Objective To investigate the correlation between spread through air space (STAS) of sub-centimeter non-small cell lung cancer and clinical characteristics and radiological features, constructing a nomogram risk prediction model for STAS to provide a reference for the preoperative planning of sub-centimeter non-small cell lung cancer patients. Methods The data of patients with sub-centimeter non-small cell lung cancer who underwent surgical treatment in Nanjing Drum Tower Hospital from January 2022 to October 2023 were retrospectively collected. According to the pathological diagnosis of whether the tumor was accompanied with STAS, they were divided into a STAS positive group and a STAS negative group. The clinical and radiological data of the two groups were collected for univariate logistic regression analysis, and the variables with statistical differences were included in the multivariate analysis. Finally, independent risk factors for STAS were screened out and a nomogram model was constructed. The sensitivity and specificity were calculated based on the Youden index, and area under the curve (AUC), calibration plots and decision curve analysis (DCA) were used to evaluate the performance of the model. Results A total of 112 patients were collected, which included 17 patients in the STAS positive group, consisting of 11 males and 6 females, with a mean age of (59.0±10.3) years. The STAS negative group included 95 patients, with 30 males and 65 females, and a mean age of (56.8±10.3) years. Univariate logistic regression analysis showed that male, anti-GAGE7 antibody positive, mean CT value and spiculation were associated with the occurrence of STAS (P＜0.05). Multivariate regression analysis showed that associations between STAS and male (OR=5.974, 95%CI 1.495 to 23.872), anti-GAGE7 antibody positive (OR=11.760, 95%CI 1.619 to 85.408) and mean CT value (OR=1.008, 95%CI 1.004 to 1.013) were still significant (P＜0.05), while the association between STAS and spiculation was not significant anymore (P=0.438). Based on the above three independent predictors, a nomogram model of STAS in sub-centimeter non-small cell lung cancer was constructed. The AUC value of the model was 0.890, the sensitivity was 76.5%, and the specificity was 91.6%. The calibration curve was well fitted, suggesting that the model had a good prediction efficiency for STAS. The DCA plot showed that the model had a good clinically utility. Conclusion Male, anti-GAGE7 antibody positive and mean CT value are independent predictors of STAS positivity of sub-centimeter non-small cell lung cancer, and the nomogram model established in this study has a good predictive value and provides reference for preoperative planning of patients.

ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.

Objective:To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022.Methods:Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed.Results:A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024.Conclusion:The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective:To investigate the correlation between the expression of GLI1 and im-mune invasion and clinical prognosis in gastric cancer.To study the effect of GLI1 expression on drug resistance in gastric cancer.Methods:The expression difference of GLI1 in gastric cancer and normal tissues was analyzed by using TCGA database,and the effect of clinical features and GLI1 gene ex-pression level on prognosis of patients with gastric cancer was analyzed.The correlation between GLI1 gene expression and tumor immune cell infiltration in gastric cancer tissues was analyzed to explore its influence on drug resistance of chemotherapy drugs and targeted drugs.Clinical samples were collect-ed to analyze the difference of GLI1 expression in gastric cancer and paracancer tissues.Results:The expression of GLI1 in gastric cancer tissues was 1.7 times that in normal tissues,and the overall sur-vival and disease-free survival of patients with high expression are shorter than those with low ex-pression(P＜0.05).The interstitial score,immune score and abundance of immunoinfiltrating cells were higher in the high expression of GLI1 in gastric cancer tissues.High expression of GLI1 reduces drug sensitivity and is positively correlated with the expression of immune checkpoint markers PDCD1(P＜0.05).GLI1 expression was significantly increased in patients with subdifferentiated gastric cancer.Conclusions:GLI1 expression is associated with the prognosis and immune infiltration of patients with gastric cancer,and it may lead to poor prognosis of patients by regulating chemotherapy resis-tance,which may be a potential therapeutic target and molecular marker for gastric cancer.

