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 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 explore the relationship between the triglyceride-glucose(TyG)index,residual cholesterol(RC)and dia-betic nephropathy(T2DM).Methods A total of 410 patients with T2DM were consecutively selected from the Endocrinology Depart-ment of Jiangsu Provincial Traditional Chinese Medicine Hospital from March 2022 to March 2023.The patients were stratified into three groups based on their morning urinary albumin-to-creatinine ratio(UACR):269 patients were in simple diabetes mellitus(SDM)group,80 in early diabetic nephropathy(EDN)group and 61 in clinical diabetic nephropathy(CDN)group.Comparative an-alyses were conducted on the three groups in terms of gender,age,past medical history,body mass index(BMI),systolic blood pres-sure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),Urea,creatinine(Cr),urinary albumin(UA)total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C).Additionally,TyG index and RC were calculated.Spearman analysis was employed to evaluate the correlation between UACR and these various parameters.Binary Logistic regression was utilized to identify independent risk factors for diabetic nephropathy(DN).The diagnostic performances of Urea,Cr,TyG index and RC for type 2 diabetic nephropathy were assessed using receiver operating charac-teristic(ROC)curve analyses.Results Compared with SDM group,diabetes duration,SBP,Urea,UA,TG,TC,TyG index and RC showed significant increases in EDN group with statistically significant differences(P＜0.05),and diabetes duration,SBP,DBP,Urea,Cr,UA,TG,TC,LDL-C,TyG index and RC in CDN group also exhibited significant increases,with statistically significant differences(P＜0.05).Spearman rank correlation analysis revealed a positive correlation between RC and UACR(r=0.278,P＜0.001),a positive correlation between TyG index and UACR(r=0.239,P＜0.001)and a positive correlation between RC and TyG in-dex(r=0.562,P＜0.001).Binary logistic regression analysis showed that diabetes duration,SBP,Urea,Cr,TyG index(OR=2.815,95％CI:1.481-5.349,P=0.002),and RC(OR=2.179,95％CI:1.038-4.574,P=0.04)were independent risk factors for DN.The area under the ROC curve(AUCROC)for RC predicting DN occurrence was 0.670(95％CI:0.616-0.725),while the AUCROC for the TyG index was 0.620(95％CI:0.564-0.676).Conclusion TyG index and RC were significantly correlated with the development of DN in the patients with T2DM,which may early facilitate clinical identification and management for the patients in the risk ofr diabetic kidney disease.

Objective To investigate the role of immunoglobulin superfamily containing leucine-rich repeat protein(ISLR)in the malignant progression of osteosarcoma cells and its potential regulatory mechanism.Methods ISLR mRNA levels in osteosarcoma tissues and cells were detected by quantitative real time polymerase chain reaction(qRT-PCR).U2OS cells were transfected with ISLR short hairpin RNA(shRNA)sequence or negative-control shRNA(NC shRNA)sequence,thus the cells were treated with phosphatidylinositol 3 kinase(PI3K)activator 740 Y-P.The cell viability,invasion ability and apoptosis rate were detected by CCK-8 assay,Transwell assay and flow cytometry,respectively.Western blot was used to detect the expressions of ISLR protein,epithelial-mesenchymal transition(EMT)-related proteins[Epitheia-cadherin(E-cadherin),Nerve cadherin(N-cadherin),Vimentin,Snail],PI3K/protein kinase B(AKT)pathline-related proteins,apoptotic proteins[Cysteinyl aspartate-specific proteinase-3(Caspase-3),B cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax)]and proliferation marker Ki67 protein.Lentivirus was used to transfect U2OS cells,and the cells were injected into nude mice to construct a xenograft tumor model,and tumor growth was monitored.Results ISLR mRNA level in osteosarcoma tissue(5.14±1.63)was up-regulated compared with para-cancerous tissue(1.01±0.02),and the difference was significant(t=-14.332,P＜0.001).Compared with normal osteoblasts hFOB1.19(1.01±0.01),osteosarcoma cells MG63(3.05±0.57),U2OS(4.55±0.79),HOS(2.46±0.41),the relative expression of ISLR mRNA in Saos-2(2.62±0.44)and 143B(3.62±0.51)were increased,and differences were significant(t=4.883,8.473,3.471,3.854,6.247,all P＜0.05).Silencing ISLR inhibited the proliferation of U2OS cells(t=6.593,6.835)and invasion(t=8.621,8.448),but promoted cell apoptosis(t=25.505,25.574),and the differences were significant(all P＜0.05).Silencing ISLR promoted Caspase-3 activity in U2OS cells(t=13.489,13.366)and Bax protein(t=8.628,8.524),but inhibited Bcl-2 protein expression(t=10.948,10.775),with significant differences(all P＜0.05).Silencing ISLR promoted EMT-related protein E-cadherin(t=15.168,15.087),inhibited N-cadherin(t=10.220,10.058),Vimentin(t=8.303,8.164)and Snail(t=9.211,9.384),but reduced the phosphorylation levels of PI3K and AKT(t=17.441,14.452),with significant differences(all P＜0.05).Additionally,740 Y-P treatment reversed the effect of silencing ISLR on U2OS cells.Experimental results in vivo showed that knockdown of ISLR significantly inhibited tumor growth.Conclusion ISLR could promote EMT,proliferation and invasion,but inhibit apoptosis of osteosarcoma cells by activating the PI3K/AKT pathway,there by promoting osteosarcoma progression.

