BACKGROUND: Ferroptosis-related genes play a crucial role in regulating intracellular iron homeostasis and lipid peroxidation, and they are involved in the regulation of tumor growth and drug resistance. The expression of ferroptosis-related genes in tumor tissues can be used to predict patients' future survival times, aiding doctors and patients in anticipating disease progression. Based on the sequencing data of lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) database, this study identified genes involved in the regulation of ferroptosis, constructed a prognostic model, and evaluated the predictive performance of the model. METHODS: A total of 1467 ferroptosis-related genes were obtained from the GeneCards database. Gene expression profiles and clinical data from 541 LUAD patients were collected from the TCGA database. The expression data of all ferroptosis-related genes were extracted, and differentially expressed genes were identified using R software. Survival analysis was performed on these genes to screen for those with prognostic value. Subsequently, a prognostic risk scoring model for ferroptosis-related genes was constructed using LASSO regression model. Each LUAD patient sample was scored, and the patients were divided into high-risk and low-risk groups based on the median score. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was calculated. Kaplan-Meier survival curves were generated to assess model performance, followed by validation in an external dataset. Finally, univariate and multivariate Cox regression analyses were conducted to evaluate the independent prognostic value and clinical relevance of the model. RESULTS: Through survival analysis, 121 ferroptosis-related genes associated with prognosis were initially identified. Based on this, a LUAD prognostic risk scoring model was constructed using 12 ferroptosis-related genes (ALG3, C1QTNF6, CCT6A, GLS2, KRT6A, LDHA, NUPR1, OGFRP1, PCSK9, TRIM6, IGF2BP1 and MIR31HG). The results indicated that patients in the high-risk group had significantly shorter survival time than those in the low-risk group (P<0.001), and the model demonstrated good predictive performance in both the training set (1-yr AUC=0.721) and the external validation set (1-yr AUC=0.768). Risk scores were significantly associated with the prognosis of LUAD patients in both univariate and multivariate Cox regression analyses (P<0.001), suggesting that this score is an important prognostic factor for LUAD patients. CONCLUSIONS This study successfully established a LUAD risk scoring model composed of 12 ferroptosis-related genes. In the future, this model is expected to be used in conjunction with the tumor-node-metastasis (TNM) staging system for prognostic predictions in LUAD patients.
Humans ; Ferroptosis/genetics* ; Prognosis ; Adenocarcinoma of Lung/pathology* ; Lung Neoplasms/pathology* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Middle Aged ; ROC Curve

OBJECTIVES: To investigate the role of activating transcription factor 3 (ATF3) in atherosclerotic plaques for regulating inflammatory responses during atherosclerosis (AS) progression. METHODS: Human coronary artery specimens from autopsy cases were examined for ATF3 protein expression and localization using immunofluorescence staining and Western blotting. Apolipoprotein E-deficient (ApoE^-/-) mouse models of AS induced by high-fat diet (HFD) feeding for 12 weeks were subjected to tail vein injection of adeno-associated virus serotype 9 (AAV9) to knock down ATF3 expression. After an additional 5 weeks of HFD feeding, the mice were euthanized for analyzing structural changes of the aortic plaques, and the expression levels of ATF3, inflammatory factors (CD45, CD68, IL-1β, and TNF-α), and NF-κB pathway proteins (P-IKKα/β and P-NF-κB p65) were detected. In the cell experiment, THP-1-derived foam cells were transfected with an ATF3-overexpressing plasmid or an ATF3-specific siRNA to validate the relationship between ATF3 and NF‑κB signaling. RESULTS: In human atherosclerotic plaques, ATF3 expression was significantly elevated and partially co-localized with CD68. ATF3 knockout in ApoE^-/- mice significantly increased aortic plaque volume, upregulated the inflammatory factors, enhanced phosphorylation of the NF‑κB pathway proteins, and increased the expressions of VCAM1, MMP9, and MMP2 in the plaques. In THP-1-derived foam cells, ATF3 silencing caused activation of the NF‑κB pathway, while ATF3 overexpression suppressed the activity of the NF-κB pathway. CONCLUSIONS AS promotes ATF3 expression, and ATF3 deficiency exacerbates AS progression by enhancing plaque inflammation via activating the NF-κB pathway, suggesting the potential of ATF3 as a therapeutic target for AS.
Animals ; Activating Transcription Factor 3/metabolism* ; Signal Transduction ; NF-kappa B/metabolism* ; Humans ; Mice ; Plaque, Atherosclerotic/metabolism* ; Inflammation/metabolism* ; Apolipoproteins E ; Atherosclerosis/metabolism* ; Diet, High-Fat

