Mechanical ventilation(MV)provides life support for critically ill respiratory patients,but in the meantime can cause fatal ventilator-induced lung injury(VILI),and the latter remains a major challenge in respiratory and critical care medicine,because the pathological mechanism has not been fully elucidated.Recent studies show that on the one hand,in the lung with VILI,there exists airway collapse at multi-sites of an individual airway,which can not be explained by traditional airway collapse models.But on the other hand,under MV conditions,airway smooth muscle cells(ASMC)exhibit abnormal mechanical behaviors,accompanied by regulation of Piezo1 expression and endoplasmic reticulum stress.These phenomenons indicate that the MV-induced abnormal mechanical behavior of ASMC is closely related to multiple airway collapse and VILI.Therefore,by studying the MV-induced changes of ASMC mechanical behaviors and their relationship with airway collapse in lung injury,as well as the related mechanochemical signal coupling process,it is expected to reveal a novel mechanism of MV-associated airway collapse and lung injury from the perspective of cell mechanics.In this review,the recent research progress of airway collapse during MV,the regulation of ASMC mechanical behavior by MV-related high stretch,especially the related mechanochemical signal coupling mechanism is summarized.These advances may provide a novel insight for exploring the roles of ASMC abnormal mechanical behavior in the pathological mechanism of VILI,alternative targets of drug intervention for prevention and treatment of VILI,as well as for optimizing the ventilation mode in clinical practice.

Objective:To study the expression level of programmed death ligand 1 (PD-L1) in combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and its correlation with the clinical characteristics and prognosis.Methods:The clinical data of 75 patients with cHCC-CCA undergoing surgery in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2019, including 61 males and 14 females, with a median age of 55 years (36 to 77). Immunohistochemistry was conducted to determine the PD-L1 expression in tumor. The status of PD-L1 expression, clinicopathological data and prognosis of patients were analyzed.Results:In low-differentiated cHCC-CCA tissues, the proportion of PD-L1 expression (21.1%, 8/38) was higher than that in moderately to well-differentiated cHCC-CCA tissues (2.70%, 1/37, χ2=4.366, P=0.037). The median disease-free survival (DFS) and overall survival (OS)of PD-L1 positive patients were 12.3 and 15.1 months, respectively, lower than those of PD-L1 negative patients (14.4 and 23.3 months). The difference of DFS was statistically significant ( χ2=4.052, P=0.044). In multivariate analysis, major vascular invasion (DFS: HR=1.965, 95% CI: 1.119-3.450, P=0.019; OS: HR=1.781, 95% CI: 1.022-3.105, P=0.042) and lymph node metastasis (DFS: HR=2.451, 95% CI: 1.1033-5.814, P=0.042; OS: HR=2.652, 95% CI: 1.120-6.279, P=0.027) were identified as independent prognostic factors affecting DFS and OS. Conclusions:The proportion of PD-L1 positive is higher inthe low-differentiated cHCC-CCA tissue compared to that in moderately to well-differentiated cHCC-CCA. The major vascular invasion and lymph node metastasis are independent factors affecting the prognosis of patients with cHCC-CCA.

Objective To investigate the value of international standardized ratio-to-platelet ratio (INPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis in patients with primary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were diagnosed with PBC in The First Affiliated Hospital of Zhengzhou University from October 2013 to March 2021. Scheuer score was used to systematically evaluate the degree of liver fibrosis (S0-S4 stage). According to the results of liver biopsy, the degree of liver fibrosis was classified as significant liver fibrosis (≥S2), progressive liver fibrosis (≥S3), and liver cirrhosis (S4). Related data including general information, liver function, routine blood test results, and blood coagulation were collected, and related formulas were used to calculate the values of the noninvasive serological models INPR, APRI, and FIB-4. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. A Spearman correlation analysis was used to evaluate the correlation between noninvasive models and liver fibrosis stage. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the noninvasive serological models in the diagnosis of liver fibrosis degree, and the DeLong method was used for comparison of the area under the ROC curve (AUC). Results A total of 143 patients with PBC were enrolled in the study, among whom 4 had stage S0 liver fibrosis, 50 had stage S1 liver fibrosis, 46 had stage S2 liver fibrosis, 26 had stage S3 liver fibrosis, and 17 had stage S4 liver fibrosis. There was a significant difference in INPR value between the PBC patients with different liver fibrosis degrees ( χ 2 =27.347, P < 0.001). INPR value gradually increased with the aggravation of liver fibrosis degree, and INPR was positively correlated with liver fibrosis degree ( r =0.419, P < 0.01). The ROC curve analysis showed that INPR, APRI, and FIB-4 had an AUC of 0.691, 0.706, and 0.742, respectively, in the diagnosis of significant liver fibrosis (≥S2) in PBC patients, at the corresponding cut-off values of 0.63, 0.59, and 2.68, respectively. INPR, APRI, and FIB-4 had an AUC of 0.731, 0.675, and 0.756, respectively, in the diagnosis of progressive hepatic fibrosis (≥S3) in PBC patients, at the corresponding cut-off values of 0.64, 1.23, and 4.63, respectively. INPR, APRI, and FIB-4 had an AUC of 0.820, 0.786, and 0.818, respectively, in the diagnosis of liver cirrhosis (S4) in PBC patients, at the corresponding cut-off values of 0.95, 1.26, and 4.63, respectively. In the evaluation of significant liver fibrosis, progressive liver fibrosis, and liver cirrhosis, there was no significant difference in AUC between INPR and APRI/FIB-4 (all P > 0.05). Conclusion INPR is a simple and accurate noninvasive model for the evaluation of liver fibrosis and has a certain value in the diagnosis of liver fibrosis in PBC.

Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.

Objective To investigate the value of age and D-dimer (D-D) combined with Model for End-Stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 111 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Zhengzhou University from December 2019 to October 2021 were enrolled, and according to their prognosis on day 90 after confirmed diagnosis, they were divided into survival group with 49 patients and death group with 62 patients. Related clinical data were collected, including age, sex, underlying liver diseases, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), Albumin (Alb), D-D, prothrombin time (PT), plasma fibrinogen (FIB), prothrombin activity (PTA), international normalized ratio (INR), serum creatinine (SCr), and serum sodium (Na), and MELD score was calculated. Immunoturbidimetric assay was used to measure the plasma level of D-D. The t -test or the Mann-Whitney U test was used for comparison of continuous data between the two groups, and the chi-square test was used for comparison of categorical data between the two groups; a binary Logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients, and the receiver operating characteristic (ROC) curve was used to predict the accuracy of variables. Results There were significant differences between the two groups in age, TBil, D-D, PT, PTA, INR, SCr, Na, and MELD score (all P < 0.05). The binary Logistic regression analysis showed that age (odds ratio [ OR ]=1.088, 95% confidence interval [ CI ]: 1.001-1.183, P =0.047), D-D ( OR =1.521, 95% CI : 1.078-2.145, P =0.017), and MELD score ( OR =1.892, 95% CI : 1.408-2.543, P < 0.001) were independent risk factors for the prognosis of HBV-ACLF patients. Age, MELD score and D-D had an area under the ROC curve (AUC) of 0.664, 0.869, and 0.887, respectively, in predicting the prognosis of HBV-ACLF, while D-D combined with age, age combined with MELD score, D-D combined with MELD score, and the combination of these three indicators had an AUC of 0.895, 0.906, 0.965, and 0.970, respectively. A combination of the three indices had a significantly increased AUC compared with other indices except D-D combined with MELD score. and the combination of these three indicators had relatively high sensitivity (0.935) and specificity (0.918). Conclusion Age, D-D, and MRLD score are independent risk factors for the prognosis of HBV-ACLF, among which D-D and MELD score have a good value in predicting prognosis, and the combination of these three indicators has a significantly better predictive value.

Objective:To investigate the significance of MLH1 protein expression and MLH1 gene methylation rate between metastatic solid pseudopapillary tumor of pancreas (SPT) and non-metastatic SPT, and to explore the correlation between MLH1 gene methylation and SPT metastasis.Methods:Twelve metastatic SPT patients admitted to Peking University People's Hospital, Rizhao Central Hospital and Chaoyang Central Hospital of Liaoning Province from January 2009 to May 2022 were studied retrospectively, including 3 males and 9 females, with a median age of 47 years old, ranging from 21 to 73 years old. Thirty non-metastatic SPT patients with clear diagnosis, clear medical history and complete follow-up data from pathological database of Peking University People's Hospital from January 2009 to May 2017 were selected as the control group, including 12 males and 18 females, with a median age of 42 years old, ranging from 34 to 69 years old. Clinical data such as gender, age and pathological data were collected. Immunohistochemical expression of MLH1 protein and methylation of MLH1 gene were detected by pathological paraffins.Results:There was no significant difference in general data between the two groups (all P>0.05). Among the 12 metastatic SPT patients, 4 cases metastasized to liver, 2 to spleen, 2 to lung, 2 to lymph nodes, 1 to mediastinum, and 1 to sacrum. Compared with the non-metastatic tissue, the MLH1 protein deletion in metastatic pancreatic lesions (metastatic SPT-P) and metastatic lesions (metastatic SPT-M) were increased [both 33.3%(4/12)], and the difference was statistically significant (both Chi square=5.00, both P=0.041). Compared with 0 (0/30) MLH1 gene methylation rate in non-metastatic SPT tissues, the methylation rate of MLH1 gene in metastatic SPT-M and metastatic SPT-P tissues [both 30% (3/10)] were higher, with statistical significance (both Chi square=0.96, both P=0.032). Conclusion:Compared with non-metastatic SPT, the loss rate of MLH1 protein expression and MLH1 gene methylation are increased in metastatic SPT. MLH1 methylation may occur before metastasis, which can be used as a predictor of SPT metastasis.

