Six compounds were isolated from the ethyl acetate fraction of Citri Sarcodactylis Fructus by using various column chromatographic methods, such as MCI Gel CHP-20, ODS, Sephadex LH-20, silica gel and semipreparative HPLC. Their structures were identified to be citrusin G (1), citrusin H (2), citrusin E (3), syringin (4), coniferin (5), methylconiferin (6) by NMR, HR-ESI-MS, UV, IR spectra. Compounds 1 and 2 were new secondary metabolism products and 3-6 were obtained from the titled material for the first time. Compound 1 showed anti-renal fibrosis activity in TGF-β1-induced kidney proximal tubular cells.

ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

OBJECTIVE: To analyze the efficacy and access safety of extracorporeal membrane oxygenation (ECMO) in series with continuous renal replacement therapy (CRRT) access for critically ill patients using propensity score matching analysis, and to explore the potential influencing factors of infection. METHODS: A total of 200 critically ill patients who received both ECMO and CRRT treatment in the intensive care unit (ICU) of Huai'an Second People's Hospital from December 2020 to December 2024 were retrospectively selected as the research subjects. They were divided into the independent operation group (72 cases) and the series system group (128 cases) according to the access connection mode of ECMO and CRRT. Propensity score matching analysis was used to perform 1 : 1 matching for patients of the two groups. The general data [age, gender, body mass index (BMI), clinical diagnosis, underlying disease, intubation method, intubation position, disease severity, ECMO support duration, catheter indwelling duration, oxygenation index (PaO₂/FiO₂) at 48 hours after ECMO initiation, serum creatinine (SCr), procalcitonin (PCT), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT)], treatment status [ECMO initiation duration, ECMO operation duration, ECMO flow, left ventricular ejection fraction (LVEF), CRRT initiation duration, CRRT catheter indwelling duration, inflow and outflow volume of replacement fluid], clinical outcome indicators (28-day survival rate, length of ICU stay, renal function recovery, fluid balance compliance rate), and access safety indicators (incidence of ECMO access thrombosis, incidence of infection, and incidence of bleeding events) of all the patients were collected. Subgroup analysis was conducted based on the occurrence of infection, and multivariate Logistic regression analysis was used to screen the potential risk factors for infection in critically ill patients receiving both ECMO and CRRT treatment. RESULTS: Finally, a total of 120 patients were successfully matched, with 60 patients in both the independent operation group and the series system group. No statistically significant differences were observed in the general data between the two groups, indicating comparability. Compared with the independent operation group, the ECMO flow at 48 hours after ECMO initiation, SCr, and alanine transaminase (ALT) of the patients in the series system group were significantly decreased, while the LVEF at 48 hours after ECMO initiation was significantly increased, additionally, the CRRT initiation duration, CRRT catheter indwelling duration, and the length of ICU stay were significantly shortened, and the inflow and outflow volume of replacement fluid were significantly increased. The incidence of infection and bleeding events in the series system group was significantly lower than that in the independent operation group [infection incidence: 11.67% (7/60) vs. 36.67% (22/60), bleeding event incidence: 8.33% (5/60) vs. 48.33% (29/60), both P < 0.05]. No significant difference was found in the other general data, treatment status, clinical outcome indicators, or access safety indicators between the two groups. Among the 120 patients, 29 cases developed infection (accounting for 24.17%), and 91 cases had no infection (accounting for 75.83%). Compared with the non-infection group, the catheter indwelling duration was significantly prolonged and PCT was significantly increased in the infection group, while the PLT and the proportion of patients with ECMO and CRRT access connected via the series system were significantly decreased. Multivariate Logistic regression analysis showed that catheter indwelling duration [odds ratio (OR) = 1.277, 95% confidence interval (95%CI) was 1.001-1.629, P = 0.049], PCT (OR = 1.529, 95%CI was 1.222-1.914, P < 0.001], PLT (OR = 0.953, 95%CI was 0.926-0.981, P = 0.001), and access connection mode (OR = 0.289, 95%CI was 0.090-0.930, P = 0.037) were potential risk factors for infection in critically ill patients. CONCLUSIONS The ECMO-in-series CRRT access can accelerate the initiation of CRRT, avoid local bleeding, stabilize patients' cardiac, hepatic and renal functions, reduce potential infection risks, and improve the prognosis of patients.
Humans ; Extracorporeal Membrane Oxygenation/adverse effects* ; Critical Illness/therapy* ; Retrospective Studies ; Continuous Renal Replacement Therapy ; Male ; Female ; Intensive Care Units ; Propensity Score ; Middle Aged ; Renal Replacement Therapy ; Adult ; Aged ; Risk Factors

