In order to explore the possible role and molecular mechanism of the combined action of leech and bear bile in liver and gallbladder diseases, this study first used network pharmacology methods to screen the components and targets of leech and bear bile, as well as the related target genes of liver and gallbladder diseases. The selected key genes were subjected to interaction network and GO/KEGG enrichment analysis. Then, using sodium oleate induced HepG2 cell lipid deposition model and DL-ethionine induced mouse fatty liver model, the activity of leech and bear bile alone and in combination in reducing liver fat was evaluated in vitro and in vivo, and the expression of key pathway related proteins suggested by network pharmacology was detected by Western blot. The results of network pharmacology analysis showed that the active ingredients of leech and bear bile have 295 intersecting targets with liver and gallbladder related diseases, involving more than 200 signaling pathways, including the PI3K/Akt signaling pathway and phospholipase D signaling pathway closely related to glucose and lipid metabolism. The results of in vitro validation experiments showed that both leech and bear bile, alone and in combination, can significantly inhibit the lipid deposition induced by sodium oleate in human liver cells, reduce the triacylglycerol level in cell culture supernatant, and inhibit the lipid content in liver cells. The observation results of Nile red staining confocal microscopy showed that the combination of leech and bear bile had better activity in reducing lipid deposition in liver cells compared to using them alone. In a mouse fatty liver model, the combination of leech and bear bile can better reduce elevated organ indices, blood lipids, and liver lipid levels, as well as lower the levels of serum liver injury biomarkers. The animals used in this experiment and related disposal meet the requirements of animal welfare. Before the experiment, it was reviewed and approved by IACUC, Institute of Materia Medica, Chinese Academy of Medical Sciences. The Western blot experiment results showed that the combination of leech and bear bile can significantly upregulate the expression levels of p-PI3K and p-Akt proteins, and increase the p-PI3K/PI3K and p-Akt/Akt ratios, which is consistent with the predicted results of network pharmacology. The combination of leech and bear bile has great potential for treating fatty liver disease, and activating the PI3K/Akt pathway may be one of the important mechanisms for reducing lipid deposition in liver cells.

This study analyzed and compared the epidemiological characteristics of foodborne listeriosis in the United States and China,to provide evidence for optimizing the listeriosis surveillance program in China.Descriptive statistical analysis was performed on the listeriosis monitoring data from 2009 to 2021 registered in the FDOSS system and the attribution estimates of Listeria monocytogenes(L.monocytogenes)from 2013 to 2021 published by IFSAC.Sporadic and outbreak data on listeriosis in China from the CNKI,Wanfang Medical,and CQVIP databases were collected.From 2009 to 2021,a total of 1 037 listeriosis cases were reported in the United States,including 902 hospitalizations and 165 deaths.The peak of cases caused by Lm con-taminated food was in July.The number of cases,hospitalizations,and deaths accounted for 18.4％(191/1 037),20.5％(185/902),and 22.4％(37/165)of the total,respectively.Most listeriosis outbreaks were attributed to three food groups:dairy products,vegetable crops,and fruits,with attribution percentages ranging from 73.8％to 89.6％.The overall incidence of list-eriosis in China was not high:619 cases were reported from 2009 to 2021,and only 177 cases were recorded in detailed inci-dence years;the maximum number of cases in 2018 was 26.A total of 220 cases were reported with detailed onset months;the highest number of cases in April was 30.Data on listeriosis cases in China are incomplete and sporadic,and only seven cases have been successfully traced to food.Listeriosis surveillance systems in the United States are relatively complete,and there are more foodborne outbreaks.Dairy products,vegetable row crops,and fruits are the most likely causes of disease outbreaks.Although only sporadic cases have been reported in China,China should take actions such as gradually improving multi-department coop-eration mechanisms,achieving data sharing and deepening data mining,and accelerating progress in the detection technology of food-borne pathogenic microorganisms,to ensure food safety and public health.

Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P＜0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P＜0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P＜0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P＜0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P＜0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P＜0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P＜0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P＜0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P＜0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P＜0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Enterogenic Candida albicans(C.albicans)infection refers to the translocation of intestinal colonized C.albicans under certain conditions,breaking through the intestinal tract,causing tissue infection or even invasive C.albicans infection.As the first contact point of Candida,the intestinal mucosa is the first line defending coloni-zation or invasion of C.albicans,often inhibiting infection by physical barrier and activating host immunity.As an-other defense mechanism,the intestinal microbiota jointly resists the invasive infection of C.albican through regula-ting pH,secreting antimicrobial peptides,and competing for adhesion points.This review summarizes the roles of three key factors,namely intestinal mucosa,intestinal immunity and microbiota,in enterogenic C.albicans infec-tion,providing new ideas for scientific research on invasive candidiasis caused by intestinal colonization.

