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
BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis ...BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.展开更多
Objectives It is unclear whether G protein-coupled receptor 61(GPR61)affecting body weight,plays a role in the association between birth weight and weather.This study aimed to assess the effects of prenatal weather an...Objectives It is unclear whether G protein-coupled receptor 61(GPR61)affecting body weight,plays a role in the association between birth weight and weather.This study aimed to assess the effects of prenatal weather and GPR61 on birth weight.Methods A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during2011–2012.We detected the maternal and neonatal GPR61 promoter methylation levels,and obtained meteorological and air pollution data.Results A positive association was observed between maternal and neonatal GPR61 methylation levels,and both of them were affected by precipitation,relative humidity(RH)and daily temperature range(DTR).Birth weight was associated negatively with RH and positively with DTR(P<0.05).A significant association was observed between birth weight and neonatal GPR61 methylation.We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight(P_(interaction)<0.10),while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight(P<0.05).Conclusions Our findings revealed the significant associations among prenatal weather,GPR61 methylation and birth weight.Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions,while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.展开更多
Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A...Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.展开更多
Low birth weight(LBW)is defined as a birth weight of less than 2,500 g.It has been estimated that 15%–20%of infants(more than 20 million worldwide)were born with LBW,and 95.6%of the overall LBW infants were born in l...Low birth weight(LBW)is defined as a birth weight of less than 2,500 g.It has been estimated that 15%–20%of infants(more than 20 million worldwide)were born with LBW,and 95.6%of the overall LBW infants were born in low and middle income countries[1].Not only is LBW a crucial cause of infant mortality and morbidity,it also plays a critical role in adverse health outcomes later in life.Therefore,exploring the factors influencing LBW may have important implications for reducing maternal-child health burden.展开更多
Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia r...Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)has emerged as a global public health cha-llenge,fueled by increasing maternal age,rising obesity rates,and lifestyle shifts.It is linked to substantial short-and long-term...BACKGROUND Gestational diabetes mellitus(GDM)has emerged as a global public health cha-llenge,fueled by increasing maternal age,rising obesity rates,and lifestyle shifts.It is linked to substantial short-and long-term health risks for both mothers and their offspring,offering a critical opportunity for intergenerational prevention of metabolic disorders.AIM To synthesize current evidence on the pathophysiology,diagnosis,management,complications,and individualized treatment strategies of GDM.METHODS We conducted a narrative review in accordance with PRISMA guidelines.Pub-Med,Scopus,Web of Science,and EMBASE were searched for English-language articles(2017-2025)using terms such as“GDM”,“pregnancy”,“insulin resis-tance”,and“maternal outcomes”.After removing duplicates,512 records were screened;102 full texts were assessed for eligibility,and 55 studies were included based on methodological quality,clinical relevance,and alignment with the review objectives.RESULTS GDM results from a complex interplay among progressive insulin resistance,β-cell dysfunction,immune dysregulation,and placental inflammation.Emerging evidence indicates that hyperglycemia before formal diagnosis can impair fetal programming via epigenetic mechanisms.GDM increases a mother’s risk of developing type 2 diabetes mellitus seven-to tenfold and raises the incidence of cardiovascular disease,preeclampsia,and cesarean delivery.Offspring are at higher risk of macrosomia,neonatal hypoglycemia,and future metabolic and cardiovascular disorders.Lifestyle modification remains the cornerstone of therapy and,when necessary,can be supplemented with pharmacologic agents such as metformin or insulin.Postpartum follow-up,breastfeeding support,and preconception counseling are vital to long-term metabolic health.CONCLUSION GDM requires precision-based,life-course care.Future priorities include early risk detection,biomarker validation,unified diagnosis,and culturally sensitive interventions to improve maternal-child outcomes.展开更多
BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging ...BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging when they undergo degenerative changes because their clinical and radiological features often mimic those of ovarian tumors.We report a rare case of a giant broad ligament fibroid with cystic degeneration,which was initially mistaken for an ovarian mass.CASE SUMMARY A 49-year-old woman presented with mild abdominal distension and pain as the only symptoms.Upon abdominal examination,a large mass measuring approximately 30 cm and extending from the pelvic cavity to just below the xiphoid process was identified.Both transvaginal ultrasound and contrast-enhanced computed tomography suggested an ovarian origin of the mass.However,laparotomy confirmed that the mass originated from the right broad ligament.The mass was separated from the uterus and bilateral ovaries,with no involvement of the uterus or ovaries.The mass was completely resected with respecting the patient’s desire to retain her uterus and adnexa.Postoperative histopathological examination confirmed leiomyoma with cystic degeneration.CONCLUSION Broad ligament myomas mimic ovarian tumors;accurate diagnosis and careful operation are critical to avoid complications and ensure safety.展开更多
BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the...BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the causative genes of this disorder.CASE SUMMARY A 30-year-old woman presented with irregular black pigmentation spots to our department.Upon examination,the pigmentations were found to be especially dense on the extremities and the face.She had no family history of inbreeding,nor any previous chemical exposure.Genetic testing confirmed that the disease occu-rred because the patient has a SASH1 gene mutation.Following the use of assisted reproductive technology and preimplantation genetic testing for monogenic disorders,the patient give birth to a health baby.CONCLUSION Using assisted reproductive technology/preimplantation genetic testing for monogenic disorders is an option for DUH patients to reduce the risk of trans-mitting the pathogenic variant to their offspring.展开更多
BACKGROUND Cervical cancer is the most commonly diagnosed cancer worldwide and the most common cancer in females living with human immunodeficiency virus(HIV).Cervical cancer is classified as an acquired immune defici...BACKGROUND Cervical cancer is the most commonly diagnosed cancer worldwide and the most common cancer in females living with human immunodeficiency virus(HIV).Cervical cancer is classified as an acquired immune deficiency syndrome-defining disease.Brain metastases(BMs)from cervical cancer are extremely rare,with an incidence rate of approximately 0.63%,and there is limited information on optimal treatment protocols and patient outcomes.Since brain lesions are sequestered behind the blood-brain barrier,multimodal treatment approaches are crucial to help improve the prognosis of cervical cancer in patients with BMs who are also living with HIV.CASE SUMMARY A 42-year-old Chinese female with HIV infection was diagnosed with stage IIIC1r cervical cancer in March 2022 based on the International Federation of Gynecology and Obstetrics system.Fourteen months after undergoing the initial treatment with concurrent chemotherapy and radiotherapy in January 2024,the patient presented to a local hospital with a severe explosive headache.The patient underwent craniotomy and postoperative pathological examination confirmed metastasis of cervical squamous cell carcinoma to the brain on February 1,2024.Following surgery,the patient received external beam radiotherapy for the metastatic lesions.The patient has been under observation for 7 months with no evidence of tumor recurrence.CONCLUSION Females living with HIV are more than three times more likely to be diagnosed with cervical cancer.Due to the scarcity of cervical cancer BMs,therapeutic protocol experience is limited.In addition to the existence of the blood-brain barrier,the treatment of cervical cancer BMs appears to be exceptionally complex,and a multi-modal treatment approach consisting of chemotherapy,surgery,and radiation may help prolong patients’life.For females living with HIV,antiretroviral therapy should be prioritized,as recommended by the Center for Disease Control in China.An intact immune system and a high CD4+count are positive indicators of treatment response and tumor reduction.The overall survival of patients with cervical cancer after brain metastasis is approximately 3-5 months.However,owing to multimodal therapy and the use of antiretroviral therapy,the patient reported in this case showed no signs of recurrence after prolonged follow-up.展开更多
BACKGROUND Serous carcinoma of the uterine cervix(USCC)represents a rare subtype of cervical adenocarcinoma,classified into human papillomavirus(HPV)-independent and HPV-associated types.It is characterized by high in...BACKGROUND Serous carcinoma of the uterine cervix(USCC)represents a rare subtype of cervical adenocarcinoma,classified into human papillomavirus(HPV)-independent and HPV-associated types.It is characterized by high invasiveness and poor prognosis,with limited global reports on this condition.CASE SUMMARY A 58-year-old Chinese woman presented with painless vaginal bleeding after sexual intercourse,which appeared as droplets.HPV testing and histopathological analysis confirmed the diagnosis of HPV-associated primary serous carcinoma of the USCC.The patient underwent radical hysterectomy and was diagnosed with primary serous carcinoma of the uterine cervix,stage III C2(FIGO 2018).A multimodal treatment approach,including surgery,radiotherapy,and chemotherapy,was administered.After additional concurrent chemoradiotherapy and three cycles of chemotherapy,the patient showed no evidence of disease progression and achieved long-term survival for 53 months.CONCLUSION USCC is a rare and aggressive malignancy.Upon diagnosis,multimodal treatment strategies,including surgery,radiotherapy,and chemotherapy,can effectively prolong patient survival and improve prognosis.展开更多
