OBJECTIVE To exc avate and evaluate the adverse reaction signals of 4 kinds of imported programmed cell death 1 （PD-1）and its ligand （PD-L1）inhibitors，and to guide rational drug use in clinic. METHODS OpenVigil 2.1 software was used to obtain the adverse event reports of four drugs as nivolumab ，pembrolizumab，atezolizumab and durvalumab from the first quarter of 2013 to the fourth quarter of 2020 in the US FDA adverse event reporting system. The reporting odds ratio and proportional reporting ratio were used for signal mining to evaluate new or potential adverse reaction signals. RESULTS A total of 46 840 reports of adverse events with PD- 1/PD-L1 inhibitors as the primary suspected drug were collected ，including 28 896 reports of nivolumab，13 298 reports of pembrolizumab ，3 398 reports of atezolizumab ，and 1 248 reports of durvalumab. From the general characteristics of these reports ，the gender distribution was more men than women ，and the age distribution was mainly in the range of 51-85 years old. The reporting year was mainly in the nearly 4-5 years，and the main reporting countries were the US and Japan，with“death”and“hospitalization or prolonged hospitalization ”as the main serious adverse events which were over 50％ of the whole of 4 kinds of adverse events. A total of 1 597 adverse reaction signals were obtained ，involving 26 systems，focusing on “benign，malignant and unspecified neoplasms （cystic and polypoid tumor ）”，“infections and infestations ”and“investigations”， etc. The analysis of the top 50 adverse reaction signals showed that the largest number of report was endocrine system disease ，the most frequency signal was “malignant neoplasm progression ”and the strongest adverse reaction signal was “radiation pneumonitis ”. And it was also found that 13 adverse reaction signals ，such as “radiation pneumonitis ”“cholangitis”“fulminant type 1 diabetes mellitus” “blood creatine phosphokinase increased ” “disseminated intravascular coagulation ”“cardiac failure ”and “cerebral infarction ”，etc.，were not reported in the drug instructions. CONCLUSIONS PD-1/PD-L1 inhibitors mediate a large number of adverse reaction signals，resulting in high safety risks in “benign，malignant and unspecified neoplasms （cystic and polypoid tumor ）”，“infections and infestations ”and “investigations”，etc. The newly discovered 13 adverse reaction signals ，such as “radiation pneumonitis ”“cholangitis”“blood creatine phosphokinase increased ”“cardiac failure ”and“cerebral infarction ”are of great significance for guiding rational drug use in clinic.

BACKGROUND: Chronic obstructive pulmonary diseases (COPD) affects 45%-63% of lung cancer patients worldwide. Lung cancer patients complicated with COPD have decreased cardiopulmonary function and increased perioperative risk, and their postoperative exercise endurance and lung function are significantly lower than those with conventional lung cancer. Previous studies have shown that postoperative exercise training can improve the exercise endurance of unselected lung cancer patients, but it is unclear whether lung cancer patients with COPD can also benefit from postoperative exercise training. This study intends to explore the effects of postoperative exercise training on exercise endurance, daily activity and lung function of lung cancer patients with COPD. METHODS: Seventy-four patients with non-small cell lung cancer (NSCLC) complicated with COPD who underwent pneumonectomy in the lung cancer center of West China Hospital of Sichuan University from August 5, 2020 to August 25, 2021 were prospectively analyzed. They were randomly divided into exercise group and control group; The patients in the two groups received routine postoperative rehabilitation in the first week after operation, and the control group was given routine nursing from the second week. On this basis, the exercise group received postoperative exercise rehabilitation training for two weeks. Baseline evaluation was performed 3 days before operation and endpoint evaluation was performed 3 weeks after operation. RESULTS: The exercise endurance, daily activity and pulmonary function test results of the two groups decreased from baseline to the end point. However, after the operation and intervention program, the maximum oxygen consumption of Cardiopulmonary Exercise Test and the walking distance of 6-Minute Walking Test in the exercise group were significantly better than those in the control group [(13.09±1.46) mL/kg/min vs (11.89±1.38) mL/kg/min, P=0.033; (297±46) m vs (243±43) m, P=0.041]. The average number of we-chat steps in the exercise group was also significantly better than that in the control group (4,381±397 vs 3,478±342, P=0.035). Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in the exercise group were better than those in the control group, but the difference did not reach a statistically significant level [(1.76±0.19) L vs (1.60±0.28) L, P=0.084; (1.01±0.17) L vs (0.96±0.21) L, P=0.467]. CONCLUSIONS Postoperative exercise rehabilitation training can improve exercise endurance and daily activity ability of patients with lung cancer complicated with COPD and promote postoperative rehabilitation.
Carcinoma, Non-Small-Cell Lung/surgery* ; Exercise ; Forced Expiratory Volume ; Humans ; Lung Neoplasms/surgery* ; Pulmonary Disease, Chronic Obstructive/complications*

