Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective: To investigate the influencing factors of overactive bladder (OAB) in college freshmen and the impacts of OAB on their mental health, quality of life and social interaction. Methods: An epidemiological questionnaire survey was conducted in an anonymous manner on the prevalence of OAB among 5300 freshmen aged 17 to 22 years enrolled in the 2023—2024 academic year in Xinxiang Medical University and Sanquan College of Xinxiang Medical University.The questionnaire included questions on basic information, history of urinary tract infection, constipation, smoking, history of alcohol consumption, history of coffee/strong tea drinking, history of carbonated beverage drinking, redundant prepuce, phimosis, holding urine, chronic insomnia, self-rating anxiety scale (SAS), quality of life score (QoL), and social avoidance and distress scale (SADS).The influencing factors of OAB were analyzed with multivariate logistic regression analysis.The subjects were grouped according to whether they had OAB, and the differences in SAS, QoL and SADS between the OAB group and non-OAB group were compared.The impacts of OAB on the anxiety level, quality of life, and social interaction were analyzed with multiple linear regression analysis. Results: The overall prevalence rate of OAB was 4.9% (244/5018).Multivariate logistic regression analysis showed that the history of urinary tract infection (OR=0.177), constipation (OR=0.636), smoking (OR=0.582), alcohol consumption (OR=0.685), coffee/strong tea drinking (OR=0.387), carbonated beverage drinking (OR=0.631), redundant prepuce (OR=0.673), phimosis (OR=0.311), urine holding (OR=0.593), and chronic insomnia (OR=0.256) were influencing factors for the occurrence of OAB (P＜0.05).The OAB group had higher SAS score [(41.18±6.54) vs. (38.61±6.36)], QoL score [(3.65±1.20) vs. (2.79±0.95)], social avoidance score [(6.25±1.86) vs. (5.86±1.51)], social distress score [(6.27±1.59) vs. (5.97±1.32)], and total SADS score [(12.51±2.35) vs. (11.84±2.01)] than the non-OAB group (P＜0.05).The results of multiple linear regression analysis showed that OAB could independently affect the scores of QoL, SAS, and SADS.The OAB group had higher scores of QoL, SAS, and SADS compared with the non-OAB group (P＜0.001). Conclusion: History of urinary tract infection, constipation, smoking, alcohol consumption, coffee/strong tea drinking, carbonated beverage drinking, redundant prepuce, phimosis, urine holding, and chronic insomnia are influencing factors for the occurrence of OAB in male college students.Moreover, OAB has negative impacts on their mental health, quality of life, and social interaction.

ObjectiveTo systematically review the intervention effect of cognitively engaging physical activity (CEPA) on executive function of children and adolescents. MethodsLiteratures in Chinese and English were retrieved from databases of Web of Science, PubMed, Medline, EBSCO and CNKI, from the establishment to November 30th, 2023. According to the inclusion and exclusion criteria, the literatures that met the requirements were screened, and their quality was evaluated and systematically reviewed. ResultsA total of 15 literatures were included, published between 2014 and 2023, from eight countries, involving 1 806 subjects aged four to 16 years. The average score of PEDro scale was 6.6. The intensity of the CEPA intervention ranged from 64% to 93% HR_max, the duration of a single session ranged from ten to 60 minutes, and the frequency of the intervention was two to five sessions a week, for four to 24 weeks. Specific forms of CEPA included football, basketball and floorball combined with cognitive tasks; running, jumping, squatting, sitting, spinning and balancing combined with cognitive tasks; and exergaming combined with cognitive tasks. Eleven researches showed positive effects of CEPA intervention on at least one component of executive function. However, six of the seven researches involving working memory failed to verify the positive effects. Twelve researches compared the intervention effects of CEPA and rutine exercise or regular physical education classes, and nine researches found that CEPA was more effective on executive function. ConclusionThe CEPA is effective on the executive function of children and adolescents, specifically on cognitive flexibility; it shows inconsistent effects on inhibitory control, and its effect on working memory has not been verified. The intervention types of CEPA are divided into ball games combined with cognitive tasks, basic motor skills training combined with cognitive tasks, and exergaming combined with cognitive tasks.