Background:Four-dimensional(4D)ultrasound is increasingly being used for prenatal diagnosis of congenital heart disease(CHD).We aimed to perform a systematic review and meta-analysis to evaluate its diagnostic accurac...Background:Four-dimensional(4D)ultrasound is increasingly being used for prenatal diagnosis of congenital heart disease(CHD).We aimed to perform a systematic review and meta-analysis to evaluate its diagnostic accuracy for fetal CHD.Methods:This systematic review was conducted in accordance with the PRISMA-DTA guidelines.We systematically searched eight databases for studies published up to July 22,2025.Data were extracted to calculate diagnostic accuracy metrics,study quality was assessed using QUADAS-2,and a bivariate random-effects model was used for the meta-analysis.Results:A total of 49 studies were included,comprising 45 retrospective and 4 prospective studies,which were mainly(91.8%)conducted in China.These studies involved 23,397 fetuses,among which 2115 were diagnosed with congenital heart disease.The pooled sensitivity of 4D ultrasound for diagnosing fetal congenital heart disease was 0.91(95%CI:0.89-0.93),the pooled specificity was 0.98(95%CI:0.97-0.99),and the area under the summary receiver operating characteristic(SROC)curve(AUC)was 0.98(95%CI:0.96-0.99).Although 4D ultrasound technology can be implemented as early as 11 weeks of gestation,its diagnostic sensitivity and specificity reached a superior level and stabilized at an average of 20 weeks of gestation(range 14-28 weeks).Meta-regression indicated that sample size and prior suspicion of fetal CHD were significant contributors to heterogeneity(p<0.05).Conclusion:Four-dimensional ultrasound has high diagnostic efficacy for fetal CHD and is suitable for prenatal screening of fetal CHD,and the diagnostic effect is optimal and stable at an average gestational age of 20 weeks(range 14-28 weeks).展开更多
Objectives:Recently,pre-/post-operative Local Estrogen Therapy(LET)has shown effectiveness in alleviating Pelvic Organ Prolapse(POP)symptoms in clinical therapy.However,there is a lack of scientific evidence to suppor...Objectives:Recently,pre-/post-operative Local Estrogen Therapy(LET)has shown effectiveness in alleviating Pelvic Organ Prolapse(POP)symptoms in clinical therapy.However,there is a lack of scientific evidence to support these claims.Therefore,we aimed to explore the anti-senescence effects and mechanisms of 17β-estradiol(E2)on POP-derived fibroblasts.Methods:The primary fibroblast cells were isolated and cultured fromthe surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse(POP)at stages III-IV(quantified using the POP-Q system)and without any other treatment within 6 months.(n=12,age 50–75).Colorimetric Cell Counting Kit(CCK-8)assay and Senescence-Associated-β-Galactosidase(SA-β-Gal)staining were used to test the cell proliferative capacity and the senescence rate.Western blotting(WB)was used to detect the expression of Collagen Type I(COL-I),Collagen Type III(COL-III),Cyclin-dependent kinase 4 inhibitor A(p16INK4a),Cyclin-dependent kinase inhibitor 1A(p21),Tumor Protein 53(p53),Sirtuin 1(SIRT-1)and Microtubule-associated protein 1A/1B-light chain 3-I/II(LC3-I/II)protein.A transmission ElectronMicroscope(TEM)was used to observe the ultrastructure of fibroblasts.Results:The results showed that E2 significantly promoted the proliferation of fibroblasts derived from POP and reduced the staining rate of SA-β-Gal.It markedly enhanced the extracellular matrix proteins COL-I and COL-III,accompanied by inhibition of the senescent maker p16INK4a.Additionally,our results improved the cells’autophagy and metabolic activity.Additionally,our results indicate the anti-senescence mechanism of E2 through the mediated SIRT-1/p53/p21 axis pathway.Conclusion:We provide preliminary evidence for the anti-aging effects and mechanisms of E2 on POP,hoping to provide a theoretical basis for estrogen against POP senescence and guide the clinical application and local administration of estrogen in POP treatment.展开更多
Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-c...Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.展开更多
BACKGROUND Adenoid cystic carcinoma(ACC)of the Bartholin’s gland represents an exceptionally rare malignancy with limited documented cases in the medical literature.It typically manifests as a solid mass that clinica...BACKGROUND Adenoid cystic carcinoma(ACC)of the Bartholin’s gland represents an exceptionally rare malignancy with limited documented cases in the medical literature.It typically manifests as a solid mass that clinically warrants suspicion for neoplastic processes.CASE SUMMARY This case series details two cases of primary ACC cases involving the Bartholin’s gland treated with radical surgical resection of the vaginal lesions.Notably,divergent therapeutic approaches resulted in contrasting prognoses:The patient receiving adjuvant radiotherapy following surgery maintained disease-free status with no locoregional recurrence or metastatic progression through 58 months of surveillance.Conversely,the non-radiated patient experienced disease recurrence within 18 months postoperatively.CONCLUSION Our findings suggest that postoperative radiation therapy may significantly decrease local recurrence rates in Bartholin’s gland ACC,potentially influencing long-term disease control.This comparative outcome analysis underscores the importance of integrating adjuvant radiotherapy integration into treatment protocols for this rare malignancy.展开更多
BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no...BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no consensus or guideline for diagnosis and treatment.CASE SUMMARY In this case report,we presented the case of a 30-year-old woman at 30 weeks of gestation who presented with irregular vaginal bleeding and was admitted to a local hospital at 35 weeks of gestation with a sudden gush of fluid and underwent a C-section.During the surgery,a rotten fish-like solid mass in the lower segment of the posterior wall of the uterus was excised for biopsy.The patient was referred to our hospital because she experienced heavy vaginal bleeding 13 days after one chemotherapy session.The solid mass was initially misdiagnosed as uterine clearcell carcinoma at local hospital but later confirmed as cervical adenosquamous carcinoma by a multidisciplinary team.Three months posttreatment,she succumbed to multiple tumor metastases.The infant was healthy at the latest 2-year follow-up.CONCLUSION Obstetricians should expand differential diagnoses when obstetric factors cannot explain symptoms of persistent vaginal bleeding during pregnancy.Atypical and insidious clinical presentations are often concealed by physiological changes during pregnancy,which may increase the difficulty of diagnosis and result in misdiagnosis.展开更多
Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators...Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.展开更多
With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely app...With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.展开更多
Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in Chi...Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014–2020were recruited in this multicenter study.Two indices(i.e.,hot night excess [HNE] and hot night duration[HND]) were used to estimate the heat intensity and duration during nighttime.Linear mixed models were used to examine the association between hot nights and semen quality parameters.Results The exposure-response relationship revealed that HNE and HND during 0–90 days before semen collection had a significantly inverse association with sperm motility.Specifically,a 1 ℃ increase in HNE was associated with decreased sperm progressive motility of 0.0090(95% confidence interval[CI]:–0.0147,–0.0033) and decreased total motility of 0.0094(95% CI:–0.0160,–0.0029).HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021(95% CI:–0.0040,–0.0003) and 0.0023(95% CI:–0.0043,–0.0002),respectively.Consistent results were observed at different temperature thresholds on hot nights.Conclusion Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.展开更多
HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, includin...HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018(approval No. 2018013).展开更多
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.
文摘BACKGROUND Congenital hypothyroidism(CH)is a common condition in both preterm and term infants characterized by either thyroid gland absence or hypofunctionality.The clinical association of refractory lactic acidosis and heart failure has rarely been observed in cases of pediatric patients with CH pathology.Here,we explored the etiological relationship between CH,heart failure,and refractory lactic acidosis to reflect the importance of thyroid function screening in neonates with heart disease.CASE SUMMARY A 33-day-old extremely premature female infant presented with tachypnea,respiratory distress,recurrent infections,and abdominal distension postnatal.On admission to our facility,she had cardiomegaly,hepatomegaly,and lactic acidosis(revealed on blood gas analysis),with lactate progressively rising to 25 mmol/L.Chest radiographs showed pulmonary congestion,while echocardiography revealed cardiac enlargement,left ventricular wall thickening,and pericardial effusion.Initial management aimed at correcting acidosis and treating heart failure proved ineffective.After reassessment,thyroid function tests showed significantly decreased triiodothyronine,free triiodothyronine,thyroxine,and free thyroxine levels,with a significantly increased thyroidstimulating hormone level,confirming a CH diagnosis.Levothyroxine was administered,resulting in rapid correction of lactic acidosis and gradual improvement of thyroid function and systemic symptoms,culminating in full recovery and discharge.We also reviewed the relevant literature on thyroid and cardiac dysfunctions in order to explore their deeper association.CONCLUSION This case links CH-induced heart failure with refractory lactic acidosis,urging prompt thyroid screening in affected neonates to reduce mortality.
基金supported by the National Natural Science Foundation of China[81972981&82003401&81673116]the Scientific and Technological Project of Henan Province[202102310622]the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention[ZD202001]。
文摘Objectives It is unclear whether G protein-coupled receptor 61(GPR61)affecting body weight,plays a role in the association between birth weight and weather.This study aimed to assess the effects of prenatal weather and GPR61 on birth weight.Methods A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during2011–2012.We detected the maternal and neonatal GPR61 promoter methylation levels,and obtained meteorological and air pollution data.Results A positive association was observed between maternal and neonatal GPR61 methylation levels,and both of them were affected by precipitation,relative humidity(RH)and daily temperature range(DTR).Birth weight was associated negatively with RH and positively with DTR(P<0.05).A significant association was observed between birth weight and neonatal GPR61 methylation.We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight(P_(interaction)<0.10),while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight(P<0.05).Conclusions Our findings revealed the significant associations among prenatal weather,GPR61 methylation and birth weight.Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions,while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.
