Objective:To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insec-ticides(NNI).Methods:Fifteen C57BL/6 male mice were randomly divided into control group(CTRI.group),exposure group(NNI group)and Lactobacillus intervention group(NNI-L group).The mice in CTRL group were given 0.02ml/g of 0.5％carboxym-ethyl cellulose sodium solution by gavage for 14 days.The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days.The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5 × 108cfu/ml of Lactobacillus reuteri powder so-lution for 14 days.Then,the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining,immunofluores-cence staining and RNA sequencing.Results:Compared with CTRL group,the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner.And the decline in the number of spermatogenic cells and sperm was observed.And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group.The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequen-cing,with significant down-regulation being found in NPFF and IGF2.While the expression of HSD3B8 was significantly up-regulated.The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.Conclusion:Testicular spermatogenesis and endocrine function can be damaged by NNI exposure.And oral administration of Lactoba-cillus reuteri protects testis from the adverse effects of NNI toxicity.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective:To explore the effect and mechanism of CD147 on differentiation of circulating fibrocytes and its pro-inflammatory and pro-fibrotic function.Methods:Circulating fibrocytes were extracted from peripheral blood of asthma patients,stimu-lated with CD147,and intervened with CD147 antagonist AP-9 or p38/MAPK inhibitor SB203580.Cell viability was detected by CCK-8 method,cell migration was assessed by Transwell method,expressions of collagen type Ⅰ(COL-Ⅰ),CD45 and α-SMA were detected by immunofluorescence staining.Levels of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 were detected by ELISA,and expression levels of COL-Ⅰ,fibronectin(FN),α-SMA,p-TAK1,p-P38 and other proteins were detected by Western blot.Results:Low dose of CD147 increased cell viability of circulating fibrocytes.CD147 significantly promoted migration of circulating fibrocytes and induces their differentiation into myofibrocytes.CD147 significantly increased secretion of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 in circulating fibrocytes.CD147 significantly increased expressions of COL-Ⅰ,FN,α-SMA,p-TAK1,p-P38 in circulating fibrocytes.AP-9 or SB203580 significantly inhibited effect of CD147 on circulating fibrocytes.Conclusion:CD147 can promote proliferation,mi-gration,differentiation and pro-inflammatory and profibrotic function of circulating fibrocytes in vitro,and TAK1-p38/MAPK signaling pathway is involved in CD147-mediated regulation of circulating fibrocytes.

Objective To investigate the perioperative use of antimicrobial agents in class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City,and provide a basis for the rational use of antimicrobial agents in such surgeries.Methods Perioperative antimicrobial prophylaxis(PAP)in patients undergoing class Ⅰ incisional ophthalmic surgery reported by secondary first-class and above hospitals in Shanghai City from 2017 to 2022 was collected retrospectively.The prophylactic use rate,types,rationality of selection,and timing of use of antimicrobial agents were analyzed comprehensively.Results From 2017 to 2022,a total of 54 868 cases of class Ⅰ incisional ophthalmic surgeries were reported from secondary first-class and above hospitals in Shanghai City.The PAP rates in tertiary comprehensive hospitals,tertiary specialty hospitals,tertiary traditional Chinese medicine hospitals,and secondary comprehensive hospitals were 4.72％,1.79％,3.22％,and 6.63％,re-spectively.The overall PAP rate showed a yearly decreasing trend,from 6.39％in 2017 to 2.31％in 2021.Among different types of hospitals,the PAP rate in secondary comprehensive hospitals decreased most significantly,from 12.72％in 2017 to 0.53％in 2022.The main types of prophylactic antimicrobial use were first-,second-and third-generation cephalosporins,and quinolones.The rational selection rates of antimicrobial agents were highest in ter-tiary comprehensive hospitals(17.13％)and lowest in tertiary specialty hospitals(1.08％).The PAP rates in sys-temic veins 0.5-1 hour before surgery were highest in tertiary specialty hospitals(88.17％)and lowest in tertiary comprehensive hospitals(71.53％).The withdrawal rates of antimicrobial agents within 24 hours after surgery were highest in tertiary traditional Chinese medicine hospitals(80.87％)and lowest in tertiary specialty hospitals(13.26％).Conclusion The PAP for class Ⅰ incisional ophthalmic surgeries in secondary first-class and above medical institutions in Shanghai City still presents certain irrational phenomena in terms of antimicrobial types and administration routes.The administration rate 0.5-1 hour before surgery and withdrawal rate of antimicrobial agents within 24 hours after surgery need to be further improved.Enhanced management is necessary to promote more rational use of antimicrobial agents.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