Objective To observe the application effect of montelukast sodium combined with terbutaline on cough variant asthma(CVA)in children and its influence on airway remodeling and peripheral blood inflammatory indicators.Methods The children with CVA were randomly classified into control group and treatment group.The control group was given aerosol inhalation of terbutaline(5 mg each time,twice a day),and on the basis of the control group,the treatment group was combined with oral administration of montelukast sodium granules(4 mg each time,once a day,taking before going to bed),and both groups were continuously treated for 3 months.The clinical efficacy,airway cross-section area(AO),airway lumen area(AI),airway wall thickness(T),airway wall area(WA),serum interleukin-5(IL-5),eosinophilic chemotactic factor(Eotaxin),macrophage inflammatory protein-1α(MIP-1α)and T lymphocyte subgroups CD4+,CD8+and CD4+/CD8+were compared between the two groups of children,and the medication safety was assessed.Results Fifty-three cases in control group and 53 cases in treatment group were included.After treatment,the total effective rates in treatment group and control group were 96.23％(51 cases/53 cases)and 83.02％(44 cases/53 cases),respectively(P＜0.05).The AO values in treatment group and control group were(39.42±3.67)and(45.69±4.92)mm2;AI values were(22.36±2.85)and(27.06±3.18)mm2;T values were(1.12±0.28)and(1.44±0.33)mm;WA values were(53.82±4.17)and(60.13±4.66)mm2;serum IL-5 levels were(25.46±5.83)and(41.46±7.64)ng·L-1;Eotaxin levels were(181.24±30.05)and(238.21±39.42)ng·L-1;MIP-1a levels were(15.24±3.67)and(22.43±4.05)ng·L-1;CD4+levels were(37.18±4.06)％and(33.57±3.82)％;CD8+levels were(24.08±3.15)％and(27.31±3.07)％;and CD4+/CD8+levels were 1.54±0.33 and 1.24±0.28,respectively(all P＜0.05).The total incidences of adverse drug reactions in treatment group and control group were 9.43％(5 cases/53 cases)and 3.77％(2 cases/53 cases),respectively(P＞0.05).Conclusion Montelukast sodium combined with terbutaline has an exact efficacy in the treatment of CVA in children,and it can effectively reverse airway remodeling,reduce inflammation level and enhance immune function,and it has good safety.

Objective To evaluate the bioequivalence of test and reference mirabegron sustained release tablets under fasting/postprandial conditions.Methods A randomized,open,single dose,four cycle,two sequence,self-crossover trial design was used.32 healthy subjects respectively for fasting and fed study were enrolled,who were randomized to a single oral dose of 50 mg of either reference or test preparation of mirabegron sustained release tablets.The plasma concentration of mirabegron in healthy subjects after oral administration was detected by liquid chromatography tandem mass spectrometry,and Phoenix WinNonlin 8.2 software was used to calculate pharmacokinetic parameters and perform bioequivalence analysis.Results Subjects received a single oral dose of the reference and test formulations of mirabegron.The main pharmacokinetic parameters of mirabegron in the fasting study were asfollows:Cmaxwere(43.91±21.40)and(40.82±24.94)ng·mL-1,AUC0-t were(464.45±149.01)and(452.67±157.63)h·ng·mL-1,AUC0-∞were(501.64±162.39)and(488.70±173.81)h·ng·mL-1.The main pharmacokinetic parameters of mirabegron in the fed study were as follows:Cmax were(16.90±8.94)and(16.90±9.66)ng·mL-1,AUC0-t were(247.09±82.53)and(243.22±78.20)h·ng·mL-1,AUC0-∞ were(269.58±86.52)and(265.66±81.89)h·ng·mL-1.The 90％confidence intervals for the geometric means of Cmax,AUC0-t and AUC0-∞ for reference and test preparations in the fasting and fed groups were in the range of 80.00％to 125.00％.Conclusions The test and reference formulation of mirabegron sustained release tablets were bioeguivalence.

Proteolysis targeting chimera (PROTAC) is a drug discovery strategy using ubiquitin proteasome system (UPS) to degrade the target protein. Unlike traditional small molecule drugs utilizing occupancy-driven pharmacology as the mode of action (MOA) to regulate protein activity, PROTACs function through forming stable target protein-PROTAC-E3 ubiquitin ligase ternary complex and use ubiquitin proteasome system to degrade the target protein. However, only a few E3 ubiquitin ligases have been used in PROTAC drug design now, and the space of target proteins that PROTAC can target needs to be further expanded. On the other hand, the complicated system of ternary crystal structures is difficult to capture and identify, computational simulation provides modeling of PROTAC-mediated ternary complex formation with effective approaches. In view of this, this review describes the recent progress of bioinformatics on expanding the landscape of E3 ubiquitin ligases and target proteins, and summarizes the methods of computation simulation in modeling PROTAC ternary complex. Finally, the trend of development about PROTAC is prospected.