基金supported by the National Natural Science Foundation Program of China[82073653,81803313,and 81974019]China Postdoctoral Science Foundation[2020M682644]+6 种基金Hunan Provincial Science and Technology Talent Support Project(2020TJ-N07)Natural Science Foundation of Hunan Province[2018JJ2551]Hunan Provincial Key Research and Development Program[2018SK2063 and 2018SK2062]Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention[KF2020006]National Key Research and Development Program of China[2018YFA0108700 and2017YFA0105602]Postgraduate Scientific Research Innovation Project of Hunan Province[grant number CX20200271]Fundamental Research Funds for the Central Universities of Central South University[grant number 2020zzts798]。
文摘Objective This study aimed to assess the associations between maternal drug use,cytochrome P450(CYP450)genetic polymorphisms,and their interactions with the risk of congenital heart defects(CHDs)in offspring.Methods A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.Results After adjusting for potential confounding factors,the results show that mothers who used ovulatory drugs(adjusted odds ratio[a OR]=2.12;95% confidence interval[CI]:1.08-4.16),antidepressants(a OR=2.56;95%CI:1.36-4.82),antiabortifacients(a OR=1.55;95%CI:1.00-2.40),or traditional Chinese drugs(a OR=1.97;95%CI:1.26-3.09)during pregnancy were at a significantly higher risk of CHDs in offspring.Maternal CYP450 genetic polymorphisms at rs1065852(A/T vs.A/A:OR=1.53,95%CI:1.10-2.14;T/T vs.A/A:OR=1.57,95%CI:1.07-2.31)and rs16947(G/G vs.C/C:OR=3.41,95%CI:1.82-6.39)were also significantly associated with the risk of CHDs in offspring.Additionally,significant interactions were observed between the CYP450 genetic variants and drug use on the development of CHDs.Conclusions In those of Chinese descent,ovulatory drugs,antidepressants,antiabortifacients,and traditional Chinese medicines may be associated with the risk of CHDs in offspring.Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.
基金supported by the National Natural Science Foundation of China[82003401&81972981]the Key Projects of Colleges and Universities of Henan Education Department[21A330006]the Opening Foundation of National Health Commission Key Laboratory of Birth Defects Prevention and Henan Key Laboratory of Population Defects Prevention[ZD202001]。
文摘Low birth weight(LBW)is defined as a birth weight of less than 2,500 g.It has been estimated that 15%–20%of infants(more than 20 million worldwide)were born with LBW,and 95.6%of the overall LBW infants were born in low and middle income countries[1].Not only is LBW a crucial cause of infant mortality and morbidity,it also plays a critical role in adverse health outcomes later in life.Therefore,exploring the factors influencing LBW may have important implications for reducing maternal-child health burden.
文摘Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2500 g),normal birth weight(2500-3999 g),and macrosomia(≥4000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.
文摘BACKGROUND Gestational diabetes mellitus(GDM)has emerged as a global public health cha-llenge,fueled by increasing maternal age,rising obesity rates,and lifestyle shifts.It is linked to substantial short-and long-term health risks for both mothers and their offspring,offering a critical opportunity for intergenerational prevention of metabolic disorders.AIM To synthesize current evidence on the pathophysiology,diagnosis,management,complications,and individualized treatment strategies of GDM.METHODS We conducted a narrative review in accordance with PRISMA guidelines.Pub-Med,Scopus,Web of Science,and EMBASE were searched for English-language articles(2017-2025)using terms such as“GDM”,“pregnancy”,“insulin resis-tance”,and“maternal outcomes”.After removing duplicates,512 records were screened;102 full texts were assessed for eligibility,and 55 studies were included based on methodological quality,clinical relevance,and alignment with the review objectives.RESULTS GDM results from a complex interplay among progressive insulin resistance,β-cell dysfunction,immune dysregulation,and placental inflammation.Emerging evidence indicates that hyperglycemia before formal diagnosis can impair fetal programming via epigenetic mechanisms.GDM increases a mother’s risk of developing type 2 diabetes mellitus seven-to tenfold and raises the incidence of cardiovascular disease,preeclampsia,and cesarean delivery.Offspring are at higher risk of macrosomia,neonatal hypoglycemia,and future metabolic and cardiovascular disorders.Lifestyle modification remains the cornerstone of therapy and,when necessary,can be supplemented with pharmacologic agents such as metformin or insulin.Postpartum follow-up,breastfeeding support,and preconception counseling are vital to long-term metabolic health.CONCLUSION GDM requires precision-based,life-course care.Future priorities include early risk detection,biomarker validation,unified diagnosis,and culturally sensitive interventions to improve maternal-child outcomes.