Objective:To explore the effect and mechanism of CD147 on differentiation of circulating fibrocytes and its pro-inflammatory and pro-fibrotic function.Methods:Circulating fibrocytes were extracted from peripheral blood of asthma patients,stimu-lated with CD147,and intervened with CD147 antagonist AP-9 or p38/MAPK inhibitor SB203580.Cell viability was detected by CCK-8 method,cell migration was assessed by Transwell method,expressions of collagen type Ⅰ(COL-Ⅰ),CD45 and α-SMA were detected by immunofluorescence staining.Levels of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 were detected by ELISA,and expression levels of COL-Ⅰ,fibronectin(FN),α-SMA,p-TAK1,p-P38 and other proteins were detected by Western blot.Results:Low dose of CD147 increased cell viability of circulating fibrocytes.CD147 significantly promoted migration of circulating fibrocytes and induces their differentiation into myofibrocytes.CD147 significantly increased secretion of cytokines such as TGF-β1,IL-4,IL-5 and IL-13 in circulating fibrocytes.CD147 significantly increased expressions of COL-Ⅰ,FN,α-SMA,p-TAK1,p-P38 in circulating fibrocytes.AP-9 or SB203580 significantly inhibited effect of CD147 on circulating fibrocytes.Conclusion:CD147 can promote proliferation,mi-gration,differentiation and pro-inflammatory and profibrotic function of circulating fibrocytes in vitro,and TAK1-p38/MAPK signaling pathway is involved in CD147-mediated regulation of circulating fibrocytes.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Respiratory viral infections such as influenza and respiratory syncytial virus infections continue to rapidly increase in patients worldwide.Host immune responses to respiratory viruses play a key role in the pathogenesis and clinical manifestations of the disease.Respiratory viruses not only activate antiviral immune responses,but also may lead to uncontrolled inflammatory re-sponses,characterized by significant release of pro-inflammatory cytokines in severely infected patients,resulting in lymphopenia,lymphocyte dysfunction,and abnormalities in immune cells such as neutrophils and macrophages.These respiratory virus-induced im-mune abnormalities may lead to microbial infection,septic shock,and severe multiorgan dysfunction.Therefore,clarifying the immu-nopathogenic mechanisms of patients with respiratory viral infections can guide clinical treatment and patient prognosis;in addition,rational regulation of the immune response of respiratory viruses in the host,including enhancing antiviral immunity while suppressing systemic inflammation,may be the key to successful treatment.This review mainly discusses the immunomodulation and related clini-cal treatment strategies for respiratory viral infections to help develop new therapeutic strategies for respiratory viral infections and pa-tient prognosis.

Objective To investigate the application effect of biofeedback electrical stimulation combined with Kegel exercises using vaginal dumbbell in pelvic floor muscle strength rehabilitation of patients with postpartum pelvic floor dysfunction(PFD).Methods A prospective study was conducted on 70 PFD patients who were divided into control group(n=34)and combined group(n=36)according to random numbers generated by Excel.Control group received Kegel exercises using vaginal dumbbell,while combined group was given biofeedback electrical stimulation on this basis.Both groups underwent 3 months of continuous treatment.GRRUG method was adopted to assess pelvic floor muscle strength after treatment;a low-frequency neuromuscular stimulation therapy device was used to detect the pelvic floor muscle fiber electromyography value and fatigue value;and female sexual function index(FSFI)was utilized to evaluate the quality of sexual life.The pelvic floor function impairments in two groups were also recorded and compared.Results After treatment,compared with control group,combined group had greater proportions of above grade Ⅲ muscle strength of class Ⅰ and class Ⅱ muscle fibers(P<0.05),higher mean pelvic floor electromyography values of class Ⅰ and class Ⅱ muscle fibers(P<0.05),and lower fatigue value of pelvic floor muscle(P<0.05).In addition,combined group had higher FSFI scores for sexual desire,sexual arousal,vaginal lubrication,orgasm,satisfaction and dyspareunia,and the total score than control group(P<0.05),and the incidence rates of frequent and urgent urination,lumbosacral pain,and vaginal relaxation were lower in combined group as compared with control group(P<0.05).Conclusion The combination of biofeedback electrical stimulation and Kegel exercises using vaginal dumbbell in the treatment of patients with postpartum PFD can significantly improve pelvic floor muscle strength,alleviate symptoms such as frequent and urgent urination,lumbosacral pain and vaginal relaxation,and improve the quality of sexual life.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.