Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury caused by a variety of intrapulmonary and/or extrapulmonary factors such as infection and trauma. Uncontrolled inflammatory response is the main pathological feature. Different functional states of alveolar macrophages have different effects on inflammatory response. Transcription activating factor 3 (ATF3) is a fast response gene in the early stage of stress. In recent years, it has been found that ATF3 plays an important role in regulating the inflammatory response of ARDS by regulating the function of macrophages. This paper reviews the regulatory effects of ATF3 on alveolar macrophage polarization, autophagy and endoplasmic reticulum stress and its effects on the inflammatory process of ARDS, aiming to provide a new research direction for the prevention and treatment of ARDS.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Objective:To explore the mechanism of Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction (hereinafter referred to as " Sanyang combined treatment" ) in alleviating colon injury in mice infected with influenza virus by transcriptome sequencing technique.Methods:The mouse model of colonic injury caused by influenza virus was induced by intranasal drip of influenza A virus H1N1 suspension. The mice were divided into Control group, Model group, and Sanyang combined treatment (SCT) group. Model group and SCT group were fed with PBS and Ma-Xing Shi-Gan decoction combined with Xiao-Chai-Hu decoction respectively. Seven days later, the colon tissues of each group were taken, the colon length and pathological damage were observed, and the transcriptome was sequenced to screen the significantly different genes between the SCT group and model group for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis(GSEA).Results:After the therapy with SCT, the length of the colon of mice was significantly improved and the pathological injury of the colon was reduced. There are 92 differentially expressed genes between the SCT group and the model group. GO analysis indicated that the differential genes were enriched in biological processes such as regulation of cytokine and chemokine production, inflammatory response, defense response, immune response, regulation of NF-κB inducing kinase(NIK)/Nuclear factor-κB(NF-κB) signal and Mitogen-activated protein kinase(MAPK) cascade, as well as cell components related to intestinal barrier such as brush border membrane, brush border and microvilli. KEGG analysis indicated that the differential genes were enriched in Toll-like receptor signaling pathway, intestinal immune network for IgA production, complement and coagulation cascade, and Peroxisome proliferator-activated receptor(PPAR) signaling pathway. GSEA indicated that the intestinal immune network for IgA production, PPAR signaling pathway, propionic acid metabolism and butyrate metabolism were significantly up-regulated after the intervention with SCT, while apoptosis and MAPK signaling pathway were significantly down-regulated.Conclusions:Sanyang combined therapy can protect the intestinal tract of mice infected with influenza virus mainly through immunity, inflammation and metabolism pathways.

Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Objective To investigate the effect of expression of Cullin 4B (CUL4B) on the prognosis of patients after liver transplantation for hepatocellular carcinoma (HCC).Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients who underwent liver transplantation for HCC in the First Affiliated Hospital of Sun Yat-sen University between January 1,2014 and June 30,2015 were collected.The specimens of HCC tissues were collected and embedded in paraffin,and then were detected by immunohistochemistry staining.Observation indicators:(1) expression of CUL4B in HCC tissues;(2) follow-up and survival;(3) prognostic factors analysis after liver transplantation;(4) association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation.Follow-up using outpatient examination and telephone interview was performed to detect tumor recurrence or metastasis and survival up to June 2018.Measurement data with normal distribution were represented as (x)±s.The comparison between groups of count data was done using the chi-square test.The survival curve drawn using the Kaplan-Meier method,and the survival analysis was done by Log-rank test.The univariate and multivariate analysis were respectively done using the COX regression model.The association analysis was done using the Pearson test.Results (1) Expression of CUL4B in HCC tissues:immunohistochemistry staining showed that CUL4B was mainly expressed in the cytoplasm,with a powerful brownish-yellow staining.The high expression and low expression of CUL4B in HCC tissues were detected in 64 and 15 patients,respectively.(2) Follow-up and survival:79 patients were followed up for 38-56 months,with an average time of 46 months.During the follow-up,37 patients had no tumor recurrence and 42 had tumor recurrence (32 with tumor extrahepatic metastasis and 10 with intrahepatic metastasis);36 had survival and 43 died;the 1-and 3-year overall survival rates were respectively 86.84％ and 63.25％,and 1-and 3-year tumorfree survival rates were respectively 62.31％ and 51.27％.(3) Prognostic factors analysis after liver transplantation:① Results of univariate analysis showed that preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Hazard Ratio (HR) =2.17,3.36,3.66,2.43,2.19,3.36,2.84,95％ confidence interval(CI):1.17-4.04,1.53-7.42,2.10-6.42,1.33-4.17,1.08-9.04,1.58-7.59,1.17-6.32,P＜ 0.05].The preoperative alpha-fetoprotein (AFP),Child-Pugh score,maximum tumour dimension,capsular invasion,intravascular tumor thrombus,Edmonson pathological grading and expression of CUL4B were related factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (HR =2.06,3.72,3.16,2.36,2.83,3.21,1.69,95％CI:1.34-4.85,1.72-8.63,1.79-7.31,1.46-4.86,1.19-8.63,1.19-7.92,1.06-4.87,P＜0.05).② Results of multivariate analysis showed that maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year overall survival rate of patients after liver transplantation for HCC [Odds ratio(OR) =3.43,3.69,2.81,95％CI:1.16-6.02,1.96-9.38,1.04-9.63,P＜0.05].The maximum tumour dimension,intravascular tumor thrombus and expression of CUL4B were independent factors affecting the 3-year tumor-free survival rate of patients after liver transplantation for HCC (OR=2.25,4.72,2.74,95％C1:1.16-4.02,1.98-9.47,1.03-7.10,P＜ 0.05).The 3-year overall survival rate in patients with high-and low-expressions of CUL4B was respectively 66.7％ and 32.8％,with a statistically significant difference (x2 =5.69,P＜0.05).The 3-year tumor-free survival rate in patients with high-and low-expressions of CUL4B was respectively 73.3％ and 18.6％,with a statistically significant difference (x2 =4.63,P＜0.05).(4) Association between expression of CUL4B and recurrence and metastasis of tumor after liver transplantation:results of Pearson test showed that expression of CUL4B was significantly associated with HCC recurrence and metastasis after liver transplantation (r =0.62,P＜0.05).The further analysis showed that expression of CUL4B was significantly associated with extrahepatic metastasis after liver transplantation (r=0.84,P ＜ 0.05).Conclusion The expression of CUL4B is associated with HCC recurrence after liver transplantation,and it can be as a predictor for HCC recurrence and distant metastasis after liver transplantation.

Objective To investigate the effect of diabetes mellitus (DM) on adenosine postcondi-tioning-induced reduction of myocardial ischemia-reperfusion (I∕R) injury in rats. Methods Adult male Sprague-Dawley rats, weighing 230-260 g, were used in the study. Type 2 DM was induced by high-fat diet and intraperitoneal l％ streptozocin 35 mg∕kg and confirmed by fasting blood glucose concentration>16. 7 mmol∕L 72 h later. Eighteen rats with type 2 DM were divided into 3 groups (n= 6 each) using a ran-dom number table: sham operation group (DS group), I∕R group (DI∕R group) and adenosine postcondi-tioning group (DAP group). Eighteen healthy nondiabetic rats were selected and randomly divided into 3 groups (n= 6 each): sham operation group (NS group), I∕R group (NI∕R group) and adenosine postcon-ditioning group (NAP group). Myocardial I∕R was induced by 30 min occlusion of the left anterior descend-ing branch of coronary artery followed by 2 h of reperfusion. Venous blood samples were collected from the femoral vein at 2 h of reperfusion for measurement of plasma cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations (by enzyme-linked immunosorbent assay). The rats were then sacrificed im-mediately after blood sampling for determination of the myocardial ischemic area and infarct size. Results The plasma cTnI and CK-MB concentrations were significantly increased, and the percentage of myocardial infarct size was increased after myocardial I∕R in nondiabetic and diabetic rats. Adenosine postconditioning significantly decreased plasma cTnI and CK-MB concentrations and percentage of myocardial infarct size in nondiabetic and diabetic rats (P<0. 05). Compared with group NAP, the plasma concentrations of cTnI and CK-MB were significantly increased, and the percentage of myocardial infarct size was increased in group DAP (P<0. 05). Conclusion DM can weaken cardioprotection induced by adenosine postcondition-ing in rats.