Objective:To investigate the global cognitive function and the function of specific cognitive domains in hypertensive patients at high risk of cardiovascular disease in China, and to explore the impact of cognition function on blood pressure control.Methods:This is a cross-sectional survey. Data were obtained from the ESPRIT study. Patients with a history of hypertension who participated in the ESPRIT study from September 2019 to July 2020 were selected. Mini-mental state examination (MMSE) was used to evaluate patients′ overall cognition and the function of each cognitive domain. According to the total MMSE score, patients were divided into the cognitive-intact group (MMSE total score=30 points), cognitive-declined group (MMSE total score<30 points, but did not reach the dementia screening threshold) and cognitive-impaired group (MMSE total score reached the dementia screening threshold). A multivariable logistic regression model was used to explore the effects of cognitive function and MMSE score on blood pressure control. The years of education were removed from the adjustment variables for sensitivity analysis. The interaction effect modeling of stratified variables and exposed variables was used for hierarchical analysis.Results:A total of 10 834 patients with hypertension at high risk of cardiovascular disease were enrolled, aged 65 (60, 69) years and 4 476 (41.3%) patients were female. There were 989 patients in cognitive-intact group, 8 676 patients in cognitive-declined group and 1 169 patients in cognitive-impaired group. The MMSE score of all included patients was (25.6±3.8) points. In the overall study population, 10.8% (1 169/10 834) of hypertensive patients had cognitive impairment, with an MMSE total score of (18.6±4.1) points. The cognitive domains with obvious impairment were recall memory (-80%), visuospatial function (-64%), attention and computation (-60%); 80.1% (8 676/10 834) of hypertensive patients did not meet the criteria for cognitive dysfunction, but had cognitive decline, and the cognitive domains with significant impairment were recall memory (-51%) and visuospatial structure (-23%). Multivariate logistic regression analysis showed that cognitive dysfunction ( OR=0.88, 95% CI: 0.72-1.08, P=0.212) and cognitive decline ( OR=0.96, 95% CI: 0.83-1.12, P=0.629) was not correlated with blood pressure control. MMSE total score and scores in each cognitive domain were not correlated with blood pressure control ( P>0.05). Sensitivity analysis showed that cognitive function was not related to blood pressure control (all P>0.05). Stratified analysis according to different frequency of medication showed that cognitive function and MMSE score were not correlated with blood pressure control ( P>0.05). Conclusion:One in ten hypertensive patients who were at high risk of cardiovascular disease have comorbid cognitive impairment. In patients with high risk of cardiovascular disease, the most affected cognitive domains were recall memory, visuospatial function, attention and calculation. Part of hypertensive patients have not reached the level of cognitive dysfunction, but have begun to show cognitive decline. Cognitive function is not an independent influencing factor on blood pressure control.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor.Dopamine receptor agonists(DA)are the primary choice for drug treatment.Most patients with prolactinomas respond well to DA.However,a minority of prolactinomas patients still show resistance to DA.Although drug-resistant and refractory prolactinomas are rare in clinical practice,their treatment is extremely challenging.Even a combination of drug therapy,multiple surgeries,and radiotherapy may not yield satisfactory outcomes.Therefore,standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved.In the clinical management of refractory prolactinomas,it is often necessary to consider the patient's condition comprehensively,replace other types of DA,or consider surgery,radiotherapy,and immunotherapy,which requires multidisciplinary diagnosis and treatment.This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy,surgery,and radiotherapy treatments for refractory prolactionmas,aiming to provide new ideas for basic research,clinical diagnosis and treatment.