreased testosterone levels in both human and animal models respectively. The mechanism is yet unclear but it could be that DM alters conventional sperm parameters, spermatogenesis, and biosynthesis of testosterone and induces degenerative changes in the testis and epididymis and ejaculatory dysfunction. These mechanisms need to be investigated.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and H...BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.展开更多
Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)...Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.展开更多
To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testic...To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.展开更多
Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d...Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.展开更多
Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whethe...Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans,and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin(CCK,known as a satiety signal),remain unclear.This study investigated the TRH signaling system in the echinoderm Apostichopus japonicus.Bioinformatic analyses and ligand-binding assays identified a functional TRH receptor(AjTRHR)that activated signaling via the MAPK/ERK1/2pathways.Experimental administration of TRH significantly reduced feeding activity,while up-regulating CCK expression.RNA interference(RNAi)experiments confirmed that both CCK and TRH are essential components of satiety signaling,working synergistically to mediate feeding inhibition.Evolutionary analysis of TRHtype peptides revealed greater conservation of the short isoform of TRH compared to the long isoform,probably driven by strong selection acting on the functional redundancy.These findings provide compelling evidence of a TRH-mediated signaling system in non-chordate deuterostomes,expandingourunderstandingof neuropeptide-regulated feeding mechanisms in marine invertebrates.展开更多
Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on th...Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on the left side;it is a frequent cause of male infertility and can lead to testicular hypofunction,pain,and discomfort.Microsurgical varicocelectomy is the gold standard for treating infertility caused by VC.VC repair is strongly recommended for couple infertility,oligoasthenoteratozoospermia(OAT),Grade 2 or 3 clinical VC,partner age<37 years,patient age<40 years,or testicular hypotrophy in children and adolescents.展开更多
Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential i...Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential in the development,registration,and quality control of rhGH pharmaceutical products[2].However,the existing in vivo bioassay procedure based on somatropin-induced weight gain in rats is complicated,and the use of a rat cell line-based approach(Nb2-11 bioassay),which measures the production of adenosine triphosphate(ATP)as a direct indicator of cell growth,has a low mechanism of action(MOA)relevance.Therefore,novel rhGH bioassays are still needed.To this end,we developed a reporter gene assay(RGA)based on the GH/insulin-like growth factor-1(IGF-1)axis.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.展开更多
BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This...BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.展开更多
Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regula...Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.展开更多
Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation o...Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.展开更多
Heat stress,a major challenge in modern agriculture due to global warming,significantly reduces crop productivity.To mitigate its adverse effects on maize yield,it is crucial to understand the mechanisms by which heat...Heat stress,a major challenge in modern agriculture due to global warming,significantly reduces crop productivity.To mitigate its adverse effects on maize yield,it is crucial to understand the mechanisms by which heat stress impacts reproductive development.This study investigated the impact of heat stress during the 12th leaf(V12)stage,where silk development begins on grain yield formation,using heat-sensitive and heat-tolerant cultivars.Compared to pollen,silks were found to be more vulnerable to heat stress.Heat stress disrupted hormone balance and inhibited hormone signaling transduction pathways in silks,delaying silk emergence from bracts and reducing fertilization and grain yield.The heat-tolerant cultivar maintained silk growth by activating more response pathways,displaying faster hormone responses,and up-regulating hormones.Taken together,we propose that hormones play an essential role in silk development and later fertilization process.展开更多
Gene expression and the content of hormones regulating feed intake and digestion are crucial for understanding gastric evacuation(GE)and feeding frequency in fish.This study assessed the effects of temperature and siz...Gene expression and the content of hormones regulating feed intake and digestion are crucial for understanding gastric evacuation(GE)and feeding frequency in fish.This study assessed the effects of temperature and size on these parameters by examining the domestication of steelhead trout(Oncorhynchus mykiss)at four temperatures(8℃,12℃,16℃,and 20℃)and with two sizes(75.99 g±10.48 g and 140.21 g±22.08 g)over two weeks.The trout were fasted for 72 h before the GE trial to ensure complete gastric emptying.In each GE trial,the expressions of peptide tyrosine(PYY),cholecystokinin(CCK),and ghrelin genes,along with corresponding serum hormone levels,were measured before feeding and at 0 h and 24 h after feeding,in conjunction with feed intake and 24-h gastric content mass.Results revealed significant effects of temperature on the expression of the three gastric genes.CCK expression increased at 8℃,correlating with reduced feed intake,while PYY and CCK increased at 20℃,correlating with accelerated gastric evacuation.Size significantly influenced serum levels of all three hormones,but the interaction between temperature and size did not affect PYY and ghrelin expression or their serum contents.This study provides molecular insights into how temperature and size regulate the digestion of steelhead trout,offering a theoretical framework for optimizing feeding frequency in aquaculture practices.展开更多
Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 pati...Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 patients were enrolled from March 21,2024 to January 13,2025,including 778 males and 624 females,with ages mainly ranging from 5 to 13 years old.Follow-up visits were completed by 488 patients for the first time,174 patients for the second time,and 81 patients for the third time.All patients were treated with PEG-rhGH(Jin Sai Zeng)as the main therapy after admission.The changes in height information,IGF-1,and thyroid examination results of each patient at the initial diagnosis,6,9,and 12 months after treatment were observed and analyzed.Results:There was no statistical difference between the baseline and the initial diagnosis,as well as the second follow-up visit(P<0.05),while there was a statistical difference between the baseline and the first and third follow-up visits(P>0.05).There was a statistically significant difference in IGF-1 between the initial diagnosis and the first follow-up visit(P<0.05),but no statistical difference between the first,second,and third follow-up visits(P>0.05).Additionally,IGF-1 levels increased with time.There was no statistical difference in TSH between the initial diagnosis and the first,second,and third follow-up visits(P>0.05).There was a statistical difference in free T3 between the initial diagnosis and the first and second follow-up visits(P<0.05),but no statistical difference between the second and third follow-up visits(P>0.05).There was no statistical difference in free T4 between the initial diagnosis and the first and second follow-up visits(P>0.05),but there was a statistical difference between the second and third follow-up visits(P<0.05).Conclusion:PEG-rhGH(Jin Sai Zeng)is significantly effective in improving height and IGF-1 levels in patients with idiopathic short stature.展开更多
Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endother...Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.展开更多
文摘BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
文摘BACKGROUND The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia,especially thyroid hormones.AIM To study the relationship between triiodothyronine(T3),thyroxine(T4),free T3(FT3),free T4(FT4),thyroid stimulating hormone(TSH)and schizophrenia.METHODS In this study,100 schizophrenia patients were selected from our hospital between April 2022 and April 2024.Their clinical data were analyzed retrospectively.Based on the Positive and Negative Syndrome Scale(PANSS)score,patients were divided into mild(1-3 points,n=39),moderate(4 points,n=45),and severe groups(5-7 points,n=16).Additionally,55 healthy individuals served as a control group.Venous blood samples were collected to measure T3,T4,FT3,FT4,TSH,and cortisol concentrations,analyzing their relationship with PANSS scores.RESULTS The serum levels of T3,FT3,FT4,TSH and cortisol in the schizophrenia group were lower than those in the control group(P<0.05).With the increase of the severity of the disease,the concentrations of T3 and T4 decreased,while the con-centrations of TSH and cortisol increased(P<0.05).The concentrations of TSH and cortisol were positively correlated with the PANSS score,while T3 and T4 were negatively correlated with the PANSS score(P<0.05).The receiver ope-rating characteristic curve results showed that T3,T4,TSH,and cortisol had good efficacy in the diagnosis of schizophrenia.Logistic results showed that decreased T3 level,decreased T4 level,decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.CONCLUSION Thyroid hormone levels are associated with the severity of schizophrenia symptoms,which can provide new solutions for the diagnosis and treatment of schizophrenia.
基金supported by the National Natural Science Foundation of China(82372624 to X.J.)Guangdong Basic and Applied Basic Research Foundation(2024A1515013102 and 2022A1515012430 to X.J.)The funders had no role in study design,data collection and interpretation,or the decision to submit the work for publication.
文摘Growth hormone-secreting pituitary adenomas(GHPAs)cause acromegaly,a condition characterized by persistent excess of growth hormone(GH)and its target hormone,insulin-like growth factor 1(IGF-1).This hormonal imbalance gives rise to diverse comorbidities,ultimately resulting in a shortened lifespan compared to the general population(Piccard et al.,2012).Extensive research has demonstrated that tumors exert a pivotal promoting effects on inflammation,and conversely,inflammatory responses exert reciprocal influence on various biological processes of tumors(Fridlender et al.,2009;Piccard et al.,2012).The microbiome profoundly impacts brain function,behavior,and neuroendocrine responses to stress.Through the hypothalamic-pituitary-adrenal(HPA)axis,the neuroendocrine system modulates the composition and permeability of the gastrointestinal tract,indicating a bidirectional network between gut microbiome and neuroendocrine system(Farzi et al.,2018).In the present study,we explored the microbiome profile in patients with GH adenomas and its potential role in inflammation,utilizing Mendelian randomization(MR)to reveal the casual relationship between microbiome and inflammation markers.
