Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigate the value of ultrasound and contrast enhanced ultrasound(CEUS)in the differential diagnosis of pancreatic neuroendocrine tumor(PNET)and pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was performed on the clinical data,ultrasound findings,and CEUS findings of 74 patients with PNET and their characteristic manifestations were analyzed and compared with those of 74 patients with PDAC.Data of the two groups were compared using the t-test and x 2 test,or Fisher's exact test.Results There were 18,26,and 30 patients with PNET lesions and 52,8,and 14 patients with PDAC located in the head,body,and tail of the pancreas,respectively.The patients with hypoechoic lesions,regular lesion morphology,clear boundaries,pancreatic duct dilatation or cutoff,and blood flow signal accounted for 86.49％,83.78％,78.38％,18.92％and 32.43％in the PNET group,respectively,whereas in the PDAC group,such patients accounted for 94.59％,29.73％,27.03％,75.68％and 21.62％,respec-tively.There was a significant intergroup differences in lesion location,morphology,boundaries and pancreatic duct dilatation or cutoff(x 2=31.862,x2=44.048,x 2=39.141,and x 2=47.815,respectively,P＜0.05),with no significant differences in hypoechoic and blood flow signal(x2=2.840 and x2=2.193,P＞0.05).Among the 52 patients with PNET,CEUS showed that 38 had hyperenhancement and 14 had iso-enhancement in the arterial phase,whereas 40 had iso-enhancement and 12 had hypoenhancement in the venous phase.CEUS was performed in 74 patients with PDAC;70 patients showed hypoenhancement in the arterial phase and 72 showed hypoenhancement in the venous phase.There were significant differences in the enhancement pattern in the arterial and venous phases between the two groups(x 2=56.582 and x 2=37.852,P＜0.05).Conclusion Ultrasound and CEUS revealed some characteristics of PNET that can be used for the differential diagnosis of PNET and PDAC,when combined with enhancement pattern.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To investigate the value of ultrasound and contrast enhanced ultrasound(CEUS)in the differential diagnosis of pancreatic neuroendocrine tumor(PNET)and pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was performed on the clinical data,ultrasound findings,and CEUS findings of 74 patients with PNET and their characteristic manifestations were analyzed and compared with those of 74 patients with PDAC.Data of the two groups were compared using the t-test and x 2 test,or Fisher's exact test.Results There were 18,26,and 30 patients with PNET lesions and 52,8,and 14 patients with PDAC located in the head,body,and tail of the pancreas,respectively.The patients with hypoechoic lesions,regular lesion morphology,clear boundaries,pancreatic duct dilatation or cutoff,and blood flow signal accounted for 86.49％,83.78％,78.38％,18.92％and 32.43％in the PNET group,respectively,whereas in the PDAC group,such patients accounted for 94.59％,29.73％,27.03％,75.68％and 21.62％,respec-tively.There was a significant intergroup differences in lesion location,morphology,boundaries and pancreatic duct dilatation or cutoff(x 2=31.862,x2=44.048,x 2=39.141,and x 2=47.815,respectively,P＜0.05),with no significant differences in hypoechoic and blood flow signal(x2=2.840 and x2=2.193,P＞0.05).Among the 52 patients with PNET,CEUS showed that 38 had hyperenhancement and 14 had iso-enhancement in the arterial phase,whereas 40 had iso-enhancement and 12 had hypoenhancement in the venous phase.CEUS was performed in 74 patients with PDAC;70 patients showed hypoenhancement in the arterial phase and 72 showed hypoenhancement in the venous phase.There were significant differences in the enhancement pattern in the arterial and venous phases between the two groups(x 2=56.582 and x 2=37.852,P＜0.05).Conclusion Ultrasound and CEUS revealed some characteristics of PNET that can be used for the differential diagnosis of PNET and PDAC,when combined with enhancement pattern.

