Preparation and Application of Polypyrrole Conductive Hydrogels in Biomedical Field / 分析化学

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

Research Advance on Smartphone-based Visual Biosensor in Point-of-Care Testing / 分析化学

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.

Mechanism of Yes-Associated Protein 1 Ameliorating Aristolochic Acid 1-Induced Liver Injury in Mice Based on Untargeted Metabolomics Techniques / 中药新药与临床药理

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Antitumor effects of redox-responsive nanoparticles containing platinum（Ⅳ）in ovarian cancer / 中华肿瘤杂志

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Antitumor effects of redox-responsive nanoparticles containing platinum（Ⅳ）in ovarian cancer / 中华肿瘤杂志

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Investigation,traceability analysis,and discussion of food poisoning caused by Salmonella typhimurium ST19 / 中国人兽共患病学报

To perform a comprehensive analysis of the pathogenic causes of a food poisoning case in a district of Wuhan Cit-y,we investigated the molecular epidemiological relationships among pathogenic bacteria,to aid in traceability analysis of food-borne disease outbreaks,as well as clinical diagnosis and treatment.The pathogenic bacteria in this food poisoning case were i-solated and identified according to GB789.4-2016.The isolated strains were subjected to genotyping with pulsed field gel elec-trophoresis(PFGE).Drug resistance gene analysis,multi-locus sequence typing(MLST),and genome-wide single-nucleotide polymorphism analysis(wgSNP)were conducted via whole genome sequencing(WGS).The evolutionary tree for cluster analy-sis was constructed in fasttree software.Drug susceptibility testing was conducted with the broth microdilution method.A total of 12 strains of Salmonella were detected in seven anal swab samples and two fecal samples from the case,as well as three anal swab samples from unaffected individuals.The serotype of the strains was Salmonella typhimurium.The strain exhibited severe multiple drug resistance,including resistance to amikacin,ampi-cillin,cefazolin,gentamicin,piperacillin,and tetracycline,but susceptibility to other antibiotics.The coincidence rate between drug resistance genes and drug resistance phenotypes was high.PFGE revealed that nine strains from this food poisoning case were highly homologous.WGS revealed that the MLST type was ST19,and varying numbers of SNPs(1-6)were present a-mong strains.The phylogenetic tree revealed nine isolated strains forming a distinct cluster,differing from other Salmonella strains in the database and belonging to a novel clonal branch.The single nucleotide site in the strains was highly homologous to that of GCF in Jiangxi_020221795.1.The food poisoning case was caused by Salmonella typhimurium ST19,and all nine iso-lated strains originated from the same source.The chef is closely connected to this food poisoning case.This strain of Salmo-nella typhimurium belongs to a new clonal branch and exhibits multiple drug resistance.

Improvement of ulcerative colitis control by searching and restricting of inflammatory trigger factors in daily clinical practice

Background/Aims@#Exacerbating factors of ulcerative colitis (UC) are multiple and complex with individual influence. We aimed to evaluate the efficacy of disease control by searching and restricting inflammation trigger factors of UC relapse individually in daily clinical practice. @*Methods@#Both patients with UC history or new diagnosis were asked to avoid dairy products at first doctor visit. Individual-reported potential trigger factors were restricted when UC flared up (Mayo endoscopy score ≥1) from remission status. The remission rate, duration to remission and medication were analyzed between the groups of factor restriction complete, incomplete and unknown. @*Results@#The total remission rate was 91.7% of 108 patients with complete restriction of dairy product. The duration to remission of UC history group was significantly longer than that of new diagnosis group (88.5 days vs. 43.4 days, P=0.006) in patients with initial endoscopic score 2–3, but no difference in patients with score 1. After first remission, the inflammation trigger factors in 161 relapse episodes of 72 patients were multiple and personal. Milk/dairy products, herb medicine/Chinese tonic food and dietary supplement were the common factors, followed by psychological issues, non-dietary factors (smoking cessation, cosmetic products) and discontinuation of medication by patients themselves. Factor unknown accounted for 14.1% of patients. The benefits of factor complete restriction included shorter duration to remission (P<0.001), less steroid and biological agent use (P=0.022) when compared to incomplete restriction or factor unknown group. @*Conclusions@#Restriction of dairy diet first then searching and restricting trigger factors personally if UC relapse can improve the disease control and downgrade the medication usage of UC patients in daily clinical practice.