文摘Background: Diabetes is a set of metabolic abnormalities typified by hyperglycemia believed to be associated with aberrant insulin secretion, insulin action, or both. Erectile dysfunction and infertility are globally prevalent complications among male diabetic patients. There is a need to understand the role of a male reproductive hormone in the etiology of infertility in diabetic patients. Objective: This study aims to determine the effect of diabetes mellitus on the Male reproductive hormone (testosterone) on diabetic patients attending the Urology unit of Federal University Teaching Hospital, Abakaliki, Ebonyi State, Nigeria and the effect of industrial sugar consumption in rats model. Materials and Methods: 30 samples (including repeats, n = 3) were collected from known diabetic patients and 30 (including repeats, n = 3) control-non diabetic healthy individuals. Five millilitres (5 ml) of blood was collected from the antecubital vein of each participant and placed into a plain container for serum testosterone measurement using the enzyme-linked immunoassay technique. Blood was also collected from the same subjects in a fluoride oxalate container for plasma enzymatic glucose estimation using a Randox Glucose oxidase kit. For in vivo rat model, the albino rats were grouped into 2 of five (5) rats. The control group (1) was only given normal rat food and water while the test group (2) was treated with 0.4 g of industrial sugar/mL/body weight in addition to rat food and water via oral intubation for 21 days. Blood samples were collected via ocular puncture into plain tubes for testosterone measurement as described above. Results: There is a significant (p Conclusion: In conclusion, data available from this study suggests that increased plasma glucose levels and excessive industrial sugar consumption are associated with decreased testosterone levels in both human and animal models respectively. The mechanism is yet unclear but it could be that DM alters conventional sperm parameters, spermatogenesis, and biosynthesis of testosterone and induces degenerative changes in the testis and epididymis and ejaculatory dysfunction. These mechanisms need to be investigated.
基金Supported by The Research Foundation of Jiangsu Province Administration of Traditional Chinese Medicine,No.MS2023088The Science and Technology Project of Changzhou,No.CE20225040+1 种基金The Research Foundation of Nanjing Medical University Changzhou Medical Center,No.CMCC202311Leading Talent of Changzhou“The 14th Five-Year Plan”High-Level Health Talents Training Project,No.2022CZLJ021.
文摘BACKGROUND Hepatocellular carcinoma(HCC)surveillance is crucial for patients with compensated cirrhosis(CC)and decompensated cirrhosis(DC).Increasing evidence has revealed a connection between thyroid hormone(TH)and HCC,although this relationship remains contentious.Complements and immunoglobulin(Ig),which serve as surrogates of cirrhosis-associated immune dysfunc-tion,are associated with the severity and outcomes of liver cirrhosis(LC).To date,there is a lack of evidence supporting the recommendation of TH,Ig,and com-plement tests in patients at high risk of HCC.AIM To assess the predictive value of TH,Ig,and complements for HCC development.METHODS Data from 142 patients,comprising 72 patients with CC and 70 patients with DC,were analysed as a training set.Among them,100 patients who underwent complement and Ig tests were considered for internal validation.Logistic regression was employed to identify independent risk factors for HCC development.RESULTS The median follow-up duration was 32(24-37 months)months.The incidence of HCC was significantly higher in the DC group(16/70,22.9%)compared to the CC group(3/72,4.2%)(χ^(2)=10.698,P<0.01).Patients with DC exhibited lower total tetraiodothyronine(TT4),total triiodothyronine(TT3),free triiodothyronine,complement C3,and C4(all P<0.01),and higher IgA and IgG(both P<0.01).In both CC and DC patients,TT3 and TT4 positively correlated with alanine transaminase(ALT),aspartate transaminase(AST),and gamma-glutamyl transpeptidase(GGT).IgG positively correlated with IgM,IgA,ALT,and AST,while it negatively correlated with C3 and C4.Multivariable analysis indicated that age,DC status,and GGT were independent risk factors for HCC development.CONCLUSION The predictive value of TH,Ig,and complements for HCC development is suboptimal.Age,DC,and GGT emerge as more significant factors during HCC surveillance in hepatitis B virus-related LC.
