OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis （HF）. METHODS Male SD rats were randomly divided into normal control group （n＝10） and modeling group （n＝50）. The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group （normal saline）， positive control group [colchicine， 0.09 mg/（kg·d）]， and P. mume low-dose， medium-dose and high-dose groups [1.35， 2.70， 5.40 g/（kg·d）]， with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically， once a day， for 8 consecutive weeks. After the last medication， the liver index was calculated， while liver function indexes， liver fiber indexes， oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats； Masson staining was used to observe the degree of HF in liver tissue of rats； transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats； TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 （TGF-β1） and platelet-derived growth factor （PDGF） in liver tissue of rats. RESULTS Compared with normal control group， the levels of alanine transaminase， alkaline phosphatase， aspartate transaminase， total bilirubin， malondialdehyde， procollagen type Ⅲ protein， Ⅳ-type pre collagenase， laminin， hyaluronic acid， interleukin-6， tumor necrosis factor-α， as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly， while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced （P＜0.01）； the HE， Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group， varying degrees of improvement in above indexes were observed in P. mume groups， and the above 2021BSZR011） indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS P. mume has an anti-HF effect， which may be achieved through mechanisms such as antioxidation， anti-inflammation， reduction of collagen production， inhibition of PDGF protein expression， and regulation of TGF- β1 signaling pathway.

ObjectiveTo investigate the whole genomic characteristics and phylogenetic relationships of clinical isolates of enteroaggregative Escherichia coli (EAEC) in diarrhea outpatients in Pudong New Area, Shanghai. MethodsBased on the diarrheal disease surveillance network in Pudong New Area, Shanghai, whole-genome sequencing was performed on a total of 55 EAEC strains isolated from fecal samples of the diarrhea outpatients from January 2015 to December 2019. The genome analyses based on raw sequencing data encompassed genome size, coding genes, dispersed repeat sequences, genomic islands, and protein coding regions, and pan-genome analyses were conducted simultaneously. Contigs sequences assays were performed to analyze molecular characteristics including serotypes, antibiotic resistance genes, and virulence factors. The phylogenetic clusters and multilocus sequence typing (MLST) were identified, and a phylogenetic tree was constructed. ResultsEAEC exhibited an open pan-genome. The predominant serotype of EAEC in diarrhea outpatients in Pudong New Area was O130:H27, and the carriage rate of β-lactam resistance genes was the highest (67.27%, 37/55). A total of 29 virulence factors and 106 virulence genes were identified, phylogenic group B1 was the predominant group, and clonal group CC31 was the dominant clonal group. The strain distribution was highly heterogeneous. ConclusionThe genomic characteristics of EAEC displayed significant strain polymorphism. It is necessary to develop effective strategies for differential diagnosis and improve detection capabilities for infection with EAEC of different serotypes and genotypes.

Objective To prepare Zishen pills as gel plaster according to the prescription,and investigate its transdermal absorption characteristics in vitro.Methods Based on preliminary experiments,the matrix prescription of the gel plaster was optimized by single-factor tests and the Box-Behnken design.Evaluation indicators included initial viscosity,viscosity retention and sensory scores.The modified Franz diffusion cell was used to investigate the effect of penetration enhancers on the transdermal characteristics of gel plaster in vitro,with the permeability of neomangiferin,phellodendrine hydrochloride,mangiferin and berberine hydrochloride as evaluation indicators.Results The prescription dosage of the preferred matrix for the Zishen gel plaster was sodium polyacrylate NP700 2.55 g,glycerin 11.04 g,polyvinylpyrrolidone K90 1.13 g,tartaric acid 0.1 g,glycyrrhizin 0.1 g,kaolin 0.3 g,and distilled water 15 g.Among different types and concentrations of permeation enhancers,5%aminoketone showed the best permeation performance.The permeation rates for neomangiferin,phellodendrine hydrochloride,mangiferin,and berberine hydrochloride were 1.5338,1.7809,2.3247 and 20.0899 μg·(cm2)-1·h-1,and the penetration rates were 2.4319,1.9408,1.9604 and 1.4701,respectively.The percutaneous absorption curve of the drug conformed to the zero-order kinetic equation.Conclusion The preparation process of the obtained gel plaste is stable and feasible,with good adhesive properties,sustained drug release,and favorable in vitro percutaneous permeability,indicating potential clinical application value.