Characteristics and management mechanism of imported malaria from overseas during the malaria elimination phase in Wuhan City / 公共卫生与预防医学

Objective To analyze the characteristics of imported malaria epidemic from overseas in Wuhan, to explore the management mechanism of on-site cases, and to accumulate experience for the treatment of imported malaria in large cities after malaria elimination. Methods The epidemiological data on imported malaria from abroad during the period of malaria elimination (2010-2019) in Wuhan were collected. The gender, age and severe illness-related factors of the cases were analyzed. Based on the characteristics of the epidemic and the current situation of prevention and control, the content and experience of the “Municipal-District 24-7” case mechanism were discussed. Results The medical resources in Wuhan were the best in the central region, resulting in a large number of imported malaria cases, with a total of 474 cases reported from 2010 to 2019 (40.79% of the total number of cases in Hubei Province), including 359 cases of falciparum malaria, 36 severe cases and one death (the death rate was 0.28%). The patients were mainly young and middle-aged men aged 20 to 49 years old (97.26%). There were many referral cases (40.30%), and there was no seasonal clustering of cases reported. The undiagnosed proportion at the first visit was 44.85%, and the time of attack-diagnosis was 4 days or more in 61.00% of cases. The occurrence of severe cases was related to unconfirmed diagnosis at the first visit (χ2=35.46, P<0.001) and attack-diagnosis time (Z=-6.49, P<0.001). Conclusion Imported malaria occurs frequently in Wuhan, mainly falciparum malaria. However, “Municipal-District 24-7” case mechanism has effectively curbed the occurrence of severe and death cases and provided valuable experience for case management in similar cities in China.

Signal transducer and activator of transcription 3 and cancer associated fibroblasts jointly generate chemo-resistance and affect prognosis in epithelial ovarian cancer / 中华妇产科杂志

Objective: To investigate the mechanism of signal transducer and activator of transcription 3 (STAT3) and cancer associated fibroblasts (CAF) jointly generate chemo-resistance in epithelial-ovarian cancer and their effect on prognosis. Methods: A total of 119 patients with high-grade ovarian serous cancer who received surgery in Cancer Hospital of Chinese Academy of Medical Sciences from September 2009 to October 2017 were collected. The clinico-pathological data and follow-up data were complete. Multivariate Cox regression model was used to analyze the prognostic factors. Ovarian cancer tissue chips of patients in our hospital were prepared. EnVision two-step method immunohistochemistry was used to detect the protein expression levels of STAT3, the specific markers of CAF activation, fibroblast activating protein (FAP), and type Ⅰ collagen (COL1A1) secreted by CAF. The relationship between the expression of STAT3, FAP, COL1A1 protein and drug resistance and prognosis of ovarian cancer patients was analyzed, and the correlation between the expression of three proteins was analyzed. These results were verified through the gene expression and prognostic information of human ovarian cancer tissues collected in the GSE26712 dataset of gene expression omnibus (GEO) database. Results: (1) Multivariate Cox regression model analysis showed that chemotherapy resistance was an independent risk factor for overall survival (OS) of ovarian cancer (P<0.001). (2) The expression levels of STAT3, FAP, and COL1A1 proteins in chemotherapy resistant patients were significantly higher than those in chemotherapy sensitive patients (all P<0.05). Patients with high expression of STAT3, FAP, and COL1A1 had significantly shorter OS than those with low expression (all P<0.05). According to the human ovarian cancer GSE26712 dataset of GEO database, patients with high expression of STAT3, FAP, and COL1A1 also showed shorter OS than patients with low expression (all P<0.05), the verification results were consistent with the detection results of ovarian cancer patients in our hospital. (3) Correlation analysis showed that the protein level of STAT3 was positively correlated with FAP and COL1A1 in our hospital's ovarian cancer tissue chips (r=0.47, P<0.001; r=0.30, P=0.006), the analysis of GEO database GSE26712 dataset showed that the expression of STAT3 gene and FAP, COL1A1 gene were also significantly positively correlated (r=0.31, P<0.001; r=0.52, P<0.001). Conclusion: STAT3 and CAF could promote chemotherapy resistance of ovarian cancer and lead to poor prognosis.

