Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. Results Finally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.

Objective To systematically evaluate the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer. Methods PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang, VIP, CNKI and Chinese Biomedical Literature database were searched for literature on the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer published from the establishment to May 2023. Newcastle-Ottawa Scale was used to evaluate the quality of researches, and meta-analysis was performed using RevMan5.4. Results A total of 9 articles were included, involving 3687 patients including 1019 in the McKeown group and 2668 in the Sweet group. NOS score was 8-9 points. There were no statistical differences in the age, sex or American Joint Committee on Cancer stage between the two groups (P>0.05). Patients in the McKeown group had longer operative time and hospital stay, more intraoperative blood loss, and higher Eastern Cooperative Oncology Group scores than those in the Sweet group (P<0.05). However, the McKeown operation could remove more lymph nodes (P=0.001). In terms of safety, the incidences of pulmonary complications [OR=2.20, 95%CI (1.40, 3.46), P=0.001] and postoperative anastomotic leakage [OR=2.06, 95%CI (1.45, 2.92), P=0.001] were higher in the McKeown group than those in the Sweet group. In addition, there were no statistical differences between the two groups in the Karnofsky score, cardiac complications, vocal cord injury or paralysis, chylous leakage, or gastric emptying (P>0.05). Conclusion Compared with McKeown, Sweet method has advantages in operation time, intraoperative blood loss and hospital stay, and has lower incidence of postoperative pulmonary complications and anastomotic leakage. However, McKeown has more lymph node dissection.

Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans ; Thyroid Neoplasms/diagnostic imaging* ; Lymphatic Metastasis/diagnostic imaging* ; Diagnosis, Differential ; Female ; Male ; Middle Aged ; Ultrasonography ; Adult ; Lymph Nodes/pathology* ; Contrast Media ; Neck ; Aged ; Young Adult ; Adolescent ; Sensitivity and Specificity

Objective To evaluate the short-term outcome of robot-assisted thoracoscopic surgery (RATS) for the treatment of posterior mediastinal neurogenic tumour. Methods The clinical data of consecutive patients with mediastinal neurogenic tumors who received RATS treatment completed by the same operator in the Department of Thoracic Surgery, Gansu Provincial People's Hospital from June 2016 to June 2022 were retrospectively analyzed. The tumors were preoperatively localized and evaluated using magnetic resonance imaging or enhanced CT. Results A total of 35 patients were enrolled, including 19 males and 16 females with a mean age of 34.9±7.1 years. All patients successfully completed the resection of posterior mediastinal neurogenic tumors under RATS, and no conversion to thoracotomy occurred during the operation. The average operative time was 62.3±18.0 min, docking time was 10.3±2.6 min, intraoperative bleeding was 33.9±21.6 mL, postoperative 24-hour chest drainage was 69.0±28.9 mL, postoperative chest drainage time was 2.0 (1.0, 3.0) d and the postoperative hospital stay was 3.0 (2.0, 4.0) d. Postoperative complications occurred in 3 patients, including 2 patients with transient Honor syndrome and 1 patient with transient anhidrosis of the affected upper limb. Conclusion RATS for posterior mediastinal neurogenic tumours is safe, effective and feasible, and allows the full benefit of the robotic surgical system to be exploited.

Objective:To construct an ensemble machine learning model for predicting the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy and evaluate its application value.Methods:This is a research on predictive model. Clinical data of 421 patients undergoing pancreaticoduodenectomy in the Department of Pancreatic Surgery,Union Hospital, Tongji Medical College,Huazhong University of Science and Technology from June 2020 to May 2023 were retrospectively collected. There were 241 males (57.2%) and 180 females (42.8%) with an age of (59.7±11.0)years (range: 12 to 85 years).The research objects were divided into training set (315 cases) and test set (106 cases) by stratified random sampling in the ratio of 3∶1. Recursive feature elimination is used to screen features,nine machine learning algorithms are used to model,three groups of models with better fitting ability are selected,and the ensemble model was constructed by Stacking algorithm for model fusion. The model performance was evaluated by various indexes,and the interpretability of the optimal model was analyzed by Shapley Additive Explanations(SHAP) method. The patients in the test set were divided into different risk groups according to the prediction probability (P) of the alternative pancreatic fistula risk score system (a-FRS). The a-FRS score was validated and the predictive efficacy of the model was compared.Results:Among 421 patients,CR-POPF occurred in 84 cases (20.0%). In the test set,the Stacking ensemble model performs best,with the area under the curve (AUC) of the subject′s work characteristic curve being 0.823,the accuracy being 0.83,the F1 score being 0.63,and the Brier score being 0.097. SHAP summary map showed that the top 9 factors affecting CR-POPF after pancreaticoduodenectomy were pancreatic duct diameter,CT value ratio,postoperative serum amylase,IL-6,body mass index,operative time,albumin difference before and after surgery,procalcitonin and IL-10. The effects of each feature on the occurrence of CR-POPF after pancreaticoduodenectomy showed a complex nonlinear relationship. The risk of CR-POPF increased when pancreatic duct diameter<3.5 mm,CT value ratio<0.95,postoperative serum amylase concentration>150 U/L,IL-6 level>280 ng/L,operative time>350 minutes,and albumin decreased by more than 10 g/L. The AUC of a-FRS in the test set was 0.668,and the prediction performance of a-FRS was lower than that of the Stacking ensemble machine learning model.Conclusion:The ensemble machine learning model constructed in this study can predict the occurrence of CR-POPF after pancreaticoduodenectomy,and has the potential to be a tool for personalized diagnosis and treatment after pancreaticoduodenectomy.

