ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

Pulmonary fibrosis is a respiratory system disorder characterized by damage to alveolar epithelial cells,pathological proliferation and transformation of fibroblasts,excessive deposition of extracellular matrix,leading to structural damage and loss of function in lung tissues,with a high mortality rate and limited effective treatment methods.This article was based on the TCM understanding of"lung connecting to large intestine",namely the theory of"lung and the large intestine being interior-exterior related",and set the modern medical understanding of"lung connecting to large intestine",namely the theory of"gut-lung axis"as the key.Combining the TCM pathogenesis of pulmonary fibrosis and the related mechanisms of"gut-lung axis"in pulmonary fibrosis,it preliminarily expounded the connotation of TCM regulating the"gut-lung axis"to treat pulmonary fibrosis,aiming to provide new ideas for clinical treatment of pulmonary fibrosis through the"gut-lung axis".

Objective To explore the expression of death domain-associated protein(DAXX)and its subcellular localization in MCF-7 cells,discussing their effect on cellular function of MCF-7 cells.Methods MCF-7 cells were transfected with LV-DAXX-RNAi-GFP plasmid and LV-DAXX-GFP overexpression lentiviral plasmid,DAXX was knocked down and overexpressed.The expression and subcellular localization of DAXX in MCF-7 cells were detected by nuclear-cytoplasm separation methods and immu-nofluorescence,cell apoptosis and cell cycle were detected by flow cytometry,and cell proliferation was detected by MTT method.Results Both of the nuclear-cytoplasm separation methods and immunofluorescence confirmed that DAXX was mainly located in nucleus of MCF-7 cells.The transfection of LV-DAXX-GFP lentiviral plasmid mainly up-regulated the expression of DAXX in the cytoplasm of MCF-7 cells,while the transfection of LV-DAXX-RNAi-GFP lentiviral plasmid mainly down-regulated the expression of DAXX in the nucleus of MCF-7 cells.Flow cytometry confirmed that down-regulated the expression of DAXX located in nucleus could increase the apoptosis rate of MCF-7 cells,decreasing the cell proliferation,and block the cells in S phase,while up-regulated the expression of DAXX in cytoplasm had no significant effect on cell apoptosis,cell cycle and cell proliferation of MCF-7 cells.Conclusion DAXX is mainly located in the nucleus of MCF-7 cells.The expression of DAXX in the nucleus or cytoplasm may have the opposite effect on the cellular function of MCF-7 cells.

Objective To investigate the relationship between sperm DNA fragmentation index(DFI),high reactive oxygen species(ROS)rate,high mitochondrial membrane potential(MMP)rate,and progressive motility(PR)in patients with idiopathic astheno-zoospermia.Methods A total of 250 patients who visited the Male Department of Reproductive Medicine Center,Tangdu Hospital,from December 2022 to November 2023 were enrolled in this study.The patients were divided into mild(20％≤PR＜32％,n=86),moderate(10％≤PR＜20％,n=67),and severe(PR＜10％,n=47)asthenozoospermia groups,and a normal group(female factor infertility,normal semen parameters,PR≥32％,n=50)was formed based on their PR values.The levels of sperm DFI,high ROS and MMP rates were measured using flow cytometry,and their correlations with PR were analyzed.Results Compared with the normal group,the asthenozoospermia groups showed significantly lower sperm concentration,motility,normal morphology percentage and high MMP rate(P＜0.05),but significantly high DFI and ROS rate(P＜0.01).The severe asthenozoospermia group had significantly high DFI and ROS rate and high MMP rate was lower than that in the mild and moderate groups(P＜0.0I).No significant differences in DFI,high ROS rate and MMP rates were found between the mild and moderate groups(P＞0.05).As the severity of asthenozoospermia increased,DFI and high ROS rate showed an increasing trend,while high MMP rate decreased.Correlation analysis revealed a signifi-cant positive correlation between PR and high MMP rate(r=0.439,P＜0.01)and significant negative correlations between PR and high ROS rate(r=-0.435,P＜0.01),DFI(r=-0.478,P＜0.01).Conclusion The patients with idiopathic asthenozoospermia ex-hibit altered levels of sperm DFI,high ROS and MMP rates,which are associated with the severity of asthenozoospermia.Elevated ROS levels may lead to sperm DNA damage and mitochondrial dysfunction,resulting in decreased sperm progressive motility.

Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

Objective To investigate the effects of high concentration of semen samples in detection by fully automated sperm quality analyzer for sperm concentration,progressive motility(PR),non-progressive motility(NP)and percentage of immotile sperm(IM).Methods The semen samples from the patients who visited the reproductive clinic in our hospital from February 2023 to May 2023 were analyzed using the fully automated sperm quality analyzer.A total of 155 semen samples with initial sperm concentration ≥100× 106/mL and semen volume ≥1.5 mL were set as the high concentration semen group(group A).The semen samples with self seminal plasma dilution group(group B)and 37 ℃ normal saline dilution group(group C)were prepared with their own seminal plasma and normal saline at 1∶2 dilution ratio respectively.The sperm concentration of group A was detected by the manual method as the control.The sperm concentration and motility parameters of each group were detected.The differences of sperm concentration and the values of PR,NP and IM among the group A,B and C were analyzed.The correlations between sperm concentration and PR,NP and IM were also assessed.Results The sperm concentration of group A was significantly lower than that of the control group and groups B and C(all P＜0.05).There was no statistically significant difference for the results between group B and group C(P＞0.05).The PR in group C was significantly lower than that in groups A and B(all P＜0.05),and there was no significant difference of PR between group A and group B(P＞0.05).The values of NP in group A was significantly higher than that in groups B and C(all P＜0.05),and there was no significant difference in NP between group B and group C(P＞0.05).The IM in group A was significantly lower than that in groups B and C(all P＜0.05),and there was no statistical difference of IM values between group B ang group C(P＞0.05).Conclusion The direct analysis of undiluted semen samples with high sperm concentration may lead to lower results of sperm concentration,increased percentage of NP sperm and decreased percentage of IM sperm.The dilution of semen samples may improve the accuracy of the detec-tion results.The dilution with 37 ℃ normal saline can lead to decrease of the percentage of PR sperm.The self seminal plasma should be recommended as the first choice of diluent for the semen samples with high sperm concentration.

