Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective To investigate the relationship between serum high mobility group protein B1(HMGB1),Golgi protein 73(GP73),interleukin-37(IL-37)and HBV-DNA load in patients with hepatitis B virus-associated chronic plus acute liver failure(HBV-ACLF)and the value of predicting prognosis.Methods A total of 112 HBV-ACLF patients from the 980th Hospital of PLA Joint Logistic Support Force from July 2018 to July 2023 were retrospectively analyzed,and were divided into death group(n=42)and sur-vival group(n=70)according to the clinical outcomes of HBV-CALF patients within 90 days after admis-sion.The clinical data and serum levels of HMGB1,GP73 and IL-37 of the two groups were compared,the prognotic factors of the HBV-CALF patient were analyzed,and the relationship between serum HMGB1,GP73 and IL-37 and HBV-DNA load was analyzed.The prognostic value of serum HMGB1,GP73 and IL-37 in HBV-CALF patients were evaluated.Results There were significant differences in disease stage,peritonitis,hepatic encephalopathy,pulmonary infection,HBV-DNA load and MELD score between the death group and the survival group(P＜0.05).Serum levels of HMGB1,GP73 and IL-37 in death group were higher than those in survival group(P＜0.05).Disease stage,peritonitis,hepatic encephalopathy,pulmonary infection,HBV-DNA load,MELD score and serum HMGB1,GP73 and IL-37 levels were all independent prognoses of HBV-ACLF patients(P＜0.05).The levels of serum HMGB1,GP73 and IL-37 in HBV-ACLF patients were negatively correlated with HBV-DNA load(P＜0.05).The area under the curve(AUC)values of serum HMGB1,GP73 and IL-37 in predicting the prognosis of HBV-ACLF patients were 0.781,0.790 and 0.782,re-spectively.The AUC value of the combined prediction was the largest(0.944),and the sensitivity and speci-ficity were 86.33％and 91.43％,respectively.Conclusion Serum HMGB1,GP73 and IL-37 levels are closely related to HBV-DNA load and prognosis of HBV-CALF patients,and the combined detection of these three indexes is helpful to improve prognosis prediction efficiency.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective: To investigate the prevalence of Internet addiction and depression of students, and to analyze the co-occurrence and trend, so as to provide a theoretical basis for prevention and controlling measures of Internet addiction and depression. Methods: A total of 6 317,7 152,81 808,71 180 and 89 932 students aged 10 to 24 years from 12 leagues (103 banners) in Inner Mongolia Autonomous Region were selected by stratified random cluster sampling in September each year from 2017 to 2021. The Internet Addiction Scale and the Central for Epidemiologic Studies Depression Scale(CES-D) was used to measure Internet addiction and depression. And the annual inspection rate, group difference and annual change trend in students were calculated. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non linear associations between Internet addiction and depression in students. Results: The Internet addiction proportion in students gradually decreased from 4.1% in 2017 to 2.1% in 2020, but increased to 3.9% in 2021. And the depressive symptoms proportion increased from 20.9% in 2017 to 28.0% in 2020 and 27.0% in 2021. The detection rate of Internet addiction and depression comorbidities remained at 1.8% to 2.5 %. The Internet addiction proportion in boys was higher than that in girls( χ 2=42.82， P <0.05). The depressive symptoms prevalence in girls was higher than that in boys( χ 2= 553.90， P <0.05). Taking reversal in prevalence of Internet addiction in urban and rural areas was observed in 2019. The detection rates of depressive symptoms and comorbidity were higher in urban areas than these in suburban counties on the whole, and the difference showed a trend of decreasing or even equalizing year by year. Internet addiction was positively correlated with depressive symptoms score ( B=1.67, 95%CI =1.64-1.71), the proportion of depressive symptoms ( OR=1.39, 95%CI =1.38-1.41) and the proportion of major depressive symptoms ( OR=1.35, 95%CI =1.33-1.36) among students in 2021 ( P <0.05). An N-shaped curve was found in the significant nonlinear associations between internet addiction and depression across sex, region and school stage. Conclusion Internet addiction and depression in students show significant linear and non-linear associations, which are consistent in different sexes, regions and school stages. Therefore, relevant measures should be made and implemented in each region, especially in suburb areas, so as to prevent the increasingly development of adolescents and children s Internet addiction and depression.