文摘BACKGROUND Leiomyomas or fibroids commonly originate from the uterus;extrauterine leiomyomas are rare and most often arise from the broad ligament.Diagnosing broad ligament leiomyomas becomes particularly challenging when they undergo degenerative changes because their clinical and radiological features often mimic those of ovarian tumors.We report a rare case of a giant broad ligament fibroid with cystic degeneration,which was initially mistaken for an ovarian mass.CASE SUMMARY A 49-year-old woman presented with mild abdominal distension and pain as the only symptoms.Upon abdominal examination,a large mass measuring approximately 30 cm and extending from the pelvic cavity to just below the xiphoid process was identified.Both transvaginal ultrasound and contrast-enhanced computed tomography suggested an ovarian origin of the mass.However,laparotomy confirmed that the mass originated from the right broad ligament.The mass was separated from the uterus and bilateral ovaries,with no involvement of the uterus or ovaries.The mass was completely resected with respecting the patient’s desire to retain her uterus and adnexa.Postoperative histopathological examination confirmed leiomyoma with cystic degeneration.CONCLUSION Broad ligament myomas mimic ovarian tumors;accurate diagnosis and careful operation are critical to avoid complications and ensure safety.
文摘BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the causative genes of this disorder.CASE SUMMARY A 30-year-old woman presented with irregular black pigmentation spots to our department.Upon examination,the pigmentations were found to be especially dense on the extremities and the face.She had no family history of inbreeding,nor any previous chemical exposure.Genetic testing confirmed that the disease occu-rred because the patient has a SASH1 gene mutation.Following the use of assisted reproductive technology and preimplantation genetic testing for monogenic disorders,the patient give birth to a health baby.CONCLUSION Using assisted reproductive technology/preimplantation genetic testing for monogenic disorders is an option for DUH patients to reduce the risk of trans-mitting the pathogenic variant to their offspring.
基金Supported by the Sichuan Science and Technology Program,No.2022NSFSC0797.
文摘BACKGROUND Cervical cancer is the most commonly diagnosed cancer worldwide and the most common cancer in females living with human immunodeficiency virus(HIV).Cervical cancer is classified as an acquired immune deficiency syndrome-defining disease.Brain metastases(BMs)from cervical cancer are extremely rare,with an incidence rate of approximately 0.63%,and there is limited information on optimal treatment protocols and patient outcomes.Since brain lesions are sequestered behind the blood-brain barrier,multimodal treatment approaches are crucial to help improve the prognosis of cervical cancer in patients with BMs who are also living with HIV.CASE SUMMARY A 42-year-old Chinese female with HIV infection was diagnosed with stage IIIC1r cervical cancer in March 2022 based on the International Federation of Gynecology and Obstetrics system.Fourteen months after undergoing the initial treatment with concurrent chemotherapy and radiotherapy in January 2024,the patient presented to a local hospital with a severe explosive headache.The patient underwent craniotomy and postoperative pathological examination confirmed metastasis of cervical squamous cell carcinoma to the brain on February 1,2024.Following surgery,the patient received external beam radiotherapy for the metastatic lesions.The patient has been under observation for 7 months with no evidence of tumor recurrence.CONCLUSION Females living with HIV are more than three times more likely to be diagnosed with cervical cancer.Due to the scarcity of cervical cancer BMs,therapeutic protocol experience is limited.In addition to the existence of the blood-brain barrier,the treatment of cervical cancer BMs appears to be exceptionally complex,and a multi-modal treatment approach consisting of chemotherapy,surgery,and radiation may help prolong patients’life.For females living with HIV,antiretroviral therapy should be prioritized,as recommended by the Center for Disease Control in China.An intact immune system and a high CD4+count are positive indicators of treatment response and tumor reduction.The overall survival of patients with cervical cancer after brain metastasis is approximately 3-5 months.However,owing to multimodal therapy and the use of antiretroviral therapy,the patient reported in this case showed no signs of recurrence after prolonged follow-up.
基金Supported by the Sichuan Science and Technology Program,No.2022NSFSC0797.
文摘BACKGROUND Serous carcinoma of the uterine cervix(USCC)represents a rare subtype of cervical adenocarcinoma,classified into human papillomavirus(HPV)-independent and HPV-associated types.It is characterized by high invasiveness and poor prognosis,with limited global reports on this condition.CASE SUMMARY A 58-year-old Chinese woman presented with painless vaginal bleeding after sexual intercourse,which appeared as droplets.HPV testing and histopathological analysis confirmed the diagnosis of HPV-associated primary serous carcinoma of the USCC.The patient underwent radical hysterectomy and was diagnosed with primary serous carcinoma of the uterine cervix,stage III C2(FIGO 2018).A multimodal treatment approach,including surgery,radiotherapy,and chemotherapy,was administered.After additional concurrent chemoradiotherapy and three cycles of chemotherapy,the patient showed no evidence of disease progression and achieved long-term survival for 53 months.CONCLUSION USCC is a rare and aggressive malignancy.Upon diagnosis,multimodal treatment strategies,including surgery,radiotherapy,and chemotherapy,can effectively prolong patient survival and improve prognosis.
