Objective To investigate the effect of remimazolam(Rem)on apoptosis of intestinal epithelial cells in burned rats by regulating Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.Methods The successfully constructed burned rat model was randomly divided into the model group,the Rem low dose treatment(Rem-L)group,the Rem medium dose treatment(Rem-M)group and the Rem high dose treatment(Rem-H)group,and Rem-H+TLR4 activator(LPS)group.Healthy rats were taken as the control group.After blood samples were collected from tail vein of rats and intestinal tissue samples were taken after euthanasia.Serum levels of inflammatory cytokines interleukin-1β and IL-6 were detected by enzyme-linked immunosorbent assay(ELISA).HE staining was applied to observe the morphology of intestinal tissue.TUNEL detection kit was used to detect apoptosis.Immunohistochemistry was used to detect the expression of tight junction proteins ZO-1 and Occludin.Immunoblotting experiments were used to detect the expression levels of apoptotic proteins Bax and TLR4/MyD88/NF-κB signaling pathway proteins.Results Compared with the control group,cell arrangement was disordered with inflammation,and IL-1β and IL-6 levels and apoptosis rate were increased,expression levels of Bax,TLR4,MyD88 and p-NF-κB/NF-κB were up-regulated,and expression levels of ZO-1 and Occludin were down-regulated in the model group(P＜0.05).Compared with the model group,inflammatory infiltration of intestinal mucosa was gradually reduced in the Rem-L,Rem-M and Rem-H groups,the apoptosis rate,IL-1β and IL-6 levels were decreased,the expression levels of Bax,TLR4,MyD88 and p-NF-κB/NF-κB were down-regulated,and the expression of ZO-1 and Occludin was up-regulated in a dose-dependent manner(P＜0.05).Compared with the Rem-H group,the tissue inflammation was aggravated,the apoptosis rate,levels of IL-1β and IL-6 were increased,expression levels of Bax,TLR4,MyD88 and p-NF-κB/NF-κB were up-regulated,and expression levels of ZO-1 and Occludin were down-regulatedin in the Rem-H+LPS group(P＜0.05).Conclusion Remimazolam may alleviate the damage of intestinal epithelial cells in burned model rats by inhibiting TLR4/MyD88/NF-κB signaling pathway,thus protecting intestinal mucosa.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective    To examine the high-risk factors and prognosis of patients with superior interlobar lymph nodes (11s nodes) metastasis in non-small cell lung cancer (NSCLC) located in the right middle or lower lobe. Methods    The clinical data of 157 patients with NSCLC in the right middle or lower lobe from January 2015 to July 2020 in our hospital were retrospectively analyzed, including 98 males and 59 females aged 23-86 (60.01±10.58) years. The patients underwent lobectomy and systemic lymph node dissection along with dissection of 11s nodes. They were divided into a 11s (+) group and a 11s (–) group according to whether the 11s nodes were involved. Results    There were 31 patients with invasion in the 11s nodes, and the overall incidence of metastasis was 19.75%, including 13.64% with middle lobe tumors and 20.74%with lower lobe tumors. The 2R+4R nodes involvement was the influencing factor associated with 11s nodes metastasis (P=0.026). The 7th nodes and the inferior mediastinal lymph nodes involvement were high-risk factors affecting the prognosis of patients (P<0.05). The 11s nodes metastasis had nothing to do with the location of the tumor, and it was not an independent factor affecting disease-free survival. Conclusion    The 11s nodes may be a transit for 2R+4R nodes metastasis in the right middle or lower lobe lung cancer, and the 11s nodes should be cleared in the surgical treatment for NSCLC in either the middle or lower lobe of the right lung. The influencing factors for disease-free survival after surgery for lung cancer in the right middle or lower lobe are the metastasis of the subcarinal lymph nodes and the inferior  mediastinal lymph nodes.

OBJECTIVE To sy stematically evaluate the relations hip between immune-related adverse events （irAEs） and efficacy of immune checkpoint inhibitors （ICIs） in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical application of ICIs and safety evaluation. METHODS PubMed，Embase，Cochrane Library ， Web of Science ，CNKI，Wanfang database ，VIP and CBM were searched to collect prospective or retrospective cohort studies on the correlation between irAEs and efficacy of ICIs in the treatment of NSCLC. The retrieval time was from the inception to June 30th，2021. After literature screening and data extraction ，Newcastle-Ottawa scale was used to evaluate the quality of included literatures. Meta-analysis and publication bias analysis were performed by using RevMan 5.3 software；Stata 15.0 software was used for sensitivity analysis. RESULTS A total of 7 957 patients were included in 31 studies. Meta-analysis showed that the objective response rate （ORR）[RR＝2.34，95％CI（1.98，2.76），P＜0.000 01]，progression-free survival （PFS）[HR＝0.49，95％CI （0.44，0.55），P＜0.000 01] and overall survival （OS）[HR＝0.45，95％CI（0.39，0.53），P＜0.000 01] of irAEs group as well as ORR[RR＝1.88，95％CI（1.57，2.25），P＜0.000 01]，PFS [HR ＝0.59，95％CI（0.50，0.69），P＜0.000 01] and OS [HR ＝0.58，95％CI （0.48，0.70），P＜0.000 01] of this group at 6th week were all significantly higher or longer than non irAEs group. According to organ specificity ，severity and quantity of irAEs，subgroup analysis showed that skin ，gastrointestinal and endocrine system ，mild irAEs（grade 1-2）and one or more than 2 kinds of irAEs were significantly correlated with the improvement of PFS and OS （P＜ 0.05），while liver and lung ，severe irAEs（≥ grade 3）were not significantly correlated with the improvement of PFS and com OS （P＞0.05）. Sensitivity analysis results showed that the results of the above-mentione d meta-analysis were relatively robust. The results of publication bias showed that there was may be some possibility of publication bias in this study. CONCLUSIONS For NSCLC patients treated with ICIS ，the occurrence of irAEs may be related to their good prognosis. The irAEs may be a predictor of the efficacy of ICIs.

OBJECTIVE：To systematically evaluate the occurren ce of non-immune related adverse events （AEs）caused by immune checkpoint inhibitors （ICIs）alone or combined with routine chemotherapy in the treatment of non-small cell lung cancer （NSCLC），and to provide evidence-based reference for clinical medication. METHODS ：Retrieved from PubMed ，Cochrane Library，Embase，CNKI，CBM，VIP and Wanfang database during the inception to Oct. 2020，randomized controlled trials （RCT） about ICIs alone or combined with routine chemotherapy （trial group ）versus routine chemotherapy or placebo combined with routine chemotherapy （control group ） were collected. After literature screening and data extraction ，the quality of included literatures were evaluated with bias risk evaluation tool recommended by Cochrane systematic evaluator manual 5.1.0. Meta-analysis was performed by using Rev Man 5.3 software and Stata 15.0 software. Sensitivity analysis was conducted with Stata 15.0 software. Inverted funnel plot and Egger ’s test were used to analyze publication bias. RESULTS ：A total of 20 RCTs were included ， involving 12 283 patients. Results of Meta-analysis showed that the incidence of all grades and s evere AEs ，anemia，neutropenia， vomiting and alopecia as well as the incidence of thrombocytopenia，nausea and peripheral neuropathy in all grades of trial group were all significantly lower than control com group（P＜0.05）. There was no statistical significance in the incidence of termination of treatment ， death， severe thrombocytopenia， severe nausea and severe peripheral neuropathy or all grades and severe diarrhea between 2 groups（P＞0.05）. Subgroup analysis showed that the incidence of all grade and total severe AEs ，the incidence of anemia ，neutropenia，thrombocytopenia，clinically relevant symptoms （except for severe diarrhea），termination of treatment and death of patients receiving ICIs alone in trial group were significantly lower than control group（P＜0.05）. The incidence of ermination of treatment and death ，the incidence of nausea ，vomiting，diarrhea and alopecia in all grade ，severe diarrhea of patients receiving ICIs and chemotherapy in trial group were all significantly higher than control group （P＜0.05）. Sensitivity analysis supported the above results. Analyze publication bias results showed that the possibility of publication bias in this study was small. CONCLUSIONS ：For NSCLC patients ，the safety of ICIs is better than that of routine chemotherapy or placebo combined with routine chemotherapy in the treatment-related AEs ，hematologic toxicity and clinically relevant symptoms ；however，the risks of treatment discontinuation ，AEs-induced deaths ，and all-grade nausea ，vomiting， diarrhea，alopecia and severe diarrhea will be increased in the ICIs combined with routine chemotherapy.

BACKGROUND: Pulmonary epithelial-myoepithelial carcinoma is a very rare type of salivary gland lung tumor. No standard treatment plan yet. This article intends to analyze the clinical characteristics of pulmonary epithelial-myoepithelial carcinoma and discuss the diagnosis and treatment of pulmonary epithelial-myoepithelial carcinoma. METHODS: The clinical data of a patient with pulmonary epithelial-myoepithelial carcinoma were analyzed and other relevant clinical literatures were reviewed. RESULTS: Epithelial cells immunohistochemically expressed cytokeratin and myoepithelial cells immunohistochemically expressed SMA and S-100. The next-generation sequencing was mainly HRAS gene mutation and the express of PD-L1 protein was negative. CONCLUSIONS Most of the patients with Pulmonary epithelial-myoepithelial carcinoma have a good prognosis. Diagnosis mainly depends on microscopic examination and immunohistochemistry. The treatment of pulmonary epithelial-myoepithelial carcinoma is mainly surgical resection. The effect of radiotherapy and chemotherapy is not clear.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

OBJECTIVETo investigate the different outcomes by dexamethasone in adults immune thrombocytopenia purpura (ITP) with different types of platelet specific-autoantibodies.

