ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.

Objectives:To investigate the association between social determinants of health(SDOH)and incident stroke and analyze the main risk factors for stroke among resident with different SDOH levels. Methods:From 2012 to 2015,30 036 residents(≥35 years old)from 30 districts in 14 provincial-level administrative divisions in China were enrolled this study based on stratified multi-stage-random-sampling method.The prevalence of cardiovascular diseases and related risk factors were investigated,and stroke events were followed up in 2018 to 2019.Principal component analysis was performed to establish SDOH scores based on 9 indicators related to socioeconomic and healthcare resources,participants were divided into low SDOH group(n=8 343)when it was≥-2.01 to<-1.14,middle SDOH group(n=7 257)when it was≥-1.14 to<0.10,and high SDOH group(n=8 457)when it was≥0.10 to≤5.79.Multivariate Cox regression was applied to estimate the association of SDOH levels with incident stroke.The random survival forest method was used to analyze the major risk factors in different SDOH levels. Results:A total of 24 057 participants were finally included,669(2.8%)participants developed stroke during a mean of(4.7±0.8)years follow-up.The incidence densities of stroke in the low,medium,and high SDOH groups were 468.39,628.85,and 700.39/100 000 person-years,respectively(Pdifference<0.05,Ptrend=0.01).Compared with individuals with low SDOH level group,fully HR for incident stroke among those with medium and high were 1.91(95%CI:1.54-2.36)and 1.59(95%CI:1.30-1.95),respectively(Ptrend<0.001).Advanced age is the primary risk factor for stroke in the population,especially in districts with high SDOH level.In districts with medium SDOH level,diabetes is an important risk factor for stroke.High blood pressure and alcohol consumption are important modifiable risk factors in low SDOH level districts. Conclusions:Present study shows that higher levels of SDOH are associated with increased risk of stroke.The main risk factors for stroke differ among participants with different SDOH level districts.Targeted interventions should be implemented to improve the prevention and treatment of stroke in populations with different levels of SDOH.

Objective To investigate the therapeutic effect of isoorientin on ulcerative colitis(UC)mice induced by dextran sulfate sodium(DSS)and its mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into control group,model group,mesalazine group(600 mg·kg-1),isoorientin low dose group(25 mg·kg-1),isoorientin high dose group(50 mg·kg-1)and isoorientin control group(50 mg·kg-1),with eight mice in each group.Mice were free to drink 2%DSS solution to replicate UC model.After three weeks of experiment,each drug administration group was given corresponding drug by intragastric administration for four weeks.After the last administration,the body weight was weighed,blood was taken from eyeballs,and colon tissue was dissected.The pathological changes of colon were observed by hematoxylin-eosin(HE)and alcian blue-periodic acid-Schiff(AB-PAS)staining.The ultrastructure of colon tissue was observed by transmission electron microscope.Serum levels of interleukin(IL)-6,IL-8,IL-10,IL-1β,tumor necrosis factor α(TNF-α),lipopolysaccharide(LPS)and myeloperoxidase(MPO)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of galectin-3(Gal-3)protein in colon tissue of mice was detected by immunohistochemistry analysis.The expression of MUC2 and the co-localization of NOD-like receptor heat protein domain associated protein 3(NLRP3)and apoptosis-associated speck-like protein(ASC)were detected by immunofluorescence assay.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,Occludin,and zonula occludens protein-1(ZO-1)in colon tissue of mice were detected by Western Blot.Results Compared with the control group,the body weight and colon length in the model group were shortened significantly,while the index of colonic weight of mice were increased significantly(P＜0.01).The intestinal mucosal structure of mice was disordered,the microvilli were sparse,the crypt structure was infiltrated by a large number of inflammatory cells,mitochondria were significantly swollen,and goblet cells were obviously decreased.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly increased,while IL-10 level was significantly decreased(P＜0.01).The positive expression of MUC2 protein in colon tissue was decreased and the co-localization of NLRP3 and ASC was enhanced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly increased,and the protein expression of Occludin and ZO-1 were significantly decreased(P＜0.01).Compared with the model group,the body weight and colon length of mice in isoorientin low-and high-dose groups were significantly increased,the index of colonic weight of mice was apparently decreased(P＜0.05,P＜0.01).The structure of intestinal mucosa,microvilli and mitochondria recovered obviously,inflammatory infiltration was alleviated,and goblet cells were increased obviously.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly decreased,while IL-10 level was significantly increased(P＜0.05,P＜0.01).The positive expression of MUC2 protein in colon tissue was increased and the co-localization of NLRP3 and ASC was reduced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly decreased,and the protein expression of Occludin and ZO-1 were significantly increased(P＜0.05,P＜0.01).Conclusion Isoorientin has a great therapeutic effect on DSS-induced UC mice.Its mechanism may be related to the protection of intestinal mucosal barrier by Gal-3/NLRP3/IL-1β signaling pathway.

Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.

Objective:To discuss the mechanism of Yueju Pill in the treatment of functional dyspepsia (FD) based on network pharmacology and molecular docking.Methods:The chemical components and action targets of Yueju Pill were screened out by TCMSP platform and HERB, BATMAN-TCM database combined with literature were used to supplement effective components of Vietnam bow. The targets of FD were screened out by GeneCards database and OMIM database, and the intersection of the two targets was used to analyze the protein interactions using the STRING platform to construct the PPI network. Metascape platform was used for GO and KEGG pathway enrichment analysis, and Cytoscape 3.7.2 software was used to construct a network of "Yueju Pill components-functional dyspepsia targets-pathways". Online mapping tools were used to obtain the Venn plot of the intersection targets of Yueju Pill, FD and its related pathogenesis. Finally, AutoDock software was used for molecular docking.Results:The main active components of Yueju Pill in the treatment of FD are quercetin, wogonin, luteolin, kaempferol, etc. The main targets are AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1, etc. Molecular docking shows that the targets and the active components of the Yueju Pill have better binding abilit. The GO enrichment analysis result shows that there are 2 273 biological processes, 152 molecular functions and 91 cell components. KEGG enrichment analysis shows that there are 344 pathways associated with FD. According to literature review, the pathways related to FD include PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway, etc.Conclusion:Yueju Pill might act on AKT1, MAPK1, JUN, RELA, IL6, BCL2, BAX, MAPK8, EGFR, ESR1 and other targets to regulate PI3K-Akt signaling pathway, AGE-RAGE signaling pathways and IL-17 signaling pathway and it could treat FD.

ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg^-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg^-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg^-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）. ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）. ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.

Objective To evaluate the diagnostic value of quantitative detection of cytomegalovirus (CMV) DNA from different sources [plasma, sputum and bronchoalveolar lavage fluid(BALF)] for CMV pneumonia after allogeneic hematopoietic stem cell transplantation. Methods Clinical data of 405 recipients undergoing allogeneic hematopoietic stem cell transplantation were retrospectively analyzed. Among them, 19 recipients diagnosed with CMV pneumonia were assigned into the CMV pneumonia group, and 229 recipients with CMV viremia alone, 11 recipients without CMV pneumonia who received fiberoptic bronchoscopy and 16 recipients diagnosed with bacterial or fungal pneumonia based on pathogenic evidence receiving sputum culture were assigned into the control A, B and C groups, respectively. The incidence of CMV pneumonia was summarized. The CMV DNA load of specimens from different sources (plasma, sputum and BALF) of recipients with CMV pneumonia was analyzed. The clinical prognosis of recipients with CMV pneumonia was evaluated. Results Among 405 recipients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases developed CMV pneumonia, and the overall incidence of CMV pneumonia was 4.7%(19/405). The CMV DNA load in the plasma, sputum and BALF of recipients with CMV pneumonia was higher than those in the control A, B and C groups (all P < 0.05). In the 19 recipients, 12 cases were cured after antiviral treatment and 7 died from treatment failure(3 cases abandoned treatment). The fatality was 37%(7/19). Conclusions Quantitative detection of CMV DNA in the plasma, sputum and BALF may increase the diagnostic rate of CMV pneumonia, thereby improving clinical prognosis of recipients undergoing allogeneic hematopoietic stem cell transplantation.

Objective To investigate the clinical efficacy of pretreatment regimen containing idarubicin (IDA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk refractory leukemia. Methods A total of 116 patients with high-risk refractory leukemia who received allo-HSCT treated with 7 types of IDA-containing pretreatment regimes were enrolled in this study. The implantation rate of 116 recipients was summed up. The 2-year overall survival (OS), 2-year disease free survival (DFS), cumulative recurrence rate, recurrent mortality, transplantation related mortality (TRM), cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were statistically analyzed by Kaplan-Meier survival curve. Results All 116 recipients successfully implanted. The median follow-up time was 28 (7-70) months. Among them, 64 recipients survived, the 2-year OS was 55.2%, 2-year DFS was 51.7%, 2-year recurrent mortality was 23.3% and 2-year TRM was 18.1%. Among 116 recipients, 72 cases suffered from aGVHD. The 2-year cumulative incidence rate of aGVHD was 62.1% including 20 cases of grade Ⅲ-Ⅳ aGVHD, the 2-year cumulative incidence rate was 17.2%. Among 116 recipients, 59 cases presented with cGVHD. The 2-year cumulative incidence rate was 55.4%, of which the 2-year cumulative incidence rate of extensive cGVHD was 14.7%. Among 116 recipients, 30 cases recurred with a 2-year cumulative recurrence rate of 25.9%. Conclusions IDA-containingpretreatment regime has high safety and effectiveness, and can be used as an effective pretreatment regime for transplantation preprocessing in patients with high-risk refractory leukemia.

Objective: To analyze the clinicopathological features of pseudotumor-like tissue around aseptic joint arthroplasty and aseptic lymphocytic vasculitis-associated lesions (ALVAL) scores. The characters of wear granules were observed. Methods: Total 122 cases were retrieved from the surgical pathology files between May 2015 and August 2018 in the department of pathology in Beijing Jishuitan Hospital, which included the knee joint arthroplasty (10 cases) and hip arthroplasty (112 cases). There were 62 females and 60 males. Patients′ age ranged from 29 to 86 years (mean 56 years). The pseudotumor-like tissue around aseptic joint arthroplasty were stained with HE and analyzed by two ALVAL score systems. The characters of wear granules were observed by light microscope and polarized light. Results: The cohort included 62 females and 60 males. Patients′ age ranged from 29 to 86 years (mean 56 years). Compbell-ALVAL system includes synovial lining,inflammatory infiltrate and tissue organization. The scores were: low (0-4): 18cases; moderate (5-8): 101 cases; high (9-10): 3 cases. Oxford-ALVAL system only evaluated the inflammatory infiltrate,and the scores were:0 grade:56 cases; 1 grade:51 cases; 2 grade: 12 cases; 3 grade:3 cases. Cases with high score in the Compbell-ALVAL system were concordant with the 3 grade of the Oxford-ALVAL system. Under light microscope,the metal particles were small black granules; the polyethylene fibers were needle-like and easily visible in polarized light. The polymethylmethacrylate showed clear spaces because of particle melting. Conclusions The Compbell-ALVAL scoring system is based on the histologic analysis of pseudotumor-like tissue around aseptic joint arthroplasty, and the Oxford-ALVAL scoring systems is based on lymphocytic response. The wear particles could be differentiated by the features in the light microscope.