Objective To understand the prevalence characteristics of influenza and changes of influenza virus strains,and provide reference for the prevention and control of influenza in the province.Methods Surveillance da-ta about influenza in Hunan Province from 2014 to 2023 were exported from China Influenza Surveillance Informa-tion System.Differences in the percentage of influenza-like illness(ILI)cases(percentage of influenza-like cases[ILI％]in outpatient and emergency department visits)among different years and different populations,as well as the positive rate of influenza virus in ILI specimens were compared.Results From 2014 to 2023,over 2.65 million cases of ILI were reported,with an ILI％of 4.70％.ILI％among different years presented statistically significant differences(P＜0.001).People aged 0-14 years old were the main population with ILI,accounting for 82.90％.The positive rate of influenza virus in ILI specimens was 14.14％,the positive rate of influenza virus among diffe-rent years and age groups were both significantly different(both P＜0.001).The main prevalent influenza strains from 2014 to 2023 included types A(H1N1),A(H3N2),B(Victoria),and B(Yamagata),alternating among di-fferent years.However,type B(Yamagata)strains were not detected from 2020 to 2023.There were basically two influenza prevalence seasons every year,namely winter-spring and summer.Conclusion People＜15 years old are the main population of influenza,and the prevalence peaks are in winter-spring and summer.From 2021 to 2023,the prevalence alternates mainly among 3 types:A(H1N1),A(H3N2),and B(Victoria).

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To study the effect of Hedysarum polysaccharides(HPS)on the farnisol X receptor(FXR)-small heterodimer chaperone(SHP)-sterol regulatory element-binding protein 1 c(SREBP-1c)signaling pathway in the non-alcoholic fatty liver disease cell model.Methods The cells were cultured with 1.2 mmol·L-1 fatty acids to construct the non-alcoholic fatty liver disease cell model.The cell were divided into normal group(complete medium),model group(1.2 mmol·L-1 fatty acid solution),positive control group(1.2 mmol·L-1 fatty acid solution+50 μmol·L-1 alpha-lipoic acid)and experimental group(1.2 mmol·L-1 fatty acid solution+80 mg·L-1 HPS),culture for 24 h.The content of triglyceride(TG)and total cholesterol(TC),the activity of glutamate transaminase(GOT)and glutamate transaminasewas(GPT)detected by GPO-PAP enzyme method;the apoptosis rate was detected by flow cytometry;the expressions of FXR,SHP,SREBP-1c protein and mRNA in hepatocytes were detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).Results The contents of TG in hepatocytes of normal group,model group,positve control group and experimental group were(2.91±1.13),(6.81±1.32),(3.72±0.52)and(4.67±0.62)mmol·gprot-1;the contents of TC in these four groups were(23.66±4.92),(67.96±5.56),(29.41±4.22)and(54.34±3.96)mmol·gprot-1;the activity of GOT in these four groups were(249.10±11.59),(322.63±28.81),(288.89±19.14)and(266.91±8.77)U·gprot-1;the activity of GPT in these four groups were(58.83±16.88),(134.55±22.96),(89.63±15.81)and(77.37±7.25)U·gprot-1,respectively;FXR mRNA expression levels were 1.01±0.16,2.09±0.12,1.83±0.17 and 1.45±0.15,respectively;SHP mRNA expression levels were 1.00±0.11,0.51±0.15,0.64±0.14 and 0.70±0.14,respectively;SREBP-1c mRNA were 1.00±0.08,1.57±0.19,1.37±0.13 and 1.21±0.15;the expression levels of FXR protein were 1.00±0.02,1.63±0.03,1.42±0.02 and 1.25±0.03,respectively;the expression levels of SHP protein were 1.00±0.02,0.23±0.01,0.54±0.21 and 0.62±0.02;the expression levels of SREBP-1c protein were 1.00±0.03,4.08±0.05,1.99±0.02 and 1.48±0.01,respectively.Compared with the normal group,there were significant differences in the above indexes of model group(all P＜0.05);compared with the model group,there were significant differences in the above indexes of experimental group(all P＜0.05).Conclusion HPS may protect liver cells by regulating the FXR-SHP-SREBP-1 c signaling pathway,reducing lipid synthesis in liver cells.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.