Objective: To investigate the efficacy of implantable neuromuscular electrical stimulation system on stress urinary incontinence (SUI) model in female rats. Methods: A total of 21 female infertile SD rats were randomly divided into the control，sham stimulation，and stimulation groups，with 7 rats in each group.All rats received vaginal dilation (VD) to simulate postpartum SUI.One week after VD，the control group was given normal feeding，stimulators were implanted in the pelvic floor muscles of the sham stimulation and stimulation groups.The sham stimulation group received normal feeding for 2 weeks，and the stimulation group received pelvic floor electrical stimulation (PFES) for 2 consecutive weeks.The leak point pressure (LPP) of each rat was measured with cystometry before VD (baseline value)，1 week after VD，and 2 weeks after PFES. Results: In the control group and sham stimulation group，LPP increased after 2 weeks of treatment compared with that after 1 week of VD，but it still did not return to the baseline level (P<0.001).In the stimulation group，after 2 consecutive weeks of PFES，LPP increased significantly compared with that 1 week after VD，and returned to the baseline value (P>0.05).There was no significant difference in the LPP baseline values and levels after 1 week of VD among the 3 groups (P>0.05).The LPP in the stimulation group after 2 weeks of PFES was significantly higher than that in the sham stimulation group and stimulation group (P<0.001). Conclusion: The implantable neuromuscular electrical stimulation system is effective in short-term intervention of SUI in female rats，the further studies are needed to confirm the long-term efficacy and safety of the system，the optimal stimulation sites，optimal stimulation parameters，and potential mechanisms of action.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

Objective To construct a universal influenza mRNA vaccine and evaluate its immunogenicity.Methods The antigen sequence of hemagglutinin(HA),nucleoprotein(NP)and matrix protein 2 ectodomain(M2e)in influenza A/California/04/2009 was optimized.HA,NP and 3 tandem M2e(3M2e)were cloned into pcDNA3.1 vector,respectively.Then the mRNAs were synthesized by linearization,in vitro transcription,enzymatic capping and enzymatic tailing,and named as mRNA-HA,mRNA-NP and mRNA-3M2e,respectively.The protein expression of the 3 kinds of mRNAs in 293T cells was detected by immunofluorescence assay.Comb-mRNA vaccine was prepared by enveloped mRNA-HA,mRNA-NP and mRNA-3M2e with lipid nanoparticles,respectively,and the particle size and potential were identified.Twenty-eight 6-week-old female BALB/c mice(18～22 g)were randomly divided into LNP group(n=14)and Comb-mRNA group(n=14).Hemagglutination inhibition(HI)method and microneutralization(MN)test were used to evaluate the serum antibody titer induced by Comb-mRNA vaccines.The mice were infected by 5LD50 wild-type H1 N1 influenza virus to evaluate the protective efficacy.Results The mRNA-HA,mRNA-NP and mRNA-3M2e were successfully constructed,and the 3 mRNAs could be expressed in 293T cells.The average size of mRNA encapsulated by lipid nanoparticles was 119.53±6.5 nm,and the average potential was-8.23±1.3 mV.The geometric mean titer(GMT)of HI and MN in the Comb-mRNA group were 179.6 and 201.6,compared with the LNP group.The ratio of IFN-γ+CD4+/CD8+Tcells was increased.The Comb-mRNA group could provide protection against 5LD50 wild type influenza H1 N1 virus after 2 weeks of booster immunization.Conclusion Comb-mRNA,an influenza vaccine candidate,can induce immune responses and protect mice from influenza virus challenge.

