The chemical constituents from the n-butanol fraction of ethanol extract of safflower (Carthamus tinctorius L.) were isolated and purified using chromatographic process including MCI Gel CHP-20, ODS, Sephadex LH-20 column chromatography, and semi-preparative HPLC method, and one alkyne and two phenylpropanoid derivants were obtained. Their structures were identified as (5R,E)-tetradecane-12-ene-8,10-diyne-1,5,14-triol (1), (E)-8-O-β-D-glucopyranosyl n-butyl cinnamate (2), and (7S,8S)-7-(4-hydroxy-3-methoxybenzene)-7-butyl-8,9-diol (3) by modern spectroscopy methods (1D NMR, 2D NMR, UV, IR and MS). 1-3 are all new compounds. Compounds 1-3 were screened for their anti-renal fibrosis activities in vitro, and none of them showed obvious effect.

Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Objective To analyze the influencing factors of pancreatic fat deposition in patients with type 2 diabetes mellitus(T2DM),and to explore the relationship between pancreatic fat deposition and islet function.Methods A survey on diabetes prevalence was conducted among 548 residents in the Nicheng community of Pudong New Area from October 2015 to December 2016,including 301 patients with T2DM and 247 subjects with normal glucose tolerance(NGT).General information of the subjects were recorded,blood biochemical and insulin indexes were measured,body composition was measured by dual-energy X-ray absorptiometry,and insulin resistance index(HOMA-IR)and islet cell sensitivity index(HOMA-β)were calculated.Fatty liver and pancreatic fat deposition were detected by ultrasound.Both the T2DM group and NGT group were further divided into two subgroups according to the pancreatic fat deposition.Differences in general demographic information,biochemical and body fat indices among the groups were compared.Multivariate logistic regression was used to analyze the influencing factors of pancreatic fat deposition.Results In the NGT group,the subgroup with pancreatic fat deposition showed higher levels of age,waist circumference,waist-to-hip ratio(WHR),body mass index(BMI),fasting insulin levels(FINS),2-hour postprandial insulin levels(2 h INS),triglycerides(TG),uric acid(UA),alanine aminotransferase(ALT),fatty liver prevalence,abdominal fat percentage,and abdomen-to-hip ratio(AHR),compared with the subgroup without pancreatic fat deposition.High-density lipoprotein cholesterol(HDL-C)and limb fat percentage were lower in the subgroup with pancreatic fat deposition.In the T2DM group,the subgroup with pancreatic fat deposition showed higher levels of waist circumference,BMI,FINS,2 h INS,TG,UA,ALT,aspartate aminotransferase(AST),fatty liver prevalence,and abdominal fat percentage,compared with the subgroup without pancreatic fat deposition,with statistically significant differences(P<0.05).The HOMA-IR and HOMA-β in both NGT and T2DM groups with pancreatic fat deposition were significantly higher than those in the groups without pancreatic fat deposition.The prevalence of insulin resistance also significantly increased,with statistically significant differences(P<0.05).The results of multivariate logistic regression analysis showed that HDL-C,HOMA-β,abdominal fat percentage,age and fatty liver were the influencing factors for pancreatic fat deposition in NGT.Conclusion Elderly individuals with abdominal obesity and fatty liver are more prone to developing pancreatic fat deposition,which can affect islet function and aggravate the insulin resistance.

