Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease， and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine， proposes a new theory of “turbid toxin pathogenesis”， analyzes the scientific connotations of “turbid”， “toxin”， and the theory of “turbid toxin pathogenesis”， and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy， thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy， in order to provide a reference for the prevention and treatment of hepatic encephalopathy.

ObjectiveTo analyze the epidemiological and clinical characteristics of surveillance cases in a sentinel hospital for pertussis in Jiangxi Province in 2019, and to provide corresponding references for the prevention and control of pertussis. MethodsCase investigation of pertussis was conducted among sentinel hospital surveillance cases, collecting their basic information, epidemiological characteristics, clinical characteristics, and other information. ResultsA total of 125 pertussis surveillance cases were investigated in 2019, including 73 clinically diagnosed cases (58.40%) and 52 confirmed cases (41.60%). The age of onset was mainly concentrated in children under 5 years old (108 cases, 86.40%), with the largest number of cases in infants aged less than 1-year-old (48 cases, 38.40%). Most cases had a history of receiving pertussis vaccine before onset (110 cases, 88.00%), and the intervals between the onset date and the date of last dose of pertussis vaccine in the 1‒2 doses group were significantly shorter than that in the 3‒4 doses group (U=-5.990, P<0.001). Probable household transmission of pertussis was found in 3 cases. All cases had cough symptoms, mainly manifested as whooping cough (77 cases, 61.60%), in addition to other main clinical manifestations, such as fever (76 cases, 60.80%), vomiting (30 cases, 24.00%), conjunctival congestion (27 cases, 21.60%), and inspiratory whoop (16 cases, 12.80%). A total of 73 cases (58.40%) experienced complications, including 1 death case. All the cases had multiple medical visit experiences before this visit, with an interval of 2 (0,3) days between the onset date and the first visit date. The misdiagnosis rate at the first medical visit was 88.00% (110/125), and the misdiagnosis rate of the first visit in secondary and primary hospitals was significantly higher than that in tertiary hospitals, exhibiting a statistically significant difference (χ²=21.582, P<0.001). ConclusionThe clinical symptoms of pertussis cases are often atypical, and the first diagnosis is prone to misdiagnosis, so it’s necessary to further strengthen the early diagnosis capabilities for pertussis cases in healthcare institutions, especially in the primary healthcare institutions.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

Objective To investigate the effect of extracellular heat shock protein(HSP)22 on Toll-like receptor(TLR)4/nuclear factor-κB(NF-κB)signaling pathway in oxidative-low-density lipoprotein(ox-LDL)-induced inflammatory damage in coronary endothelial cells(HCAECs).Methods HCAECs were cul-tured in vitro and pretreated with ox-LDL to establish a model of high-lipid-induced endothelial cell injury.Re-combinant human HSP22(rhHSP22)was exogenously treated.The effects of rhHSP22 on the expression of inflammation-related proteins such as interleukin(IL)-8,vascular cell adhesion molecule(VCAM)-1 and NF-κB in endothelial cells and endothelial cell apoptosis were observed.The relationship between HSP22 and TLR4/NF-κB signaling pathway was investigated under the action of TLR4 inhibitor E5564.Western blot was used to detect the expression of IL-8,VACM-1 and NF-κB proteins,and flow cytometry was used to detect the apoptosis of endothelial cells in each group.Results Compared with the CNT group,the relative expression levels of IL-8,VACM-1 and NF-κB protein in the rhHSP22 group,rhHSP22+ox-LDL group,rhHSP22+E5564 group and rhHSP22+E5564+ox-LDL group were significantly increased,and the differences were sta-tistically significant(P<0.05).Compared with the rhHSP22 group,the relative expression levels of IL-8,VACM-1 and NF-κB protein in the rhHSP22+ox-LDL group were significantly increased,and the differences were statistically significant(P<0.05).Compared with the rhHSP22+ox-LDL group,the relative expression levels of IL-8 and VACM-1 in the rhHSP22+E5564+ox-LDL group were decreased,and the differences were statistically significant(P<0.05).Compared with the CNT group,the apoptosis rate in the rhHSP22 group,rhHSP22+ox-LDL group and rhHSP22+E5564+ox-LDL group was significantly increased,and the differ-ence was statistically significant(P<0.05).Compared with the rhHSP22 group,the apoptosis rate in the rhHSP22+ox-LDL group was increased,and the difference was statistically significant(P<0.05).Compared with the rhHSP22+ox-LDL group,the apoptosis rate in the rhHSP22+E5564+ox-LDL group was de-creased,and the difference was statistically significant(P<0.05).Conclusion In ox-LDL-induced inflamma-tory damage of HCAECs,extracellular HSP22 induces the expression of IL-8,VACM-1 and NF-κB proteins by activating the TLR4/NF-κB signaling pathway,and promotes endothelial cell apoptosis.