Harmine(HM)is a type of β-Carboline alkaloid abundant in nature and has many biological effects.In recent years.Studies have found that HM had a significant positive effect on Alzheimer's disease(AD)both in vivo and in vitro.Its mechanism may be related to the reduction of abnormal deposition of β-amyloid protein(Aβ),excessive phosphorylation of Tau protein,regulation of the cholinergic system,antioxidant stress,and antineuritis.This article reviews the research progress on the improvement effect and mechanism of HM in AD in order to provide an experimental basis for the clinical application of HM and the development of drugs in the area of AD the prevention and treatment.

Previous studies have found that As2 O3 can interfere with serum thyroid hormone TH levels in rats and cause chronic liver damage,but the mechanism remains unclear.In order to ex-plore the role of TH signaling pathway in As2 O3-induced chronic liver injury,qRT-PCR and West-ern blot techniques were used to detect the expression changes of genes and protein of TRβ1(a key regulator of TH signaling pathway in rat liver)and cyclin D1(the downstream factor of TRβ1 in nuclear pathway).Meanwhile,the changes in the protein of key factors(Bax,Bcl-2)of the TH sig-nal nuclear outside pathway were detected.The results indicated that:after As2 O3 treatment for 110 days,compared with the control group,the expression of TRβ1 protein in the liver of female mice significantly decreased(P＜0.01),the expression of cyclin D1 significantly increased in the 0.1 and 0.2 mg/L groups(P＜0.01).Meanwhile,the expression of TRβ1 protein in male mice sig-nificantly decreased in 0.4 mg/L group(P＜0.01),and the expression of cyclin D1 in each group significantly increased(P＜0.01).The mRNA expression results were basically the same as those of protein expression.After As2 O3 treatment for 194 days,compared with the control group,the expression of TRβ1 protein in each group significantly decreased(P＜0.01),and the expression of cyclin D1 significantly increased(P＜0.01).The mRNA expression results were basically consist-ent with the protein.As2 O3 interfered with the expression of Bcl-2 and Bax proteins in rats and in-duced the increase in the ratio of Bcl-2/Bax protein as the action time increased.Among them,the Bcl-2/Bax ratio of female rats in each group and male rats in the 0.4 mg/L group significantly in-creased(P＜0.01),and male rats in the 0.1 mg/L group significantly increased(P＜0.05).It shows that As2O3 can cause abnormal levels of TRβ1,cyclin D1 and the Bcl-2/Bax ratio in rat liv-er.

Objective To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization (MR) approach. Methods Summary data for exposure factors and outcome were obtained from different genome-wide association studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted (IVW) method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results. Results The random-effects model of IVW analysis showed that heel bone mineral density (OR=0.986;95% CI,0.974 to 0.998;P=0.023) as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density (OR=1.031;95% CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density (OR=1.014;95% CI,0.973 to 1.057;P=0.505),and forearm bone mineral density (OR=1.011;95% CI,0.935 to 1.094;P=0.775) as outcome datasets showed no causal effect with bronchial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results. Conclusion MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone mineral density in patients with bronchial asthma to timely detect and intervene osteoporosis.