【Objective】 To analyze the efficacy of scrotum cold compress combined with antibiotics on necrospermia patients with seminal tract infection. 【Methods】 We made a retrospective analysis of the patients who were confirmed as necrospermia by more than 2 times of semen examination and positive by sperm bacteria culture at the Andrology Department of our center from January 2019 to September 2022. The experiment group patients who were cured by scrotum cold compress combined with sensitive antibiotics and L-carnitine were divided into experiment group A (1 time/day) and experiment group B (2 times/day) according to the daily times of scrotum cold compress. Meanwhile, only sensitive antibiotics and L-carnitine were administered in the control group patients. We recorded the improvement of sperm parameters and the number of negative sperm bacterial cultures in different groups at 4 weeks, 8 weeks, and 12 weeks of treatment. 【Results】 A total of 145 patients were enrolled in the study. According to the principle of randomization, 49 patients in group A, 49 patients in group B, and 47 patients in the control group were enrolled. After 4 weeks of treatment, there was no significant difference between the experiment group and the control group in terms of abstinence time, the number of negative sperm bacterial cultures, semen pH, sperm ratio of forward motility, or the sperm survival rate (all P>0.05). In terms of the sperm survival rate, group B (53.1±14.1) was superior to group A (46.2±16.4) (P<0.05). In the results of the treatment at 8 weeks, the number of negative sperm bacterial cultures was significantly higher in the experiment group (74/98) than in the control group (26/47) (χ²=5.14, P<0.05). Sperm ratio of forward motility was higher in the experiment group (26.5±11.9) than in the control group (22.8±12.6). The experimental group (53.1±14.6) also had a significantly higher sperm survival rate than the control group (47.6±13.4) (P<0.05). However, the number of negative sperm bacterial cultures, sperm ratio of forward motility, and the sperm survival rate were lower in experiment group A (35/49, 25.5±10.3, 51.1±15.0) than in experiment group B (39/49, 27.5±13.2, 55.1±14.2), but there was no statistical difference between the two groups (all P>0.05). After 12 weeks of treatment, the number of negative sperm bacterial cultures in the experimental group (67/98) was significantly higher than that in the control group (21/47) (χ²=6.11, P<0.05). Sperm ratio of forward motility in the experiment group (30.9±11.2) was higher than that in the control group (24.7±13.4) (P<0.05). The experiment group (56.3±13.0) had a significantly higher sperm survival rate than the control group (46.7±12.0, P<0.01). However, in terms of the number of negative sperm bacterial cultures, sperm ratio of forward motility, and the sperm survival rate, there were no statistical differences between group A (31/49, 28.8±10.0, 55.9±12.7) and group B (36/49, 32.8±12.1, 56.7±13.4) (all P>0.05). 【Conclusion】 Scrotum cold compress combined with antibiotics is superior to only antibiotic treatment on necrospermia patients with seminal tract infection, especially in the sperm ratio of forward motility and sperm survival rate, but it has little relationship with the times of cold compressions per day. Therefore, the method deserves application in this type of patients’ diagnosis and treatment.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified. Parbendazole was further proved as an effective tubulin polymerization inhibitor, which can block the cell cycle, cause apoptosis and prevent cell migration, and it exhibited reasonable therapeutic effect and low toxicity in the in vivo and in vitro anti-tumor evaluation. Our study repositioned an anthelmintic parbendazole to treat HNSCC, which revealed a therapeutic utility and provided a new treatment option for human cancers.

OBJECTIVE To provide reference for chronic disease management in grass-root institution . METHODS System structure design and audit class setting of the regional pretrial center in Changning district of Shanghai were introduced. The number of prescriptions/medical orders from the start of application to February 28，2022 were counted. The prescriptions/medical orders intercepted by the system ，prescriptions/medical orders intervened by physicians ，chronic disease types and drug use of regional multiple chronic diseases were counted and analyzed. RESULTS Compared with the data when the center was on line in September 2021，total qualified rate of prescriptions/medical orders （97.67％ vs. 86.42％）significantly increased ，the number of prescriptions/ medical orders intercepted by the system and intervened by physicians decreased by 55.39％ and 72.67％ in February 2022， respectively. The top five diseases were hypertension （26.52％），coronary heart disease （20.53％），sleep disorders （16.71％），diabetes（15.24％）and bone diseases （14.09％）. Among them ， there were many problematic prescriptions involving coronary heart disease ，sleep disorder and bone disease. CONCLUSIONS The incidence of chronic diseases among community residents remains high. In addition to common chronic diseases such as coronary heart disease ，hypertension and diabetes ，the incidence of sleep disorders and bone diseases is also increasing. With the help of the regional pretrial center ，the focus of chronic disease management can be adjusted timely ，drug supervision can be carried out in real time so as to improve the level of rational drug use in grass-root institution.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.