Objective To establish a DNA quantitation method based on dithiothreitol(DTT)-crystal vio-let.Methods DTT was used to decolorize crystal violet,mixed with different concentrations of λ-DNA and salmon sperm DNA standard samples or concentration standard samples,and the absorbance was read at 595 nm wavelength by microplate reader,and compared with the results of ultraviolet absorbance method.DTT-crystal violet method and ultraviolet absorbance method were used to compare the concentration of plasmid samples and the concentration of genomic DNA samples of cervical exfoliated cells.The protein tolerance of the two methods was assessed by simulating protein contaminants with bovine serum albumin(BSA).Results In the quantification of λ-DNA and salmon sperm DNA,the DTT-crystal violet method had a robust linear correlation between the absorbance at 595 nm and DNA concentration(r2＞0.95),and the measured concentrations of the standard samples were not significantly different from the theoretical concentrations of the prepared standard samples(P＞0.05).There was no significant difference in the concentration of plasmid samples measured by DTT-crystal violet method and ultraviolet absorption method(P＞0.05).The concen-tration of DNA samples from cervical exfoliated cells measured by ultraviolet absorption method was positive-ly correlated with that by DTT-crystal violet method(r=0.94,P＜0.01).The concentration of the standard sample containing BSA 1 μg/μL measured by ultraviolet absorption method was higher than that of the con-trol sample,and the difference was statistically significant(P＜0.01),whereas the DTT-crystal violet method was not significantly affected(P＞0.05).Conclusion DTT-crystal violet method has obvious advantages over the existing DNA quantitation method,and is suitable for DNA quantitative analysis in scientific research and clinic.

Objective To investigate whether exposure pathways influence the distribution pattern and toxicity of polystyrene nanoplastics(PSNPs)in hepatic cells.Methods Male C57BL/6J wild-type healthy mice aged 6 to 8 weeks old and weighed 18 to 22 g were administered with PSNPs via gavage or tail vein injection.Then,we tracked PSNPs distribution in the major organs of mice via an in vivo imaging system(IVIS).After that,we analyzed the cellular accumulation patterns in hepatic cell subpopulations(hepatocytes and Kupffer cells)using immunofluorescence and transmission electron microscopy(TEM).300 nm PSNPs were administered via gastric gavage or tail vein injection,and 70 nm PSNPs were injected via the portal vein.The cellular localization of PSNPs in the liver was analyzed using immunofluorescence.Subsequently,using AML-12 cells,a normal mouse liver cell line,as the parenchymal hepatocyte model,the uptake of PSNPs in AML-12 cells was analyzed by confocal laser scanning microscope(CLSM).Flow cytometry was performed to observe and quantify PSNPs uptake,and to analyze the underlying endocytosis mechanisms.IVIS was used to analyze PSNPs uptake features in vivo.Finally,using mouse macrophage line RAW264.7 as a Kupffer cell model and AML-12 cells as a parenchymal hepatocyte model,the cell-type-specific toxic effects induced by 100 μg/ml PSNPs were examined through transcriptomics and metabolomics analyses.Results IVIS revealed predominant hepatic accumulation of PSNPs regardless of exposure pathways via intragastric gavage or tail vein injection.Immunofluorescence/TEM demonstrated exposure pathway-dependent cellular distribution:intragastric PSNPs were localized mainly in hepatocytes,while intravenous PSNPs were accumulated in Kupffer cells.Changes in particle size(300 nm vs.70 nm)did not alter the cellular distribution pattern,while 70 nm PSNPs injected via the portal vein accumulated in Kupffer cells,which suggested that the cell-type-specific distribution of PSNPs in the liver was independent of PSNPs size and might be related to the transport of PSNPs in the gastrointestinal tract.Flow cytometry showed that PSNPs uptake by AML-12 was time-dependent and that the underlying endocytosis mechanism involved pathways mediated by clathrin(P<0.000 1),macropinocytosis(P=0.002 6),and lipid rafts(P<0.000 1).Findings on PSNPs distribution in blood revealed that the uptake of PSNPs by hepatocytes exhibited a rate saturation phenomenon.Multi-omics analysis identified distinct toxicity patterns:PSNPs disrupted lipid metabolism and neurotransmitter homeostasis in AML-12 cells and induced inflammation and oxidative stress in Kupffer cells.Conclusion Exposure pathways mediate the hepatic cell-type-specific distribution of PSNPs,thereby altering the downstream toxicological consequences induced by exposure to PSNPs.

