The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
Objective To qualitatively assess the diagnostic performance of dynamic contrast enhancement(DCE),diffusionweighted imaging(DWI),and T2-weighted imaging(T2WI),alone or in combination,in the evaluation of breast cancer...Objective To qualitatively assess the diagnostic performance of dynamic contrast enhancement(DCE),diffusionweighted imaging(DWI),and T2-weighted imaging(T2WI),alone or in combination,in the evaluation of breast cancer.Methods We retrospectively reviewed the records of 394 consecutive patients with pathologically confirmed breast lesions who had undergone 3-T magnetic resonance imaging(MRI).The morphological characteristics of breast lesions were evaluated using DCE,DWI,and T2WI based on BI-RADS lexicon descriptors by trained radiologists.Patients were categorized into mass and non-mass groups based on MRI characteristics of the lesions,and the differences between benign and malignant lesions in each group were compared.Clinical prediction models for breast cancer diagnosis were constructed using logistic regression analysis.Diagnostic efficacies were compared using the area under the receiver operating characteristic curve(AUC)and DeLong test.Results For mass-like lesions,all the morphological parameters significantly differentiated benign and malignant lesions on consensus DCE,DWI,and T2WI(P<0.05).The combined method(DCE+DWI+T2WI)had a higher AUC(0.865)than any of the individual modality(DCE:0.786;DWI:0.793;T2WI:0.809)(P<0.05).For non-mass-like lesions,DWI signal intensity was a significant predictor of malignancy(P=0.036),but the model using DWI alone had a low AUC(0.669).Conclusion Morphological assessment using the combination of DCE,DWI,and T2WI provides better diagnostic value in differentiating benign and malignant breast mass-like lesions than assessment with only one of the modalities.展开更多
White light illumination is essential in daily life,however,the substantial amount of blue light it contains can damage human eyes.Therefore,it is important to block this high-energy blue light to protect visual healt...White light illumination is essential in daily life,however,the substantial amount of blue light it contains can damage human eyes.Therefore,it is important to block this high-energy blue light to protect visual health.In this study,yellow-emitting carbon dots(CDs)with a quantum yield exceeding 94%were synthesized using citric acid and urea.These CDs effectively absorb blue light.By incorporating them into polystyrene,multiple films termed CDs-based blue light blocking films(CBFs)were developed,each offering different levels of blue light absorption.These CBFs exhibited excellent transparency and efficient blue light filtering capabilities.This study highlights the potential of high quantum yield CDs,which specifically absorb blue light,as foundational materials for developing light-blocking solutions against highenergy short-wavelength light.展开更多
Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more th...Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more than one in 10 births worldwide.Compared to full-term births,PTBs are associated with a higher risk of short-and long-term complications,including bronchopulmonary dysplasia,necrotizing enterocolitis,visual impairment,and cerebral injuries[2].Despite substantial research efforts to prevent PTB,the global PTB rate has shown little improvement over the past decade[1].Therefore,identifying additional risk factors remains a critical goal in preventing PTB.展开更多
In 2024,the U.S.Food and Drug Administration approved a total of 50 drug marketing applications,with small molecule drugs accounting for half of the medications.Upon surveying these endorsed pharmaceuticals,it becomes...In 2024,the U.S.Food and Drug Administration approved a total of 50 drug marketing applications,with small molecule drugs accounting for half of the medications.Upon surveying these endorsed pharmaceuticals,it becomes evident that certain structures exhibit familiarity,potentially resulting from structural modifications applied to previously approved drugs.Consequently,exploring the latest advancements in drug research not only aids comprehension of cutting-edge technologies used in drug development but also fosters invaluable experience and knowledge accumulation while nurturing innovative ideas for future drug discovery.This review comprehensively analyzes the research progress related to approved small molecule drugs,including aspects such as drug design,structural modification,activity enhancement,and druggability improvement.The aim is to provide valuable insights and assistance for researchers in pharmacology.展开更多