METHODSA total of 185 ITP were enrolled, 61 males and 124 females, with a median age of 42 (18-83) years, including 117 newly diagnosed, 35 persistent, and 33 chronic cases. All the patients received the dexamethasone at an initial dose of 40 mg per day for 4 days and a low dose of 5-10 mg for 3-4 weeks. The platelet specific-autoantibodies were identified by the modified monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay.

RESULTSAmong the IgG positive patients, the response rates in anti-GPIIb/IIIa antibody, anti-GPIbα antibody, both antibody positive, and both antibody negative were 87.5%, 50.0%, 68.0%, and 72.3% (χ²=11.489, P<0.05), respectively. Among the IgM positive patients, the response rates in the four groups were 82.1%, 71.4%, 61.9%, and 68.9% (χ²=2.719, P=0.437), respectively. Among the GPIbα antibody positive patients, the response rates in IgG alone, IgM alone, both positive, and both negative were 52.4%, 59.1%, 76.1%, and 77.9% (χ²=10.811, P<0.05), respectively. Among the GPIIb/IIIa antibody positive patients, the response rates in the four groups were 73.3%, 71.0%, 78.6%, and 66.3% (χ²=1.374, P=0.719), respectively.

CONCLUSIONITP patients with GPIbα-IgG antibody have worse response to dexamethasone treatment.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Autoantibodies ; Blood Platelets ; Dexamethasone ; Female ; Humans ; Male ; Middle Aged ; Platelet Glycoprotein GPIIb-IIIa Complex ; Purpura, Thrombocytopenic, Idiopathic ; Young Adult

Objective To investigate the effect of sufentanil postconditioning on myocardial ischemiareperfusion (I/R) injury in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB).Methods Sixty ASA Ⅱ or Ⅲ patients ( NYHA Ⅱ or Ⅲ ) of both sexes,aged 19-64 yr,scheduled for cardiac valve rreplacement under CPB,were randomly divided into 4 groups ( n =15 each):control group ( group C),sufentanil 0.5 μg/kg group (group S1 ),sufentanil 1.0 μg/kg group (group S2 ) and sufentanil 2.0 μg/kg group ( group S3 ).In groups S1,S2 and S3,sufentanil 0.5,1.0 and 2.0 μg/kg were infused over 2 min via aortic root 5 min before aortic unclamping respectively.In group C,the equal volume of normal saline (2 ml/kg) was infused instead of sufentanil.Blood samples were taken from the radial artery immediately before induction of anesthesia ( T2 ) and at 2,4,8,24 and 48 h after aortic unclamping ( T1-5 ) for determination of plasma concentrations of cardiac troponin-I (cTnI) and malondialdehyde (MDA) and activities of creatine kinase isoenzyme-MB (CK-MB) and superoxide dismutase (SOD).The duration of CPB,time of aortic clamping,extubation time,duration of stay in ICU,and myocardial contractility score and volume of drainage at 24 h after the operation were recorded.The restoration of spontaneous heart beat and adverse cardiovascular events were observed.Results The plasma cTnI,and MDA concentrations and CK-MB activity were significantly lower,while the SOD activity was significantly higher at T1-3 in group S1 than in group C ( P ＜ 0.05).The plasma cTnl concentration and CK-MB activity were significantly lower at T1-5,the plasma MDA concentration was significantly lower at T1-4,and SOD activity was significantly higher at T1-4,the extubation time and duration of stay in ICU were significantly shorter,and the myocardial contractility score at 24 h after the operation and incidence of adverse cardiovascular events were significantly lower in groups S2,3 than in group C ( P ＜ 0.05),The plasma cTnl concentration and CK-MB activity were significantly lower at T4,5,The plasma MDA concentration was significantly lower at T4,the SOD activity was significantly higher at T3,4,and the myocardial contractility score at 24 h after the operation was significantly lower in groups S2,3 than in group S1 ( P ＜ 0.05).Conclusion Sufentanil postconditioning can relieve myocardial I/R injury in patients undergoing cardiac valve replacement under CPB,and the mechanism is related to inhibition of lipid peroxidation.

Objective To observe the curative effect of the acute pelvic inflammatory disease through the combination of Penyanjing capsule and Miconazole. Methods Grouping the research patients into two groups with 32 patients respectively:the control group was given the Miconazole and the treating group was given the combination of Penyanjing capsule and Miconazole.Results The research group had the total effective power 100% but the control group only had 62.5% and the difference had obvious significance.Conclusion The combination of Penyanjing capsule and Miconazole has conditioning effects to the acute pelvic inflammatory disease.