OBJECTIVE To provide reference for optimizing or formulating unified evaluation methods for evidence and recommendation in expert consensus on off-label use of drugs. METHODS Retrieved from CNKI， Wanfang data， VIP， CBM， PubMed and Web of Science， Chinese expert consensuses on off-label use of drugs involving evaluation methods for evidence and recommendations were collected from the inception to August 1， 2024. After screening the literature and extracting relevant data， descriptive statistical analysis was conducted. RESULTS & CONCLUSIONS Among the 32 articles included， 14 articles （43.8%） used Micromedex’s Thomson grading system， only 7 articles （21.9%） considered economic factors when forming recommendations， 10 articles （31.3%） reported the conflicts of interest； only 2 articles （6.3%） involved experts in the field of evidence-based medicine methodology. There were differences in the sources of evidence， factors considered in forming recommendations， and the grading standards for evidence and recommendations among different expert consensus evidence evaluation methods. There were also differences in evidence levels and recommendation strength of the same drug off-label use in different expert consensus. It is recommended that in future consensus-building processes， greater attention should be paid to potential conflicts of interest among participants， collaboration with methodological experts should be enhanced， and efforts should be expedited to establish unified standards for evaluating evidence and recommendation methodologies.

BACKGROUND:There is still no consensus on the optimal internal fixation for the treatment of Pauwels Ⅲ femoral neck fracture,and most of the related finite element analyses have been performed using a single simplified loading condition,and the biomechanical properties of commonly used internal fixation devices need to be further investigated. OBJECTIVE:To analyze the biomechanical characteristics of Pauwels Ⅲ femoral neck fractures treated with cannulated compression screw,dynamic hip screw,and femoral neck system by finite element method under different loading conditions of single-leg standing loads and sideways fall loads. METHODS:The DICOM data of healthy adult femur were obtained by CT scanning,imported into Mimics 15.0 software to obtain the rough model of bone tissue.The data exported from Mimics were optimized by Geomagics software,and then three internal fixation models were built and assembled with the femur model according to the parameters of the clinical application of the cannulated compression screw,dynamic hip screw,and femoral neck system by using Pro/E software.Finally,the three internal fixation models were imported into Ansys software for loading and calculation to analyze the stress distribution and displacement of the femur and the internal fixation under different working conditions of single-leg standing loads and sideways fall loads,as well as the stress characteristics of the calcar femorale and Ward's triangle. RESULTS AND CONCLUSION:(1)Under the single-leg standing load and the sideways fall load,the proximal femoral stress of the three internal fixation models was mainly distributed above the fracture end of the femoral neck.The peak stress of the proximal femoral end,fracture end,Ward triangle,and calcar femorale of the three internal fixation models were the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(2)Under the single-leg standing load and the sideways fall load,the peak displacement of the proximal femur of the three internal fixation models was all located at the top of the femoral head,and the peak displacement was the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(3)The peak displacement of the three internal fixation models was all located at the top of the internal fixation device under the single-leg standing and sideways fall loading conditions,and the peak displacement values were the smallest in the femoral neck system internal fixation model and the largest in the cannulated compression screw internal fixation model.(4)The internal fixation stress of the three internal fixation models was mainly distributed in the area near the fracture end of the internal fixation device under the single-leg standing and sideways fall loads,and the peak value of internal fixation stress was the smallest in the femoral neck system model and the largest in the cannulated compression screw model.(5)These results suggest that the mechanical stability of the femoral neck system is the best,but there may be a risk of stress shielding of the fracture end and calcar femorale.The stress of the internal fixation device of the femoral neck system is more dispersed,and the risk of internal fixation break is lower.