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review / 中华儿科杂志

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.

Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy / 医学前沿

The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

MicroRNA21-5p alleviates hyperoxia-induced acute lung injury in rats through activating phosphatidylinositol 3 kinase/serine-threonine protein kinase signaling pathway by regulating type Ⅱ alveolar epithelial cell apoptosis / 中华危重病急救医学

Objective:To investigate whether microRNA-21-5p (miR-21-5p) alleviates hyperoxia-induced acute lung injury (HALI) through activating the phosphatidylinositol 3 kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathway by regulating apoptosis of type Ⅱ alveolar epithelial cell (AECⅡ).Methods:Seventy-two male Sprague-Dawley (SD) rats were divided into normozone-controlled group, HALI group, PI3K/Akt signaling pathway inhibitor LY294002+HALI group (LY+HALI group), miR-21-5p overexpression+LY294002+HALI group (miR-21-5p+LY+HALI group), miR-21-5p overexpression+HALI group (miR-21-5p+HALI group), and dimethyl sulfoxide (DMSO)+HALI group by random number table method with 12 rats in each group. Animal models of HALI were prepared using 95% concentrations of oxygen. The animals in the normozone-controlled group were fed normally under normoxia. Transfection of lung tissue by miR-21-5p adeno-associated viral vector AAV6-miR-21-5p was performed by instillation of 200 μL titer (1×10 12 TU/mL) through a tracheal catheter 3 weeks prior to modeling. DMSO and LY294002 were administered via the tail vein at 0.3 mg/kg 1 hour before modeling. After 48 hours of modeling, carotid artery blood was collected to detect oxygenation index (OI) and respiratory index (RI), and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect miR-21-5p expression. Lung tissue was collected, and the levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA), and the ratio of pulmonary wet/dry weight (W/D) was determined, and the pathological changes of lung histopathology were observed under the light microscopy after hematoxylin-eosin (HE) staining. Each group was purified AECⅡ cells from 6 rats, the apoptosis rate was detected by flow cytometry, and the expression levels of phosphatase and tensin homologous gene (PTEN), and proteins from the PI3K/Akt signaling pathway were detected by Western blotting. Results:Compared with the normozone-controlled group, alveolar septal thickening and massive inflammatory cell infiltration were found after hyperoxia exposure, RI, inflammatory factors, lung W/D ratio, pathological score, AECⅡ cells early apoptosis rate, PTEN protein expression and phosphorylation level of Akt were increased, while OI and miR-21-5p expression were decreased, indicating the successful preparation of the model. After pretreatment, LY294002 could aggravate the pathological injury of lung tissue in HALI rats, RI, inflammatory factors and lung W/D ratio were further increased, and OI was further reduced compared with HALI group. At the same time, it could promote the AECⅡ cell apoptosis, further up-regulate the expression of PTEN, and reduce the phosphorylation of Akt. However, miR-21-5p pretreatment could negatively regulate PTEN, activate PI3K/Akt signal pathway, inhibit AECⅡ cell apoptosis, and reduce HALI, which was shown by the decreased level of inflammatory factors in miR-21-5p+LY+HALI group compared with LY+HALI group [TNF-α (μg/L): 100.33±3.48 vs. 116.55±2.53, IL-6 (ng/L): 141.06±3.70 vs. 161.31±3.59, IL-1β (μg/L): 90.82±3.69 vs. 112.23±2.87, all P < 0.05], RI, lung injury pathology score, lung W/D ratio, and AECⅡ cell early apoptosis rate were significantly decreased [RI: 0.81±0.02 vs. 1.05±0.07, pathology score: 0.304±0.008 vs. 0.359±0.007, lung W/D ratio: 5.29±0.03 vs. 5.52±0.08, apoptosis rate: (27.20±2.34)% vs. (34.17±1.49)%, all P < 0.05], OI and expressions of miR-21-5p were significantly increased [OI (mmHg, 1 mmHg≈0.133 kPa): 266.71±2.75 vs. 230.12±4.04, miR-21-5p (2 -ΔΔCt): 2.21±0.13 vs. 0.33±0.03, both P < 0.05], and PTEN protein expression in AECⅡ cell was significantly reduced (PTEN/GAPDH: 0.50±0.06 vs. 0.93±0.06, P < 0.05), and phosphorylation level of Akt was significantly increased [phosphorylated Akt (p-Akt) protein (p-Akt/GAPDH): 0.86±0.05 vs. 0.56±0.06, P < 0.05]. Conclusion:miR-21-5p attenuates HALI by inhibiting AECⅡ cell apoptosis, possibly through negative regulation of PTEN to activate PI3K/Akt signaling pathway.