Objective To explore the effects of modified prone ventilation combined with bronchoscopic alveolar lavage on respiratory mechanics and hemodynamics in children with Acute Respiratory Distress Syndrome(ARDS),as well as to evaluate the clinical treatment efficacy.Methods A total of 96 ARDS children receiving mechanical ventilation treatment in the emergency intensive care unit of Kunming Children's Hospital from January 2021 to December 2023 were selected and randomly assigned into three groups:Group A(prone ventilation group,n=32),Group B(modified prone ventilation group,n=32),and Group C(modified prone ventilation combined with bronchoscopic alveolar lavage group,n=32).The changes in the following parameters before and after treatment among the three groups were compared:oxygenation indicators:arterial oxygen partial pressure(PaO2),arterial oxygenation index(PaO2/FiO2);respiratory mechanics indicators:lung compliance,mean airway pressure,plateau airway pressure,and total airway resistance;hemodynamic indicators:cardiac output,cardiac index,systemic vascular resistance index,and mean arterial pressure;clinical efficacy indicators time to disappearance of rales,mechanical ventilation duration,and length of hospital stay;and incidence of complications:arrhythmia,airway obstruction,pressure injuries,total incidence of catheter dislodgment,and gastric content reflux.Results The oxygenation indicators in Group C after treatment were superior to those in Groups A and B(P<0.05).The respiratory mechanics indicators in Group C after treatment were also better than those in Groups A and B(P<0.05).In terms of hemodynamics,there were no statistically significant differences in cardiac output,cardiac index,and mean arterial pressure among Groups A,B,and C after treatment(P>0.05).However,the SVRI in Group C was better than that in Groups A and B(P<0.05).Curative effect for Group C were also better than those for Groups A and B(P<0.05).The incidence of complications in Group C showed no significant difference compared to Groups A and B(P>0.05).Conclusion The modified prone ventilation combined with bronchoscopic alveolar lavage treatment scheme demonstrates better therapeutic effects compared to traditional treatment methods,significantly improving oxygenation and respiratory mechanics indicators as well as the systemic vascular resistance index in children,and is worthy of clinical promotion.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.

Objective To investigate the therapeutic mechanism of Pterocarya hupehensis Skan total flavonoids(PHSTF)for rheumatoid arthritis(RA).Methods Twenty-five male SD rats were randomly divided into normal control group,RA model group,PHSTF treatment(45 and 90 mg/kg)groups,and Tripterygium glycosides(TPG)tablet(10 mg/kg)group(n=5).Except for those in the normal control group,all the rats were subjected to collagen-induced arthritis(CIA)modeling using a secondary immunization method,after which PHSTF and TPG were administered via gavage once daily for 4 weeks.After the treatments,serum levels of TNF-α and IL-1β were measured using ELISA,and ankle joint pathologies were assessed with HE staining;the expression of citrullinated histone H3(Cit-H3),a neutrophil extracellular trap(NET)marker,in the ankle joints was evaluated with immunohistochemistry.In primary cultures of rat peripheral blood neutrophils stimulated with phorbol ester(PMA),the effects of PHSTF(100 and 200 μg/mL)on the expressions of Cit-H3,peptidylarginine deiminase 4(PADI4),neutrophil elastase(NE),and myeloperoxidase(MPO)were examined with Western blotting;immunofluorescence assay was used to observe Cit-H3 expression and NET formation in the cells.Results In the CIA rat models,PHSTF significantly alleviated ankle swelling,decreased serum levels of TNF-α and IL-1β,improved histopathological changes in the ankle joints,and reduced Cit-H3 expression in both the serum and ankle joint cartilage.In the isolated rat neutrophils,PHSTF showed no significant effect on cell viability but strongly inhibited PMA-induced NET release.Conclusion PHSTF can alleviate RA by inhibiting the formation of NETs.