Early postoperative hemorrhage (EPOH) is a common complication of pancreaticoduodenectomy (PD) and a main cause of death. The cause of EPOH is related to inappropriate vascular treatment during the operation, which may be recognized as a technical failure and avoided theoretically. PD is characterized by varieties of tissues that need to be separated and resected, large wound surface, many operations such as vascular separation, dissection, resection and reconstruction, and complex anastomoses. Therefore, the causes of EPOH are complex and varied. The most effective measure to prevent EPOH is to handle the vessels carefully and properly during the operation. In this paper, we systematically summarized the blood vessels involved in PD procedure, and the treatment strategies of these potential bleeding sites, and the clinical thinking and treatment principles of EPOH, so as to improve the quality of vascular treatment in PD procedure and to prevent EPOH.

The right hepatic artery (RHA) is the terminal artery supplying the right hepatic lobe. There are many anatomic variations of RHA, including low RHA and left hepatic artery bifurcation, aberrant course, tortuosity, abnormal branches of cystic artery and origin variation. The origin variation of RHA is divided into replaced RHA and accessory RHA. The replaced artery origins include superior mesenteric artery, celiac trunk, aorta, common hepatic artery, gastroduodenal artery, left gastric artery, splenic artery and right renal artery. The variations of RHA are important causes of intraoperative adverse events and postoperative complications in hepatobiliary-pancreatic-splenic surgery. It is an important guarantee for the safety of operation to know and master these RHA variations well before operation, to separate it carefully and to protect it properly during operation.

Objective:To explore the influencing factors of long-term survival for hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods:A retrospective analysis of 255 patients who underwent RFA as the main treatment modality for HCC from May 1, 2004 to Feb 28, 2015 was performed. All patients were divided into two groups according to the postoperative survival time: the 5-year or more survival group and the less than 5-year survival group. Clinical indicators such as age, maximum tumor size and number, and frequency of radiofrequency ablation were compared between the two groups. Cox single factor and multiple factors were used to analyze the influencing factors of long-term survival.Results:The median overall survival of all the 255 patients was 4.3 years (range 0.5-15.5 years). There were 115 patients (45.1%) who survived for 5 years or more and 140 patients (54.9%) who survived for less than 5 years. The 1-, 3-, 5-, and 10-year survival rates of all the patients were 86.7%, 61.2%, 44.8% and 34.8%, respectively. There were no significant differences in gender, age, accompanying symptoms, aetiology of liver disease, level of alpha fetoprotein and treatment ( P>0.05), but there were significant differences in Child-Pugh class, liver cirrhosis, maximum diameter of tumor, tumor number, tumor stage, and frequency of RFA ( P<0.05) between the 2 groups of patients. Multivariate analysis showed that age ≥70 years old, Child-Pugh class B, maximum diameter of tumor >5.0 cm, multiple tumor were independent risk factors of long-term survival, but the number of sessions of RFA was a protective factor. Conclusions:For medium sized HCC and solitary large HCC, RFA combined with other therapeutic modalities could achieve satisfactory therapeutic results. Age, Child-Pugh class, maximum diameter of tumor, tumor number and RFA frequency were influencing factors for long-term survival of HCC patients.

Objective To analyze the effects of different supplements on anemia related indexes in rural children. Methods A stratified method was adopted, and six villages (towns) in and around Qinghai Province were selected as intervention sits for the present study. A total of 304 children from 2 to 6 years old at each intervention site meeting the inclusion criteria were screened and divided into three groups (A, B, and C), who were intervened for 3 months. Serum vitamin A, vitamin D and hemoglobin levels were measured before and after the intervention. Results The hemoglobin level of 304 children before intervention was (118.65±16.07) g /L, and the prevalence of anemia was 9.54%. The vitamin A value, vitamin D value and hemoglobin value were increased after three months of the intervention. The changes of vitamin A value, vitamin D value and hemoglobin value in rural children in group C were significantly higher than those in groups A and B. The increase in vitamin A value in rural children aged 3 years was significantly higher than that in other age groups, and the increase in hemoglobin in rural children of 1 year old was significantly higher than that in other age groups. The increase in vitamin A value of rural children of other ethnic groups (mainly Tibetans) was significantly higher than that of Han and Hui nationalities, and the increase of hemoglobin value in Hui rural children was significantly higher than that in Han and other ethnic groups. Conclusion Vitamin A combined with iron dextran tablets was effective in preventing anemia in rural children.