基金supported by the Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(ZD202308).
文摘Background:Four-dimensional(4D)ultrasound is increasingly being used for prenatal diagnosis of congenital heart disease(CHD).We aimed to perform a systematic review and meta-analysis to evaluate its diagnostic accuracy for fetal CHD.Methods:This systematic review was conducted in accordance with the PRISMA-DTA guidelines.We systematically searched eight databases for studies published up to July 22,2025.Data were extracted to calculate diagnostic accuracy metrics,study quality was assessed using QUADAS-2,and a bivariate random-effects model was used for the meta-analysis.Results:A total of 49 studies were included,comprising 45 retrospective and 4 prospective studies,which were mainly(91.8%)conducted in China.These studies involved 23,397 fetuses,among which 2115 were diagnosed with congenital heart disease.The pooled sensitivity of 4D ultrasound for diagnosing fetal congenital heart disease was 0.91(95%CI:0.89-0.93),the pooled specificity was 0.98(95%CI:0.97-0.99),and the area under the summary receiver operating characteristic(SROC)curve(AUC)was 0.98(95%CI:0.96-0.99).Although 4D ultrasound technology can be implemented as early as 11 weeks of gestation,its diagnostic sensitivity and specificity reached a superior level and stabilized at an average of 20 weeks of gestation(range 14-28 weeks).Meta-regression indicated that sample size and prior suspicion of fetal CHD were significant contributors to heterogeneity(p<0.05).Conclusion:Four-dimensional ultrasound has high diagnostic efficacy for fetal CHD and is suitable for prenatal screening of fetal CHD,and the diagnostic effect is optimal and stable at an average gestational age of 20 weeks(range 14-28 weeks).
基金supported by 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC21048)Foundation of Sichuan Provincial Science and Technology Program(2022JDR0091,2023NSFSC0004,2023NSFSC0639,2023NSFSC1742)+5 种基金Cooperation Project for Academician&Expert Workstation(HXYS20001)Sichuan University Education Foundation(0040206107011)National Natural Science Foundation of China(Nos.82371883,82402191)China Postdoctoral Science Foundation(2023M732456)Postdoctor Research Fund of West China Hospital(2024HXBH142)Sichuan University“From 0 to 1”Innovation Research Project(2023SCUH0056).
文摘Objectives:Recently,pre-/post-operative Local Estrogen Therapy(LET)has shown effectiveness in alleviating Pelvic Organ Prolapse(POP)symptoms in clinical therapy.However,there is a lack of scientific evidence to support these claims.Therefore,we aimed to explore the anti-senescence effects and mechanisms of 17β-estradiol(E2)on POP-derived fibroblasts.Methods:The primary fibroblast cells were isolated and cultured fromthe surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse(POP)at stages III-IV(quantified using the POP-Q system)and without any other treatment within 6 months.(n=12,age 50–75).Colorimetric Cell Counting Kit(CCK-8)assay and Senescence-Associated-β-Galactosidase(SA-β-Gal)staining were used to test the cell proliferative capacity and the senescence rate.Western blotting(WB)was used to detect the expression of Collagen Type I(COL-I),Collagen Type III(COL-III),Cyclin-dependent kinase 4 inhibitor A(p16INK4a),Cyclin-dependent kinase inhibitor 1A(p21),Tumor Protein 53(p53),Sirtuin 1(SIRT-1)and Microtubule-associated protein 1A/1B-light chain 3-I/II(LC3-I/II)protein.A transmission ElectronMicroscope(TEM)was used to observe the ultrastructure of fibroblasts.Results:The results showed that E2 significantly promoted the proliferation of fibroblasts derived from POP and reduced the staining rate of SA-β-Gal.It markedly enhanced the extracellular matrix proteins COL-I and COL-III,accompanied by inhibition of the senescent maker p16INK4a.Additionally,our results improved the cells’autophagy and metabolic activity.Additionally,our results indicate the anti-senescence mechanism of E2 through the mediated SIRT-1/p53/p21 axis pathway.Conclusion:We provide preliminary evidence for the anti-aging effects and mechanisms of E2 on POP,hoping to provide a theoretical basis for estrogen against POP senescence and guide the clinical application and local administration of estrogen in POP treatment.