Application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair / 国际外科学杂志

Abdominal hernia repair is a challenging surgery with high complication rate and recurrence rate, especially in potentially contaminated or contaminated abdominal wall hernias. The application of hernia mesh has significantly reduced the recurrence rate. However, different types of meshes have their own advantages and disadvantages. There are still controversies regarding the selection of mesh in the environment of potential contaminated and contaminated abdominal hernia repair. The biological mesh, which was once considered that have anti-infection advantages and was widely used, has not been found to reduce the infection rate in recent studies, but instead leads to a higher recurrence rate and expensive medical costs. On the contrary, synthetic mesh represented by monofilament and large mesh polypropylene mesh have achieved good results in potentially contaminated or contaminated hernia repairs recently. The emergence of new types of meshes such as absorbable synthetic mesh may be a better choice for potentially contaminated or contaminated abdominal hernia repair. This article reviews the application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair, aiming to provide reliable evidence for the selection of mesh for these patients.

Evolution and research progress of mesh fixation in laparoscopic trans-abdominal preperitoneal hernia repair / 国际外科学杂志

Since the development of tension-free hernia repair, the choice of mesh type and fixation mode has become a problem that surgeons must consider in operation. The selection of appropriate mesh fixation mode is of great significance to the prognosis of patients. In recent years, with the development of laparoscopic technology and hernia repair materials, new mesh types and mesh fixation techniques have been popularized in clinical practice, tack fixation and suture fixation have been less used in trans-abdominal preperitoneal hernia repair, and medical glue and self-gripping mesh have become the mainstream choice. Some scholars believe that in addition to large direct hernia, vacuum suction fixation is also a safe and effective fixation method. The best method of mesh fixation is still controversial, and the choice of intraoperative fixation methods is also to reach a unified standard. This paper reviews the advantages and disadvantages of different mesh fixation methods in trans-abdominal preperitoneal hernia repair, as well as the selection of intraoperative fixation methods, in order to provide basis for clinicians' intraoperative selection.

Progress in the diagnosis and treatment of chronic postoperative inguinal pain / 国际外科学杂志

Inguinal hernia is one of the most common diseases in general surgery. Surgery is the only treatment. In recent years, with the emergence and popularization of tension-free hernia repair, the recurrence rate has been lower than before. Chronic Postoperative Inguinal Pain (CPIP) has gradually become the focus of research. CPIP has now become one of the important efficacy indicators for inguinal hernia surgery. The etiology of CPIP is more complicated, mainly including neuropathic pain, non-neuropathic pain, somatic pain and visceral pain. Female, young, obese, low pain control, preoperative anxiety, preoperative pain, high pain sensitivity and other patient factors, and experience of the surgeon, open hernia repair, weight patch, patch fixation, surgery Surgical factors such as post-acute pain are risk factors for CPIP. CPIP is not only a product of neuropathic and nociceptive pain, but is also affected by various factors such as psychology, emotion, cognition, and genetics. Therefore, detailed medical history, physical examination, and correct pain and quality of life assessment tools are essential for the diagnosis of CPIP is very necessary. The treatment of CPIP should follow certain steps. The first choice is anticipatory treatment, drug treatment, psychological and behavioral treatment, physical therapy and other conservative treatments and interventional treatments, If the pain relief is not obvious after 6 months to 1 year by the above methods, surgical treatment is considered. So far, preventive analgesia and standardized surgery are the most important means to improve the prognosis of patients.