Objective:While albumin and the weight-standardized hand grip strength(HGS/W)serve as valuable prognostic indicators for cancer patients,their correlation with the prognosis in frail cancer patients remains inadequate...Objective:While albumin and the weight-standardized hand grip strength(HGS/W)serve as valuable prognostic indicators for cancer patients,their correlation with the prognosis in frail cancer patients remains inadequately explored.This study aimed to investigate the prognostic importance of the albumin level and HGS/W in cancer patients with frailty and to further investigate their combined prognostic value.Moreover,this comprehensive evaluation aimed to facilitate timely intervention and treatment for frail patients.Methods:The research enrolled 5,794 cancer patients identified with frailty from a multicenter research database.The diagnosis of frailty was based on the FRAIL scale.An Albumin-HGS/W score was constructed by combining the albumin and HGS/W values.Cox proportional hazard regression was utilized to examine the association between the albumin level and HGS/W and patient outcomes.Results:Among these patients,2,543 were females and 3,251 were males,with a median age of 60.0 years.Optimal stratification based on patient survival revealed the ideal threshold for HGS/W to be 0.48 for males and 0.39 for females,and for albumin to be 38 for both sexes.The fully adjusted model revealed that higher Albumin-HGS/W scores were correlated with a poorer patient prognosis.Notably,an Albumin-HGS/W score of 2 was associated with a higher risk of mortality compared with a score of 0 in the total population(HR:1.813,95%CI:1.580-2.080,P<0.001).Conclusions:Low albumin or HGS/W values are associated with low survival in cancer patients with frailty.Elevated Albumin-HGS/W scores were linked to decreased survival rates in cancer patients with frailty.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury a...Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion.Among these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury.In this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing factor.The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical scavenger.We also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be clarified.Finally,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.展开更多
BACKGROUND The pathological diagnosis and follow-up analysis of gastric mucosal biopsy have been paid much attention,and some scholars have proposed the pathological diagnosis of 12 kinds of lesions and accompanying p...BACKGROUND The pathological diagnosis and follow-up analysis of gastric mucosal biopsy have been paid much attention,and some scholars have proposed the pathological diagnosis of 12 kinds of lesions and accompanying pathological diagnosis,which is of great significance for the treatment of precision gastric diseases,the improvement of the early diagnosis rate of gastric cancer,and the reduction of missed diagnosis rate and misdiagnosis rate.AIM To perform a histopathological classification and follow-up analysis of chronic atrophic gastritis(CAG).METHODS A total of 2248 CAG tissue samples were collected,and data of their clinical characteristics were also gathered.Based on these samples,the expression levels of Mucin 1(MUC1),MUC2,MUC5AC,and MUC6 in CAG tissue were tested by immunohistochemical assay.Moreover,we followed these patients for up to four years.The difference between different stages of gastroscopic biopsy was observed.RESULTS Through observation,it is believed that CAG should be divided into four types,simple type,hyperplasia type,intestinal metaplasia(IM)type,and intraepithelial neoplasia(IEN)type.Simple CAG accounted for 9.1%(205/2248),which was more common in elderly people over 60 years old.The main change was that the lamina propria glands were reduced in size and number.Hyperplastic CAG accounted for 29.1%(654/2248),mostly occurring between 40 and 60 years old.The main change was that the lamina propria glands were atrophy accompanied by glandular hyperplasia and slight expansion of the glands.IM CAG accounted for 50.4%(1132/2248),most of which increased with age,and were more common in those over 50 years.The atrophy of the lamina propria glands was accompanied by significant IM,and the mucus containing sialic acid or sulfate was distinguished according to the nature of the mucus.The IEN type CAG accounted for 11.4%(257/2248),which developed from the previous types,with severe gland atrophy and reduced mucus secretion,and is an important precancerous lesion.CONCLUSION The histological typing of CAG is convenient to understand the property of lesion,determine the follow-up time,and guide the clinical treatment.展开更多
Objective:To investigate the role of epidermal growth factor(EGF) in the pathogenesis of uterine leiomyomas.Methods:Human myometrial smooth muscle cells(HM-SMCs) and smooth muscle cells of human uterine leiomyomas(HL-...Objective:To investigate the role of epidermal growth factor(EGF) in the pathogenesis of uterine leiomyomas.Methods:Human myometrial smooth muscle cells(HM-SMCs) and smooth muscle cells of human uterine leiomyomas(HL-SMCs) were separated from patients' specimens and cultured.After processed by EGF or PD98059(inhibitor of MKK/MEK) +EGF,the proliferation rate of both SMCs was detected by BrdU method and the phosphorylation level of p44/42 mitogen-activated protein kinase(MAPK) was determined by Western-blot.After different processing time by EGF,the phosphorylation levels of p44/42 MAPK and AKT and p27 expression level in both SMCs were detected by Western-blot.Results:EGF could significantly promote HL-SMCs proliferation and PD98059 could inhibit this effect(P<0.05);besides,PD98059 could inhibit the increase of the phosphorylation level of p44/42 MAPK in both SMCs induced by EGF.When the processing time by EGF was over 15 min,the phosphorylation levels of p44/42 MAPK and AKT in both SMCs decreased sharply and were close to zero:p27 expression in HM-SMCs raised significantly while the upregulation in HL-SMCs was little.Conclusions:EGF could not cause activation of EGFR because of the dephosphorylation of p44/42 MAPK and AKT in HL-SMCs,which caused p27 expression insufficiently and cell cycle dysregulation.展开更多