文摘Background:Few studies compared the effectiveness of the 3-monthly goserelin 10.8-mg and the monthly 3.6-mg depot in inducing ovarian function suppression for premenopausal patients with hormone receptor positive(HR+)breast cancer.We conducted a large-scale real-world study(RWS)in China to validate the non-inferiority of goserelin 10.8-mg to the 3.6-mg depot.Methods:This multicenter,retrospective-prospective,non-inferiority study compared goserelin 10.8-mg with 3.6-mg in suppressing estradiol(E2)levels in premenopausal and perimenopausal patients with HR+breast cancer.Eligible patients were identified,and their demographic and clinical data were obtained from hospital medical records.The observation period was 28 weeks.Propensity score matching(PSM)ensured baseline comparability.The primary endpoint was the proportion of patients with E2 suppression to postmenopausal level at Week 12±4.Difference in proportions and 95%CI was calculated by Newcombe-Wilson score method.The non-inferiority margin was-10%.Subgroup and sensitivity analyses assessed result robustness.Results:From 1st January,2015 to 15th December,2023,15,629 patients from 16 hospitals nationwide were screened,with 1,060 eligible patients included in the full analysis set(3.6-mg group:678;10.8-mg group:382).Post-PSM,the primary endpoint was analyzed in 590 patients(295 in each group).At Week 12±4,the proportion of patients with E2 suppression was 99.1%(95%CI:96.9%-99.8%)for goserelin 10.8-mg and 95.3%(95%CI:91.0%-97.6%)for goserelin 3.6-mg.The difference was 3.8%(95%CI:0.6%-8.1%)with the lower limit of 95%CI greater than the non-inferiority margin.All subgroup analyses,including those based on age(≤45 or>45 years)and previous chemotherapy(yes/no),and all sensitivity analyses on the primary endpoint were consistent with the main analysis.
基金supported by the Shenzhen Fundamental Research Program(No.JCYJ20210324121807021).
文摘To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.
基金supported in part by the National Natural Science Foundation of China(Nos.32270555 and 32072954).
文摘Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.
基金supported by the National Natural Science Foundation of China (42276103)。
文摘Feeding behavior is regulated by a complex network of endogenous neuropeptides.In chordates,this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone(TRH).However,whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans,and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin(CCK,known as a satiety signal),remain unclear.This study investigated the TRH signaling system in the echinoderm Apostichopus japonicus.Bioinformatic analyses and ligand-binding assays identified a functional TRH receptor(AjTRHR)that activated signaling via the MAPK/ERK1/2pathways.Experimental administration of TRH significantly reduced feeding activity,while up-regulating CCK expression.RNA interference(RNAi)experiments confirmed that both CCK and TRH are essential components of satiety signaling,working synergistically to mediate feeding inhibition.Evolutionary analysis of TRHtype peptides revealed greater conservation of the short isoform of TRH compared to the long isoform,probably driven by strong selection acting on the functional redundancy.These findings provide compelling evidence of a TRH-mediated signaling system in non-chordate deuterostomes,expandingourunderstandingof neuropeptide-regulated feeding mechanisms in marine invertebrates.
文摘Dear Editor,Varicocele(VC)is a vascular condition characterized by abnormal tortuosity and dilation of the pampiniform plexus veins within the spermatic cord.VC is commonly observed in young adults,predominantly on the left side;it is a frequent cause of male infertility and can lead to testicular hypofunction,pain,and discomfort.Microsurgical varicocelectomy is the gold standard for treating infertility caused by VC.VC repair is strongly recommended for couple infertility,oligoasthenoteratozoospermia(OAT),Grade 2 or 3 clinical VC,partner age<37 years,patient age<40 years,or testicular hypotrophy in children and adolescents.
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金supported by the first batch of grants from the State Key Laboratory of Drug Regulatory Science,China(Grant No.:2023SKLDRS0108).
文摘Recombinant human growth hormone(rhGH)has been widely used for the treatment of disorders associated with GH deficiency and multiple clinical indications[1].Accurate determination of biological activity is essential in the development,registration,and quality control of rhGH pharmaceutical products[2].However,the existing in vivo bioassay procedure based on somatropin-induced weight gain in rats is complicated,and the use of a rat cell line-based approach(Nb2-11 bioassay),which measures the production of adenosine triphosphate(ATP)as a direct indicator of cell growth,has a low mechanism of action(MOA)relevance.Therefore,novel rhGH bioassays are still needed.To this end,we developed a reporter gene assay(RGA)based on the GH/insulin-like growth factor-1(IGF-1)axis.
基金National Natural Science Foundation of China,No.82270881 and No.82200928National High-Level Hospital Clinical Research Funding,No.BJ-2023-124 and No.BJ-2023-130.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.
基金Supported by the National Natural Science Foundation of China,No.82270942.
文摘BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.