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective: To investigate the current status and influencing factors of occupational stress among couriers. Methods: Couriers (n=925) were selected on this study used cluster sampling method from January to March 2018. They were from SF and Zhongtong Express Co., Ltd., on the Wechat platform, and surveyed by a job stress questionnaire based on a job demand-control model.Valid questionnaires(n=617) were obtained. Results: A total of 418 workers were occupational stress positive (67.7%). The results of Chi-square analysis showed that there were significant differences in occupational stress among workers categorized by job position, working years, mealtime, sleeping time, and weekly work time (P<0.05). The multivariate logistic analysis indicated that non-regular meals, short-term sleep and less than 0.5 working years were risk factors for occupational stress(P<0.05). Conclusion Couriers generally have occupational stress. The main influencing factors are job position, working years mealtime, sleeping time, and weekly work time. It is necessary to guide healthy lifestyle, rationally organize labor and assign tasks, and improve working environment to relieve their occupational stress.

Objective To explore the relationship between ulcerative colitis (UC) susceptibility and tumor necrosis factor superfamily member (TNFSF) 15 gene polymorphisms and haplotypes in Han nationality in Zhejiang province of China. Methods A total of 408 UC patients and 574 healthy controls were recruited in this study. Three single nucleotide polymorphisms of TNFSF15 (rs3810936, rs4263839, rs4979462) were examined by improved multiple ligase detection reaction (iMLDR) technique. Analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 software in all study subjects. Results The variant allele A and genotype (GA+AA) of rs4263839 were less frequent in UC patients than in controls (45.34% vs. 50.17%, P=0.035; 68.38% vs. 76.66%, P=0.004). According to the severity and location of disease, UC patients were divided into different subgroups. After multiple comparison correction (α=0.012 5), the frequencies of variant allele A and genotype (GA+AA) of rs4263839 were lower in patients with severe UC than in the controls (37.69% vs. 50.17%, P=0.007;60.00% vs. 76.66%, P=0.004). Similar findings were also drawn for patients with extensive colitis in contrast with the controls (42.22% vs. 50.17%, P=0.009; 63.33% vs. 76.66%, P<0.001). Furthermore, the haplotype analysis indicated that three SNPs above were in a strong LD. The frequency of haplotype TAC was lower in UC patients than in the controls (40.83% vs. 46.04%, P=0.023). Also it was less prevalent in patients with severe UC and patients with extensive colitis when compared with controls respectively (33.38% vs. 46.04%, P=0.005;37.22% vs. 46.04%, P=0.003). Conclusions TNFSF15 (rs4263839) variation might not only reduce the risk of UC, but also affect the severity and lesion location of UC. The haplotype TAC formed by rs3810936, rs4263839 and rs4979462 might be related to a lower risk of UC, especially in patients with severe colitis or patients with extensive colitis.

Objective To investigate the curative effect of complete ablation and partial ablation of parathyroid for secondary hyperparathyroidism (SHPT) by using ultrasound-guided radiofrequency ablation (RFA) or microwave ablation (MWA). Methods A total of 26 patients with hyperparathyroidism secondary to uremia, who were admitted to authors’ hospital during the period from October 2012 to September 2013 to receive full ablation (n=11) or partial ablation (n=15) of parathyroid with MWA or RFA and were followed up for at least 9 months after the treatment, were included in this study. The clinical data were retrospectively analyzed. The therapeutic effect and the influence of MWA and RFA on the serum calcium levels were compared between the two ablation methods. Results Analysis of parathyroid hormone (PTH) levels indicated that in full ablation group the postoperative PTH level was gradually decreased , when compared with the preoperative level, until it became stable and maintained the normal level, and no recurrence was observed;in partial ablation group the postoperative PTH level was decreased first with a subsequent rebound about nine months after the treatment, and this PTH level was higher than the PTH level of full ablation group as well as higher than the normal level (P<0.05). On the 15 patients of partial ablation group, recurrence was seen in 5. Analysis of serum calcium levels showed that the postoperative serum calcium level was decreased in both groups, but in partial ablation group the serum calcium levels determined at 3 and 9 months after the treatment were higher than those in full ablation group (P<0.05). In 11 patients of full ablation group, hypocalcemia occurred in 4. Conclusion In treating SHPT, full ablation of parathyroid is not likely to have postoperative relapse, but it might carry the risk of hypocalcemia; while partial ablation of parathyroid is likely to have postoperative relapse, but the serum calcium level can be well controlled. Considering from the view that controlling of the serum calcium level is clinically very important, partial ablation of parathyroid may be more suitable for clinical purpose.

