Objective To investigate the effect of icotinib on right ventricular remodeling in rats with monocrotaline(MCT)-induced pulmonary hypertension(PH).Methods Sprague-Dawley rats were randomly divided into control group(0.3％sodium carboxymethyl cellulose),model group and low,high dose experimental groups(30,60 mg·kg-1 icotinib),8 rats in each group.PH rat model was established by single intraperitoneal injection of 60 mg·kg-1 MCT in model group and low,high dose experimental groups.The drug was administered continuously for 4 weeks after MCT injection.The hemodynamic indexes of each group were detected.Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL)staining was used to detect the apoptosis of right ventricular cardiomyocytes.The protein levels of B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cleaved cysteine aspartic acid specific protease-3(cleaved-caspase-3),epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),optic atrophy 1(Opa1)and mitofusin 2(Mfn2)were detected by Western blot analysis.Results The right ventricular systolic pressure in low,high dose experimental groups and control group,model group were(38.58±4.98),(34.15±3.88),(23.66±2.45)and(45.07±5.78)mmHg;the mean pulmonary artery pressure were(27.85±3.77),(24.25±3.09),(17.33±2.46)and(33.07±4.15)mmHg;the right ventricle(RV)to left ventricle+septum were(36.38±5.51)％,(33.63±4.69)％,(22.25±2.96)％and(42.50±7.33)％;the RV to tibial length were(69.33±7.86),(62.69±7.17),(49.12±6.42)and(78.22±9.07)mg·cm-1.There were significant differences in the above indexes between low,high dose experimental groups and model group(all P＜0.01).There were significant differences in Bcl-2,Bax,cleaved caspase-3,p-EGFR,Opa1,Mfn2 between low,high dose experimental groups and model group(P＜0.05,P＜0.01).Conclusion Icotinib can inhibit right ventricular remodeling in PH rats induced by MCT,and its mechanism may be related to reducing the phosphorylation level of EGFR in the right ventricle,alleviating mitochondrial dysfunction and inhibiting cardiomyocyte apoptosis.

Objective To explore the potential relationship between ubiquitination of transforming growth factor kinase 1(TAK1)/nuclear factor-κB(NF-κB)signaling pathway mediated by ring finger protein 99(RNF99)and septic acute respiratory distress syndrome(ARDS).Methods Plasmid and siRNA transfection were conducted to overexpress or knock down RNF99 in MLE12,and expressions of p65 phosphate and p65 protein were analyzed.The protein interaction between RNF99 and TRAF6 or TAK1 was analyzed by immunoprecipitation assay.Forty mice were randomly divided into WT plus PBS,WT plus LPS,RNF99 specific expression(TG)plus PBS,and TG plus LPS groups,with 10 mice in each group.Sepsis was induced by intraperitoneal injection of 30 mg/kg LPS.Results As compared with vector group,protein expression levels of TRAF6 and TAK1 in MLE12 cells decreased significantly in RNF99 group(P<0.05).Ubiquitinated TRAF6 protein increased in MLE12 cells with RNF99 knockdown.As compared with LPS plus vector group,phosphorylation level of p65 in MLE12 cells was signifi-cantly lower in LPS plus RNF99 group(P<0.05).As compared with si-NC group,protein expression levels of RNF99 and IκBα in si-RNF99 group decreased significantly(P<0.05).As compared with LPS plus si-NC group,phosphorylation level of p65 in LPS plus si-RNF99 group increased significantly(P<0.05).The staining percentage of CD68 macrophages in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Phosphorylation level of p65 in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Conclusion RNF99 regulates NF-κB signaling pathway by interacting with the key regulator of NF-κB signaling pathway(TRAF6/TAK1),and improves lung injury after intraperitoneal injection of LPS in mice.