ObjectiveTo investigate the pharmacological effect and metabolic mechanism of Linderae Radix on the intrauterine adhesion （IUA） rat model. MethodAn IUA rat model was induced by mechanical injury and infection. Molecular biology and pharmacology techniques were employed to evaluate the inhibitory effect of Linderae Radix extract （LAE） on fibrosis in IUA. Serum metabolomics analysis based on gas chromatography-mass spectrometry （GC-MS） was conducted to explore the metabolic regulation mechanism of LAE. ResultAnimal experiments showed that LAE significantly improved the morphology and structural damage of uterine tissue cells in the IUA rat model， promoted endometrial proliferation， vascular regeneration， and morphological recovery， inhibited the mRNA expression of transforming growth factor-β₁ （TGF-β₁）， Smad2， and Smad3， and increased the expression of Smad7 mRNA to suppress fibrosis. Additionally， LAE significantly suppressed the levels of estrogen （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and tumor necrosis factor-α （TNF-α） expression （P<0.01）， thereby improving the uterine microenvironment. Metabolomics analysis revealed significant metabolic abnormalities in the serum of IUA rats compared with the results in the normal group， and nine differential metabolites were identified. LAE effectively ameliorated these metabolic abnormalities， primarily by influencing six differential metabolites， including five shared metabolites among the nine identified markers： L-aspartic acid， L-pyroglutamic acid， L-serine， glucose， and L-norvaline. Pathway enrichment analysis indicated that the aminoacyl-tRNA biosynthesis pathway was the main affecting mechanism. ConclusionIn combination with the pharmacological research results， LAE effectively improved uterine damage and inhibited fibrosis in the IUA rat model. Its mechanism may involve the inhibition of the aminoacyl-tRNA biosynthesis pathway and the improvement of the microenvironment.

Objective:To observe the effect of abdominal electroacupuncture(EA)on intestinal function in patients with constipation after stroke. Methods:A total of 100 patients with post-stroke constipation were divided into an observation group and a control group by the random number table method,with 50 cases in each group.The control group was treated with oral lactulose,10 mL each time,3 times a day,for 2 consecutive weeks.The observation group was treated with additional abdominal EA at Tianshu(ST25),Fushe(SP13),and Daheng(SP15)on the basis of oral lactulose,30 min for needle retention each time,once a day,for 2 consecutive weeks.The total effective rate after treatment,constipation symptom score,the score of patient assessment of constipation quality of life scale(PAC-QOL),serum motilin(MTL)level,and the score of mini-mental state examination(MMSE)were compared between the two groups. Results:After 2 weeks of treatment,the total effective rate was 93.5%in the observation group and 76.1%in the control group,and the difference between the two groups was statistically significant(P<0.05).The constipation symptom score,PAC-QOL score,MMSE score,and MTL level changed significantly after treatment in both groups(P<0.05).After treatment,the constipation symptom score and PAC-QOL score in the observation group were lower than those in the control group,while the MMSE score and MLT level were higher than those in the control group,and the differences between the two groups were statistically significant(P<0.05). Conclusion:On the basis of oral lactulose,EA at abdominal points can significantly improve the intestinal and cognitive function of stroke patients simultaneously.

OBJECTIVE: To analyze the clinicopathological characteristics and risk factors of 4L lymph node metastasis in left non-small cell lung cancer. METHODS: We retrospectively analyzed the data of 134 patients undergoing surgical resection of left non-small cell lung cancer and 4L lymph node dissection, including 60 patients with squamous cell carcinoma (SCC) and 74 with lung adenocarcinoma (ADC). The clinicopathological characteristics of the patients were analyzed, and logistic regression analysis was used to identify the predictors of station 4L metastasis. RESULTS: Of these patients, 16.4% (22/134) presented with station 4L metastasis. The patients with SCC and ADC showed significant differences in age, gender, smoking history, neoadjuvant chemotherapy, tumor size, tumor location and type, visceral pleural invasion, Ki-67 index, 4L metastasis and pathological TNM stage (stage Ⅱ). The rate of station 4L metastasis was significantly lower in SCC group than in ADC group. Univariate analysis revealed that pathological types (SCC or ADC), visceral pleural invasion, lymphovascular invasion, tumor markerabnormality, and station 5 to 10 metastasis were all high-risk factors for station 4L metastasis. Multivariate analysis suggested that the pathological type (OR=0.120, CONCLUSIONS In patients with left non-small cell lung cancer, station 4L metastasis is not rare and is more likely to occur in patients with lung adenocarcinoma. Dissection of the 4L lymph nodes should be performed in cases with low risk of damages of the adjacent tissues and high risk of station 4L metastasis.
Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Lung Neoplasms/pathology* ; Lymph Node Excision ; Lymph Nodes/pathology* ; Lymphatic Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors