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

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

Objective:To evaluate knee biomechanics of patients about 12 months after anterior cruciate ligament(ACL)reconstruction during cutting and determine the abnormal biomechanical characteristics.Methods:Sixteen males about 12 months after ACL reconstruction were recruited for this study.Three-dimensional kinematic and kinetic data were collected during cutting movement.Knee joint angles and moments were calculated.Paired t-tests were used to compare the differences in knee biomechanics be-tween the surgical leg and nonsurgical leg.Results:The peak posterior ground reaction force(surgical leg:0.380±0.071;nonsurgical leg:0.427±0.069,P=0.003)and vertical ground reaction force(surgical leg:1.996±0.202,nonsurgical leg:2.110±0.182,P=0.001)were significantly smaller in the surgical leg than in the nonsurgical leg.When compared with the uninjured leg,the surgical leg demonstrated a smaller knee flexion angle(surgical leg:38.3°±7.4°;nonsurgical leg:42.8°±7.9°,P＜0.001)and larger external rotation angle(surgical leg:10.3°±2.4°;nonsurgical leg:7.7°±2.1°,P=0.008).The surgical leg also demonstrated a smaller peak knee extension moment(surgical leg:0.092±0.031;nonsurgical leg:0.133±0.024,P＜0.001)and peak knee external rotation moment(surgical leg:0.005±0.004;nonsurgical leg:0.008±0.004,P=0.015)when com-pared with the nonsurgical leg.Conclusion:The individuals with ACL reconstruction mainly showed asymmetrical movements in the sagittal and horizontal planes.The surgical leg demonstrated a smaller peak knee flexion angle,knee extension moment,and knee external rotation moment,with greater knee external rotation angle.

Objective:To explore the safety and effectiveness of laparoscopic local pancreatectomy in the treatment of cystic neoplasms of pancreatic head.Methods:Retrospective analysis was conducted of data on patients with pancreatic head cystic neoplasms who received laparoscopic surgery at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University from February 2017 to October 2022. A total of 83 patients were enrolled, including 30 males and 53 females, aged (43.7±16.7) years old. All patients were divided into an observation group ( n=55) and a control group ( n=28) based on different surgical procedures. The observation group underwent laparoscopic local pancreatectomy (laparoscopic duodenum-preserving pancreatic head resection or laparoscopic enucleation), while the control group underwent laparoscopic pancreaticoduodenectomy (LPD). The age, gender, body mass index, postoperative hospital stay, proportion of discharged patients with drainage tubes, surgical time, intraoperative blood loss, intraoperative blood transfusion rate, and fistula were compared between two groups. Results:All patients successfully completed the surgery, and there were no cases of conversion to laparotomy or perioperative deaths. There was no statistically significant difference in age, male proportion, body mass index, postoperative hospital stay, and discharge rate with drainage tube between the two groups of patients (all P>0.05). The observation group had a surgical time of (194.4±114.0) min, intraoperative bleeding of 50 (50, 200) ml, and intraoperative blood transfusion rate of 5.5%(3/55), all of which were better than that of the control group, (380.0±71.6) min, 200 (100, 400) ml, and 32.1%(9/28), with statistical significance (all P<0.05). Among them, the B/C fistula rates in the laparoscopic local pancreatectomy group and LPD group were 12.7%(7/55) and 10.7%(3/28) ( P=0.790), respectively. Conclusion:Compared with traditional LPD, laparoscopic local pancreatectomy can shorten surgical time, reduce intraoperative bleeding, and lower intraoperative blood transfusion rate. And there is no significant disadvantage in the B or C grade fistula.

Objective:To investigate the application value of laparoscopic pancreatic tumor enucleation (LapEN).Methods:The retrospective and descriptive study was conducted. The clinical data of 47 patients who underwent LapEN in Second Hospital of Hebei Medical University from September 2016 to June 2022 were collected. There were 18 males and 29 females, aged (49±12)years. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) postoperative recovery; (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All 47 patients underwent LapEN successfully, with the operation time as (135±19)minutes and the volume of intraoperative blood loss as 100(50,100)mL. (2) Postoperative complications. Of the 47 patients, there were 12 patients with postoperative pancreatic fistula, 3 patients with postoperative abdominal infection, 1 case with postoperative hemorrhage, 1 case with postoperative gastric emptying disorder. (3) Postoperative recovery. Of the 47 patients, there were 13 cases with pancreatic solid pseudopapillary neoplasm, 12 cases with insulinoma, 11 cases with pancreatic serous cystadenoma, 7 cases with pancreatic intraductal papillary mucinous neoplasm (branched type), 4 cases with pancreatic mucinous cyst-adenoma. The tumor diameter of 47 patients was 1.9(1.6,2.3)cm and all patients with R 0 resection. There was no patient with perioperative death in the 47 patients. The postoperative duration of hospital stay and total hospital expenses of 47 patients was (13±4)days and (6.8±1.2) ten thousand yuan, respectively. (4) Follow-up. All 47 patients were followed up for 14(range, 8?18)months. None of the 47 patients had new onset diabetes or situations required postoperative exocrine replacement therapy, and no patient died. Conclusion:LapEN is safe and feasible for patients with pancreatic benign tumor or low potential malignancy.

