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*

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis.Methods:A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group(n=68)and a control group(n=64),the former following the Mediterranean dietary pattern,the latter adhering to their own dietary habits,and meanwhile both receiving lifestyle guidance,psychological counseling,symptomatic medication and physiotherapy according to their specific symptoms.The patients were followed up for 4 weeks,therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment.Re-sults:Compared with the baseline,the quality of life(QOL)scores,pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment(P<0.05),even more decreased in the former than in the latter,but with no statistically significant difference between the two(P>0.05).The rate of therapeutic effective-ness was higher in the observation group than in the control(87.1%vs 79.7%,but showed no statistically significant difference be-tween the two groups(P>0.05).Conclusion:Multimodal therapy is suitable for the management of different clinical manifesta-tions of individual patients,while dietary habits vary from person to person as well as from region to region.Therefore,scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.

Objective:To investigate the selection of the modality of transperineal surgery and its effect in the treatment of pel-vic fracture-induced posterior urethral atresia(PUA).Methods:This study included 116 cases of PUA caused by pelvic fractures treated in our hospital from January 2012 to December 2021.We used transperineal resection of the urethral stricture and end-to-end u-rethral anastomosis(EEUA)as the first choice in the treatment of 79 cases.For the patients with the urethral atresia segment longer than 3 cm and evident urethral involution tension,we incised the penile septum,separated and removed the muscle tendon and scar tis-sue attached to the lower border of the pubis,and anastomosed with 4-0 absorbable thread for 8 stitches.For the other 37 cases for which we were not sure of effective suture of the membrane due to obvious scarring of the proximal urethra,the remaining urethra shor-ter than 5 mm or incomplete urethral mucosa,we selected conventional urethral pull-through operation(UPTO).We followed up the patients for 3-24 months postoperatively.Results:The total success rate of surgery was 78.4％(91/116),81.1％(30/37)in the UPTO and 77.2％(61/79)in the EEUA group,significantly higher in the former than in the latter(P=0.05).The rate of post-operative dysuria was remarkably lower in the UPTO than in the EEUA group(13.5％[5/37]vs 16.5％[13/79],P=0.05),and so was that of surgical failure(5.4％[2/37]vs 6.3％[5/79],P=0.05).The main causes of postoperative dysuria in the EEUA group included restenosis resulting from incomplete scar resection and the two sides of the anastomosed urethral segment not being at the coaxial level,while those in the UPTO group included the formation of mucosal flaps in the pulled-through urethra,and re-scarring leading to stricture or the pulled-through urethra not being at the coaxial level.Among the 7 cases of surgical failure due to recurrence,1 refused reoperation and opted for cystostomy tube drainage,and the other 6 underwent EEUA again 6 months later.Conclusion:EEUA is preferred as the first-choice surgery for PUA,while UPTO remains an effective treatment option in hospitals with preliminary skills and less experience in the management of PUA.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

The male patient was referred to the hospital at 44 days old due to dyspnea after birth and inability to wean off oxygen. His brother died three days after birth due to respiratory failure. The main symptoms observed were respiratory failure, dyspnea, and hypoxemia. A chest CT scan revealed characteristic reduced opacity in both lungs with a "crazy-paving" appearance. The bronchoalveolar lavage fluid (BALF) showed periodic acid-Schiff positive proteinaceous deposits. Genetic testing indicated a compound heterozygous mutation in the ABCA3 gene. The diagnosis for the infant was congenital pulmonary alveolar proteinosis (PAP). Congenital PAP is a significant cause of challenging-to-treat respiratory failure in full-term infants. Therefore, congenital PAP should be considered in infants experiencing persistently difficult-to-treat dyspnea shortly after birth. Early utilization of chest CT scans, BALF pathological examination, and genetic testing may aid in early diagnosis.
Infant ; Infant, Newborn ; Humans ; Male ; Bronchoalveolar Lavage/adverse effects* ; Pulmonary Alveolar Proteinosis/pathology* ; Dyspnea/etiology* ; Respiratory Insufficiency

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Objective:To investigate the risk factors of low-level viremia (LLV) among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients after combined anti-retroviral therapy (ART), and to provide evidence for reducing the risk of LLV.Methods:It was a cross-sectional observation study that enrolled HIV/AIDS patients with LLV (plasma HIV-1 RNA was 50 to 1 000 copies/mL) receiving ART over one year (LLV group) from January 2019 to December 2020 in Guangzhou Eighth People′s Hospital, Guangzhou Medical University. Contemporaneous patients with ART over one year and successful viral suppression (plasma HIV-1 RNA<50 copies/mL) were randomly selected as the control group (suppression group) with a ratio of 1∶2.5, and the risk factors for LLV were analyzed by unconditional logistic regression.Results:A total of 128 and 297 patients were enrolled in LLV group and the suppression group, respectively.ART durations were 3.62(1.83, 4.89) years and 4.91(2.90, 5.88) years, respectively. Multivariate logistic regression analysis showed that the risk factors associated with LLV included the age of initial ART treatment above 50 years old (odds ratio ( OR)=1.82, 95% confidence interval ( CI) 1.01 to 3.26, P=0.046), the baseline HIV-1 RNA over 1×10 5 copies/mL ( OR=2.18, 95% CI 1.30 to 3.68, P=0.003), using the simplified initial ART regimen ( OR=1.82, 95% CI 1.02 to 3.26, P=0.044), missing medication more than three times per year ( OR=2.49, 95% CI 1.55 to 4.01, P<0.001) and changing regimen during ART ( OR=1.90, 95% CI 1.14 to 3.14, P=0.013), while the duration of ART longer than five years could reduce the risk of LLV ( OR=0.37, 95% CI 0.22 to 0.64, P<0.001). In patients with simplified initial ART regimen, the baseline CD4 + T lymphocyte count of whom with LLV was lower than that of whom with viral suppression, and the difference was statistically significant (94.00 (24.00, 281.00)/μL vs 375.00 (310.00, 435.00)/μL, Z=-2.60, P<0.001). Conclusions:The occurrence of LLV is related to the age of initial ART treatment, the baseline HIV-1 RNA, the initial ART regimen, the medication adherence and the change of ART regimen during ART. Strategies may be beneficial to reducing the risk of LLV for HIV/AIDS patients, such as initiating ART as soon as possible, using simplified regimen as initial regimen with caution in patients with low baseline CD4 + T lymphocyte counts, strengthening compliance education, avoiding unnecessary ART regimen changes.