Objective To evaluate the molluscicidal effect of spraying different formulations of niclosamide ethanolamine salt with drones against Oncomelania hupensis in ditches. Methods A semi-dry and semi-wet ditch with O. hupensis snails was selected in the second branch field of Jiangbei Farm, Jiangling County, Hubei Province in May 2023, and divided into 4 experimental areas, named groups A1, A2, B1 and B2. Environmental cleaning was performed in groups A1 and B2, and was not conducted in groups A2 or B2. Then, 50% wettable powder of niclosamide ethanolamine salt was sprayed with drones at an effective dose of 2 g/m² in groups A1 and A2, and 5% niclosamide ethanolamine salt granule was sprayed with drones at an effective dose of 2 g/m² in groups B1 and B2. O. hupensis snails were surveyed using the systematic sampling method 1, 3, 5, 7, 14 days after spraying, and the natural mortality and corrected mortality of O. hupensis snails were calculated. Results The occurrence of frames with living snails, mean density of living snails and natural mortality of snails were 97.50% (117/120), 6.30 snails/0.1 m² and 1.18% (9/765) in the test ditch before spraying, respectively. There were significant differences in the mortality of snails among four groups 1, 3, 5, 7 and 14 days after spraying niclosamide formulations with drones (χ² = 17.230, 51.707, 65.184, 204.050 and 34.435, all P values < 0.01). The overall mortality rates of snails were 94.51% (1 051/1 112), 79.44% (908/1 143), 96.54% (977/1 012) and 88.55% (1 021/1 153) in groups A1, A2, B1 and B2 (χ² = 207.773, P < 0.05), respectively. In addition, there was no significant difference in the overall snail mortality between groups A1 and B1 (P > 0.05), and the snail mortality in groups A1 and B1 were both statistically different from that in groups A2 and B2 (all P values < 0.05). Conclusion Both 50% wettlable powder of niclosamide ethanolamine salt and 5% niclosamide ethanolamine salt granule sprayed with drones are active against O. hupensis snails in ditches, and environmental cleaning may improve the molluscicidal effect.

Objective: To investigate the protective effect of neurotrophic factor(MANF) derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway. Methods: 48 mice were randomly divided into 4 groups: control group, recombinant mouse MANF(rmMANF) group, cecal ligation and puncture(CLP) group and CLP+rmMANF group, with 12 mice in each group.The survival rate, sepsis score, anal temperature, blood biochemical indexes, pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS) related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group, LPS+rmMANF group, LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were analyzed. Results: Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased significantly(P<0.01),and the anal temperature and serum albumin(ALB) levels increased significantly(P<0.05).Compared with CLP group, the expression of MANF in CLP+rmMANF group increased significantly(P<0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and the percentage of TUNEL positive cells decreased significantly(P<0.05).In vitro, LPS stimulation down-regulated the expression of SIRT1 and AMPK in H9C2 cells, while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group, the expression of GRP78 and CHOP protein and the apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05). Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.

Objective:To explore the potential categories of post-traumatic stress disorder (PTSD) trajectories in women with multiple in vitro fertilization-embryo transfer (IVF-ET) failures, and to analyze the effects of different demographic characteristics and psychological factors on the potential categories of PTSD trajectories.Methods:This was a prospective empirical research, from May 2021 to October 2022, women with IVF-ET failure ≥ 2 times in the reproductive department of Shanghai First People′s Hospital from May 2021 to October 2022 were selected as the research objects. Post-traumatic stress disorder civilian version scale was used for 4 follow-ups at 3 d (T1), 10 d (T2), 20 d (T3) after the last transplantation failure and 3 d before the next transplantation cycle (T4). Telephone follow-up and online follow-up were combined to obtain the PTSD level at 4 time points. Potential categories of PTSD score trajectories at four time points were identified using a latent category growth model, and analyze influencing factors using unordered multi classification logistic analysis.Results:Totally 196 IVF-ET women were admitted, aged (29.42 ± 4.13) years. Three PTSD trajectories were fitted in this study, including 82 cases (42%) in non-PTSD group, 61 cases (31%) in mild PTSD group and 53 cases (27%) in elevated PTSD group. Logistic regression analysis showed that age, education level, fertility pressure and marital adjustment level were the predictors of PTSD trajectory in women with multiple IVF-ET failures. Compared with the non-PTSD group, women aged ≥35 years, with lower education level and marital adjustment level were more likely to enter the elevated PTSD group ( OR=4.570, 8.540, 0.949, all P<0.05). Women aged 35 years and with greater reproductive pressure were more likely to enter the mild PTSD group ( OR=3.871, 1.063, both P<0.05). Conclusions:There is group heterogeneity in the trajectories of PTSD in women with multiple IVF-ET failures in the next transplantation cycle. Old age, low education level, high fertility pressure and poor marital adjustment can predict the trajectories of PTSD. Fertility stress and marriage adjustment are changeable variables. Medical staff can relieve women′s fertility pressure through health education and mindfulness intervention, promote a good state of marriage adjustment, and minimize the adverse effects of PTSD on the next cycle of conception.