Child ; Humans ; Case-Control Studies ; East Asian People ; Genetic Predisposition to Disease/genetics* ; Methyltransferases/genetics* ; Polymorphism, Genetic ; Wilms Tumor/pathology*

Influenza viruses are responsible for a large number of infections and deaths annually, posing a serious threat to public health. Vaccination is the most effective measure to prevent influenza virus infection. However, current seasonal influenza vaccines only protect against closely matched circulating strains. Even with extensive surveillance and annual reformulation, yearly updated vaccines are still a step behind the fast-evolving viruses, often resulting in poor matches or less effective vaccines. Due to the relatively complex evolution of influenza A viruses, it is a new idea and a new means to prevent influenza epidemics by using a series of innovative technologies to develop universal influenza vaccines that can provide extensive and long-lasting protection against influenza viruses. This review summarized the latest progress in the development of universal vaccines targeting HA in the past three years, including design methods for universal vaccines targeting HA, HA stem and other conserved epitopes, compared the advantages and disadvantages of different technologies, explored the impact of immunization programs and strategies, and discussed the potential challenges to be overcome, hoping to provide reference for the successful development of universal vaccines.

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

OBJECTIVE To study the neuroprotective effects of Shenzao jianna o oral liquid （SZJN）on Alzheimer ’s disease （AD）model mice and its mechanism. METHODS The mice were randomly divided into sham operation group ，model group ， Donepezil hydrochloride tablet group （0.65 mg/kg），SZJN low-dose ，medium-dose and high-dose groups （0.3，1.5 and 7.5 g/kg， calculated by crude drug quantity ），with 12 mice in each group ，half male and half female. Each group was given relevant medicine（intragastric administration of water at constant volume in sham operation group and model group ），twice a day ，for consecutive 28 d. On the 15th day of administration ，intracerebroventricular injection of β-amyloid 1-42（Aβ1-42）combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein （CREB） and expression of brain-derived neurotrophic factor （BDNF） in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group ，the escape latency of the model group was significantly prolonged ，and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced （P＜0.01）. The level of SOD in brain tissue ，the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly （P＜0.01），while the level of MDA increased significantly （P＜ 0.01）. In hippocampal CA 1 area and cortical tissue ，nerve cells showed significantly decreased number ，the disordered arrangement and large gap ；the shape of nucleus was irregular and deeply stained ，and Nissl body was blurred ，loosely arranged and the number decreased. Compared with model group ，the escape latency of mice in each dose group of SZJN was significantly shortened ，and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly jing- increased（P＜0.01）. Above indexes of brain tissue in mice were reversed sig nificantly in SZJN high-dose group （P＜0.01），and pathological damage of brain tiss ue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice ，and alleviate the pathological injury and oxidative stress of brain tissue ，which may be related to the activation of CREB/BDNF signaling pathway.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

Objective:To explore the mediating role of boredom tendency in anxiety, depression and meaning in life in college students.Methods:Totally 590 college students in Shijiazhuang were selected to carry out a questionnaire survey, including general questionnaire, boredom proneness questionnaire (BPQ), meaning in life questionnaire (MLQ), patient health questionnaire (PHQ-9) and general anxiety disorder-7(GAD-7). Spearman correlation analysis and hierarchical regression analysis were conducted to analyze the data by using SPSS 20.0, and Amos 24.0 was used to analyze the mediating effect of boredom tendency on anxiety, depression and sense of life meaning in college students.Results:Correlation analysis found that the total score of boredom tendency was negatively correlated with meaning in life ( r=-0.260, P<0.05) and education ( r=-0.110, P<0.05). The total score of boredom tendency was positively correlated with depression ( r=0.649, P<0.05) and anxiety ( r=0.555, P<0.05). The mediating effect model fit well(χ 2/ df=0.582, GFI=1.000, AGFI=0.994, RMSEA=0.000). Boredom tendency played a partial mediating role between anxiety meaning in life(standard effect size=-0.054), a complete mediating role between depression and meaning in life(standard effect size=-0.175), and a complete mediating role between educational background and meaning in life(standard effect size=0.025). Conclusion:Boredom tendency plays a mediating role in the model between related factors and meaning in life, and attentions should be paid to the psychological development of college students.