ObjectiveTo explore the effect of Yishen Tongluo prescription on sperm DNA fragmentation index （DFI） and sperm mitochondrial membrane potential （MMP） in patients with asymptomatic idiopathic asthenospermia infertility. MethodsA total of 128 patients with asymptomatic idiopathic asthenospermia were randomly assigned to an experimental group （64 cases） and a control group （64 cases）. The experimental group received Yishen Tongluo prescription， while the control group was treated with Wuzi Yanzongwan combined with L-carnitine oral solution. One treatment course lasted 12 weeks. Spouse pregnancy rate， sperm progressive motility （PR）， total sperm motility （PR+NP）， sperm function （sperm tail hypotonic swelling rate， sperm acrosin activity）， sperm DFI， and sperm MMP were compared between the two groups before and after treatment. Adverse reactions were observed and recorded during the study， and clinical efficacy and safety were systematically evaluated. ResultsA total of 121 patients completed the study， including 61 in the experimental group and 60 in the control group. The spouse pregnancy rate in the experimental group was 14.75% （9/61）， higher than that in the control group at 6.67% （4/60）， though the difference was not statistically significant. Clinical efficacy in the experimental group was superior to that in the control group （P<0.05）. Compared with the results before treatment， sperm PR， PR + NP， sperm tail hypotonic swelling rate， sperm acrosin activity， sperm DFI， and sperm MMP were significantly improved in both groups after treatment （P<0.05）， with greater improvements in the experimental group （P<0.05）. However， there was no significant change in sperm concentration in either group after treatment. During the study， no abnormal safety indicators or significant adverse reactions occurred in either group. ConclusionThe kidney-tonifying and collateral-dredging method shows good clinical efficacy in the treatment of asymptomatic idiopathic asthenospermia infertility. Yishen Tongluo prescription can improve sperm motility， increase spouse pregnancy rate， enhance sperm function， and demonstrates good safety. Its mechanism may be related to reducing sperm DFI and increasing sperm MMP.

Objective: To understand the dynamic temporal evolution pathways of Internet addiction among university students and to identify the core driving nodes, so as to provide theoretical evidences for the precise implementation of targeted interventions. Methods: Using a convenient cluster sampling method, a total of 1 066 full time freshmen and sophomores were recruited from three universities in Guizhou, Jiangxi, and Guangdong Provinces for a follow up survey (T1:January-March 2024; T2:January-March 2025). The Revised Chen Internet Addiction Scale (CIAS-R) was employed to assess the status of Internet addiction among university students, and cross sectional as well as cross lagged panel network models were constructed to analyze Internet addiction and its multidimensional influencing factors. Results: The T1 network comprised 19 nodes and 114 non zero edges, while the T2 network comprised 19 nodes and 126 non zero edges. Cross sectional network analysis revealed the strongest association between "insufficient sleep" and "daytime fatigue"; the core nodes were "first thought upon waking for going online" and "feeling low after disconnection" (characteristics of psychological dependence) at T1, while the core nodes shifted to "impaired health" and "excitement when online" (characteristics of functional impairment and addictive psychodynamic features) at T2. Cross lagged network analysis further indicated that "reduced leisure" directly predicted "sleep compression", and a bidirectional relationship was observed between "needing more time to achieve satisfaction" and "academic decline". Conclusions Internet addiction among university students exhibits dynamic evolutionary characteristics. Stage specific targeted interventions focusing on core driving nodes are needed, integrating behavioral regulation and academic support to break the vicious cycle and enhancing the ability to cope with real life demands.