Objective To investigate the differences of hepatic pathology between the chronic hepatitis B (CHB) with pulmonary tuberculosis patients and CHB patients.Methods Seventy-nine treatment-naive patients with CHB complicated with pulmonary tuberculosis (co-infection group) were collected from January 2009 to December 2014,and 79 CHB patients were selected randomly during the same period as CHB group.Hepatic tissue inflammation and fibrosis between the two groups were compared according to Ishak scoring system.Comparison between two groups were conducted by t test when the variance was equal and Mann-Whitney U test when the variance was unequal.Categorical data were compared by x2 test.Results A total of 59 (74.7％) patients in co-infection group had inflammation≥ G2,compared to 59.5％ in the CHB group.The difference between the two groups was statistically significant (x2=4.128,P=0.042).Forty-one (51.9％) patients in co-infection group had fibrosis≥S2,compared with 44.3％ in the CHB group.The difference was not statistically significant (x2 =0.913,P=0.339).Ishak scoring system showed that piecemeal necrosis,portal area inflammation score and totalscore in co-infection group were all significantly higher than those in CHB group (2.45± 1.19 vs 2.05± 1.28,2.70±1.22 vs 2.32±1.08,13.16±6.51 vs 11.22±5.72,respectively),with all the differences statistically significant (t=2.055,2.068 and 1.984,respectively;P=0.042,0.040 and 0.049,respectively).However,the confluent necrosis in co infection group was 2.60±1.91 compared to 2.13± 1.68 in CHB group (Z=1.137,P=0.257),focal (dot) soluble necrosis was 2.35± 1.06 versus 2.16± 0.86 (Z=-1.148,P=0.251),and fibrosis was 3.03±1.63 versus 2.45±1.53 (Z=I.541,P=0.125).Conclusion The liver damage in co-infection patients is more severe compared with CHB patients.

Objective To explore the clinical value of total hemihepatic vascular exclusion (THHVE) in right hepatectomy for hepatocellular carcinoma (HCC). Methods One hundred and twenty-three consecutive patients who underwent right hepatectomy for HCC between February 2006 and December 2008 were studied retrospectively. THHVE was used in 58 patients (group A) and Pringle maneuver in 65 patients (group B). The patient's demographics,surgical procedure and outcome were collected and compared between the two groups.ResultsThe tumor size was significantly bigger in group A than group B (7.69±3.70 cm vs.6.08±4.07 cm,P＜0.05).The vascular occlusion time in group A was significantly longer than groupB (28.55±8.67 min vs.19.85±6.71 min,P＜0.05). However, intraoperative blood loss in group A was significantly less than group B (304.31±270.36 ml vs.542.62±876.84 ml,P＜0.05),and the elevation of serum alanine aminotransferase (ALT) on day- 1,-3 and- 7 after operation in group A were significantly lower than group B (P＜0.05).The postoperative complication rate in group A was lower than group B (18.97％ vs.38.46％,P＜0.05).ConclusionTHHVE was a safe and efficacious technique in right hepatectomy for HCC.It significantly decreased blood loss,alleviated liver injury and reduced postoperative morbidity and mortality.

Objective To investigate the clinical effect of IFNα combined with mannan peptide in treatment of patients with HBeAg-positive chronic hepatitis B ( CHB ). Methods Eighty HBeAg-positive CHB patients with HBV DNA quantity ranging from 10 to 10 eopies/mL were enrolled and randomized into the treatment group and the control group ( n = 40 for each ). Patients in treatment group were given daily subcutaneous injection of IFNα-2b 5,000,000 U for 52 weeks, and received mannan peptide 10 mg per intravenous injection or 2. 5 mg per intramuscular injection for a total of 2 to 3 treatment courses (12 weeks for each). The control group received only IFNα-2b treatment. Liver function, serum markers of hepatitis B, HBV DNA quantity and blood tests were performed before the treatment and at 2, 4, 8, 16, 26 and 52-week during the treatment; and the adverse effects were recorded. Results The rates for ALT normalization, negative HBsAg, negative HBeAg, HBeAg seroconversion and negative HBV DNA were 91. 8% , 17. 5% , 52. 5% , 27. 5 % and 47. 5% at 52nd week in the treatment group, while those in the control group were 80. 0% , 12. 5% , 30. 0% , 10. 0 % and 25. 0% , respectively. There were significant differences in HBeAg-negative, HBeAg-seroeonversion and HBV DNA-negative rates between two groups (χ2 = 4. 178, 4.021 and 4.381, P < 0. 05 ) , and these indexes in the treatment group were increased to 57. 5% , 30. 0% and 50. 0 respectively at 52nd week after drug withdraw. White blood cells began to be elevated at 4th week and were restored to the normal levels at 8th week in the treatment group, while the count in the control was lower than the normal value even at 52nd week of the treatment with the average of (3.45±1. 18)×109/L. Conclusion Alpha-interferon combined with mannan peptide therapy is effective for patients with HBeAg-positive CHB, which may restore the declined peripheral WBC counts induced by interferon and improve the compliance.