Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.

INTRODUCTION: Adverse childhood experiences (ACEs) are associated with significant long-term impacts, yet few interventions specifically target ACE exposure, especially in Asian populations. Anchor, Singapore's first home visitation programme, addresses maltreat-ment among preschool children. This study evaluated Anchor's impact on children's developmental and behavioural outcomes. METHOD: We conducted a prospective evaluation of children under 4 years assessed for maltreatment from November 2019 to July 2023. Developmental and behavioural progress was measured every 6 months using the Ages and Stages Questionnaires (ASQ-3) and ASQ:Social-Emotional (ASQ:SE-2), and annually using the Child Behaviour Checklist (CBCL). RESULTS: The results of 125 children (mean age 20.0 months, 48% female) were analysed. The mean length of stay in programme was 21.2 (7.3) months. At baseline, 92 (73.6%) children were at risk of develop-mental delay and 25 (31.7%) children aged ≥18 months had behavioural concerns. The programme was associated with significant improvements in gross motor (P=0.002) and fine motor (P=0.001) domains of the ASQ-3 and internalising problem scale (P=0.001) of the CBCL. CONCLUSION Anchor effectively enhances develop-mental and behavioural outcomes for children exposed to maltreatment. Targeted early intervention through such programmes can mitigate adverse impacts, optimising developmental trajectories and potentially reducing the long-term clinical and economic burdens associated with ACEs.
Humans ; Female ; Male ; Child Abuse/therapy* ; Child, Preschool ; Singapore ; House Calls ; Infant ; Prospective Studies ; Child Development ; Developmental Disabilities/epidemiology* ; Program Evaluation ; Child Behavior Disorders ; Child Behavior

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

This paper outlines the common aspects of constructing integrated urban medical groups,focusing on governance,organizational restructuring,operational modes,and mechanism synergy.It then delves into the challenges in China's group construction,highlighting issues with power-responsibility alignment,capacity evolution,incentive alignment,and performance evaluation.Finally,the paper suggests strategies to enhance China's compact urban medical groups,focusing on governance reform,capacity building,benefit integration,and performance evaluation.

Objective To observe the clinical efficacy of meridian massage in the treatment of lumbar disc herniation(LDH).Methods Between July 2020 and April 2023,82 patients with lumbar disc herniation were selected,including 58 males and 24 females,aged from 23 to 55 years old with an average of(43.76±6.64)years old.According to the different treatment methods,they were divided into observation group and control group with 41 cases in each group.The control group was treated with routine treatment,and the observation group was treated with meridian massage on the basis of routine treatment.In the control group,there were 30 males and 11 females;aged from 22 to 52 years old with an average of(42.27±9.34)years old;the Body mass index(BMI)ranged from 19 to 28 kg·m-2 with an average of(23.82±1.08)kg·m-2;the course of disease ranged from 0.5 to 3.0 years(2.40±0.48)years.There were 28 cases in L4,5 segment and 13 cases in L5S1 segment.In the observation group,there were 28 males and 13 females;the age ranged from 19 to 54 years old(42.19±9.26)years old;the BMI ranged from 18 to 29 kg·m-2 with an average of(23.73±1.15)kg·m-2;the course of disease ranged from 0.6 to 2.8 with an average of(2.56±0.45)years;there were 26 cases in L4,5 segment and 15 cases in L5S1 segment.Visual analogue scale(VAS),Oswestry disability index(ODI),M-JOA score and TCM syndrome score were measured before and after 3 courses of treatment,and the clinical efficacy was evaluated by the standard of curative effect evaluation.Results After treatment,VAS[(3.24±1.45)vs(4.46±0.64)],ODI[(11.45±1.98)％vs(17.21±2.74)％]and TCM symptom score[(2.03±0.27)vs(3.99±0.54)]of the observation group were lower than those of the control group.The score of M-JOA[(23.43±2.61)vs(19.37±1.62)]increased(P＜0.05).The scores of VAS,ODI andTCM symptoms in the observation group were lower than those in the control group,while the scores of M-JOA were higher than those in the control group(P＜0.05).Conclusion Meridian massage is effective in the treatment of LDH,which can effectivelyrelieve low back pain,improve clinical symptoms and increaselumbar function,which is worthy of clinical promotion.

Humans ; Lymphoma, Large-Cell, Anaplastic ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Soft Tissue Neoplasms

Humans ; Fibrosarcoma/surgery* ; Sarcoma ; Temporal Bone ; Soft Tissue Neoplasms/surgery*

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.
Mice ; Animals ; Alzheimer Disease/pathology* ; Receptor, Nerve Growth Factor ; Amyloid beta-Peptides ; Autoantibodies ; Mice, Transgenic

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

Abstract: Objective　To evaluate the influence of coronavirus disease 2019 (COVID-19) prevention and control measures on the transmission and epidemic of influenza in Chongqing, so as to provide references for formulating targeted influenza prevention and control strategies. Methods　The influenza surveillance data, during the year 2018 to 2020, were collected through the "China Influenza Surveillance Information System", and the seasonal characteristics of influenza epidemic were analyzed. The percentage of influenza like cases (ILI%) and influenza virus positive rate between 2020 and 2018-2019 were compared, so as to evaluate the impact of COVID-19 prevention and control measures on influenza epidemic characteristics. Results　The annual proportions of ILI cases in Chongqing were respectively 3.53%, 2.23% and 1.2% from 2018 to 2020, while the positive rates of influenza virus were respectively 13.97%, 23.81% and 2.65%. The distribution trend of ILI% from 2018 to 2019 fluctuated were similar, but it continued to drop and remain at a low level since February 2020. The positive rate of influenza virus showed an epidemic peak from December to March in 2018-2019, also peaked from November 2019 to January 2020, but decreased to 0 in March. ILI% was positively correlated with the positive rate of influenza virus (r=0.404 8, P<0.05). In 2020, compared with the same period of 2018-2019, the growth rate of ILI% was -66.09% and -46.32%, respectively. The positive rate of influenza virus in 2020 decreased by 81.03% and 88.87% compared with the same period of 2018-2019, respectively. The growth rates of influenza virus positive rate in January 2020 were decreased with a small rate of about 39.87%, and with a significantly decline of more than 93.65% from February. No influenza epidemic was found after March. Conclusions　Since COVID-19 prevention and control measures were implemented in January 2020 in Chongqing, the ILI% and the positive rate of influenza virus in sentinel hospitals decreased significantly. In the season of high incidence of respiratory infectious diseases, personal protection and other measures can effectively reduce influenza virus infection.