Objective:To evaluate the cost-effectiveness of hepatitis C screening in general population in China, and find the age group in which hepatitis C screening can achieve the best cost-effectiveness.Methods:A decision-Markov model was constructed by using software TreeAge pro 2019 to simulate the outcomes of hepatitis C disease pregression of 100 000 persons aged 20-59 years. The cost-effectiveness of the strategies were evaluated from societal perspectives by using incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB). One-way sensitivity analysis and probability sensitivity analysis were used to evaluate the uncertainty of parameters and model.Results:Hepatitis C screening was cost-effective in people aged 20- 59 years and the cost effectiveness was best in age group 40-49 years. Compared with non-screening strategy of hepatitis C in people aged 20-59 years, the incremental cost was 161.24 yuan, the incremental utility was 0.003 6 quality adjusted life years (QALYs)/per person, ICER was 45 197.26 yuan/QALY, ICER was less than the willing payment threshold. The ICER and NMB in all age groups were 42 055.06-53 249.43 yuan/QALY and 96.52-169.86 yuan/per person. Hepatitis C screening in people aged 40-49 years had the best cost-effectiveness. The results of one-way sensitivity analysis showed that the discount rate, anti-HCV detection cost, anti-HCV infection rate and the cost of direct antiviral agents were the main factors influencing economic evaluation. The results of the probability sensitivity analysis indicated that the model analysis was stable.Conclusions:Implementing hepatitis C screening based on medical institutions is cost-effective in people aged 20- 59 years, especially in those aged 40-49 years. Implementing the HCV screening strategy of be willing to test as far as possible in general population can reduce hepatitis C disease burden in China.

【Objective】 To investigate the effects of radical prostatectomy (RP) or brachytherapy (BT) on the prognosis of patients with high-risk prostate cancer as initial treatment, in order to provide a reference for the selection of clinical treatment options. 【Methods】 The clinical data of 133 191 patients diagnosed with high-risk prostate cancer and treated with RP or BT during 2005 and 2014 were extracted from the SEER database.The 5-year and 10- year cancer-specific survival (CSS) and overall survival (OS) were compared with K-M analysis and univariate and multivariate Cox regression.The clinical data of another 253 patients diagnosed with high-risk prostate cancer in Subei People’s Hospital during 2015 and 2020 were collected, including 153 patients who received RP and 100 patients who received BT.The 5-year biochemical progress-free survival (bPFS) and CSS were compared with K-M analysis. 【Results】 Univariate analysis of SEER data showed that BT was associated with a higher risk of death (HR=1.319, 95%CI: 1.256-1.386, P<0.001); age, marital status and TNM stage were associated with higher risk of death (P<0.001).Multivariate analysis, adjusted for relevant variables, showed that BT did not result in a higher risk of death compared with RP (HR=0.964, 95%CI:0.924-0.996, P=0.808). The OS curve showed that the longer the observed survival time, the better OS of RP as compared to BT (P<0.001); however, the CSS survival curve showed that the longer the observed survival time, the better CSS of BT compared to RP (P<0.001).The single-center data analysis showed no significant difference between BT and RP in the 5-year bPFS (P=0.263) and CSS (P=0.946). 【Conclusion】 For patients with high-risk prostate cancer, there is a significant difference in the prognosis of the two treatments if there is no adjustment of age, marital status, TNM stage and other factors, and the efficacy of RP is better than that of BT, especially in patients with survival more than 10 years.However, there is no statistically significant difference in the prognosis after the possible confounding factors are adjusted.Therefore, the initial treatment choice for these patients should be weighed from multiple perspectives, and patients’ choices must be respected after they are fully informed.

Objective:To evaluate the efficacy of preoperative three-dimensional (3D) image reconstruction combined with intraoperative dynamic ultrasonography (IOUS) in laparoscopic precision hepatectomy for intrahepatic bile duct stones.Methods:The clinical data of 66 patients with intrahepatic bile duct stones undergoing laparoscopic hepatectomy in the First People's Hospital of Fuyang District, Hangzhou from January 2018 to January 2023 were retrospectively analyzed, including 32 males and 34 females, aged (49.6±15.2) years old. Patients were divided into the study group ( n=32), who underwent laparoscopic precision hepatectomy using 3D reconstruction combined with IOUS, and the control group ( n=34), who underwent conventional laparoscopic hepatectomy. Perioperative data including the operation time, intraopera-tive blood loss, total volume of drainage on postoperative day (POD) 3, and the rates of complications were compared between the groups. Serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), liver function indices including total bilirubin (TBil) and alanine aminotransferase (ALT) were monitored preoperatively and on POD 1, 3, 5, and 7. Results:The operation time was shorter in the study group [(178±17) min vs. (189±18) min, t=2.55, P=0.010]. The intraoperative blood loss was reduced in the study group [(218±19) ml vs. (395±21) ml, P<0.001]. The incidence of total volume of drainage >300 ml on POD 3 were comparable between the groups [9.4%(3/32) vs. 14.7%(5/34), P=0.507]. There were no significant differences in preoperative serum level of TBil, ALT, CRP and IL-6 between the groups (all P>0.05). Compared to the control group, serum levels of TBil, ALT and CRP in the study group were decreased on POD 1, 3, 5 and 7, and IL-6 was decreased on POD 1 and 3 (all P<0.05). The occurrences of postoperative bile leakage [9.4% (3/32) vs. 29.4% (10/34)] and liver cutting surface fluid accumulation [12.5% (4/32) vs. 35.3% (12/34)] and the rate of stone retention [3.0% (1/32) vs. 20.6% (7/34)] were lower in the study group (all P<0.05). Conclusion:Preoperative 3D image reconstruction combined with IOUS in laparoscopic precision hepatectomy for intrahepatic bile duct stones could reduce intra-operative blood loss, hepatic inflammatory response, and postoperative complications.