BACKGROUND:Currently,exercise therapy is an effective non-pharmacological treatment for low back pain,and exercise therapy can maintain lumbar spine stabilization through mechanical-chemical coupling between bones and muscles,but there is no clear description of the research progress and optimal treatment protocols for exercise therapy to relieve chronic non-specific lower back pain through mechanical-chemical coupling. OBJECTIVE:To review the research progress related to the influence of paravertebral muscles on lumbar spine stabilization during exercise therapy through mechanical-chemical coupling,which in turn relieves chronic non-specific lower back pain,as well as the current optimal treatment protocols of exercise therapy for chronic non-specific lower back pain. METHODS:Literature searches were performed in WanFang database,CNKI,VIP,Web of Science,and PubMed database,with search terms of"chronic non-specific low back pain,lumbar spine stabilization,paravertebral muscles,exercise therapy"in Chinese and English.Relevant literature published from database inception to January 2024 was searched and 93 articles were included for final summarization. RESULTS AND CONCLUSION:Exercise therapy can act on the paravertebral muscles and bones through appropriate mechanical stimulation and produce corresponding changes.Exercise therapy is an important intervention for chronic non-specific lower back pain as it improves the quality of the paravertebral muscles,primarily through mechanical-chemical coupling,and thus maintains lumbar spine stabilization for better relief of chronic non-specific lower back pain.However,there are no clear reports on the exact effective protocols for exercise therapy to treat chronic non-specific lower back pain through lumbar spine stabilization.The development of an individualized exercise program is particularly important for the treatment and prognosis of chronic non-specific low back pain.Muscle mass and bone mass of the same individual are closely related,and imaging assessment of paravertebral muscle mass and quantity is important for disease detection and intervention.

This study aims to establish a multiplex TaqMan fluorescence quantitative PCR(qPCR)assay for Pasteurella multocida(P.multocida).Specific primers and fluorescent labeling probes were designed based on the sequences of five podoplanar genes of P.multocida hyaC-hyaD,bcbD,dcbF,ecbJ,and fcbD in the NCBI database.We adjusted the annealing temperature by gradient setting,optimized the primer and probe concentrations by matrix method,constructed standard curves,and performed specificity,sensitivity and reproducibility tests,and finally established mul-tiplexed TaqMan qPCR assays for these five genes.The results showed that the established assay had a good linear relationship between the amplification curves.The sensitivity of this method was high,10-100 times higher than that of ordinary PCR;the specificity was strong,and there was no amplification curve in the DNA detection of eight pathogenic bacteria such as Bacillus,Proteus mirabilis,Staphylococcus aureus,and Rhizoctonia rad iodurans.This assay had a good linear rela-tionship,and the coefficients of variation for Ct values of the inter-and intra-group reproducibility tests were all less than 3％,and the detection rate of this assay was 11.25％higher than the con-ventional PCR assay through the detection of 90 clinical samples.The method established in this study is able to detect P.multocida rapidly and sensitively,which is important for its rapid clinical and laboratory diagnosis.

Indocyanine Green/therapeutic use* ; Photochemotherapy ; Combined Modality Therapy ; Anti-Infective Agents

Objective:To analyze the relevant factors of bacteriological diagnosis rate in pulmonary tuberculosis in Zhejiang Province, and to provide basis for the control of tuberculosis.Methods:The results of etiology detection of pulmonary tuberculosis in Zhejiang Province from 2015 to 2020 were collected from the China Tuberculosis Information Management System. Positive detection of etiology of pulmonary tuberculosis cases was analyzed. Joinpoint regression model was constructed to evaluate the annual trend of the positive rate of etiology, and linear regression model was used to analyze the influence of new diagnostic technology on the positive detection rate of etiology in smear-negative pulmonary tuberculosis cases.Results:From 2015 to 2020, the positive rate of etiology of pulmonary tuberculosis in Zhejiang Province increased from 38.66%(10 588/27 385) to 64.12%(14 275/22 262), with an average annual growth rate of 8.80%. All of the 11 prefecture cities in Zhejiang Province showed an increasing trend of the positive rate of etiology. The average annual growth rates in Wenzhou City and Lishui City were 10.27% and 11.21%, respectively, and the positive rates of etiology in Jinhua City and Lishui City were 70.13%(2 007/2 862) and 73.34%(707/964) in 2020, respectively. From 2015 to 2020, smear-negative cases accounted for 61.66%(92 935/150 733) in Zhejiang Province, and the further detection rate by culture and molecular test increased from 0.13%(22/16 650) to 84.74%(11 384/13 434). The positive rate of bacteriological tests in smear-negative pulmonary tuberculosis patients increased from 0.04%(6/16 650) to 41.28%(5 546/13 434). If the culture and molecular detection rate increased to 100.00%, the linear regression model predicted positive rate of etiology could increase to 44.20%. Thus, the positive rate of etiology of pulmonary tuberculosis in Zhejiang Province would reach 66.00%. Up to 2020, 95.56%(86/90) and 92.22%(83/90) of tuberculosis designated hospitals were equipped with molecular and liquid diagnostic equipments, respectively, and the detection positive rates of molecular and liquid diagnostics in the etiology positive pulmonary tuberculosis cases were 71.24%(10 169/14 275) and 53.44%(7 629/14 275), respectively.Conclusions:The implementation and promotion of the new diagnostic techniques for tuberculosis, especially the molecular diagnostic techniques, could significantly improve the positive rate of etiology of pulmonary tuberculosis etiology. Methods and strategies of etiological diagnosis of tuberculosis should be paid more attention in prevention and control of tuberculosis.

