Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.

Objective To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma.Methods We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January,2013 to December,2021.The 5-year disease-free survival(DFS)and overall survival(OS)rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors(EGFR-TKIs group,n=111),chemotherapy(CT group,n=108)and clinical observation(CO group,n=434).Results In TKIs,CT,and CO groups,the 5-year DFS rates were 92.8%,80.7%,and 81.7%,respectively,significantly higher in TKIs group than in CO group(P<0.01).The 3-year OS rates of the 3 groups were 96.8%,97.1%,and 91.7%,respectively.Subgroup analysis showed that in TKIs,CT,and CO groups,the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%,84.0%,and 81.4%,respectively,significantly higher in TKIs group than in CO group(P<0.05);the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%,71.4%,and 83.5%,respectively.Multivariate COX regression analysis showed that age(P<0.05;HR=0.631,95%CI:0.401-0.993),solid nodules(P<0.01;HR=7.620,95%CI:3.037-19.121),micropapillary or solid component(P<0.05;HR=1.776,95%CI:1.010-3.122),lymphovascular invasion(P<0.05;HR=2.981,95%CI:1.198-7.419),and adjuvant therapy(P<0.01)were independent predictors of DFS.The most common adverse effects included rashes,paronychia,and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy,and TKIs were associated with a higher incidence of grade 3 or above adverse effects(44.4%vs 9.0%).Conclusion Adjuvant therapy with TKIs helps improve DFS in patients with stage IB(T3-4cmN0M0)lung adenocarcinoma but not in patients with T2ViscPlN0M0.Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

For patients receiving mechanical ventilation, mechanical ventilation is also an injury factor at the same time of treatment, which can lead to or aggravate lung injury, that is, ventilator-induced lung injury (VILI). The typical feature of VILI is that the mechanical stress is transmitted to cells through the pathway, leading to uncontrollable inflammatory cascade reaction, which causes the activation of inflammatory cells in the lung and the release of a large number of cytokines and inflammatory mediators. Among them, innate immunity is also involved in the occurrence and development of VILI. A large number of studies have shown that damaged lung tissue in VILI can regulate inflammatory response by releasing a large number of damage associated molecular pattern (DAMP). Pattern recognition receptor (PRR) participates in the activation of immune response by combining with DAMP, and releases a large number of inflammatory mediators to promote the occurrence and development of VILI. Recent studies have shown that inhibition of DAMP/PRR signaling pathway can play a protective role in VILI. Therefore, this article will mainly discuss the potential role of blocking DAMP/PRR signal pathway in VILI, and provide new ideas for the treatment of VILI.
Humans ; Respiration, Artificial ; Respiration ; Immunity, Innate ; Ventilator-Induced Lung Injury ; Inflammation ; Inflammation Mediators ; Lung

Injury monitoring is an important approach for injury control and is an important part of comprehensive disease monitoring. With the development of medical digitalization, an intelligent injury monitoring system has been created in Yinzhou District, Ningbo City, Zhejiang Province using artificial intelligence techniques based on Ningbo Municipal Health Information Platform and has been applied across the district since 2019. The manual card-reporting mode has been transformed to intelligent card-reporting mode in this system, which achieves functions of epidemiological analyses of the monitoring data, early warning of high-incidence injuries, classified management of injury and quality control of report cards. Nearly 300 thousand cards have been automatically reported since the system was online available since November 2022, and the epidemiological characteristics of injury were preliminarily understood, which provide data supports to early earning and interventions of injury. The intelligent injury monitoring system greatly improves the injury monitoring efficiency and card-reporting quality, and saves a large number of manpower and material resources, which provides a powerful technical support to widespread injury monitoring.

Background In recent years gut microbiota has been found to play an important role in the occurrence and development of various chronic diseases, and diet is an important factor influencing gut microbiota. However, the effects of maternal high-fat diet in pre-pregnancy and pregnancy-and-lactation periods on offspring gut microbiota are still unclear. Objective To investigate the effects of maternal high-fat diet in pre-pregnancy and pregnancy-and-lactation periods on gut microbiota of offspring mice. Methods C57BL/6J female mice were divided into four groups according to the diet patterns (high-fat diet, HFD; control diet, CD) given before and after conception, namely the pre-pregnancy control diet and post-pregnancy control diet group (CD-CD group), the pre-pregnancy control diet and post-pregnancy high-fat diet group (CD-HFD group), the pre-pregnancy high-fat diet and post-pregnancy control diet group (HFD-CD group), and the pre-pregnancy high-fact diet and post-pregnancy high-fat diet group (HFD-HFD group). Female mice were conceived in the same cage with male mice after 6 weeks of feeding, and the successfully conceived females continued to be randomly divided into two groups receiving either high-fat or control diet, and when the offspring mice were born, they were breastfed directly by the mothers, with each mother nursing only one offspring mouse. The number of offspring mice in each group was 6, with half males and half females. The body weight of offspring mice were recorded and body weight gain was compared between the four groups. After the lactational period, fresh feces of the offspring were collected, and the fecal DNA was extracted. Specific primers were designed according to the bacterial 16S rDNA(V3+V4) sequence and then the sequencing was performed using the Illumina HiSeq 2500 platform. Species annotation and operational taxonomic unit (OTU) analysis of sequencing data were conducted using QIMME, USEARCH and R software. In alpha diversity analysis, ACE and Chao1 indices were used to evaluate species richness, Shannon and Simpson indices considered both species richness and evenness. In beta diversity analysis, principal coordinates analysis (PCoA) and analysis of similarities (Anosim analyses) were used to find the differences in composition of gut microbiota between four groups, and line discriminant analysis effect size (LefSe) was conducted to identify which specific taxa contributed to the significant differences between groups. Results A greater effect of post-pregnancy diet on offspring body weight was observed, and the lowest body weight was recorded in the HFD-CD group during the whole experimental period. The results of OTU analysis showed that high-fat diet during post-pregnancy period reduced the number of OTUs in offspring mice, and the results of alpha diversity analysis showed that high-fat diet during post-pregnancy period reduced the richness of intestinal flora (ACE, P<0.05; Chao1, P<0.05), whereas differences in the α-diversity indices did not show statistical significance in the offspring mice with pre-pregnancy high-fat diet. The high-fat diet at different periods also led to changes in the dominant intestinal flora of the offspring. The high-fat diet during post-pregnancy period increased the abundance of Tenericutes (P<0.05), and decreased the abundance of Bacteroides, Epsilonbacteraeota, Cyanobacteria, and Deferribacteres (all Ps<0.05). At the genus level, high-fat diet during both pre-pregnancy and post-pregnancy periods decreased the abundance of Lactobacillus (P<0.05), and high-fat diet during pre-pregnancy period increased the abundance of Alistipes (P<0.05), while high-fat diet during post-pregnancy period increased the abundance of Lachnospira and Ruminococcus, and decreased the abundance of Muribaculaceae and Helicobacter (all Ps<0.05). The results of beta diversity analysis showed that the CD-CD group had a similar flora composition to the HFD-CD group, and the CD-HFD group had a similar flora composition to the HFD-HFD group, and the results of Anosim analysis showed statistically significant differences between groups (R=0.743, P<0.01). The LEfSe analysis counted all species with an effect on the differences between groups greater than the set value, which were Lactobacillus in the CD-CD group, Clostridiales in the CD-HFD group, Bacteroidetes and Helicobacters in the HFD-CD group, and Blautia, Ruminococcaceae, and Roseburia in the HFD-HFD group. Conclusion It is found that varied effects of high-fat diet in different periods on the flora of the offspring mice. The high-fat diet during pre-pregnancy and post-pregnancy periods could reduce the abundance of Lactobacillus, but show different effects on the abundance of other intestinal flora such as Muribaculaceae, Lachnospiraceae, and Helicobacter differed. Diet during post-pregnancy period has a greater influence on modeling the offspring gut microbiota.