Objective:To analyze the efficacy and safety of FOLFOX-hepatic arterial infusion chemotherapy (HAIC) combined with targeted immunotherapy for initial unresectable hepatocellular carcinoma.Methods:A retrospective analysis was conducted on the data of initial unresectable hepatocellular carcinoma patients who visited Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2022 to June 2023. A total of 51 patients were enrolled, including 47 males and 4 females, with the age of (56.1±10.7) years. All 51 patients received HAIC combined with immune targeted therapy. After each HAIC combined with immune targeted therapy, the efficacy was evaluated according to the modified response evaluation cirteria in solid tumor (mRECIST). Objective response rate and disease control rate were calculuted. The conversion surgery rate and adverse events during treatment were recorded. Follow up patients' disease progression and survival status, and meanwhile analyze prognosis.Results:According to mRECIST assessment, the number of patients with complete remission, partial remission, disease stability, and disease progression were 4 (7.8%), 27 (52.9%), 14 (27.4%), and 6 (11.8%), respectively. The disease remission rate was 60.8%(31/51), and the disease control rate was 88.2%(45/51). After HAIC combined with immune targeted therapy, 13 patients underwent liver cancer resection, with a surgical conversion rate of 25.5%(13/51). The median progression free survival of 51 patients was 14.2 months, and the median overall survival has not yet been reached. The progression free survival rates of 51 patients at 6 and 12 months were 90.2% and 64.7%, respectively, and the cumulative survival rates at 6 and 12 months were 100% and 86.3%, respectively. During the treatment period, all patients experienced various degrees of adverse reactions, 38(75.5%) patients were grade 1-2 adverse accidents, which could be relieved and controlled after corresponding treatment.Conclusion:FOLFOX-HAIC combined with targeted immunotherapy provides an effective and safe treatment option for unresectable hepatocellular carcinoma, offering surgical resection opportunities for unresectable hepatocellular carcinoma patients.

Some Chinese herbs have been used to prevent and treat diseases, and are also used as common food ingredients. These Chinese herbs are potential resource for research and development of new drugs. Leek roots is a typical medicine of food and medicine continuum. It has a long history of medicinal applications and edible food in China. In this paper, the origin, biological active components, pharmacological action and clinical application of leek roots were introduced. We hope that this review will contribute to the development of leek roots for pharmaceutical research and clinical applications, as well as related health products.

Objective To explore the expression profile of the JAK/STAT pathway in patients with acute myeloid leukemia(AML)and to analyze its impact on the survival prognosis of patients.Methods This study compared differentially expressed genes between AML patients and healthy controls in 2 independent cohorts(n=64,n=121),and these genes were enriched by pathways.The expression levels of JAKs and STATs genes were compared between AML patients and healthy controls.The clinical values of JAK/STAT genes were analyzed using gene expression data,patients'clinical and prognostic information from 2 AML cohorts(n=163,n=403).Results Gene microarray expression results in 26 AML patients and 38 healthy controls showed 1266 genes with significantly differential expression(Padj≤0.05,| log2FC| ≥0.5),of which 426 genes were significantly upregulated in AML patients and 840 genes were significantly downregulated in AML patients.Pathway enrichment of these genes was performed in the JAK/STAT pathway,which was found to be active in AML patients(P＜0.05).Comparison of mi-croarray data from the GSE1159 cohort(n=121)showed AML patients had higher levels of JAK1(P=0.019),J AK2(P=0.047)and STAT4(P＜0.001)gene expression than the healthy controls,and their STAT5A(P=0.028)and STAT6(P=0.022)gene expression levels were lower than those in the healthy controls.Univariate survival analysis identified shorter over-all survival(P=0.02,HR=1.463;P=0.041,HR=1.293)and event-free survival(P=0.01,HR=1.510)in patients with high STAT4 expression than in those with a lower STAT4 expression in the TCGA and GSE6891 cohorts(n=163;n=403).Univa-riate and multifactorial COX analyzes confirmed that high STAT4 expression was an independent prognostic risk factor for AML patients(EFS:P=0.002,HR=1.958;OS:P=0.036,HR=1.556).Conclusion In AML patients,the JAK/STAT path-way is activated,and the STAT4 expression level is higher than that of the healthy controls.High expression of STAT4 suggest poor prognosis,wihich is an independent risk factor for the prognosis of AML patients.

OBJECTIVE To provide a method to reduce environmental residues for pharmacy intravenous admixture service （PIVAS）， and ensure the occupational health of medical staff. METHODS The residues of 15 cytotoxic antineoplastic drugs such as gemcitabine were detected by UPLC-Q-Orbitrap-HRMS. The cleaning process was optimized with the residual quantity as the index. Nitrogen blowing method was used for alcohol volatilization experiment. CCK-8 assay was used to detect the effect of chlorine-containing disinfectant on the toxicity of cytotoxic antitumor drugs. RESULTS The linear range of 15 cytotoxic antineoplastic drugs such as gemcitabine were 0.5-1 000 ng/mL. RSDs of intra-day and intra-day precision were no higher than 20.00%. Six drugs including gemcitabine， isocyclophosphamide and cyclophosphamide were detected in the PIVAS environment of our hospital， and the residue of cyclophosphamide was relatively high. The optimal cleaning procedure was cleaning once with water + cleaning once with 1 000 mg/L chlorine-containing disinfectant + cleaning once with 75% alcohol， wiping with dry gauze method. The results of alcohol volatilization test showed that there was no significant difference in drug residues between control group and 75% alcohol group （P＞0.05）. The results of CCK-8 test showed that compared with control group， the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs were decreased significantly （P＜0.01）； the survival rates of the cells treated with 15 cytotoxic antineoplastic drugs+chlorine-containing disinfectant were significantly higher than those treated with 15 cytotoxic antineoplastic drugs （P＜0.01）. CONCLUSIONS A method for the simultaneous determination for residues of 15 cytotoxic antineoplastic drugs such as gemcitabine in PIVAS is successfully established； the optimal cleaning procedure can significantly reduce the residues of drugs， the use of chlorine- containing disinfectant can significantly reduce the toxicity of drug， and the residual drugs will not cause secondary contamination of the operating area with alcohol volatilization.