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Objective To investigate the possible role and mechanism of activation of pyroptosis classical pathway and alterations in cell adhesion in calcium-containing kidney stones after the action of high concentration of Ca2+ on HK-2 cells.Methods HK-2 cells were cultured in the presence of different concentrations of CaCl2(0,0.1,0.5,1.0,2.0,4.0 and 8.0 g/L)for 24 hours,and cell counting Kit-8(CCK-8)and flow cytometry were used to determine the optimal treatment concentration.Subsequently,the ultrastructure of renal tubular epithelial cells under high Ca2+ condition was observed by transmission electron microscopy after Ca2+ treatment.DCFH-DA staining was used to detect intracellular reactive oxygen species production,and quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot analysis were performed to examine the expression of pyroptosis-related proteins NLRP3,Caspase-1,gasdermin D(GSDMD),adhesive molecules osteopontin(OPN)and CD44 at mRNA and protein levels after high concentration Ca2+ treatment.The expression levels of pyroptosis-related inflammatory factors interleukin(IL)-1β,IL-18 and adhesive molecule monocyte chemotactic protein-1(MCP-1)were detected by enzyme-linked immunosorbent assay(ELISA)after high Ca2+ stimulation.Results Ca2+ showed cytotoxicity for HK-2 cell growth and can promote apoptosis.The higher the Ca2+ concentration,the more toxicity and apoptosis rate for HK-2 cell growth.High concentration of Ca2+ can promote pyroptosis-like morphological changes in HK-2 cells,including loss of cell membrane integrity,release of contents and numerous intracellular vacuoles.Compared with the control group,the expression levels of ROS were sequentially increased in the 1.0 g/L CaCl2 group and the 2.0 g/L CaCl2 group,and the expression levels of pyroptosis-related genes NLRP3,Caspase-1,GSDMD,and the pyroptosis-associated inflammatory factors IL-1β and IL-18,as well as the adhesion molecules OPN,CD44 and MCP-1 were significantly increased(P＜0.05).Conclusion High Ca2+ treatment can cause oxidative stress damage in HK-2 cells to produce ROS,which activates NLRP3 inflammasome,leads to the activation of the classical pathway of pyroptosis and increase the adhesion of cells,and ultimately leads to the formation of kidney stones.

Differentiated thyroid cancer usually has a good prognosis;however,recurrence occurs in 5％to 20％of patients after initial treatment,which causes physiopsychological and financial burdens for the patients.In the meantime,it complicates the treatment decision-making for clinicians.Different from initial treatment,the management of recurrent thyroid cancer should take comprehensive consideration of factors such as risks and benefits.Surgery is considered to be the first choice of treatment while radioactive iodine therapy is recommended for radioiodine-avid recurrent disease.Smaller lesions can be managed with active surveillance temporarily,and thermal ablation should only be applied to patients not suitable for additional surgery.In contrast,external beam radiotherapy and systemic therapies are considered only after all therapy options have been exhausted.

Objective:To compare clinical characteristics,treatment patterns and physiological indicators in bipolar disorder(BD)patients with different age of onset.Methods:Totally 380 patients with DSM-5 BD were se-lected in this study.Psychiatrists diagnosed the patients using the Mini International Neuropsychiatric Interview.The clinical information questionnaire and the Global Assessment of Functioning scale were utilized to collected clinical characteristics,treatment status,and physiological indicators.The onset age of BD was divided into 21 and 35 years as cut-off points.Multivariate logistic regression and linear regression were used to analyze related factors.Results:Among the 380 patients with BD,199 cases were early-onset group(52.4％),121 cases were middle-onset group(31.8％),and 60 cases were late-onset group(15.8％).There were 26.6％of patients in the early-onset group in-itially diagnosed as depression,23.1％in the middle-onset group,and 11.7％in the late-onset group.Multivariate analysis revealed that compared to the early-onset group of BD,the middle-onset(OR=2.22)and late-onset(OR=4.99)groups had more risk to experience depressive episodes,and the late-onset group(OR=6.74)had 6.74 times of risk to suffer from bipolar Ⅱ disorder.Additionally,patients in the middle-onset(β=-1.52)and late-on-set(β=-4.29)groups had shorter durations of delayed treatment,and those in the middle-onset(β=-1.62)and late-onset(β=-3.14)groups had fewer hospitalizations.Uric acid levels were lower in both the middle-onset(β=-28.39)and late-onset(β=-31.47)groups,and total cholesterol level was lower in the middle-onset group(β=-0.23).Conclusion:Patients with BD in different age of onset show significant differences in clinical charac-teristics,treatment conditions and physiological indicators.

AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

Rare diseases still lack effective treatments, and the development of drugs for rare diseases (known as orphan drugs) is an urgent medical problem. As natural active ingredients in living organisms, some biomacromolecule drugs have good biocompatibility, low immunogenicity, and high targeting. They have become one of the most promising fields in drug research and development in the 21st century. However, there are still many obstacles in terms of in vivo delivery. In view of the unique advantages of nanocarriers prepared from polymers, lipids, organic biomimetic and inorganic materials in drug delivery, researchers are committed to building an efficient delivery system with versatility and synergy to solve the bottleneck issues in treating rare diseases with biomacromolecule drugs. Therefore, this article reviews the research progress of nanocarrier delivering proteins, peptides and nucleic acids in the field of rare disease treatment in the past ten years, which provides ideas for researches on biomacromolecule drug nanosystems in the field of treatment of rare diseases.

Objective To observe the clinical effect of ursodeoxycholic acid capsules combined with laparoscopic-assisted choledochoscopic lithotomy in the treatment of intrahepatic and extrahepatic bile duct stones.Methods Patients with intrahepatic and extrahepatic bile duct stones were divided into the control group and the treatment group.The control group was treated with laparoscopic-assisted choledochoscopic lithotomy,and was given general maintenance treatment after operation,such as anti infection,liver protection,and nutritional support.On this basis,the treatment group was treated with ursodeoxycholic acid capsules(0.25 g,tid,orally administration,for 6 months).The symptom disappearance rate,liver function indicators[glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),total bilirubin(TBIL)],lipid metabolism indicators[total cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL)]and stone recurrence rate were compared between the two groups.The incidence rates of postoperative complications were calculated.Results Forty-five cases were included in the treatment group and forty-three cases in the control group,respectively.After treatment,the total effective rates in the treatment group and the control group were 95.56％(43 cases/45 cases)and 81.40％(35 cases/43 cases)(P＜0.05).Six months after surgery,the disappearance rates of upper abdominal pain in the treatment group and the control group were 95.56％(43 cases/45 cases)and 81.40％(35 cases/43 cases);the disappearance rates of hepatic tenderness were 100.00％(45 cases/45 cases)and 86.05％(37 cases/43 cases);GPT levels were(31.54±6.27)and(38.29±6.63)U·L-1;GOT levels were(38.75±5.52)and(43.46±5.08)U·L-1;total bilirubin(TBIL)levels were(26.57±6.39)and(32.28±7.61)μmol·L-1;total cholesterol(TC)levels were(5.29±1.06)and(6.12±1.03)mmol·L-1;triglyceride(TG)levels were(1.45±0.43)and(1.69±0.46)mmol·L-1;high density lipoprotein(HDL)levels were(1.69±0.36)and(1.51±0.39)mmol·L-1;stone recurrence rates were 0(0 cases/45 cases)and 11.63％(5 cases/43 cases).The differences between groups were statistically significant(all P＜0.05).The main adverse drug reactions in the treatment group were nausea and diarrhea,while there were no adverse drug reactions in the control group.The total incidence of adverse drug reactions in the treatment group and control group were 6.67％(3 cases/45 cases)and 0(0 cases/43 cases),with no statistically significant difference(P＞0.05).Conclusion The application of ursodeoxycholic acid capsules after laparoscopic-assisted choledochoscopic lithotomy can promote the improvement of clinical symptoms and liver function in patients with intrahepatic and extrahepatic bile duct stones,accelerate lipid metabolism,and prevent stone recurrence.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.