[摘 要] 目的：研究芳香烃受体（AHR）在乳腺癌中的表达及其对乳腺癌细胞增殖、凋亡和药物敏感性的调控机制。方法：通过GEPIA数据库数据分析乳腺癌组织及癌旁组织中AHR的表达水平，探讨其与患者生存期的关联。利用基因敲低和过表达技术构建AHR表达变化的乳腺癌细胞，采用CCK-8实验、细胞计数和流式细胞分析等方法评估AHR对细胞增殖、凋亡和药物敏感性的影响，通过免疫印迹法验证相关分子机制。此外，利用AHR激动剂6-甲酰基吲哚并[3,2-B]咔唑（FICZ）研究外源性激活AHR对乳腺癌细胞多柔比星（DOX）敏感性的影响。结果：GEPIA数据库数据分析结果显示，乳腺癌组织中AHR呈明显低表达（P < 0.05）；对155例乳腺癌患者的生存期进行统计分析也显示AHR低表达与不良预后呈正相关（P < 0.05）。敲低AHR促进细胞增殖（P < 0.05），过表达则能抑制其增殖（P < 0.05）并促进其凋亡（P < 0.05）。外源激活AHR能增强乳腺癌细胞对DOX的敏感性（P < 0.05）。AHR可与MYC基因启动子结合，抑制MYC表达（P < 0.05），从而影响乳腺癌的进展。结论：AHR在乳腺癌中通过调控MYC表达影响细胞增殖和凋亡，外源激活AHR可能成为提高乳腺癌细胞对DOX敏感性的治疗策略。

Diabetes is a common chronic non-infectious disease. Diabetic patients not only suffer from metabolic disorders, but are also prone to immune deficiencies and are at a higher risk of being infected with human papillomavirus (HPV). Many studies at home and abroad have shown that the HPV infection rate of patients with diabetes is higher than that of non-diabetic patients. Patients with diabetes can benefit from HPV vaccination, and the tolerance is good. HPV vaccination is recommended for diabetic patients. This article reviews the research on diabetes, HPV infection, and HPV vaccine, which will provide references for HPV vaccination in diabetic patients.

Objective To assess the value of 18 F-FDG PET/CT, contrast-enhanced ultrasound, and their combination in the differential diagnosis of benign and malignant pancreatic lesions. Methods A retrospective analysis was performed on patients with pancreatic lesions who underwent 18 F-FDG PET/CT and contrast-enhanced ultrasound who were admitted to Tangshan Gongren Hospital from January 2015 to December 2020. The imaging results were confirmed by pathology examination to evaluate diagnostic sensitivity, specificity, accuracy, positive and negative predictive value. The t -test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. Results There were 83 malignant lesions and 25 benign lesions in 108 patients. The sensitivity, specificity, accuracy, positive and negative predictive value were 86.75%, 80.00%, 85.19%, 93.51% and 64.52% for 18 F-FDG PET/CT; and 69.88%, 76.00%, 71.30%, 90.63% and 43.18% for contrast-enhanced ultrasound, respectively. The two methods differed significantly in sensitivity and accuracy (all P < 0.05), but not in specificity, negative and positive predictive value (all P > 0.05). When combined with the contrast-enhanced ultrasound, 18 F-FDG PET/CT had an increased sensitivity, specificity, accuracy, positive and negative predictive value of 90.36%, 84.00%, 88.89%, 94.94% and 72.41%, respectively, though this was not statistically significant due to the increased signal of blood supply in the lesions. Conclusion 18 F-FDG PET/CT has a better performance than contrast-enhanced ultrasound in the differential diagnosis of benign and malignant pancreatic lesions, and their combination can improve the diagnostic value.

This paper reviews the status quo of recent years’ research on autophagy and damage of chondrocytes in Kashin-Beck disease （KBD） and osteoarthritis （OA）. PI3K/AKT signaling pathway and mTOR regulate the autophagy activity of chondrocytes. PI3K/AKT signaling pathway can promote the proliferation of chondrocytes and cause their damage by inhibiting their autophagy activity. This might play an important role in the occurrence and progression of bone and joint diseases such as KBD and OA， and provide scientific basis for revealing the pathogenesis and treatment plan of them.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.

Chondroitin sulfate (CS) is a sulfurated glycosaminoglycan, a major component of the extracellular matrix, widely distributed in skin, cartilage and vascular tissue. CS plays an important role in the physiological state regulation of articular cartilage, which affects tensile strength and elasticity of tissues by influencing aggrecan. Previous studies have shown that CS sulfate modification may be related to the growth and development disorders of cartilage tissue and the occurrence of osteoarticular diseases. At the same time, CS is also a common joint supplement, often used in the treatment of osteoarthritis and Kashin-Beck disease. In this paper, the research progress of CS sulfate modification characteristics in Kashin-Beck disease and osteoarthritis and the application of the preparation in the treatment of Kashin-Beck disease and osteoarthritis are reviewed, aiming to provide help for the investigation of the etiology of Kashin-Beck disease and the treatment of osteoarthritis and Kashin-Beck disease.