Objective:To investigate the clinical efficacy of laparoscopic radical resection of hilar cholangiocarcinoma (LRHCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of 211 patients who under LRHCCA in the Second Hospital of Hebei Medical University from May 2014 to June 2022 were collected. There were 135 males and 76 females, aged (63±8)years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rate and draw survival curve. Results:(1) Surgical situations. All 211 patients underwent LRHCCA successfully, with the operation time as 350 (300,390)minutes, volume of intraoperative blood loss as 400(200,800)mL, and intraoperative red blood cell transfusion as 2.0(range, 0-15.0)U, respectively. As partial portal vein invasion, 10 of 211 patients underwent portal vein resection and reconstruction. Results of intraoperative histopathology examination showed negative margin of portal vein. The operation time, volume of intraoperative blood loss, intraopera-tive red blood cell transfusion of the 10 patients was (400±53)minutes, 1 200(range, 800-3 000)mL, 5.5(range, 4.0-15.0)U, respectively. (2) Postoperative situations. Of the 211 patients, there were 63 cases of the Bismuth type Ⅰ, 65 cases of the Bismuth type Ⅱ, 22 cases of the Bismuth type Ⅲa, 26 cases of the Bismuth type Ⅲb, 35 cases of the Bismuth type Ⅳ. The R 0 resection rate was 95.73%(202/211). There were 202 patients identified as adenocarcinoma of the bile duct, including 7 cases with poorly differentiated tumor, 189 cases with moderate to poorly differentiated tumor, 3 cases with moderate to well differentiated tumor, 3 cases with well differentiated tumor. There were 8 patients with poorly differentiated biliary mucinous adenocarcinoma, 1 patient with intraductal papillary neoplasm with high-grade epithelial dysplasia. There were 24 cases of stage Ⅰ, 98 cases of stage Ⅱ, 30 cases of stage ⅢA, 34 cases of stage ⅢB, 19 cases of stage ⅢC, 6 cases of stage ⅣA. Of the 211 patients, there were 25 cases with postoperative biliary fistula, 11 cases with postoperative abdominal infection, 3 cases with postoperative bleeding as anastomotic bleeding after biliary fistula, 2 cases with postoperative gastric emptying disability, 1 case with postoperative acute liver failure. There were 7 patients undergoing postoperative unplanned reoperation, including 3 cases with emergency operation for hemostasis, 4 cases with abdominal exploration debridement and drainage for severe abdominal infection. There were 3 cases dead during perioperative period, including 1 case of acute liver failure, 1 case of systemic infection and multiple organ failure, 1 case of exfoliated deep venous thrombosis of lower extremities and acute pulmonary embolism. The postoperative duration of hospital stay was (15±5)days of the 211 patients and (17±4)days of patients undergoing portal vein resection and reconstruction. The cost of hospital stay of the 211 patients was (11.7±1.7)ten thousand yuan. (3) Follow-up. Of the 211 patients, 188 patients were followed up for 21(range, 4?36)months. The median survival time of 188 patients was 22 months, and the postoperative 1-, 2- and 3-year survival rate was 90.9%, 43.1% and 18.7%, respectively. Conclusion:LRHCCA is safe and feasible, with satisfactory short-term effect, under the coditions of clinicians with rich experience in laparoscopic surgery and patients with strict surgical evaluation.

The genomic instability may lead to an initiation of cancer in many organisms. Homologous recombination repair (HRR) is vital in maintaining cellular genomic stability. RAD51 associated protein 1 (RAD51AP1), which plays a crucial role in HRR and primarily participates in forming D-loop, was reported as an essential protein for maintaining cellular genomic stability. However, recent studies showed that RAD51AP1 was significantly overexpressed in various cancer types and correlated with poor prognosis. These results suggested that RAD51AP1 may play a significant pro-cancer effect in multiple cancers. The underlying mechanism is still unclear. Cancer stemness-maintaining effects of RAD51AP1 might be considered as the most reliable mechanism. Meanwhile, RAD51AP1 also promoted resistance to radiation therapy and chemotherapy in many cancers. Thus, researches focused on RAD51AP1, and its regulatory molecules may provide new targets for overcoming cancer progression and treatment resistance. Here, we reviewed the latest research on RAD51AP1 in cancers and summarized its differential expression and prognostic implications. In this review, we also outlined the potential mechanisms of its pro-cancer and drug resistance-promoting effects to provide several potential directions for further research.
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Humans ; DNA-Binding Proteins/metabolism* ; RNA-Binding Proteins/metabolism* ; Lung Neoplasms ; DNA Repair ; Genomic Instability ; Rad51 Recombinase/metabolism*

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Objective:To study the safety and therapeutic effects of the modified pancreaticogastrostomy based on the concept of " Hong's one-stitch method" in digestive tract reconstruction in pancreatic surgery.Methods:The clinical data of 44 patients who underwent modified pancreaticogastresstomy at the Department of Hepatobiliary Surgery, the Second Hospital of Hebei Medical University from May 2022 to October 2022 were analyzed retrospectively. There were 23 males and 21 females , with a median age of 54 years old (range 18 to 70 years old). The operation time, intraoperative blood loss, postoperative condition and complications were analysed.Results:All the 44 patients completed the operation successfully. There were 29 patients who underwent laparoscopic pancreaticoduodenectomy, 11 patients laparoscopic duodenum-preserving pancreatic head resection, 1 patient laparoscopic central pancreatectomy, and 3 patients open pancreaticoduodenectomy. The time required for the pancreaticogastrostomy was (15.4±1.0) min in laparoscopic surgery, and (9.1±0.5) min in open surgery. There were 2 patients who developed grade A pancreatic fistula (4.55%, 2/44) and 7 patients gastric emptying disorder (15.91%, 7/44). There were no grade B or C pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, abdominal infection, postoperative bleeding and perioperative death.Conclusion:The modified pancreaticogastrostomy for digestive tract reconstruction in pancreatic surgery was safe and reliable. It effectively reduced the incidence of postoperative pancreatic fistula and improved prognosis of patients.

【Objective】 To investigate the improvement of motor function recovery and the activation of endogenous neural stem cells (eNSCs) via voluntary exercise in mice with hyperlipidemia after intracerebral hemorrhage (ICH). 【Methods】 Four-month-old male Nestin-CreERT2: tdTomato transgenic mice were fed with high-fat diet (HFD) for eight weeks. Type Ⅳ collagenase was micro-injected into the corpus striatum to construct mouse ICH model with the help of stereotaxic apparatus. Voluntary exercise (wheel running) was initiated on the second day after ICH and monitored daily for seven days. Neurological severity score (NSS) and beam walking test were applied to evaluate motor function and coordination. Liver and brain tissues were collected at day 9 after ICH and sliced for staining. Then the Nestin-labeled cells, Ki67⁺, and doublecortin (DCX)⁺ in subventricular zone (SVZ) were counted to evaluate eNSCs activation. 【Results】 ① Compared with those of mice fed by chow diet (CD), the body weight, blood glucose level, concentration of lipid metabolism factors and the number of Nile Red positive cells in liver tissue were significantly higher in HFD-fed mice, confirming hyperlipidemia. ② Compared with the sham group, NSS score increased and the distance of cross-beam walking of ICH mice significantly decreased, showing the deficiency of motor function. It could be rescued by 7-day wheel running, as shown by a lower NSS score and a longer cross-beam walking distance. ③ Compared with the sham group, the number of Nestin⁺/Ki67⁺ cells decreased and Nestin⁺/DCX⁺ cells increased after ICH. After 7-day voluntary exercise, the number of Nestin⁺/Ki67⁺ cells decreased but that of Nestin⁺/DCX⁺ cells further increased significantly. However, compared with ICH, the increase of Nestin⁺/DCX⁺ cells in ICH+Ex was not significant. 【Conclusion】 Short-term voluntary exercise during the acute stage of ICH improved the recovery of motor function and enhance the proliferation of eNSCs in mice with hyperlipidemia. This provides a new idea for further developing ICH accelerated rehabilitation strategy based on eNSCs.