Advance in abdominal hernia repair based on enhanced recovery after surgery / 国际外科学杂志

Enhanced recovery after surgery (ERAS) is a systematic approach to care that optimizes perioperative management, improves clinical outcomes, and reduces healthcare costs. ERAS has been introduced into abdominal hernia repair in recent years. Preoperative management was optimized through health education, smoking cessation, weight control, blood glucose and pain management, infection and thrombosis prophylaxis. And prevention of hypothermia, standardized anesthesia management, fluid replacement control, minimally invasive operation, controlled catheter placement and other intraoperative management optimization measures. And multi-mode analgesia, early postoperative activity, recovery of gastrointestinal function and control of blood glucose and other postoperative management optimization measures effectively reduced the incidence of complications such as surgical site infection, alleviated the pain of patients, and shortened the hospital stay. ERAS factors such as perioperative pain management, early postoperative activity, and recovery of gastrointestinal function are the key to shorten hospital stay and improve prognosis during abdominal wall hernia repair. ERAS can be used safely and effectively for abdominal hernia repair.

Evaluation of cytokine immunotyping on the condition and prognosis of children with sepsis / 中国小儿急救医学

Objective:To evaluate the effect of serum cytokines and immune typing on the severity and prognosis of children with sepsis.Methods:One hundred and sixty children with sepsis admitted to No.2 PICU from May 2018 to May 2019 at Hunan Children′s Hospital were enrolled.Vital signs, blood routine and blood biochemical indexes of the children were collected within 24 hours after admission.Serum cytokine concentrations of interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor(TNF)-α, and interferon (IFN)-γ were tested at the same time.According to the worst condition during the first 24 h after admission, and the consensus diagnostic criteria of experts in the diagnosis and treatment of septic shock in children in 2015, the patients were divided into sepsis group(76 cases) and severe sepsis group(84 cases). According to the prognosis of 28 days, the patients were divided into survival group(134 cases)and death group(26 cases). The differences of cytokine concentration and the composition of immune state among groups were compared.Results:The levels of IL-2[2.40(2.40, 2.55)pg/mL vs. 2.40(2.40, 3.76)pg/mL], IL-6[60.54(23.22, 250.38)pg/mL vs. 21.47(8.83, 57.94)pg/mL], IL-10[50.85(21.74, 217.12)pg/mL vs. 14.99(9.23, 28.79)pg/mL] , TNF-α[2.75(2.40, 5.15)pg/mL vs. 2.40(2.40, 3.23)pg/mL] and IFN-γ[8.01(4.34, 37.28)pg/mL vs.2.62(2.62, 28.56)pg/mL] in the severe sepsis group were significantly higher than those in the sepsis group( P<0.05). The levels of IL-10[99.57(10.51, 646.96)pg/mL vs. 23.17(11.74, 57.30)pg/mL] and TNF-α[3.08(2.40, 5.13)pg/mL vs. 2.45(2.40, 3.80)pg/mL] in the death group were significantly higher than those in the survival group( P<0.05). The risk of death in children with mixed antagonistic response syndrome (MARS) was significantly higher than those without MARS( OR 3.75, 95% CI 1.302-10.804). Conclusion:The increased concentrations of IL-2, IL-6, IL-10, TNF-α, and IFN-γ are significantly correlated with the severity of sepsis in children.Increased IL-10 concentration and the occurrence of MARS are significantly correlated with poor prognosis.The occurrence of MARS in children with sepsis should be highly vigilant for the poor prognosis.

Analysis of correlation factors between peripapillary duodenal diverticulum and choledochectasia by CT scan / 中国医师进修杂志