The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.

Abstract: Objective ， To explore the effects of lead exposure on copper level copper transporter protein expression and Methods oxidative stress in mouse cerebral cortex. The specific pathogen free adult male C57BL/6 mice were randomly ， - - - divided into control group low lead exposure group and high lead exposure group with 10 mice in each group. The mice in low - ， and high lead exposure groups were respectively given 250 and 500 mg/L lead acetate in drinking water every day and the mice - ， in the control group were given double distilled water for 12 weeks. Twenty four hours after exposure Morris water maze and ， elevated cross maze were used to test the neurobehavioral function of mice. The cerebral cortex of mice was isolated and the levels of lead and copper were detected by inductively coupled plasma mass spectrometry. The activities of glutathione （ - ）， （ ） （ ） peroxidase GSH Px catalase CAT and malondialdehyde MDA were detected by histochemical method. The relative （ ） ， ， expression levels of copper transporter such as synthesis of cytochrome C oxidase SCO 1 SCO 2 and cytochrome C oxidase （ ） Results - - assembly protein 11 COX11 were detected by western blot. The escape latencies of mice in the low and high lead （ P ）， ， - exposure groups were prolonged all <0.05 while the number of crossing the platform the percentage of open arm entry - （ P ） times and the percentage of open arm retention time decreased all <0.05 compared with the control group. Mice in both the - - （ P ）， - low and high lead exposure groups increased levels of lead and copper in the cerebral cortex all <0.05 decreased GSH Px （ P ）， （ P ） and CAT activity all <0.05 and increased SCO1 relative expression all <0.05 compared with the control group. Mice in - （P ）， - the high lead exposure group showed prolonged escape latency <0.05 reduced GSH Px and CAT activities in the cerebral （ P ）， （ P ） - cortex all <0.05 increased MDA level and relative expression of SCO1 and SCO2 all <0.05 compared to mice in the low Conclusion - lead exposure group. Lead exposure increased the expression of copper and copper transport related proteins in mouse cerebral cortex and induced oxidative stress leading to central nervous system damage resulting in neurobehavioral abnormalities in mice.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective:To evaluate the outcomes of posterior-column dominating three-column tibial plateau fractures treated by raft-nailing and cannulated screwing via the posteromedian approach.Methods:From October 2017 to June 2019, 15 patients with posterior-column dominating three-column tibial plateau fracture were surgically treated at Department of Orthopedics, The First Affiliated Hospital to Harbin Medical University. They are 11 males and 4 females, aged from 26 to 65 years (average, 41.2 years). All patients were operated on under general anesthesia or spinal anesthesia. After full exposure via the posteromedian approach using a popliteal S-shaped incision, their fractures were treated with raft-nailing and cannulated screwing. Wound healing and neurovascular injury were observed after operation. X-ray films were taken regularly to monitor fracture union and measure the tibial plateau angle (TPA) and posterior slope angle (PA) of the tibial plateau. The knee function was assessed using The Hospital for Special Surgery (HSS) scoring system at 12 months after operation.Results:Incisions healed by the first intention after surgery in 14 patients but the healing was delayed due to fat liquefaction in one patient. No symptoms of neurovascular injury were observed in the 15 patients who were followed up for 12 to 29 months (average, 16.5 months). All fractures united after 12 to 20 weeks (average, 15.4 weeks). At 3 days and 12 months after operation, respectively, their PA was 9.3°±2.1° and 9.7°±1.6° and their TPA 4.3°±1.2° and 4.1°±1.1°, showing no significant difference ( P>0.05). At 12 months after operation, their HSS scores ranged from 84 to 95 (average, 89.3), their knee flexion from 105° to 138° (average, 126.5°) and their knee extension from 0° to 8° (average, 3.4°). Conclusions:In the treatment of posterior-column dominating three-column tibial plateau fractures, raft-nailing combined with cannulated screwing via the posteromedian approach can achieve not only full exposure by a single incision but also stable plateau fixation, reduce operative invasion, and simplify operative procedures, leading to fine surgical outcomes.