ObjectiveTo observe the clinical efficacy and safety of Chaihu Shugansan combined with Xuanfu Daizhetang （CHSG-XFDZ） in the management of Barrett's esophagus （BE） with liver-stomach disharmony. MethodA randomized， parallel， controlled， double-blind clinical trial was conducted. BE patients who met the inclusion criteria were randomized into an observation group and a control group， with 34 patients in each group. The observation group was treated with CHSG-XFDZ combined with omeprazole capsules， and the control group was treated with CHSG-XFDZ mimetic combined with omeprazole capsules. Both groups were treated for 12 weeks. The traditional Chinese medicine （TCM） symptom scores， response rate， BE lesion area， BE pathological changes， and bile acid profile were taken as the indicators to jointly evaluate the clinical efficacy and safety of the two groups. ResultA total of 62 patients who completed the trial were included for statistical analysis， including 32 in the observation group and 30 in the control group. There were no statistically significant differences in baseline demographics or disease characteristics between two groups， which suggested that the two groups were comparable. The total response rate in the observation group was 93.7% （30/32）， which was higher than that （60.0%， 18/30） in the control group （χ²=24.766， P<0.05）. After treatment， the response rate regarding the pathological changes in the observation group was 62.5% （20/32）， which was higher than that （23.3%， 7/30） in the control group （χ²=10.270， P<0.05）. The response rate regarding the BE lesion area change in the observation group was 21.9% （7/32）， which had no statistically significant difference from that （6.7%， 2/30） in the control group， which indicated that the advantages of the two regimens were not obvious in terms of reducing the area of BE lesions. Compared with the control group after treatment， the observation group regulated the bile acid profile， which pointed out the direction for further exploring the mechanism of CHSG-XFDZ in treating BE. Neither group showcased adverse reactions with clinical significance during the treatment period. ConclusionCHSG-XFDZ outperformed the control group in terms of alleviating TCM symptoms， ameliorating pathological changes， and improving the bile acid profile in the BE patients with liver-stomach disharmony. It demonstrates certain potential in reducing the lesion area. This formula is safe and effective in treating BE patients with liver-stomach disharmony and deserves further clinical research and widespread application.

Objective:To investigate the effect and mechanism of isorhynchophylline (IRN) on angiotensin Ⅱ(Ang Ⅱ)-induced cardiac hypertrophy.Methods:H9c2 cells were co-cultured with Ang Ⅱ and different concentrations of IRN (0, 5, 10, 25, 50 μmol/L). The cell surface area and mRNA levels of cardiac hypertrophy markers atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC) were detected to elucidate the effect of IRN on myocardial hypertrophy and the most effective concentration. H9c2 cells were co-cultured with Ang Ⅱ and IRN (25 μmol/L) at different times (0, 6, 12, 24 h) to elucidate the most effective time of inhibition. The phosphorylation levels of the signaling pathway were detected, and the effects of IRN and Akt inhibitor MK2206 on the phosphorylation levels of the signaling pathway were further explored to elucidate the underlying mechanisms.Results:Compared with the control group, the surface area of H9c2 cells, and the mRNA expression of myocardial hypertrophy markers ANP, BNP and β-MHC were significantly increased (all P<0.05). Pretreated with different concentrations of IRN (5, 10, 25, 50 μmol/L) could inhibit the increase in cell surface area induced by AngⅡ (all P<0.05), especially at the concentration of 25 μmol/ L ( P<0.01). IRN could time-dependently inhibit AngⅡ-induced activation of ANP, BNP, β-MHC mRNA (all P<0.05). AngⅡ caused increased phosphorylation levels of Akt, GSK3β, mTOR and FOXO3a. IRN could block AngⅡ-induced phosphorylation of the Akt signaling pathway. Conclusion:IRN attenuates AngⅡ-induced cardiomyocyte hypertrophy by inhibiting the Akt signaling pathway.