MicroRNA-9 （miR-9） has been shown to promote the differentiation of bone marrow mesen-chymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study conifrmed that increased autophag...MicroRNA-9 （miR-9） has been shown to promote the differentiation of bone marrow mesen-chymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study conifrmed that increased autophagic activity improved the efifciency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 （LC3）-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Re-sults showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron speciifc enolase and microtubule-associated protein 2 increased in the miR-9＋ group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.展开更多
OBJECTIVE: To analyze treatment effectiveness in terms of the medication injection site. METHODS: The medical records of 423 patients with cerebral palsy who were admitted to Maternal and Child Health Hospital between...OBJECTIVE: To analyze treatment effectiveness in terms of the medication injection site. METHODS: The medical records of 423 patients with cerebral palsy who were admitted to Maternal and Child Health Hospital between January 2009 and December 2016 were collected. All cases were divided into T1, T2, T3, and T4 groups based on the use of conventional medication sites and acupoints for administering injectable medicines. RESULTS: In the T1 group, patients received injections at conventional medication sites between 2009 and 2010. In the T2 group, patients received injections at conventional medication sites combined with acupoint injection therapy I from 2011 to 2012. In the T3 group, injection at conventional medication sites plus acupoint injection II was applied between 2013 and 2014. Acupoint injection only was used in the T4 group from 2015 to 2016. Therapeutic effects were statistically compared among the different injection procedures. The overall Gross Motor Function Measure (GMFM) and Fine Motor Function Measure (FMFM) scores were significantly improved after hospital discharge. The GMFM score was considerably higher in the T4 group than in the other groups (all P = 0.001 < 0.05). The GMFM scores were significantly higher in the T2 groups than in the T1 group (P = 0.001< 0.05), but no significant difference was observed between the other paired comparions (P > 0.05). Meanwhile, the FMFM scores were significantly higher in the T2 and T4 groups than in the T1 and T3 groups (all P = 0.001 < 0.05). Site injection therapy can significantly improve gross and fine motor function in children with cerebral palsy. CONCLUSION: It is feasible to administer injectable medicines at acupoints instead of convention sites to enhance the therapeutic effect of treatment in patients with cerebral palsy.展开更多
Objective:To discuss the liver function damage mechanism of patients with clonorchiasis by analyzing the ultrasound characteristics,liver function,change of the serum inflammatory factors and cell apoptosis factors.Me...Objective:To discuss the liver function damage mechanism of patients with clonorchiasis by analyzing the ultrasound characteristics,liver function,change of the serum inflammatory factors and cell apoptosis factors.Methods:Color Doppler ultrasound technique was adopted to detect the portal vein and blood flow change of patients with clonorchiasis;ELISA was used to determine the level of different serum inflammatory factors.The levels of serum total bilirubin,serum albumin and glutamic-pyruvic transaminase were detected by automatic biochemical analyzer.Western blot was used to determine the expression of proteins relevant to apoptosis.Results:Compared with the health control group,the trunk diameter of portal vein and the thickness of spleen,as well as the hepatic artery pulsation index of clonorchiasis patients increased obviously,the mean blood flow velocity of portal vein(P<0.05 or P<0.01) decreased.The content of total bilirubin and transaminase in plasma increased significantly,but albumin decreased(P<0.05).Levels of TNF-α,IL-6 and IFN-γ increased remarkably,and the level of every factor was significantly different among patients with Child-Pugh Ⅰ,Child-Pugh Ⅱ and Child-Pugh Ⅲ classification of liver function(P<0.05 or P<0.01).With the exacerbation of liver dysfunction,levels of TNF-α,IL-6 and IFN-γ gradually increased(P<0.05).Compared with the healthy control group,the expression quantity of apoptosis protein Fas,FasL,Bax and Caspase-3 increased significantly(P<0.05 or P<0.01),but Bcl-2 decreased(P<0.05).Conclusions:Changes of ultrasonic characteristics and liver dysfunction,caused by liver fluke infection,may be related to that both inflammatory response and apoptosis response have participated in the pathogenic process and liver damage course of clonorchiasis.展开更多
Cryptorchidism affects the growth of testicular volume.Testicular volume is associated with reproductive function.The testicular atrophy index evaluates the degree of damage caused by cryptorchidism,but it remains unc...Cryptorchidism affects the growth of testicular volume.Testicular volume is associated with reproductive function.The testicular atrophy index evaluates the degree of damage caused by cryptorchidism,but it remains unclear whether changes in testicular atrophy index are related to age.We selected patients who underwent surgery for unilateral palpable cryptorchidism.Testicular volume was measured using ultrasonography.The testicular atrophy indices of the undescended testes were then reviewed,and their correlation with age was analyzed.We studied 228 cases(age range:6–53 months).Scatter plots were constructed,and Loess curves were fitted,revealing a turning point at 24 months of age.The patients were divided into age groups of 6–24 months and 25–53 months.The testicular volume of the cryptorchid side was smaller than that of the normal side in both groups(both P<0.001).In the 6–24-month group,the testicular atrophy index was positively correlated with age,testicular volume on the cryptorchid side was not correlated with age,and testicular volume was positively correlated with age on the normal side.In the 25–53-month group,testicular atrophy index and testicular volumes on either side were not correlated with age.A palpable unilateral cryptorchid testis is smaller than the contralateral testis.The testicular atrophy index increases with age between 6 months and 24 months,but not between 25 months and 53 months.Testicular volume increased with age on the normal side between 6 months and 24 months,but not on the cryptorchid side.Trends in testicular atrophy index with age contribute to the decision of operation time.展开更多
Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of nefer...Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of neferine on Nav1.5 channels that are stably expressed in HEK 293 cells. We found that neferine potently and reversibly inhibited Nav1.5 currents in a concentration dependent manner with a half-maximal inhibition（IC50） being 26.15 μmol/L. The inhibitory effects of neferine on Nav1.5 currents were weaker than those of quinidine at the same concentration. The steady-state inactivation curve was significantly shifted towards hyperpolarizing direction in the presence of 30 μmol/L neferine, while the voltage-dependent activation was unaltered. Neferine prolonged the time to peak of activation, increased the inactivation time constants of Nav1.5 currents and markedly slowed the recovery from inactivation. The inhibitory effect of neferine could be potentiated in a frequency-dependent manner. These results suggested that neferine can block Nav1.5 channels under the open state and inactivating state and it is an open channel blocker of Nav1.5 channels.展开更多
Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and method...Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and methods: A total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone(10 mg) was dispensed into a 100 ml PCA pump with normal saline. Pump administration was initiated 15 min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 h after the procedure. Side effects were also observed.Results: Thirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed.Conclusion: Patients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.展开更多
Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progre...Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.展开更多
Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and...Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.展开更多
Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in...Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.展开更多
BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointest...BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointestinal symptoms as the first sign of CGD.CONCLUSION Gastrointestinal symptoms representing the first sign of CGD are very rare,and prompt diagnosis and treatment with broad-spectrum antibiotics were of crucial importance.展开更多
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
文摘Objective To qualitatively assess the diagnostic performance of dynamic contrast enhancement(DCE),diffusionweighted imaging(DWI),and T2-weighted imaging(T2WI),alone or in combination,in the evaluation of breast cancer.Methods We retrospectively reviewed the records of 394 consecutive patients with pathologically confirmed breast lesions who had undergone 3-T magnetic resonance imaging(MRI).The morphological characteristics of breast lesions were evaluated using DCE,DWI,and T2WI based on BI-RADS lexicon descriptors by trained radiologists.Patients were categorized into mass and non-mass groups based on MRI characteristics of the lesions,and the differences between benign and malignant lesions in each group were compared.Clinical prediction models for breast cancer diagnosis were constructed using logistic regression analysis.Diagnostic efficacies were compared using the area under the receiver operating characteristic curve(AUC)and DeLong test.Results For mass-like lesions,all the morphological parameters significantly differentiated benign and malignant lesions on consensus DCE,DWI,and T2WI(P<0.05).The combined method(DCE+DWI+T2WI)had a higher AUC(0.865)than any of the individual modality(DCE:0.786;DWI:0.793;T2WI:0.809)(P<0.05).For non-mass-like lesions,DWI signal intensity was a significant predictor of malignancy(P=0.036),but the model using DWI alone had a low AUC(0.669).Conclusion Morphological assessment using the combination of DCE,DWI,and T2WI provides better diagnostic value in differentiating benign and malignant breast mass-like lesions than assessment with only one of the modalities.
基金supported by Medical Science and Technology Research Project of Henan Province(Joint Construction Project)(No.LHGJ20200433)National Natural Science Foundation of China(No.52122308)。
文摘White light illumination is essential in daily life,however,the substantial amount of blue light it contains can damage human eyes.Therefore,it is important to block this high-energy blue light to protect visual health.In this study,yellow-emitting carbon dots(CDs)with a quantum yield exceeding 94%were synthesized using citric acid and urea.These CDs effectively absorb blue light.By incorporating them into polystyrene,multiple films termed CDs-based blue light blocking films(CBFs)were developed,each offering different levels of blue light absorption.These CBFs exhibited excellent transparency and efficient blue light filtering capabilities.This study highlights the potential of high quantum yield CDs,which specifically absorb blue light,as foundational materials for developing light-blocking solutions against highenergy short-wavelength light.
基金supported by the National Natural Science Foundation of China(8200340181972981)+1 种基金the Scientific and Technological Project of Henan Province(222102310150,China)the Open Research Fund of the National Health Commission Key Laboratory of Birth Defects Prevention(NHCKLBDP202504,China).
文摘Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more than one in 10 births worldwide.Compared to full-term births,PTBs are associated with a higher risk of short-and long-term complications,including bronchopulmonary dysplasia,necrotizing enterocolitis,visual impairment,and cerebral injuries[2].Despite substantial research efforts to prevent PTB,the global PTB rate has shown little improvement over the past decade[1].Therefore,identifying additional risk factors remains a critical goal in preventing PTB.
基金the National Natural Science Foundation of China(No.82304286 by S.Yuan,Nos.U21A20416 and 82020108030 by H.-M.Liu)the Scientific and Technological Project of Henan Province(No.232102311165 by S.Yuan,No.242102311236 by Y.-R.Bai)for financial support。
文摘In 2024,the U.S.Food and Drug Administration approved a total of 50 drug marketing applications,with small molecule drugs accounting for half of the medications.Upon surveying these endorsed pharmaceuticals,it becomes evident that certain structures exhibit familiarity,potentially resulting from structural modifications applied to previously approved drugs.Consequently,exploring the latest advancements in drug research not only aids comprehension of cutting-edge technologies used in drug development but also fosters invaluable experience and knowledge accumulation while nurturing innovative ideas for future drug discovery.This review comprehensively analyzes the research progress related to approved small molecule drugs,including aspects such as drug design,structural modification,activity enhancement,and druggability improvement.The aim is to provide valuable insights and assistance for researchers in pharmacology.
基金supported by a Henan Province Science and Technology Research Project(No.252102311033)the National Key Research and Development Program(No.2022YFC2009600 and No.2022YFC2009601).
文摘Objective:While albumin and the weight-standardized hand grip strength(HGS/W)serve as valuable prognostic indicators for cancer patients,their correlation with the prognosis in frail cancer patients remains inadequately explored.This study aimed to investigate the prognostic importance of the albumin level and HGS/W in cancer patients with frailty and to further investigate their combined prognostic value.Moreover,this comprehensive evaluation aimed to facilitate timely intervention and treatment for frail patients.Methods:The research enrolled 5,794 cancer patients identified with frailty from a multicenter research database.The diagnosis of frailty was based on the FRAIL scale.An Albumin-HGS/W score was constructed by combining the albumin and HGS/W values.Cox proportional hazard regression was utilized to examine the association between the albumin level and HGS/W and patient outcomes.Results:Among these patients,2,543 were females and 3,251 were males,with a median age of 60.0 years.Optimal stratification based on patient survival revealed the ideal threshold for HGS/W to be 0.48 for males and 0.39 for females,and for albumin to be 38 for both sexes.The fully adjusted model revealed that higher Albumin-HGS/W scores were correlated with a poorer patient prognosis.Notably,an Albumin-HGS/W score of 2 was associated with a higher risk of mortality compared with a score of 0 in the total population(HR:1.813,95%CI:1.580-2.080,P<0.001).Conclusions:Low albumin or HGS/W values are associated with low survival in cancer patients with frailty.Elevated Albumin-HGS/W scores were linked to decreased survival rates in cancer patients with frailty.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
基金the Swedish Research Council(2018-02667)the National Natural Science Foundation of China(31761133015,U1704281,81901335)+3 种基金the Swedish Childhood Cancer Foundation(PR2018-0082)Swedish Governmental Grants to Scientists Working in Health Care(ALFGBG-717791)the Swedish Brain Foundation(FO2018-0034)the Chinese Scholarship Council to TL(201707040025)and to YX(201507040082)。
文摘Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion.Among these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury.In this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing factor.The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical scavenger.We also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be clarified.Finally,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.
文摘BACKGROUND The pathological diagnosis and follow-up analysis of gastric mucosal biopsy have been paid much attention,and some scholars have proposed the pathological diagnosis of 12 kinds of lesions and accompanying pathological diagnosis,which is of great significance for the treatment of precision gastric diseases,the improvement of the early diagnosis rate of gastric cancer,and the reduction of missed diagnosis rate and misdiagnosis rate.AIM To perform a histopathological classification and follow-up analysis of chronic atrophic gastritis(CAG).METHODS A total of 2248 CAG tissue samples were collected,and data of their clinical characteristics were also gathered.Based on these samples,the expression levels of Mucin 1(MUC1),MUC2,MUC5AC,and MUC6 in CAG tissue were tested by immunohistochemical assay.Moreover,we followed these patients for up to four years.The difference between different stages of gastroscopic biopsy was observed.RESULTS Through observation,it is believed that CAG should be divided into four types,simple type,hyperplasia type,intestinal metaplasia(IM)type,and intraepithelial neoplasia(IEN)type.Simple CAG accounted for 9.1%(205/2248),which was more common in elderly people over 60 years old.The main change was that the lamina propria glands were reduced in size and number.Hyperplastic CAG accounted for 29.1%(654/2248),mostly occurring between 40 and 60 years old.The main change was that the lamina propria glands were atrophy accompanied by glandular hyperplasia and slight expansion of the glands.IM CAG accounted for 50.4%(1132/2248),most of which increased with age,and were more common in those over 50 years.The atrophy of the lamina propria glands was accompanied by significant IM,and the mucus containing sialic acid or sulfate was distinguished according to the nature of the mucus.The IEN type CAG accounted for 11.4%(257/2248),which developed from the previous types,with severe gland atrophy and reduced mucus secretion,and is an important precancerous lesion.CONCLUSION The histological typing of CAG is convenient to understand the property of lesion,determine the follow-up time,and guide the clinical treatment.
基金supported by Program for New Century Excellent Talents in University(NCET-11-0949)
文摘Objective:To investigate the role of epidermal growth factor(EGF) in the pathogenesis of uterine leiomyomas.Methods:Human myometrial smooth muscle cells(HM-SMCs) and smooth muscle cells of human uterine leiomyomas(HL-SMCs) were separated from patients' specimens and cultured.After processed by EGF or PD98059(inhibitor of MKK/MEK) +EGF,the proliferation rate of both SMCs was detected by BrdU method and the phosphorylation level of p44/42 mitogen-activated protein kinase(MAPK) was determined by Western-blot.After different processing time by EGF,the phosphorylation levels of p44/42 MAPK and AKT and p27 expression level in both SMCs were detected by Western-blot.Results:EGF could significantly promote HL-SMCs proliferation and PD98059 could inhibit this effect(P<0.05);besides,PD98059 could inhibit the increase of the phosphorylation level of p44/42 MAPK in both SMCs induced by EGF.When the processing time by EGF was over 15 min,the phosphorylation levels of p44/42 MAPK and AKT in both SMCs decreased sharply and were close to zero:p27 expression in HM-SMCs raised significantly while the upregulation in HL-SMCs was little.Conclusions:EGF could not cause activation of EGFR because of the dephosphorylation of p44/42 MAPK and AKT in HL-SMCs,which caused p27 expression insufficiently and cell cycle dysregulation.