Objective To compare the effect and toxicity of domestic idarubicin (IDA) and imported daunorubicin (DNR) in the treatment of acute leukemia (AL).Methods According to the random number table method,68 patients were randomly divided in IDA group with 35 patients and DNR group with 33 patients.In IDA group,the patients with acute myelocytic leukemia were treated following IA scheme (domestic idataubicin plus cytosine arabinoside) and the patients with acute lymphoblastic leukemia were treated following VICLP scheme (vincristine,domestic idataubicin,cyclophosphamide,lasparaginase and prednisone).In DNR group,the patients with acute myelocytic leukemia were treated following DA scheme (imported daunorubicin plus cytosine arabinoside) and the patients with acute lymphoblastic leukemia were treated following VDCLP scheme (vincristine,imported daunorubicin,cyclophosphamide,lasparaginase and prednisone).Results In IDA group,21 patients achieved a complete remission(CR),5 patients achieved a partial remission(PR),with a 74.2 ％ (26/35) remission rate (RR).In DNR group,the remission rate was 62.3 ％ (20/33).No differences of the remission rate was found between the two groups (t =0.89,P =0.50).17 patients were found remission over one year in IDA group,and 6 patients were in DNR group.The difference was statistically significant between the two groups (x2 =5.56,P =0.02).Conclusion IDA is more effective than DNR in AL treatment.The higher RR and longer remission time are found in IDA group than DNR group.IDA is effective and safe in the treatment of AL.

Objective To investigate the osteogenesis capability of different frequency extracorporeal shock wave.Methods 39 rabbits received different frequency extracorporeal shock wave at the middle potion of tibia for 3 or 7 days,these rabbits were then sac rificed and the tibia bones were collected to process for HE and toluidine blue staining,the pathological changes were observed under the light microscope.Results After different frequency extracorporeal shock wave treatment,the typical periosteal reaction were observed,external periosteum bleeded and thickened but there was no reaction at internal periosteum,marrow cavity opened and fibrosed.the osteoblast-1iking cell proliferated,however,no cartilage cells were observed;The rabbits received 7 days shock wave treatment showed more severe reaction than those for 3 days.The shock wave at lower frequency showed more severe reaction than higher frequency.Conclusion shock wave induced osteogenesis through the periosteal reaction of external periosteum;the osteogenesis capability of different frequency extracorporeal shock wave were affected by the frequency.Higher frequency of shock wave was not the ideal way to promote osteogenesis.

Objective To summarize the clinical effect of arthroscopic Pridie drilling technique for repairing full-thickness articular chondral defects of the knee.Methods A retrospective study was made on clinical data of 28 patients(29 knees) with full-thickness articular cartilage defects treated with arthroscopic Pridie drilling technique from November 1999 to July 2005 in this hospital.A Kirschner wire 1.0~1.2 mm in diameter was used in the procedure to puncture holes in the subchondral bone plate.Holes were made adjacent to each other as closely as possible,but not to break into neighbouring ones,with normally 2~3 mm apart.The depth of the hole was 3~4 mm.A protected weight-bearing protocol lasting 6~8 weeks and continous passive motion(CPM) were used postoperatively.The Tegner activity levels,the Meyers scores,and the Lysholm knee scores were used for evaluation before and after the operation.Results The surgical outcomes were classified as "excellent" in 19 cases,"good" in 5 cases,and "poor" in 4,with the total effective rate being 85.7%(24/28).The Tegner activity levels were elevated from 1.9?1.2 preoperatively to 4.9?1.9 postoperatively(t=10.912,P=0.001),the Meyers scores from 10.3?1.3 preoperatively to 15.9?2.6 postoperatively (t=10.101,P=0.005),and the Lysholm knee scores from 47.7?12.5 to 83.2?15.4(t=10.302,P=0.003),respectively.Conclusions Arthroscopic Pridie drilling is a simple,safe,mini-invasive,and effective technique, which appears to be a practical surgical option for the treatment of full-thickness articular chondral lesions of the knee.

OBJECTIVETo investigate the effect of rupture and reconstruction of the anterior cruciate ligament (ACL) on the degeneration of rabbit knee articular cartilage.

METHODS14 mature New Zealand white rabbits were divided into four groups. In group I, the ACL of the right knees in 7 rabbits was resected and immediately reconstructed, and the contralateral ACL was resected only in controll f group I. In group II, the ACL of the right knees in 7 rabbits was reconstructed 3 weeks after the ACL was resected and the contralateral joints in control group II, in which only a medial arthrotomy was performed. The rabbits were killed 8 weeks after the operation. The methods of ink straining, histology and SEM were used to analyze the changes in articular cartilage of the joints.

RESULTSThe results of ink method and HE straining were analyzed quantitatively. The degeneration of knee articular cartilage in group I was significantly weaker than that in control group I (Hc = 5.9889, P = 0.0144). The degeneration of knee articular cartilage in group II was as serious as that in control group I (Hc = 0.7143, P = 0.785).

CONCLUSIONSImmediate reconstruction of the ACL can effectively prevent articular cartilage from degeneration. Once the articular cartilage damaged moderately, delayed reconstruction of the ACL could not effectively reduce the development of degeneration. So once the ACL is ruptured, reconstruction should be performed in the early stage to restore the stability of knee joint to prevent the articular cartilage from degeneration.