The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Objective:To construct an ensemble machine learning model for predicting the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy and evaluate its application value.Methods:This is a research on predictive model. Clinical data of 421 patients undergoing pancreaticoduodenectomy in the Department of Pancreatic Surgery,Union Hospital, Tongji Medical College,Huazhong University of Science and Technology from June 2020 to May 2023 were retrospectively collected. There were 241 males (57.2%) and 180 females (42.8%) with an age of (59.7±11.0)years (range: 12 to 85 years).The research objects were divided into training set (315 cases) and test set (106 cases) by stratified random sampling in the ratio of 3∶1. Recursive feature elimination is used to screen features,nine machine learning algorithms are used to model,three groups of models with better fitting ability are selected,and the ensemble model was constructed by Stacking algorithm for model fusion. The model performance was evaluated by various indexes,and the interpretability of the optimal model was analyzed by Shapley Additive Explanations(SHAP) method. The patients in the test set were divided into different risk groups according to the prediction probability (P) of the alternative pancreatic fistula risk score system (a-FRS). The a-FRS score was validated and the predictive efficacy of the model was compared.Results:Among 421 patients,CR-POPF occurred in 84 cases (20.0%). In the test set,the Stacking ensemble model performs best,with the area under the curve (AUC) of the subject′s work characteristic curve being 0.823,the accuracy being 0.83,the F1 score being 0.63,and the Brier score being 0.097. SHAP summary map showed that the top 9 factors affecting CR-POPF after pancreaticoduodenectomy were pancreatic duct diameter,CT value ratio,postoperative serum amylase,IL-6,body mass index,operative time,albumin difference before and after surgery,procalcitonin and IL-10. The effects of each feature on the occurrence of CR-POPF after pancreaticoduodenectomy showed a complex nonlinear relationship. The risk of CR-POPF increased when pancreatic duct diameter<3.5 mm,CT value ratio<0.95,postoperative serum amylase concentration>150 U/L,IL-6 level>280 ng/L,operative time>350 minutes,and albumin decreased by more than 10 g/L. The AUC of a-FRS in the test set was 0.668,and the prediction performance of a-FRS was lower than that of the Stacking ensemble machine learning model.Conclusion:The ensemble machine learning model constructed in this study can predict the occurrence of CR-POPF after pancreaticoduodenectomy,and has the potential to be a tool for personalized diagnosis and treatment after pancreaticoduodenectomy.

Intestinal dysbiosis and disrupted bile acid(BA)homeostasis are associated with obesity,but the precise mechanisms remain insufficiently explored.Hepatic protein phosphatase 1 regulatory subunit 3G(PPP1R3G)plays a pivotal role in regulating glycolipid metabolism;nevertheless,its obesity-combatting potency remains unclear.In this study,a substantial reduction was observed in serum PPP1R3G levels in high-body mass index(BMI)and high-fat diet(HFD)-exposed mice,establishing a positive correlation between PPP1R3G and non-12α-hydroxylated(non-12-OH)BA content.Additionally,hepatocyte-specific overexpression of Ppp1r3g(PPP1R3G HOE)mitigated HFD-induced obesity as evidenced by reduced weight,fat mass,and an improved serum lipid profile;hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology.PPP1R3G HOE considerably impacted systemic BA homeostasis,which notably increased the non-12-OH BAs ratio,particularly lithocholic acid(LCA).16S ribosomal DNA(16S rDNA)sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population,and elevating the relative abundance of Blautia,which exhibited a positive correlation with serum LCA levels.A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent.Mechanistically,PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase(CYP7A1)and sterol-12α-hydroxylase(CYP8B1),and concurrently upregulated oxysterol 7-α hydroxylase and Takeda G protein-coupled BA receptor 5(TGR5)expression under HFD conditions.Furthermore,LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels.These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis,which may serve as potential ther-apeutic targets for obesity-related disorders.