基金supported by a grant from the Science and Technology Bureau of Zhengzhou City in China,No.121PPTGG507-11the National Natural Science Foundation of China,No.81071114,81371385
文摘MicroRNA-9 （miR-9） has been shown to promote the differentiation of bone marrow mesen-chymal stem cells into neuronal cells, but the precise mechanism is unclear. Our previous study conifrmed that increased autophagic activity improved the efifciency of neuronal differentiation in bone marrow mesenchymal stem cells. Accumulating evidence reveals that miRNAs adjust the autophagic pathways. This study used miR-9-1 lentiviral vector and miR-9-1 inhibitor to modulate the expression level of miR-9. Autophagic activity and neuronal differentiation were measured by the number of light chain-3 （LC3）-positive dots, the ratio of LC3-II/LC3, and the expression levels of the neuronal markers enolase and microtubule-associated protein 2. Re-sults showed that LC3-positive dots, the ratio of LC3-II/LC3, and expression of neuron speciifc enolase and microtubule-associated protein 2 increased in the miR-9＋ group. The above results suggest that autophagic activity increased and bone marrow mesenchymal stem cells were prone to differentiate into neuronal cells when miR-9 was overexpressed, demonstrating that miR-9 can promote neuronal differentiation by increasing autophagic activity.
基金Sponsored by the Natural Science Fund Project of Jiangsu Provincial Science and Technology Department(No.BK20131418)the Jiangsu Provincial Social Science Fund Project(No.13LSB007)the Jiangsu Colleges and Universities Superior Subject(Traditional Chinese Medicine)Fund(No.PAPD)
文摘OBJECTIVE: To analyze treatment effectiveness in terms of the medication injection site. METHODS: The medical records of 423 patients with cerebral palsy who were admitted to Maternal and Child Health Hospital between January 2009 and December 2016 were collected. All cases were divided into T1, T2, T3, and T4 groups based on the use of conventional medication sites and acupoints for administering injectable medicines. RESULTS: In the T1 group, patients received injections at conventional medication sites between 2009 and 2010. In the T2 group, patients received injections at conventional medication sites combined with acupoint injection therapy I from 2011 to 2012. In the T3 group, injection at conventional medication sites plus acupoint injection II was applied between 2013 and 2014. Acupoint injection only was used in the T4 group from 2015 to 2016. Therapeutic effects were statistically compared among the different injection procedures. The overall Gross Motor Function Measure (GMFM) and Fine Motor Function Measure (FMFM) scores were significantly improved after hospital discharge. The GMFM score was considerably higher in the T4 group than in the other groups (all P = 0.001 < 0.05). The GMFM scores were significantly higher in the T2 groups than in the T1 group (P = 0.001< 0.05), but no significant difference was observed between the other paired comparions (P > 0.05). Meanwhile, the FMFM scores were significantly higher in the T2 and T4 groups than in the T1 and T3 groups (all P = 0.001 < 0.05). Site injection therapy can significantly improve gross and fine motor function in children with cerebral palsy. CONCLUSION: It is feasible to administer injectable medicines at acupoints instead of convention sites to enhance the therapeutic effect of treatment in patients with cerebral palsy.
基金supported by Trans-Century Training Programme Foundation for the Talents by the Ministry of Education (NO.NCET-11-0949)
文摘Objective:To discuss the liver function damage mechanism of patients with clonorchiasis by analyzing the ultrasound characteristics,liver function,change of the serum inflammatory factors and cell apoptosis factors.Methods:Color Doppler ultrasound technique was adopted to detect the portal vein and blood flow change of patients with clonorchiasis;ELISA was used to determine the level of different serum inflammatory factors.The levels of serum total bilirubin,serum albumin and glutamic-pyruvic transaminase were detected by automatic biochemical analyzer.Western blot was used to determine the expression of proteins relevant to apoptosis.Results:Compared with the health control group,the trunk diameter of portal vein and the thickness of spleen,as well as the hepatic artery pulsation index of clonorchiasis patients increased obviously,the mean blood flow velocity of portal vein(P<0.05 or P<0.01) decreased.The content of total bilirubin and transaminase in plasma increased significantly,but albumin decreased(P<0.05).Levels of TNF-α,IL-6 and IFN-γ increased remarkably,and the level of every factor was significantly different among patients with Child-Pugh Ⅰ,Child-Pugh Ⅱ and Child-Pugh Ⅲ classification of liver function(P<0.05 or P<0.01).With the exacerbation of liver dysfunction,levels of TNF-α,IL-6 and IFN-γ gradually increased(P<0.05).Compared with the healthy control group,the expression quantity of apoptosis protein Fas,FasL,Bax and Caspase-3 increased significantly(P<0.05 or P<0.01),but Bcl-2 decreased(P<0.05).Conclusions:Changes of ultrasonic characteristics and liver dysfunction,caused by liver fluke infection,may be related to that both inflammatory response and apoptosis response have participated in the pathogenic process and liver damage course of clonorchiasis.