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT₇ receptor protein expression in the cells, indicating potential antidepressant activity.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

Objective To investigate the mechanism of the interaction between Wnt/β-catenin signaling and the epithelial mesenchymal transition(EMT)pathway in mediating sunitinib-resistance in renal cancer cells.Methods The sunitinib-resistant kidney cancer cell lines were constructed by stepwise increase in drug concentrations method with sunitinib,and were divided into resistance group,lv-NC group and lv-Twist group,and human kidney cancer cell lines were selected as normal group.The normal and drug-resistant groups were treated with conventional culture;the lv-NC group was treated with 40 μL of lv-NC lentivirus supernatant containing 2.25 × 108 TU·mL-1 for 72 h,and the lv-Twist group was treated with 50 μL of Twist lentivirus supernatant containing 1.64 × 108 TU·mL-1 for 72 h.The apoptosis ability was detected by flow cytometry;the cell migration ability was detected by cell scratch assay;the cell invasion ability was detected by Transwell assay;and the protein expression levels of Wnt1,β-catenin and Twist were detected by Western blotting assay.Results The apoptosis rates of control,resistant,lv-NC and lv-Twist groups were(17.60±0.59)％,(8.61±0.34)％,(8.60±0.40)％and(3.10±0.34)％;the migration rates were(14.10±0.12)％,(27.64±0.41)％,(14.24±0.45)％and(32.74±2.53)％;the number of invading cells was 27.33±1.15,53.33±1.53,46.00±2.65 and 99.33±2.52;the relative expression levels of Wnt1 protein were 0.10±0.01,0.96±0.06,0.39±0.03 and 3.09±0.31;the relative expression levels of β-catenin protein were 0.39±0.01,1.48±0.16,0.81±0.05 and 1.24±0.14;the relative expression levels of Twist protein were 0.10±0.02,0.91±0.04,0.39±0.03 and 3.09±0.31,respectively.The differences of above indexes were statistically significant between the resistant group and the normal group,and between the lv-Twist group and the lv-NC group(all P＜0.05).Conclusion Twist(EMT related protein)mediates sunitinib resistance in renal cell carcinoma by interacting with Wnt/β-catenin signaling pathway.

Objective To investigate the value of urodynamic study(UDS)in guiding the treatment of lower urinary tract dysfunction(LUTD)in elderly patients with ischemic stroke(IS)during convalescence,in order to provide reference for clinical treatment.Methods A total of 50 LUTD patients with IS who were admitted to the First Affiliated Hospital of Xinxiang Medical University during Jan.2020 and Jan.2022 were selected.Oral tolterodine was administered to patients with detrusor overactivity(DO),clean intermittent catheterization(CIC)to those with no detrusor reflex and symptomatic increased residual urine,and oral administration of tamsulosin to those with functional obstruction of bladder outlet.The lower urinary tract symptoms(LUTS)relief rate,UDS parameters and quality of life(QoL)scores were compared before treatment and 3 months after treatment.Results The UDS examination results showed that 25 cases(50.0％)had simple DO,9 cases(18.0％)had DO with impaired detrusor muscle contraction function,5 cases(10.0％)had DO with bladder outlet functional obstruction,4 cases(8.0％)had no detrusor reflex,and 7 cases(14.0％)had simple bladder outlet functional obstruction.After 3 months of treatment,the symptoms of LUTS,including frequent urination,urgent urination,incontinence,dysuria and urinary retention were significantly improved(P＜0.05).The maximum urine flow rate and urine output were significantly increased,the residual urine volume was significantly reduced,QoL scores were significantly reduced,with significant differences(P＜0.001).Conclusion UDS is significant in guiding the treatment of LUTD in elderly patients with IS during convalescence.

Objective To explore the changes of metabonomics in blood of mice after high-voltage electric shock,then screen out the significantly changed differential metabolites and metabolic pathways.Methods The head of C57BL/6J mice was subjected to high-voltage electric shock(electric shock group)or exposed to acoustic and optical stimulation of high-voltage electric(control group),then the whole blood from mice were collected to separate serum.The dual platform combined metabonomic analysis based on gas chromatography-mass spectrometer(GC-MS)and liquid chromatography-mass spectrometer(LC-MS)was performed and orthogonal partial least squares discriminant analysis(OPLS-DA)was used to screen the differential metabolites and related metabolic pathways.Results A total of 415 differential metabolites were screened out in metabonomics in blood of mice after high-voltage electric shock,including 187 up-regulated and 228 down-regulated metabolites.These differentially metabolites were significantly enriched in metabolic pathways including central carbon metabolism in cancer,glucagon signaling pathway,etc.Conclusion By establishing the model of high-voltage electrical injury on experimental mice,this study reveals the significant change of metabolite content and metabolic pathway in blood by high-voltage electrical injury.Which provides a basis for the damage of blood metabolic activity by high-voltage electrical injury,and suggests the potential harm of high-voltage electrical injury to blood metabolic activity in the whole body.