Objective:To analyze the correlation factors between peripapillary duodenal diverticulum (PDD) and choledochectasia by CT scan.Methods:The clinical data of 220 patients with duodenal diverticulum detected by multi-slice spiral CT scan and confirmed by gastrointestinal angiography or endoscopic retrograde cholangiopancreatography (ERCP) in Dahua Hospital, Xuhui District of Shanghai City were retrospectively analyzed. The correlation of the PDD, the contact of common bile duct (CBD), length of contact and exudation with choledochectasia in patients with PDD were analyzed.Results:A total of 236 duodenal diverticulum were found in 220 patients. Among them, there were 152 PDD, 41 diverticulum located superior to the duodenal papilla, 28 diverticulum located inferior to the duodenal papilla, 3 diverticulum located lateral to the duodenal papilla, and 12 diverticulumlocated in the horizontal portion. The incidence of choledochectasia in patients with PDD contacted with CBD was significantly higher than that in patients with PDD not contacted with CBD: 59.35% (73/123) vs. 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in patients with contact length of PDD and CBD ≥1.5 cm was significantly higher than that in patients without contact of PDD and CBD and patients with contact length of PDD and CBD <1.5 cm: 82.43% (61/74) vs. 24.49% (12/49) and 37.93% (11/29), and there was statistical difference ( P<0.05); the incidence of choledochectasia in PDD patients with exudation was significantly higher than that in PDD patients without exudation: 10/11 vs. 52.48% (74/141), and there was statistical difference ( P<0.05). Conclusions:The patients with contact length of PDD and CBD ≥1.5 cm and patients with PDD combined with exudation could be prone to choledochectasia.

Application of objective performance criteria in post-marketing evaluation schemes of traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicines(TCMs) have certain limitations in the clinical research design in their post-marketing evaluation, so that randomized controlled programs cannot be strictly implemented in some studies, while the objective performance criteria is a reasonable external controlled research method that has been gradually recognized at home and abroad in recent years in addition to randomized controlled trial(RCT) method. It is more mature in medical devices, surgery and other research fields, but there is no relevant report in the field of post-marketing evaluation of Chinese patent medicines. In this paper, the application prospect of the objective performance criteria and the problems were discussed in the field of post-marketing evaluation of TCM. The characteristics of as TCM are more consistent with the scope of the objective performance criteria, the application of the objective performance criteria in post-marketing evaluation of Chinese patent medicines, especially in single arm research, can break through the limitations of existing conventional clinical research methods, and improve the level of evidence, with good feasibility and advantages. However, in the application process, we should pay attention to the key issues such as the selection of index, research population, follow-up period and the reference selection, to ensure the quality of research. This research group has carried out some exploration and practice in the field of post-marketing evaluation of TCM injections by using single arm combined with the objective performance criteria, hoping to establish the key technology in this field, and provide certain research and design reference for the secondary development of Chinese patent medicines.

Modified transverse tibial bone transplantation and microcirculation reconstruction for the treatment of end-stage diabetic foot / 中国骨伤

OBJECTIVE@#To explore clinical effect of modified transverse tibial bone transfer microcirculation reconstruction in treating end-stage diabetic foot.@*METHODS@#From August 2016 to June 2018, 87 patients with diabetic foot treated with modified tibial transverse bone removal and microcirculation reconstruction, inclduing 54 males and 33 females;aged from 39 to 95 years old with an average of (68.9±11.3) years old;2 patients were grade 2, 37 patients were grade 3 and 50 patients were grade 4 according to Wagner's classification;the courses of diabetic were for 10 to 16 years with an average of (13.0±2.2) years;the courses of diabetic feet were for 21 to 48 days with an avergae of (34.2±8.6) days. Postoperative comlications were observed. Skin temperature, visual analogue scale(VAS) and ankle brachial index(ABI) and wound healing were recorded before and 3 months after operation.@*RESULTS@#All patients were followed up for 4 to 19 months with an average of (12.6±2.8) months. Two patients occurred subcutaneous tissue liquefaction and seepage under needle passage during bone transfer, and scabed without special treatment. One patient was performed amputation above 5 cm of ankle joint because of severe infection, and 1 patient occurred re-ulceration at 1 year after wound healing, bone transfer was performed again at the same site, and was completely healed at 8 weeks after operation. The healing time of wound ranged from 3 to 24 weeks with an average of (11.9± 3.8) weeks. Foot skin temperature before operation was (28.9±0.91) ℃, and increased to (31.70±0.32)℃ at 3 months after operation(@*CONCLUSION@#Modified lateral tibial bone transfer could effectively reconstruct microvascular network under lower leg, promote recovery of peripheral blood vessels, and promote wound healing of foot, reduce or avoid amputation. At the same time, the improved osteotomy is one of the effective methods for the treatment of diabetic foot which has advantags of less trauma, simple opertaion.