基金funded by the Medical Science and Technology Research Project of Henan Province provided by the Health Commission of Henan Province(No.LHGJ20190383).
文摘Cryptorchidism affects the growth of testicular volume.Testicular volume is associated with reproductive function.The testicular atrophy index evaluates the degree of damage caused by cryptorchidism,but it remains unclear whether changes in testicular atrophy index are related to age.We selected patients who underwent surgery for unilateral palpable cryptorchidism.Testicular volume was measured using ultrasonography.The testicular atrophy indices of the undescended testes were then reviewed,and their correlation with age was analyzed.We studied 228 cases(age range:6–53 months).Scatter plots were constructed,and Loess curves were fitted,revealing a turning point at 24 months of age.The patients were divided into age groups of 6–24 months and 25–53 months.The testicular volume of the cryptorchid side was smaller than that of the normal side in both groups(both P<0.001).In the 6–24-month group,the testicular atrophy index was positively correlated with age,testicular volume on the cryptorchid side was not correlated with age,and testicular volume was positively correlated with age on the normal side.In the 25–53-month group,testicular atrophy index and testicular volumes on either side were not correlated with age.A palpable unilateral cryptorchid testis is smaller than the contralateral testis.The testicular atrophy index increases with age between 6 months and 24 months,but not between 25 months and 53 months.Testicular volume increased with age on the normal side between 6 months and 24 months,but not on the cryptorchid side.Trends in testicular atrophy index with age contribute to the decision of operation time.
文摘Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of neferine on Nav1.5 channels that are stably expressed in HEK 293 cells. We found that neferine potently and reversibly inhibited Nav1.5 currents in a concentration dependent manner with a half-maximal inhibition（IC50） being 26.15 μmol/L. The inhibitory effects of neferine on Nav1.5 currents were weaker than those of quinidine at the same concentration. The steady-state inactivation curve was significantly shifted towards hyperpolarizing direction in the presence of 30 μmol/L neferine, while the voltage-dependent activation was unaltered. Neferine prolonged the time to peak of activation, increased the inactivation time constants of Nav1.5 currents and markedly slowed the recovery from inactivation. The inhibitory effect of neferine could be potentiated in a frequency-dependent manner. These results suggested that neferine can block Nav1.5 channels under the open state and inactivating state and it is an open channel blocker of Nav1.5 channels.
文摘Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and methods: A total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone(10 mg) was dispensed into a 100 ml PCA pump with normal saline. Pump administration was initiated 15 min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 h after the procedure. Side effects were also observed.Results: Thirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed.Conclusion: Patients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.
基金supported by the National Natural Science Foundation of China,No.U21A20347(to CZ)the National Key Research and Development Program of China,No.2022YFC2704801(to CZ)+1 种基金the Henan Key Laboratory of Population Defects Prevention,No.ZD202103(to YX)the Department of Science and Technology of Henan Province of China,No.212102310221(to YX)。
文摘Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.
基金This work was supported by the Natural Science Foundation of China （30470598）.
文摘Objective To study the developmental changes of glutamic acid decarboxylase-67 （ GAD-67, a GABA synthetic enzyme） in normal and hypoxic ischemic （HI） brain. Methods C57/BL6 mice on postnatal day （P） 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature （P21, P60） and immature （P5, P9） brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia （HI） insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that （15.6±7.0）% TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.
基金This work was supported by the National Key Research&Development Program of China(No.2021YFC2701402).
文摘Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.
文摘BACKGROUND Chronic granulomatous disease(CGD)characterized by recurrent and severe bacterial and fungal infections is most common in childhood.CASE SUMMARY We reported a 24-d-old male infant who developed gastrointestinal symptoms as the first sign of CGD.CONCLUSION Gastrointestinal symptoms representing the first sign of CGD are very rare,and prompt diagnosis and treatment with broad-spectrum antibiotics were of crucial importance.