Objective To analyze the difference of echocardiography in patients with chronic Keshan disease (CKD) at different altitudes areas,explore the effects of altitude on the structure and functional of right heart in CKD patients,and provide a reference for imaging diagnosis of CKD.Methods According to the three step distribution of the terrain in China,30 cases of CKD patients in the first step (altitude ＞ 4 000 m) of Tibet autonomous region were randomly selected as the Tibetan plateau group.In the second step (altitude:1 000-2 000 m),31 cases were randomly selected in Gansu Province as the Loess plateau group.In the third step (altitude ＜ 500 m),42 cases were randomly selected in Shandong Province as the plain group.Echocardiography was used to analyze the morphology,hemodynamics and function of right heart.Results Right atrial transverse diameter (RATD),right ventricular transverse diameter (RVTD),right ventricular lateral wall thickness (RVWT) and main pulmonary artery diameter (MPAD) of the Tibetan plateau group,the Loess plateau group and the plain group (mm:49.75 ± 8.40,45.64 ± 7.63,43.56 ± 7.34;50.89 ± 7.13,46.56 ± 5.62,43.27 ± 6.01;4.75 ± 1.02,3.53 ± 0.61,3.37 ± 0.51;32.87 ± 3.62,28.93 ± 2.12,28.44 ± 2.71) were significant differences among the three groups (F =5.36,12.91,37.08,23.33,P ＜ 0.01).The above indexes of the Tibetan plateau group were higher than those of the Loess plateau group and the plain group (P ＜ 0.05).RVTD of Loess plateau group was higher than that of plain group (P ＜ 0.05).The fractional area change [FAC,(24.85 ± 2.75)％,(26.26 ± 3.42)％,(26.73 ± 3.14)％],tricuspid annular plane systolic excursion [TAPSE,(12.87 ± 1.12),(14.59 ± 1.63),(14.13 ± 1.31) mm] of the Tibetan plateau group,the Loess plateau group and the plain group were significant differences among the three groups (F =3.36,13.47,P ＜ 0.05 or ＜ 0.01);the above indexes of the Tibetan plateau group were lower than those of the Loess plateau group and the plain group (P ＜ 0.05).Tei index (0.87 ± 0.18,0.78 ± 0.16,0.71 ± 0.14),tricuspid flap diastolic maximum filling speed/tricuspid annulus early diastolic peak velocity (E/E',9.48 ± 1.22,8.64 ± 0.91,8.12 ± 1.13),systolic pulmonary artery pressure [SPAP,(49.58 ± 11.76),(44.35 ± 11.41),(42.67 ± 12.13) mmHg,1 mmHg =0.133 kPa] of the Tibetan plateau group,the Loess plateau group and the plain group were significant differences among the three groups (F =12.89,13.99,3.12,P ＜ 0.01 or ＜ 0.05);the Tei index and E/E'of the Tibetan plateau group were higher than those of the Loess plateau group and the plain group (P ＜ 0.05).Tei index,E/E'of the Loess plateau group were higher than those of the plain group (P ＜ 0.05).Conclusions The right heart structure and function of CKD patients are affected by the altitude of their residence.With the increase of altitude,the right heart is enlarged,the right ventricular systolic and diastolic functions are decreased,and SPAP is increased in CKD patients.

Objective:To explore the academic procrastination (AP) status and related factors in college students. Methods: Totally 828 undergraduates (277 male, 551 female, age 18-25 years) from Sun Yat-Sen University were investigated with a self-made questionnaire for basic information and Undergraduate Academic Procrastination Questionnaire (UAPQ) for AP status. UAPQ included overall learning procrastination (OLP), homework procrastination (HP), exam preparing procrastination (EPP) and self-learning procrastination (SLP). Students who scored more than 3 in OLP, HP, EPP, SLP were regarded as procrastinator. Result: The procrastination rates of OLP, HP, EPP, SLP were 40.7％, 29.7％, 41.5％, and 47.6％. Multiple linear regression analysis results showed that bigger (β = 0.32) and normal (β =0.15) influence for academic by mobile-phone, higher level of computer dependence (β =0.15) were positively related with academic procrastination. Higher (β =-0.27) and normal (β =-0.17) levels of grade satisfaction were negatively correlated with academic procrastination. The seniors' academic procrastination levels were lower than those in other grade (β =-0.12). Conclusion: It suggests that undergraduates procrastinate widely in many academic activities. Bigger and normal influence for academic by mobile-phone, higher level of computer dependence may be risk factors of procrastination, while being satisfied with grades and seniors may be protective factors.