Objective:To evaluate the clinical efficacy of biplane osteotomy in the treatment of malunion of Stephens-Sanders type Ⅱ calcaneal fracture.Methods:A retrospective study was conducted to analyze the clinical data of 31 patients who had been treated by biplane osteotomy at Sports Medicine Center, The First Affiliated Hospital of Army Medical University for malunion of Stephens-Sanders type Ⅱ calcaneal fracture from January 2019 to January 2022. There were 21 males and 10 females, with an age of (41.4±13.9) years and a duration from injury to diagnosis of (12.8±8.9) months. Functional and image scores were compared before surgery, 6 months after surgery, and at the last follow-up. Functional scores included the visual analogue scale (VAS) score, the American Orthopedic Foot and Ankle Society (AOFAS) score, and the pain interference (PI) and physical function (PF) indices in the Patient-Reported Outcomes Measurement Information System (PROMIS). Image scores included the Gissane angle, B?hler's angle, calcaneal pitch angle, length of the calcaneus, absolute foot height, and axial calcaneal width as measured on X-rays.Results:The operation time was (106.6±29.9) minutes for this cohort. All the 31 patients were followed up for (18.4±5.8) months. At 6 months after surgery and the last follow-up, the VAS scores [3 (2, 3), 2 (1, 3)], AOFAS scores [83 (76, 87), 85 (83, 87)], PI scores [(57±9), (48±6)], PF scores [53 (39, 61), 56 (54, 66)], Gissane angles (109.6°±14.1°, 109.3°±14.9°), B?hler angles (26.5°±11.6°, 26.9°±11.8°), calcaneal pitch angles [19.1° (14.5°, 23.9°), 19.9° (14.5°, 23.9°)], absolute foot heights [(76.5±9.6) mm, (76.0±9.9) mm], and axial calcaneal widths [(38.5±4.1) mm, (38.3±4.1) mm] were all significantly improved compared to the preoperative values [5 (4, 6), 62 (56, 67), (62±6), 47 (38, 51), 126.8°±13.1°, 11.8°±10.9°, 13.8° (8.2°, 18.7°), (71.0±9.1) mm, (42.8±5.5) mm] (all P<0.05). However, there was no statistically significant difference in the length of the calcaneus among pre-surgery, 6 months after surgery, and the last follow-up ( P>0.05). Conclusion:Biplane osteotomy is a surgical technique that demonstrates good clinical efficacy in the treatment of malunion of Stephens-Sanders type Ⅱ calcaneal fracture so that it should be promoted in clinic.

Objective:To investigate the clinical efficacy of hip arthroscopy in the treatment of acetabular labral injury combined with cysts.Methods:A total of 14 patients (5 males and 9 females) aged 35.46±12.62 years (range, 26-57 years) with acetabular labral injury complicated with cyst who underwent hip arthroscopy in Department of Sports Injury and Arthroscopy, Tianjin Hospital from January 2017 to April 2022 were retrospectively analyzed. There were 8 cases of left hip and 6 cases of right hip with an average body mass index of 24.35±3.14 kg/m 2 (range, 20.2-28.4 kg/m 2). The duration of symptoms was 6.25±4.39 months (range, 3-11 months). All patients underwent hip arthroscopic cyst cleaning and glenoid labral suturing. The femoral neck α angle, lateral center rim angle, visual analogue score (VAS), Harris hip score (HHS), and international hip outcome tool scores (iHOT-12) were compared before and after operation. Results:All patients successfully completed the operation and were followed up for 10.23±2.45 months (range, 1.5-18 months). The difference between the patients' hip VAS before and after operation was statistically significant ( F=108.47, P<0.001). The VAS score at 18 months after operation was 1.34±0.83, which was significantly lower than that before operation 7.85±1.12 and at 6 weeks after operation 5.03±1.60 ( P<0.05). The difference between the patients' hip HHS scores before and after operation was statistically significant ( F=96.89, P<0.001). The HHS score at 18 months after operation was 85.58±4.65, which was significantly higher than that before operation 54.36±2.31 and 6 weeks after operation 61.12±1.20 ( P<0.05). The differences of iHOT-12 scores before and after operation were statistically significant ( F=117.92, P<0.001). The iHOT-12 score of 18 months after operation was 78.36±2.28 points, which was higher than that before operation 31.39±5.21 points and 6 weeks after operation 47.88±2.20 points, and the difference was statistically significant ( P<0.05). The difference of α angle of femoral neck before and after operation was statistically significant ( F=101.56, P<0.001). The α angle of femoral neck at 12 months after operation was 45.32°±3.16°, which was significantly lower than that before operation 50.86°±8.41° ( P<0.05). The difference of lateral center rim angle before and after operation was statistically significant ( F=100.38, P<0.001). The lateral center rim angle was 28.23°±5.32° at 12 months after operation, which was smaller than that before operation 32.16°±5.13°, and the difference was statistically significant ( P<0.05). Conclusion:Hip arthroscopy in the treatment of acetabular labral injury with cysts can relieve hip pain and improve hip function.