基金supported by grants from the Natural Science Research Project of Shanxi Basic Research Program [20210302123246]the Scientific Research Project of Shanxi Provincial Health Commission [2020079]+1 种基金the Natural Science Foundation Youth Fund of Hebei Province[C2022402032]the Shanxi Province Higher Education “Billion Project” Science and Technology Guidance Project [BYJL036]。
文摘Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
文摘BACKGROUND Adenoid cystic carcinoma(ACC)of the Bartholin’s gland represents an exceptionally rare malignancy with limited documented cases in the medical literature.It typically manifests as a solid mass that clinically warrants suspicion for neoplastic processes.CASE SUMMARY This case series details two cases of primary ACC cases involving the Bartholin’s gland treated with radical surgical resection of the vaginal lesions.Notably,divergent therapeutic approaches resulted in contrasting prognoses:The patient receiving adjuvant radiotherapy following surgery maintained disease-free status with no locoregional recurrence or metastatic progression through 58 months of surveillance.Conversely,the non-radiated patient experienced disease recurrence within 18 months postoperatively.CONCLUSION Our findings suggest that postoperative radiation therapy may significantly decrease local recurrence rates in Bartholin’s gland ACC,potentially influencing long-term disease control.This comparative outcome analysis underscores the importance of integrating adjuvant radiotherapy integration into treatment protocols for this rare malignancy.
基金Supported by National Key Research and Development Program of China,No.2021YFC2701603.
文摘BACKGROUND The special physiological changes during pregnancy pose a huge challenge to the diagnosis of cervical cancer in pregnancy(CCIP).However,due to the poor prognosis of advanced-stage CCIP,there is currently no consensus or guideline for diagnosis and treatment.CASE SUMMARY In this case report,we presented the case of a 30-year-old woman at 30 weeks of gestation who presented with irregular vaginal bleeding and was admitted to a local hospital at 35 weeks of gestation with a sudden gush of fluid and underwent a C-section.During the surgery,a rotten fish-like solid mass in the lower segment of the posterior wall of the uterus was excised for biopsy.The patient was referred to our hospital because she experienced heavy vaginal bleeding 13 days after one chemotherapy session.The solid mass was initially misdiagnosed as uterine clearcell carcinoma at local hospital but later confirmed as cervical adenosquamous carcinoma by a multidisciplinary team.Three months posttreatment,she succumbed to multiple tumor metastases.The infant was healthy at the latest 2-year follow-up.CONCLUSION Obstetricians should expand differential diagnoses when obstetric factors cannot explain symptoms of persistent vaginal bleeding during pregnancy.Atypical and insidious clinical presentations are often concealed by physiological changes during pregnancy,which may increase the difficulty of diagnosis and result in misdiagnosis.
基金supported by the National Natural Science Foundation of China(82271197,81974175,31820103006,32070971,32200792,32200776).
文摘Astrocyte maturation is crucial for brain function,yet the mechanisms regulating this process remain poorly understood.In this study,we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation.We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression.Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology,including reduced process complexity and an immature gene expression profile.Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state,marked by elevated levels of HOPX and GFAP,resembling human astrocytes.Mechanistically,Olig1 and Olig2 bind directly to the Bmp7 enhancer,repressing its expression to promote astrocyte maturation.Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants,confirming the critical role of BMP7 signaling in this process.These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation,with potential implications for understanding glial dysfunction in neurological diseases.
基金supported by 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD23030)National Natural Science Foundation of China(No.82172254)Science and Technological Supports Project of Sichuan Province,China(No.2024YFFK0214).
文摘With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.
基金funded by the Guangdong Provincial Natural Science Foundation of China(No.2022A1515011517).
文摘Objective To explore and quantify the association of hot night exposure during the sperm development period(0–90 lag days) with semen quality.Methods A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014–2020were recruited in this multicenter study.Two indices(i.e.,hot night excess [HNE] and hot night duration[HND]) were used to estimate the heat intensity and duration during nighttime.Linear mixed models were used to examine the association between hot nights and semen quality parameters.Results The exposure-response relationship revealed that HNE and HND during 0–90 days before semen collection had a significantly inverse association with sperm motility.Specifically,a 1 ℃ increase in HNE was associated with decreased sperm progressive motility of 0.0090(95% confidence interval[CI]:–0.0147,–0.0033) and decreased total motility of 0.0094(95% CI:–0.0160,–0.0029).HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021(95% CI:–0.0040,–0.0003) and 0.0023(95% CI:–0.0043,–0.0002),respectively.Consistent results were observed at different temperature thresholds on hot nights.Conclusion Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
基金supported by the National Natural Science Foundation of China,No.81771642(to WMX)the New Bud Research Foundation of West China Second University Hospital of China(to GQH)
文摘HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018(approval No. 2018013).