Objective To investigate the effects of oral care using hydrogen peroxide and sodium bicarbonate to prevent neonatal ventilator associated pneumonia(VAP). Methods Totally 209 neonates were recruited and divided into the experimental group with 104 cases and the control group with 105 cases by using random number table method. Based on conventional mechanical ventilation nursing,the experimental group received oral care using 1.5%hydrogen peroxide combined with 2.5% sodium bicarbonate,Q8H,while the control group received oral care using only 2.5% sodium bicarbonate,Q8H. Positive results of bacteria detection in tracheal sputum culture,the incidence rate of VAP,mechanical ventilation time,hospitalization time and hospitalization costs were compared between two groups. Results After 48 hours of mechanical ventilation,the difference in positive results of bacteria detection in tracheal sputum culture between two groups was statistically significant(P<0.05). The difference of incidence rate of VAP between two groups showed no statistical significance(P>0.05) when the duration of the mechanical ventilation was 48 hours. While after 48 hours of the mechanical ventilation,the difference of the incidence rate of VAP between two groups was statistically significant(P<0.05). The differences in mechanical ventilation time and hospitalization time between two groups were statistically significant(P<0.05). The hospitalization costs of the experimental group was higher than that of the control group,while the difference showed no statistical significance(P>0.05). Conclusion The combined usage of hydrogen peroxide and sodium bicarbonate for oral care can effectively eliminate neonatal oral bacteria colonization and prevent neonatal VAP,so as to reduce the time of mechanical ventilation and hospitaliza-tion, and decrease hospitalization costs.

Objective To establish the method of identifying MRSA with Taqman-fluorescence quantitative PCR basing on mecA/nuc/fem B three gene combined detecting.Methods Taking the coagulase positive MRSA,which isolated from the clinical samples and confirmed by VITEK 2 compact microbial analyzer,as the research obj ect,designed mecA/nuc/fem B specific PCR primers and Taqman fluorescent probe by bio-software PrimerPremier 5 and Designer Beacon 7,FAM,HEX and ROX markers were used to label the fluorescent probe at 5’,and the end of 3’was labeled with BHQ1,detected by fluo-rescence quantitative PCR instrment.Results ①1 g/dl gel electrophoresis results showed that the primer’s specificity of mec A/nuc/fem B were good,and molecular weight of the amplification band consistent with the expected molecular weight and no non-specific amplification band.②Three genes were obtained specific amplification in a single tube single channel and single tube multiple channel detection in PCR,and the three gene amplification effect in a single tube single tube single chan-nel and multichannel PCR similar.Conclusion Successfully established a method of multi channel Taqman-probe fluores-cence quantitative PCR identification of MRSA,mec A/nuc/fem B combined detection can effectively differentiate coagulase negative and positive MRSA,improve the accuracy of identification.

Objective To observe the effect of Bacillus coagulans tablets Combined with minus Xiaoyao powder, Nifuratel nystatin soft capsule in treatment of VVC. Methods A total of 108 cases of VVC. patients were randomly divided into 2 groups:observation group and control group. In the observation group (n=54), patients were given vaginal placement of Nifuratel nystatin soft capsule, 1 capsule daily, for 6 days;oral administration of minus Xiaoyao powder, 1 agent daily, for 7 days; and oral administration of Bacillus coagulans tablets, 3 tablets one time, 3 times a day, for 14 days, double dose at first. In control group (54 cases), patients were given vaginal placement of Nifuratel nystatin soft capsule, 1 capsule daily, for 6 days;and oral placement of vitamin C tablet, 1 tablet one time, 3 times a day,for 14 days. The short-term effect and the long-term recurrence of were observed 3-7 days, 1 months, 3 months, 6 months after stopping drug treatment. Results 3 days after stopping drugs, the effective rate in the observation group and the control group was 92.59%and 81.48%, respectively, the difference between the two groups was statistically significant (P<0.05) . 6 months after stopping drugs, the recurrence rate was 9.26% in the observation group, and 20.37% in the control group, the difference was statistically significant (P<0.05) . Conclusion For Vaginal candidiasis, on the basis of antifungal therapy, giving Bacillus coagulans tablets for regulation of intestinal micro ecological environment, and traditional Chinese medicine minus Xiaoyao powder for clearing heat and removing dampness, soothing the liver, can significantly improve the short term and long term curative effects,and reduce the recurrence rate.