Objective:Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube.Methods:3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length.Results:In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice.Conclusion:MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective To explore the regulatory role of Abelson interactor 2(ABI2)in progression and prognosis of gastric cancer.Methods TIMER2.0,GEPIA,Kaplan-Meier Plotter and DAVID databases were used to analyze ABI2 expression in pan-cancer and its association with the prognosis of gastric cancer.Gastric cancer and adjacent tissues from 120 patients undergoing radical gastrectomy in our hospital between January,2016 and October,2018 were examined for ABI2 expression and its correlation with disease progression and prognosis.MGC-803 cell models of ABI2 knockdown and overexpression were established for observing the changes in cell proliferation,migration,and invasion,and the impact of ABI2 expression modulation on xenograft growth was evaluated in nude mice.Results Database analysis and examination of the clinical samples showed that ABI2 was highly expressed in gastric cancer tissues.Survival analysis suggested that gastric cancer patients with a high expression of ABI2 had a reduced postoperative 5-year survival rate(P<0.0001),and further Cox univariate and multivariate survival analyses indicated that a high ABI2 expression was an independent risk factor affecting the patients survival outcomes(P=0.022,HR=1.887,95%CI:1.096-3.249).Enrichment analysis suggested the involvement of ABI2 in Wnt signaling.In MGC-803 cells,ABI2 overexpression promoted cell proliferation and xenograft growth in nude mice,increased the expressions of vimentin and N-cadherin,and lowered E-cadherin expression,while ABI2 knockdown produced the opposite effects.Mechanistic analysis revealed that ABI2 overexpression promoted the expressions of Wnt2 and β-catenin in both MGC-803 cells and the xenografts,and their expressions were significantly lowered by ABI2 knockdown.Conclusion ABI2 is highly expressed in gastric cancer,which affects long-term prognosis of the patients,possible due to its regulatory effect on Wnt signaling to promote proliferation,migration and invasion of gastric cancer cells.

Using methylated pyrroloxicam as a starting material and following the principles of drug design such as bioisosterism and active site binding,we designed and synthesized ten structurally novel target compounds,whose structures were characterized by 1H NMR and MS analysis.The in vitro antitumor activity of these title compounds was evaluated by measuring their inhibitory activity against pancreatic cancer cells Capan-1,leukemia cells L1210,and human liver cancer cells SMMC-7721.The results showed that compound 6f(IC50=4.8±0.5 μmol/L)exhibited good inhibitory activity against Capan-1 pancreatic cancer cells,that compound 6b(IC50=2.6±0.3 μmol/L)showed good inhibitory activity against L1210 leukemia cells,and that compound 6c(IC50=2.1±0.2 μmol/L)displayed good inhibitory activity against SMMC-7721 human liver cancer cells.These preliminary results from the antitumor activity experiments suggest that the introduction of benzothiazine derivatives plays a certain role in enhancing the antitumor activity of this class of compounds.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.