Objective:To discuss the perioperative symptom change rule of patients with myasthenia gravis(MG), and to provide a theoretical basis for preventing and reducing the surgical risk of patients with MG.Methods:The clinical data of 104 patients who underwent thymectomy in the Department of Thoracic Surgery of the Second Affiliated Hospital of Zhengzhou University from 2015 to 2019 were retrospectively analyzed. According to the degree of the impact of MG symptoms on the body's physiology and life, the "MG dynamic classification standard" was formulated, which was divided into type 0-type Ⅳ according to the severity of MG symptoms. The symptoms of each patient of "admission", "preoperative" and "postoperative" are classified according to the "dynamic classification criteria", and the number of "admission", "preoperative" and "postoperative" were counted respectively. Based on the statistical analysis of each patient's type changes, the perioperative symptom changes of myasthenia gravis patients were summarized.Results:1. "Admission" classification: 12 cases of type 0, 42 cases of type Ⅰ, 32 cases of type Ⅱ, 12 cases of type Ⅲ, 5 cases of type Ⅳa, and 1 case of type Ⅳb. 2. "Preoperative" classification: 44 cases of type 0, 34 cases of type Ⅰ, 14 cases of type Ⅱ, 12 cases of type Ⅲ; 68 cases of preoperative symptom reduction (65.4%, 68/104), 36 cases of preoperative symptom stable (34.6%, 36/104). Asymptomatic aggravation. 3. "Postoperative" classification: 49 cases of type 0, 21 cases of type Ⅰ, 11 cases of type Ⅱ, 10 cases of type Ⅲ, 9 cases of type Ⅳa, 4 cases of type Ⅳb; 33 cases (31.7%, 33/104) had postoperative symptoms aggravated. Among the patients with worsening symptoms after surgery, 5 cases (15.2%, 5/33) worsened on the first day after surgery, 9 cases (27.2%, 9/33) worsened on the second day after surgery, and 13 cases (39.4%, 13/33) worsened on the third day after surgery. There were 4 cases (12.1%, 4/33) worsened on the 4th day, and 2 cases (6.1%, 2/33) worsened on the 5th day after surgery.Conclusion:MG patients had different conditions at admission. After individualized perioperative treatment, more than half of the patients' symptoms alleviated to varying degrees. After the operation, the symptoms of MG will be temporarily aggravated due to the effects of surgery and anesthesia, and the aggravation period is mostly on 1-3 days. Reasonable selection of low-risk MG patients for surgery, avoiding the superposition of other influencing factors in the postoperative exacerbation period, is expected to reduce the occurrence of postoperative crises in MG patients.

Objective:To investigate the effect of IKKε on autophagy during abdominal aortic aneurysm formation in mice.Methods:We stimulated ApoE -/- mice and ApoE -/-IKKε -/- mice with AngⅡ and saline for 28 days. Metaboilic levels and aortic diameter of ApoE -/- mice and ApoE -/-IKKε -/- mice were measured. The arterial fibrosis of mice was detected by Masson staining and HE staining, mitochondrial reactive oxides were detected by fluorescence assay, the expression levels of autophagy factors LC3B and Beclin-1 were detected by immunohistochemistry, and the protein level of LC3B was detected by Western blot. Results:There was no significant difference in metaboilic levels between ApoE -/- mice and ApoE -/- IKKε -/- mice. However, the aortic diameterf ApoE -/-IKKε -/- mice was significantly less than that of ApoE -/- mice. The fibrosis level of ApoE -/-IKKε -/- mice was significantly lower than that of ApoE -/- mice. Furthermore, ROS in ApoE -/-IKKε -/- mice was lower than that in ApoE -/- mice. In addition, immunohistochemical and western blot showed that the expression levels of LC3B and Beclin-1 in ApoE -/-IKKε -/- mice were significantly lower than in ApoE -/- mice. Conclusion:IKKε -/- deficiency can significantly inhibit autophagy, thus reducing the development of abdominal aortic aneurysm in mice.