基金Guangzhou Medical and Health Science and Technology Project(Project No.:20231A011103)General projects of Guangzhou municipal Science and Technology Bureau(Project No.:2023A04J0598)Guangdong Basic and Applied Basic Research Foundation(Project No.:2022A1515111122)。
文摘Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.
基金made possible by the National Natural Science Foundation of China (32060422)。
文摘Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.
基金supported by the National Natural Science Foundation of China(32071959)the National Key Research and Development Program of China(2023YFD2303304)+1 种基金the Key Research and Development Program of Shandong Province(LJNY202103)the Shandong Province Key Agricultural Project for Application Technology Innovation(SDAIT02-08)to Peng Liu.
文摘Heat stress,a major challenge in modern agriculture due to global warming,significantly reduces crop productivity.To mitigate its adverse effects on maize yield,it is crucial to understand the mechanisms by which heat stress impacts reproductive development.This study investigated the impact of heat stress during the 12th leaf(V12)stage,where silk development begins on grain yield formation,using heat-sensitive and heat-tolerant cultivars.Compared to pollen,silks were found to be more vulnerable to heat stress.Heat stress disrupted hormone balance and inhibited hormone signaling transduction pathways in silks,delaying silk emergence from bracts and reducing fertilization and grain yield.The heat-tolerant cultivar maintained silk growth by activating more response pathways,displaying faster hormone responses,and up-regulating hormones.Taken together,we propose that hormones play an essential role in silk development and later fertilization process.
基金National Key Research and Development Program of China(Nos.2024YFD2400300 and 2019YFD0901000)the Natural National Science Foundation of China(No.32373104).
文摘Gene expression and the content of hormones regulating feed intake and digestion are crucial for understanding gastric evacuation(GE)and feeding frequency in fish.This study assessed the effects of temperature and size on these parameters by examining the domestication of steelhead trout(Oncorhynchus mykiss)at four temperatures(8℃,12℃,16℃,and 20℃)and with two sizes(75.99 g±10.48 g and 140.21 g±22.08 g)over two weeks.The trout were fasted for 72 h before the GE trial to ensure complete gastric emptying.In each GE trial,the expressions of peptide tyrosine(PYY),cholecystokinin(CCK),and ghrelin genes,along with corresponding serum hormone levels,were measured before feeding and at 0 h and 24 h after feeding,in conjunction with feed intake and 24-h gastric content mass.Results revealed significant effects of temperature on the expression of the three gastric genes.CCK expression increased at 8℃,correlating with reduced feed intake,while PYY and CCK increased at 20℃,correlating with accelerated gastric evacuation.Size significantly influenced serum levels of all three hormones,but the interaction between temperature and size did not affect PYY and ghrelin expression or their serum contents.This study provides molecular insights into how temperature and size regulate the digestion of steelhead trout,offering a theoretical framework for optimizing feeding frequency in aquaculture practices.
文摘Objective:To investigate the clinical efficacy and safety evaluation of Polyethylene Glycol Recombinant Human Growth Hormone Injection(PEG-rhGH)in the treatment of idiopathic short stature.Methods:A total of 1402 patients were enrolled from March 21,2024 to January 13,2025,including 778 males and 624 females,with ages mainly ranging from 5 to 13 years old.Follow-up visits were completed by 488 patients for the first time,174 patients for the second time,and 81 patients for the third time.All patients were treated with PEG-rhGH(Jin Sai Zeng)as the main therapy after admission.The changes in height information,IGF-1,and thyroid examination results of each patient at the initial diagnosis,6,9,and 12 months after treatment were observed and analyzed.Results:There was no statistical difference between the baseline and the initial diagnosis,as well as the second follow-up visit(P<0.05),while there was a statistical difference between the baseline and the first and third follow-up visits(P>0.05).There was a statistically significant difference in IGF-1 between the initial diagnosis and the first follow-up visit(P<0.05),but no statistical difference between the first,second,and third follow-up visits(P>0.05).Additionally,IGF-1 levels increased with time.There was no statistical difference in TSH between the initial diagnosis and the first,second,and third follow-up visits(P>0.05).There was a statistical difference in free T3 between the initial diagnosis and the first and second follow-up visits(P<0.05),but no statistical difference between the second and third follow-up visits(P>0.05).There was no statistical difference in free T4 between the initial diagnosis and the first and second follow-up visits(P>0.05),but there was a statistical difference between the second and third follow-up visits(P<0.05).Conclusion:PEG-rhGH(Jin Sai Zeng)is significantly effective in improving height and IGF-1 levels in patients with idiopathic short stature.
基金financially supported by grants from the National Natural Science Foundation of China (Nos.32371573,32171497,and 31971420)。
文摘Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.
