Objective To investigate the transcriptome differences of ovarian cancer cells after cisplatin(DDP)resistance,and to find potential antagonists based on this screening.Methods DDP-resistant cell line A2780-DDP was constructed with A2780 cells as the research object.Through transcriptome sequencing anal-ysis,the key factors of DDP resistance were found and verified by quantitative real-time PCR(qPCR)and Western blot experiments.Through the screening of small molecule inhibitors,CCK-8 cell viability assay was used to find potential antagonists.Results A2780-DDP were successfully constructed,and it was found that there was no difference in cell proliferation after drug resistance,but the ability of cell invasion and migration was enhanced.Through transcriptome sequencing analysis,it was found that ITGB7 and Akt may be the key genes of A2780-DDP,and qPCR and Western blot showed that they were highly expressed in A2780-DDP.CCK-8 results showed that triptolide(TPL)and Olaparib had good inhibitory effects in DDP-resistant cell lines.Conclusion The ITGB7/Akt pathway plays an important role in DDP resistance,and potential DDP re-sistance antagonists such as TPL can provide new ideas for the treatment of ovarian cancer.

Objective　To understand the trends of serum lipid concentration and the prevalence of dyslipidemia in adults aged 35 years and older, and to compare the regional differences in lipids. Methods　Based on the data of Anhui Province in the Early Screening and Comprehensive Intervention Project for High-risk Groups of Cardiovascular Disease in China from 2017 to 2021, the change trend of blood lipid level and the prevalence rate of each region were plotted according to the year and different regions in the province, and the influencing factors of dyslipidemia were analyzed by multivariate regression model. Results　The overall average levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) demonstrated an increase followed by a slight decrease with age annually, while the levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) fluctuated minimally. From 2017 to 2020, TC levels improved annually but increased again in 2021. Similar to TG and non-HDL-C, the average LDL-C level decreased annually from 2017 to 2019, while rebounded in 2020 and 2021 compared with the previous three years. In contrast, the HDL-C level continued to decline. With the exception of HDL-C, the overall blood lipid levels in the northern Anhui (n=31 716) were higher than those in the southern Anhui (n=50 681), and the lowest levels were found in the central Anhui (n=38 246). The prevalence of hypercholesterolemia (7.400%, 2 347/31 716), high LDL-C (5.228%, 1 658/31 716), low HDL-C (9.935%, 3 151/31 716), hypertriglyceridemia (18.212%, 5 776/31 716), and high non-HDL-C (5.789%, 1 836/31 716) were highest in the northern Anhui. Age, region, senior high school or above, smoking, drinking, systolic blood pressure, blood glucose, and body mass index were independent factors for dyslipidemia (P<0.05). Conclusion　The blood lipid level and prevalence of dyslipidemia in adults aged ≥35 years in Anhui Province have not yet reached an ideal control level, especially in the northern part of Anhui Province where there is a need for enhanced awareness and timely intervention measures for lipid-related diseases to effectively extend the life expectancy of residents.

Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Thyroid carcinoma is closely related to environmental factors. Gene mutations and molecular biological changes of gland tissue caused by environmental changes are important factors inducing thyroid carcinoma. Although the molecular mechanism of thyroid carcinoma has not been fully elucidated,increasingly specific genetic changes and molecular markers for thyroid carcinoma have been discovered with the development of molecular biology techniques. This article reviews the recent progresses on the etiology,specific molecular markers,diagnosis and targeted therapies of thyroid carcinoma,so as to provide theoretical support for the clinical diagnosis and treatment of thyroid carcinoma.

Objective To analyze the diagnostic value of systemic immune inflammation index(SII)and systemic inflammation response index(SIRI)in rheumatoid arthritis(RA).Methods A total of 470 RA pa-tients diagnosed in the hospital from January to December 2023 were selected.According to the results of anti-cyclic citrullinated peptide(anti-CCP)antibody and rheumatoid factor(RF),RA was divided into four groups:anti-CCP antibody and RF negative group(52 cases),anti-CCP antibody positive RF negative group(70 cases),anti-CCP antibody negative RF positive group(18 cases),anti-CCP antibody and RF positive group(330 cases),and 300 healthy subjects were selected as control group.After calculating SII and SIRI in each group,Kruskal-Wallis was used to examine the difference between SII and SIRI in the anti-CCP antibody and RF negative group,anti-CCP antibody positive RF negative group,anti-CCP antibody negative RF positive group,anti-CCP antibody and RF positive group of RA patients and the control group,and the receiver operat-ing characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of SII and SIRI in the anti-CCP antibody and RF negative group,anti-CCP antibody positive RF negative group,anti-CCP antibody negative RF positive group,anti-CCP antibody and RF positive group of RA patients.Results SII and SIRI in four groups of RA patients were significantly higher than those in control group(P＜0.05).The area under the curve(AUC)of SII in evaluating the four groups of RA patients were 0.689,0.724,0.709,and 0.774,respec-tively.SIRI had an AUC of 0.679,0.729,0.679,and 0.772 in the evaluation of the four groups of RA pa-tients,respectively.Conclusion SII and SIRI are both elevated in patients with RA,and have certain predictive value for RA.