Objective    To investigate the optimal treatment scheme for the first primary spontaneous pneumothorax (PSP) in young patients. Methods    The clinical data of 171 patients with the first PSP were retrospectively analyzed who were treated in Huaihe Hospital of Henan University between November 2011 and October 2017. There were 157 males and 14 females with a median age of 18 years at onset and a median body mass index of 18.51 kg/m2. According to the treatment methods, they were classified into two groups, a conservative treatment group (a non-surgical group, n=86) and a surgical group (n=85). The characteristics including clinical data, efficacy evaluation criteria, complications and recurrence of the two groups were analyzed. Results    As a result, 73.68% of the patients suffered PSP in their daily routine. The drainage duration in the non-surgical group was longer than that in the surgical group (4 d vs. 3 d, P=0.008). There was no statistical difference in the success rate of lung re-expansion between the two groups (98.85% vs. 100.00%, P=1.000). The proportion of the surgical group using postoperative analgesic drugs was higher than that in the non-surgical group (48.23% vs. 10.46%, P=0.000). The recurrence rate of the surgical group was lower than that of the non-surgical group (3.53% vs. 46.51%, P=0.000). No relationship between smoking and recurrence of pneumothorax was found in both groups (P=0.301, P=1.000). The success rate of lung re-expansion in the non-surgical group was not statistically different between the 24F subgroup and the 12F subgroup (39/39 vs. 33/34, P=0.458). No advantage of intraoperative pleural fixation was found in the surgical group (P=0.693). Conclusion    Thoracoscopic surgery is the first choice for the treatment of the first PSP in young patients.

Objective To investigate the risk factors for anastomotic leakage (AL) after laparoscopic intersphincteric resection (Lap-ISR) for patients with low-lying rectal cancer.Methods This retrospective study was conducted in the Characteristic Medical Center of PLA Rocket Force from Jun 2011 to Nov 2018.151 patients undergoing Lap-ISR were enrolled for this study.Results All patients in this series had a defunctioning ileostomy.The overall leakage rate was 17.2％ (26/151),including peri-operative AL (n =20) and delayed AL (n =6).In accordance with the grading system of the International Study Group of Rectal Cancer,there were 24 patients (15.9％) with AL Grade B (requiring active therapeutic intervention) and two patients (1.3％) with AL Grade C (requiring re-laparotomy).Univariate analysis showed that BMI (≥ 25 kg/m2),tumor annularity (≥ 3/4) and operation time (≥ 240 min) were associated with AL (P ＜ 0.05).Multivariate analysis showed that operation time (≥ 240 min,OR =7.390,95％ CI:2.483-21.988,P =0.000),tumor annularity (≥ 3/4,OR =6.233,95％ CI:1.932-20.107,P=0.002) and higher BMI (≥ 25 kg/m2,OR=3.523,95％ CI:1.275-9.738,P=0.015)were independently predictive of AL Conclusion Tumor annularity,operation time and higher BMI are independently associated with symptomatic AL after Lap-ISR.