Objective To evaluate the status of home medication safety among elderly patients with chronic diseases and analyze its influencing factors in urban and rural areas of Henan Province.Methods Convenient sampling method was adopted.Data was collected through a designed and optimized questionnaire.Pharmacists conducted in-home surveys.Excel and SPSS 26.0 software were used for data analysis.Results A total of 352 valid questionnaires were analyzed.Most respondents were aged 60～70 years,with a female proportion of 56.2%,and 52.0%of them had a junior high school education or lower.The top-ranked chronic diseases were hypertension(62.2%)and hyperlipidemia(33.2%),and 61.1%of patients suffered from multiple chronic diseases.Antipyretic and analgesic drugs were most common in home medicine cabinets(90.1%).The proportion of drugs being stored in accordance with the instructions(46.9%)was slightly low,and 93.8%of the elderly handled expired drugs improperly.Awareness of medication guidance services was low(34.9%).Logistic regression analysis showed that factors such as education level and monthly income had significant effects on the understanding of drug package insert,rational drug storage,proper disposal of expired drugs,and awareness of medication guidance services(P<0.05).Conclusion There are still some potential safety risks in the home medication use of elderly patients with chronic diseases in urban and rural areas of Henan Province.It is necessary to enhance education on drug storage and medication guidance,particularly for low-income and less-educated groups,to improve the safety of home medication use.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective To investigate the effect of dexmedetom idine(DEX)on lung tissue and Ras homolog gene family member A(RhoA)/Rho kinase 1(ROCK1)signaling pathway in lung tissue of rats with ventilator-induced lung injury(VILI).Methods A VILI rat model was established and separated into control group,model group(VILI group),dexmedetomidine low and high dose groups(DEX-L,DEX-H group),and high dose dexmedetomi-dine+lysophosphatidic acid(LPA)group(DEX-H+LPA group).Determination of wet/dry mass ratio of rat lung tissue(W/D);HE staining microscopy was applied to observe morphology of lung tissue;ELISA kit was applied to detect the level of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid(BALF);TUNEL staining method was applied to detect lung epithelial cell death;Immunoblotting was applied to detect the expression levels of apoptosis-related proteins,and RhoA,ROCK1 pro-teins.Results DEX could reduce lung injury,lung injury score,W/D,apoptosis rate,levels of TNF-α,IL-1β,IL-6,and expression of Bax,cleaved caspase-3,RhoA,ROCK,α-SMA in VILI rats(P＜0.05),while increased the expression of Bcl-2(P＜0.05);LPA could aggravate lung injury and increase lung injury score,W/D,apopto-sis rate,level of TNF-α,IL-1β,IL-6 and expressions of Bax,cleaved caspase-3,RhoA,ROCK and α-SMA(P＜0.05);Bcl-2 expression level was decreased(P＜0.05).Conclusions Dexmedetomidine may protect rats with ventilator-induced lung injury by the inhibition of RhoA/ROCK1 signaling pathway.

Objective : To explore the effect of MPZL1 knockdown in A549 Taxol resistant (A549 / Tax) cells and whether it affect drug resistance and tumor cell stemness by regulating β-catenin． Methods : A549 and A549 / Tax cells were treated with different concentrations of doxorubicin and paclitaxel to observe the differences in drug resist- ance between the two cells．Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the MP- ZL1 expression level in A549 and A549 / Tax cells． After knockdown or overexpression of MPZL1 in A549 / Tax cells，cells were divided into control group，small hairpin RNA negative control ( sh-NC) group，MPZL1 knock- down(sh-MPZL1) group，overexpression negative control ( OE-NC) group，MPZL1 overexpression ( OE-MPZL1) group．Cell counting kit-8 ( CCK-8 ) and clone formation assay were utilized to investigate cell proliferation and clone formation ablity．Western blot assay was used to detect the protein expression after the cells treated with Wnt / β-catenin signaling inhibitor XAV939 and activator CHIR-99201 . Results : The half inhibitory concentration ( IC50 ) of doxorubicin and paclitaxel in A549 / Tax cells significantly increased compared to A549 cells(P＜0. 01) . MPZL1 presented a higher expression trend in A549 / Tax cells．The IC50 values of A549 / Tax for doxorubicin and paclitaxel were 2. 731 mg / ml and 4. 939 μg / ml after MPZL1 knockdown，compared to 4. 541 mg / ml and 13. 55 μg / ml in the NC group (P＜0. 01) ．The results of CCK-8 and clone formation assay showed that the knockdown of MPZL1 reduced the viability of cells proliferation and clonal formation ability (P＜0. 05) ．Western blot results in- dicated that the expression levels of MPZL1 protein，tumor cell stemness associated proteins ( CD44，CD133) ，β - catenin and multidrug resistance protein 1 (MDR1) ，lung resistance-related protein ( LRP) were significantly re- duced in the sh-MPZL1 group． Furthermore ，XAV939 could inhibit the expression levels of MPZL1 ，CD44， CD133，MDR1，LRP and β-catenin(P＜0. 01) ．The inhibitory effect of knockdown MPZL1 on the aforementioned proteins was significantly reversed by CHIR-99201 treatment． Conclusion MPZL1 is highly expressed in A549 / Tax cells．Knockdown MPZL1 suppresses the tumor cell stemness and proliferation，thereby reversing the drug re- sistance of doxorubicin and paclitaxel in A549 / Tax cells.

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.