This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

BACKGROUND:Deep muscle stimulation has the effects of releasing muscle adhesion,relieving muscle spasm,improving and restoring muscle compliance and elasticity.Electromyographic biofeedback therapy can promote nerve recovery and improve lower limb motor function and gait. OBJECTIVE:To observe the effect of the effect of deep muscle stimulation combined with electromyographic biofeedback therapy on the spasm of the triceps surae and gait changes after stroke by using a digital muscle detector and three-dimensional gait analysis system. METHODS:A total of 72 patients who met the inclusion criteria were selected from the Rehabilitation Department of the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2020 to October 2023.And they were enrolled and randomly divided into two groups(n=36 per group):a control group and a combined group.The control group received routine rehabilitation therapies,electromyographic biofeedback and pseudo deep muscle stimulation,while the combined group received true deep muscle stimulation treatment on the basis of the control group,five times per week,for 4 consecutive weeks.The oscillation frequency and dynamic stiffness of the affected gastrocnemius muscle,active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,Fugl-Meyer assessment of the lower limbs,and three-dimensional gait analysis parameters were statistically analyzed before and after treatment in two groups. RESULTS AND CONCLUSION:After treatment,oscillation frequency and dynamic stiffness values of the inner and outer sides of the affected gastrocnemius muscle in both groups of patients were significantly reduced compared with before treatment(P<0.05),and the combined group showed a more significant decrease compared with the control group(P<0.05).The active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,and Fugl-Meyer scores after treatment were significantly increased or improved compared with before treatment(P<0.05),while the combined group showed a more significant increase or improvement compared with the control group(P<0.05).In terms of gait parameters,the walking speed,frequency,and stride in both groups of patients were significantly increased compared with before treatment(P<0.05),while the combined group showed a more significant increase compared with the control group(P<0.05).The percentage time of support phase on the healthy side was shortened compared with before treatment(P<0.05),while the combined group showed a more significant decrease compared with the control group(P<0.05).In addition,there was no significant difference between the two groups except for the percentage of healthy side support(P>0.05).To conclude,the combination of deep muscle stimulation and electromyographic biofeedback can effectively alleviate triceps spasm in the short term after stroke,improve ankle dorsiflexion function,enhance lower limb motor function,and improve gait.The treatment effect is significant and worthy of clinical promotion and application.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

Purpose: Gold-standard urodynamic examination is widely used in the diagnosis and treatment of lower urinary tract dysfunction. The purpose of urodynamic quality control is to standardize urodynamic examination and ensure its clinical reference value. In our study, we attempted to use a deep learning (DL) algorithm model, mainly for the recognition of typical urodynamic signal, to help physicians complete high-quality urodynamic examinations. Methods: Urodynamic image data from 2 cohorts of adult patients with neurogenic bladder were used: (1) 300 patients with neurogenic bladder in our center from 2012 to 2018 (1,960 images used to train and validate the DL model); and (2) 100 patients with neurogenic bladder from 2020 to 2021 (695 images used to test the performance of the DL model). This resulted in a total of 2,655 images to train, validate and test the DL algorithm to predict the urdynamic signals. Results: Yolov5l had the best detection performance and the highest comprehensive index score (F1, 0.81; mean average precision, 0.83). Our study is a retrospective single-center study, and the generalization ability of the model has not been verified. Conclusions DL algorithms can help operators identify typical urodynamic signals in real time, improve the interpretation and quality of urodynamic examination, and benefit patients.

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.

BACKGROUND: The urban-rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions. METHODS: We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7-18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups. RESULTS: The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33-12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10-11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72-33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33-6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82-27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43-8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985-2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025. CONCLUSIONS The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban-rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Humans ; Child ; Adolescent ; Female ; Male ; Rural Population/statistics & numerical data* ; Overweight/epidemiology* ; Prevalence ; China/epidemiology* ; Pediatric Obesity/epidemiology* ; Obesity/epidemiology* ; Urban Population