Calcium ; Homeostasis ; Humans ; Parkinson Disease/therapy*

Objective:To observe the effects of self-designed Yiqi Huoxue Huayu Decoction on cardiac function and serum endothelin (ET-1) and matrix metalloproteinase-9 (MMP-9) levels in patients with chronic heart failure (GHF) complicated with atrial fibrillation.Methods:A total of 100 patients with GHF complicated with atrial fibrillation treated in our hospital from January 2019 to June 2021 were selected as the study subjects, and divided into experimental group and control group according to random number table method, with 50 patients in each group. Patients in both groups were given cardiotonic, diuretic, vasodilator and other conventional treatment, and patients in the experimental group added self-designed Yiqi Huoxue Huayu Decoction. TCM syndrome score, left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF), serum ET-1 and MMP-9 levels, clinical efficacy, safety and incidence of adverse reactions were observed and compared between 2 groups before and after treatment.Results:The total response rate was 82.0% (41/50) in the observation group and 62.0% (31/50) in the control group, and the difference was statistically significant ( χ 2=4.96, P=0.026). After treatment, the symptoms scores of palpitation, shortness of breath, fatigue, chest and hypochasm pain in the observation group were significantly significantly lower than those in the control group ( t=5.28, 5.29, 5.62, 5.42, P<0.01). After treatment, the LVEDD[(51.23±6.59)mm vs. (55.65±6.17)mm, t=3.46], LVESD[(43.10±4.76)mm vs. (45.99±5.31)mm, t=2.87], serum ET-1[(65.79±8.29)μg/L vs. (79.83±10.08)μg/L, t=7.61], MMP-9 [(175.86±24.81)ng/L vs. (189.49±26.13)ng/L, t=2.68] in experimental group were significantly lower than those in the control group ( P<0.05), while LVEF [(50.01±7.6)% vs. (46.25±6.96)%, t=2.57] was significantly higher than that of the control group ( P<0.05). There were no significant differences in GPT, GOT, UA, SCr levels between both groups before and after treatment ( P>0.05). There were no obvious adverse reactions betewwn both groups. Conclusion:The self-designed Yiqi Huoxue Huayu Decoction can relieve the clinical symptoms, improve the heart function and serum ET-1 and MMP-9 levels in patients with GHF complicated with atrial fibrillation safely.

OBJECTIVE：To study the improvement effects of paeon iflorin（PF）on myocardial injury in type 2 diabetes mellitus（T2DM）model rats and its mechanism. METHODS ：The experiment was set up in the normal group ，model group ， positive control group （metformin 90 mg/kg），PF high-dose ，medium-dose and low-dose groups （90，60，30 mg/kg），with 8 rats in each group. Except for normal group ，other groups were given high-glucose and high-fat diet and intraperitoneal injection of streptozotocin （30 mg/kg） to induce T 2DM model. After modeling ， administration groups were given relevant medicine intragastrically，normal group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 4 weeks. The body weight ，fasting blood glucose and oral glucose tolerance were measured ；serum levels of glycosylated serum protein （GSP），total cholesterol （TC），triacylglycerol（TG），glutathione peroxidase （GSH-Px），superoxide dismutase（SOD），malondialdehyde（MDA），creatine kinase isoenzyme-MB （CK-MB） and troponin Ⅰ （cTn Ⅰ） were determined. The pathomorphological changes of myocardium were observed. The apoptosis index of rat cardiomyocytes was （ detected. The protein expression of B-cell lymphoma 2 （Bcl-2），Bcl-2 related X protein （Bax）and caspase- 3 in rat myocardium were detected by immunohistochemistry and Western blot. RE SULTS：Compared with normal group ，the body weight ，serum levels of GSH-Px and SOD ，protein expression of Bcl- 2 in myocardium were decreased significantly in model group（P＜0.01）；while fasting blood glucose ，area under blood glucose curve ，serum levels of biochemical indexes （GSP，TC， TG，MDA，CK-MB，cTnⅠ），cardiomyocyte apoptosis index ，protein expression of Bax and caspase- 3 in myocardium were increased significantly （P＜0.05 or P＜0.01）. The arrangement of myocardium was relatively irregular ，and some muscle fibers were broken. Compared with model group ，except for body weight ，serum levels of SOD and MDA ，the protein expression of Bax in myocardium in PF low-dose group ， above indexes of PF groups were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：PF can regulate glycolipid metabolism ，enhance antioxidant ability ，inhibit cardiomyocyte apoptosis and improve myocardial injury in T 2DM model rats ；the mechanism may be associated with increasing the protein expression of Bcl- 2 and down-regulating the protein expression of Bax and caspase- 3 in myocardium.