Objective To develop a rapid and accurate Monte Carlo program(simplified code for dosimetry of carbon ions,SPEEDO)for carbon ion therapy.Methods For electromagnetic process,type Ⅱ condensed history simulation scheme and continuous slowing down approximation were used to simulate energy straggling,range straggling,multiple scattering,and ionization processes.For nuclear interaction,5 types of target nuclei were considered,including hydrogen,carbon,nitrogen,oxygen,and calcium.The produced secondary charged particles followed the same condensed history framework.The study simulated the transport of carbon ions in 4 materials(water,soft tissues,lung,and bone),and the calculated doses were validated against TOPAS(a Monte Carlo simulation software for radiotherapy physics),followed by a comparison with dose measurements in a water phantom from the HIMM-WW(a medical heavy-ion accelerator facility in Wuwei).Results SPEEDO's simulation results showed good consistency with TOPAS.For each material,in the voxel region where the physical dose was greater than 10％of the maximum dose point,the relative maximum dose error of both was less than 2％.At treatment energy of 400 MeV/u,SPEEDO's computation time was significantly less than that of TOPAS(13.8 min vs 105.0 min).SPEEDO's calculation results also showed good agreement with HIMM-WW measurements in terms of lateral dose distribution and integrated dose depth curve.Conclusion SPEEDO program can accurately and rapidly perform Monte Carlo dose calculations for carbon-ion therapy.

This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.

Background/Aims: The shortage of donor liver hinders the development of liver transplantation. This study aimed to clarify the poor outcomes of functionally marginal liver grafts (FMLs) and provide evidence for the improvement of ischemia-free liver transplantation (IFLT) after FML transplantation. Methods: Propensity score matching was used to control for confounding factors. The outcomes of the control group and FML group were compared to demonstrate the negative impact of FMLs on liver transplantation patients. We compared the clinical improvements of the different surgical types. To elucidate the underlying mechanism, we conducted bioinformatic analysis based on transcriptome and single-cell profiles. Results: FMLs had a significantly greater hazard ratio (HR: 1.969, P=0.018) than did other marginal livers. A worse 90-day survival (Mortality: 12.3% vs. 5.0%, P=0.007) was observed in patients who underwent FML transplantation. Patients who received FMLs had a significant improvement in overall survival after IFLT (Mortality: 10.4% vs 31.3%, P=0.006). Pyroptosis and inflammation were inhibited in patients who underwent IFLT. The infiltration of natural killer cells was lower in liver grafts from these patients. Bulk transcriptome profiles revealed a positive relationship between IL-32 and Caspase 1 (R=0.73, P=0.01) and between IL-32 and Gasdermin D (R=0.84, P=0.0012). Conclusions FML is a more important negative prognostic parameter than other marginal liver parameters. IFLT might ameliorate liver injury in FMLs by inhibiting the infiltration of NK cells, consequently leading to the abortion of IL-32, which drives pyroptosis in monocytes and macrophages.

Objective:To explore the efficacy and safety of laparoscopy for acute appendicitis (AA)in kidney transplant(KT)recipients.Methods:From May 2016 to December 2022, retrospective review is conducted for 99 AA patients operated at Tianjin First Central Hospital.They are assigned into two groups of observation(kidney transplant recipients, 33 cases)and control(normal renal function patients, 66 cases). Laparoscopic perioperative data of white blood cell(WBC), neutrocyte percentage(NEUT%), C-reactive protein(CRP), procalcitonin(PCT), operative duration, intraoperative blood loss, postoperative drainage volume, postoperative hospitalization length, total hospitalization expense and morbidity of postoperative complications are compared.Results:After propensity score matching, no statistically significant inter-group difference existed in clinical profiles.WBC and NEUT% pre-operation are lower in observation group than those in control group[11.85(9.54~13.99)×10 9/L vs 13.74(12.42~14.66)×10 9/L, Z=-3.908, P<0.01; 85.00(73.65~89.60)% vs 88.20(83.85~90.20)%, Z=-2.522, P=0.012]. No significant inter-group difference existed in preoperative CRP/PCT(all P>0.05). No significant inter-group differences existed in WBC, NEUT, CRP or PCT at Day 3 post-operation(all P>0.05). No significant difference existed in creatinine level in observation group before and after operation( P>0.05). As compared with control group, operative duration was longer[86(74~99)vs 62(57~68)min, Z=-6.290, P=0.020], intraoperative blood loss greater[25(20~33)vs 15(15~20)ml, Z=-6.104, P<0.01], postoperative drainage volume larger[75(65~85)vs 35(25~36)ml, Z=-8.103, P<0.01], postoperative hospitalization time longer[7(6~9)d vs 5(4~5)d, Z=-7.064, P<0.01]and total hospitalization expense higher[(1.98±0.22)vs (1.73±0.22)ten thousand yuan, t=5.401, P<0.01]. No significant inter-group differences existed in time of postoperative passage of flatus( P=0.669). No significant inter-group difference existed in morbidity of postoperative complications( P=0.893). Conclusions:The efficacy of laparoscopic appendectomy in patients post-KT is basically comparable to that in counterparts with normal renal function.