BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

[Objective] To analyze the influence of the cycle length of hepatitis B surface antigen (HBsAg) double reagent positive samples collected from voluntary blood donors in Guangzhou on the detection results. [Methods] A total of 127 044 blood samples from voluntary blood donors at Guangzhou Blood Center from August 10 to December 9, 2023 were selected. Two ELISA reagents were used for HBsAg detection, and samples with HBsAg double reagent positive and S/CO values<10 were tested continuously for 7 days to observe the changes in their S/CO values. [Results] A total of 505 HBsAg double reagent positive samples were detected, of which 52 had S/CO values less than 10. After 7 consecutive days of uninterrupted testing, the S/CO values of Wantai (median 5 decreased to 3) and Xinchuang (median 5 decreased to 3) showed an overall downward trend, and the HBsAg missed detection rate showed an upward trend (from 0 on the first day to 1/10 000 on the seventh day). A total of 13 cases had negative double reagent test results within the 7-day testing cycle. [Conclusion] With the extension of the detection cycle, the S/CO value of HBsAg detection shows a downward trend, and the missed detection rate of HBsAg shows an upward trend. Samples used for HBsAg detection should be tested promptly after sampling to improve the quality of blood testing.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.
Aconitum ; Antiviral Agents ; COVID-19/epidemiology* ; Calcium Sulfate ; Communicable Disease Control ; Communicable Diseases/virology* ; Creatinine ; Cyclooxygenase 2 ; Drugs, Chinese Herbal/therapeutic use* ; Endothelial Growth Factors ; Epidemics/prevention & control* ; ErbB Receptors ; Humans ; Matrix Metalloproteinase 9 ; Medicine, Chinese Traditional ; Mitogen-Activated Protein Kinase 14 ; Pinellia ; SARS-CoV-2 ; TOR Serine-Threonine Kinases ; Tumor Necrosis Factors ; COVID-19 Drug Treatment

Chemical constituents of ethanol extract of Pulsatillae Radix were investigated. The n-butanol fraction of ethanol extract of Pulsatillae Radix was isolated and purified by macroporous resin and silica gel column chromatography and semi-preparative high performance liquid chromatography. The triterpenoid glycosides were identified by multiple spectral methods. Six compounds were obtained from the n-butanol fraction of ethanol extract of Pulsatillae Radix and identified as 23-aldehyde-cussosaponin C(1), cussosaponin C(2), anemoside B4(3), akebia saponin D(4), pulchinenoside E3(5), and hederacoside C(6). Among them, compound 1 was a new compound.
1-Butanol ; Drugs, Chinese Herbal ; Glycosides/chemistry* ; Ethanol/chemistry*

Wulingsan， a classic prescription first recorded in the Treatise on Cold Damage （Shang Han Lun） by ZHANG Zhong-jing for patients with water retention syndrome due to the disturbance of Qi transformation in bladder， has often been modified by ancient and modern doctors for the treatment of renal diseases. It produced satisfactory outcomes without inducing adverse reactions. The databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， and PubMed were searched for articles concerning the clinical application and pharmacological mechanism of Wulingsan in the treatment of renal diseases published by domestic and foreign scholars in recent years. The summary of the included articles revealed that Wulingsan has been widely employed for the treatment of renal edema， diabetic nephropathy， acute and chronic glomerulonephritis， nephrotic syndrome， renal insufficiency， abnormal urination， etc.， and the resulting outcomes were satisfactory. Wulingsan alone or in combination with western medicine yielded better clinical outcomes than the western medicine alone. In the exploration of its pharmacological mechanism， there existed some individual reports by Korean scholars， while Chinese scholars tended to work as a team. After years of research， each team has found that Wulingsan was superior to Wulingsan decoction in excreting water， which might be related to the absence of massive low-polarity and volatile components in the decoction that were responsible for regulating the expression of aquaporins （AQP） in kidney of saline-loaded rats. Wulingsan regulates the endocrine state of rats with kidney yang deficiency， inhibits the reabsorption of water， increases the activity of Na⁺-K⁺-ATPase， and reduces the expression of AQP 1， AQP 2， AQP 3， and AQP 4. Besides， it bi-directionally regulates the human water metabolism， which is achieved via the dual-directional regulation of purinergic P2X3 receptor expression on bladder detrusor. The efficacy of Wulingsan in treating chronic renal failure is attributed to its protection against the damaged renal tissue，structure and fanction. Hence， this paper summarized the research progress of Wulingsan in the treatment of renal diseases in recent years， aiming to provide a reference for the clinical and basic exploration of Wulingsan against renal diseases in the future.

Objective:To investigate the taxonomic structure and diversity of endophytic fungi from Datura metel and screen the strains with anti-dermatophyte activities， so as to provide resources for the development of new lead compounds against dermatomycosis. Method:Endophytic fungi were isolated from the roots， stems and leaves of D. metel after tissue block incubation and then identified by morphological analysis and rDNA-internal transcribed spacer（ITS） sequencing. Their anti-dermatophyte activities were detected by agar diffusion assay. Result:A total of 292 strains of endophytic fungi were isolated from D. metel， belonging to 34 genera， with Fusarium （72.97%） in roots， Fusarium （37.25%） and Plectosphaerella （28.43%） in stems， and Colletotrichum （39.66%） in leaves as the dominant species. The isolation rate （89.23%）， colonization rate （84.62%）， and diversity index （1.82） of endophytic fungi in leaves were significantly higher than those in roots （70.48%， 70.48% and 1.23） and stems （69.39%，68.03% and 1.64）. The determination of anti-dermatophyte activities of 35 endophytic fungal fermented filtrates showed that the strains exhibiting inhibitory activities against Microsporum canis， Trichosporon mucoides， Trichophyton rubrum and Candida albicans accounted for 97.14%， 71.43%， 45.71%， and 25.71%， respectively. Among them， six strains （17.14%）， namely Fusarium sp. R1， Penicillium sp. R5， Aspergillus sp. R7， Metarhizium sp. S18， Diaporthe sp. S19， and Glomerella sp. L57， all inhibited the four types of cutaneous fungal pathogens. Conclusion:The endophytic fungi in D. metel are diverse， and the proportion of endophytic fungi possessing anti-dermatophyte activities is high， allowing them to serve as potential resources for the development of new anti-dermatophyte agents.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.