Objective:To understand the hepatitis C diagnosis type, progression and treatment in medical institutions.Methods:Monitoring posts were set up in the secondary and tertiary-level hospitals in some parts of the country. Reported infectious diseases cases of hepatitis C in sentinel hospitals during the three consecutive years from 2017 to 2019 were investigated to understand their general demographic characteristics, diagnosis, liver fibrosis degree, and treatment. The diagnosis, treatment and related factors were analyzed by chi square test and trend.Results:A total of 16 241 cases of hepatitis C were investigated in three years. Among them, 7 538 cases were clinically diagnosed (46.41%) and 8703 cases (53.59%) were confirmed as hepatitis C. Among the confirmed cases, 60 cases (0.69%) were acute and 8643 cases (99.31%) were chronic. In the past three years, the proportion of cases diagnosed by liver diseases related departments decreased from 62.23% to 40.01%, while the proportion of medical and surgical cases of non-liver diseases increased from less than 30% to nearly 60%. The proportion of confirmed cases in secondary hospitals (26.27%) was significantly lower than that in tertiary hospitals (62.48%), and the difference was statistically significant ( χ2 = 1594.833, P < 0.001). There were also differences in the proportion of confirmed cases in different regions ( P < 0.001). The cases with FIB-4 > 3.25 accounted for 35.78%, and the proportion was increased significantly with age ( χ2 trend = 1159.624, P < 0.001). The average proportion of antiviral treatment was less than 10%, and the proportion of antiviral treatment in secondary hospitals was very low (2.13%); however, the proportion of liver-protective monotherapy treatment was decreased from 30.40% in 2017 to 11.14% in 2019, and the difference was statistically significant ( P < 0.001). Conclusion:The large-scale screening of hepatitis C by medical institutions is increasing year by year, but only about half of the cases can be diagnosed, and the diagnostic capacity of secondary hospitals is particularly unsatisfactory. Most of the confirmed cases are chronic hepatitis C, and more than one third of them have abnormal liver fibrosis indicators, and the proportion increases with age. The proportion of antiviral treatment for hepatitis C is lower in secondary than tertiary-level hospitals. Therefore, there is an urgent need to raise the attention of both parties (doctors and patients) to enhance diagnostic capabilities and expand the coverage of antiviral treatment for hepatitis C.

Objective: To study laparoscopic ultrasound assisted hepatectomy in treatment of intrahepatic and extrahepatic bile duct stones. Methods: The data of 52 patients with hepatolithiasis who underwent laparoscopic hepatectomy from May 2014 to January 2019 at the Fuyang District First People's Hospital in Hangzhou were analyzed retrospectively. There were 28 men and 24 women. The median age was 56 years. Operative laparoscopic ultrasonography was used to detect the location, size, distribution of stones and their relations to blood vessels. A total of 43 patients underwent anatomic hepatectomy, while 38 patients underwent choledochoscopic stone extraction. A " T" tube was used according to intraoperative conditions. Results: Laparoscopic surgery was successfully carried out in 50 patients, while conversion to open surgery was required in 2 patients because of adhesions and bleeding. Laparoscopic ultrasonography revealed intrahepatic calcifications in 5 patients and choledochoscopy in 2 patients. Postoperative complications included 5 patients who devleoped abdominal abscesses. The operation time was (289.0±132.0) minutes. The intraoperative blood loss was (451.0±256.0) ml. The hospitalization after operation was (12.0±3.0) days. In 52 patients, 4 patients had residual stones and the residual rate was 7.7%. All of them were completely removed by T-tube sinus 8 weeks after operation. Conclusions Laparoscopic ultrasound helped to detect relevant bile ducts containing stones, reduced chance of bleeding in surgery, helped to clarify location and distribution of stones, improved accuracy of diagnosis, and reduced unnecessary hepatectomy by clearly defining intrahepatic bile duct stones intraoperatively. The residual intrahepatic and intrahepatic bile duct stones rates were reduced, and the safety and accuracy of the operations were improved.

Objective To study the safety,efficacy and advantages of enhanced recovery after surgery (ERAS) combined with clinical pathway management in laparoscopic common bile duct exploration and lithotomy (Laparoscopic common bile duct exploration,LCBDE).Methods 78 patients who underwent LCBDE in the Department of Hepatobiliary and Pancreatic Surgery in the First Hospital of Fuyang District in Hangzhou were selected as the non-ERAS group (the control group).76 patients who underwent LCBDE treated with fast track surgery and ERAS clinical pathway management were selected as the ERAS group.The data between the two groups which included the postoperative insulin resistance index,changes in C-reactive protein,duration of postoperative analgesic use and analgesia,timing of first passage of postoperative flatus,postoperative abdominal tube removal,postoperative bile leakage,recurrence of biliary stones,intestinal ileus and other complications.Results All the two groups were discharged home successfully.On preoperative 7 day,the differences on the postoperative insulin resistance index and the levels of C reactive protein were significantly different (P＜0.05).The time to first get out of bed after operation,the postoperative analgesic use,the time to first passage of flatus,the time to postoperative abdominal drainage tube removal,and the time to clamping of the T tube after operation were significantly different (all P＜0.05).The postoperative complications of pulmonary infection,abdominal infection and the incidence of prolonged intestinal ileus were significantly different (all P＜0.05).Conclusions ERAS combined with clinical pathway management reduced postoperative stress reaction and complication rate.The treatment accelerated recovery and shortened hospital stay for patients who underwent LCBDE,which led to good social and economic benefits.