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.

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.

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.

[摘 要] 目的：探讨甲硫氨酸限制对肺腺癌（LUAD）细胞增殖、凋亡及磷酸戊糖途径的影响。方法：将H1299、A549细胞分为Met+组和Met−组，分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d，采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响，PI染色法检测细胞周期分布，Annexin Ⅴ-PE/7AAD标记细胞凋亡，利用DCFH-DA探针检测细胞内ROS水平，WST-8法和DTNB法分别测定细胞内NADPH与GSH含量；通过癌症基因组图谱（TCGA）数据库分析葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）表达与甲硫氨酸代谢通路的关系；采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸（SAM）对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果：甲硫氨酸限制显著抑制H1299和A549细胞增殖（均P < 0.01），将细胞周期阻滞于G2/M期（均P < 0.05），显著升高细胞内总ROS水平（均P < 0.001）并促进细胞凋亡（均P < 0.001）；同时，甲硫氨酸限制显著降低了细胞内NADPH和GSH水平（均P < 0.01），抑制DNA合成（均P < 0.01）。分析TCAG数据发现，G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关（均P < 0.001），甲硫氨酸限制下调G6PD和6PGD蛋白表达（均P < 0.01），而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制（均P < 0.01），提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论：甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖，为甲硫氨酸限制疗法治疗LUAD提供实验依据。

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.

The combination of anti-angiogenesis,immune checkpoint inhibitors(ICIs)and chemotherapy(target-immune-chemo)has achieved initial results in the comprehensive treatment of gastric cancer.Experimental studies have shown that among various determinants of tumor immunotherapy,tumor microenvironment(TME)plays a crucial role in affecting ICIs efficacy.The biological mechanism leading to immunosuppressive TME is multi-factorial and very complex,but one of clear and important mechanisms is the influence of abnormal neoangiogenesis in tumors.The use of low-dose targeted tumor angiogenesis drugs(such as anti-VEGF/VEGFR monoclonal antibody,etc.)is expected to make tumor vessels normalization and reverse immunosuppressive TME to immunesupportive TME,so as to play synergistic,complementary,anti-tumor effects with ICIs and chemotherapy drugs.Perioperative treatment of locally advanced gastric cancer(LAGC)has become an indispensable and important strategy in surgical comprehensive treatment of gastric cancer.In recent years,a therapeutic combination regimen of anti-angiogenesis,ICIs and chemotherapy(target-immune-chemo)has been clinically applied in the perioperative treatment of LAGC,and the preliminary efficacy[pathologic complete response(pCR),major pathological response(MPR),tumor regression grade(TRG)and treatment-related adverse events(TRAEs),etc.]has shown encouraging results.This article reviewed the relevant clinical research results and made a summary and analysis.

AIM:To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction(UUO).METHODS:Eight-week-old male C57BL/6J mice were divided into four groups randomly:sham group,UUO group,UUO+new dosage form of tadalafil(1 mg/kg)group and UUO+original patented drug of tadalafil(5 mg/kg)group.Surgery was performed to create a mouse UUO model,and therapeutic drugs were administered intragastrically for 7 d after modeling.A fully automated biochemi-cal analyzer was used to detect serum creatinine(SCr)levels of each group.Through renal histopathological staining(HE staining,Masson trichrome staining,and immunohistochemistry staining)and Western blot,we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice,as well as its effect on the expression and distribution of fibronectin(FN)and α-smooth muscle actin(α-SMA).RESULTS:Compared with sham group,the SCr levels were significantly increased in mice with renal fibrosis,and renal tubules were dilated and in-filtrated with inflammation.Moreover,the expressions of FN and α-SMA were increased significantly(P<0.05).New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis,im-proved the renal tissue structure on the affected side,reduced collagen fiber deposition,and inhibited FN and α-SMA ex-pression(P<0.05).CONCLUSION:Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral ob-struction.New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness.

Objective:To compare the application differences of disposable drainage double tube laryngeal mask airway (LMA) in gynecological general anesthesia surgery with patients weighing 50-70 kg, and to explore the selection criteria for LMA size suitable for gynecological general anesthesia patients.Methods:A total of 300 patients who underwent general anesthesia gynecological surgery at the Shengjing Hospital of China Medical University from May to November 2023 were selected as the study subjects, weighing 50-70 kg. They were randomly divided into group A (No. 3 laryngeal mask group) and group B (No. 4 laryngeal mask group) according to a random number table method, with 150 patients in each group. Comparisons were made between two groups of patients in terms of the success rate of one tube placement, final tube placement failure rate, tube placement time, fiberoptic bronchoscopy positioning level, airway pressure, mean arterial pressure, heart rate, and postoperative pharyngeal complications (sore throat, hoarseness, dryness, bleeding, etc.) after laryngeal mask insertion.Results:There was a statistically significant difference in the success rate and catheterization time between the two groups of patients (all P<0.05), while there was no statistically significant difference in the final catheterization failure rate, post catheterization airway pressure, mean arterial pressure (MAP), and heart rate (all P>0.05). The proportion of grade 1 fiberoptic bronchoscopy localization in group A (14%, 21/150) was lower than that in group B (26.67%, 40/150), while the proportion and average grade of grade 3 and 4 were higher than those in group B, and the differences were statistically significant (all P<0.05). The total number of postoperative pharyngeal complications in group A was less than that in group B, with statistically significant differences in sore throat and bleeding ( P<0.05), but no statistically significant differences in dry hair, hoarseness, and other discomforts (all P>0.05). Conclusions:In gynecological general anesthesia surgery for patients weighing 50-70 kg, using a No. 3 laryngeal mask is easier to insert than a No. 4 laryngeal mask, with better alignment of the laryngeal mask airway and glottis, and fewer postoperative pharyngeal complications. Therefore, selecting a No. 3 laryngeal mask based on gender criteria is more suitable.

Objective To explore the prescription law of Chinese materia medica for the treatment of epilepsy based on National Patent Database;To provide references for clinical treatment.Methods Patent data on TCM compounds for treating epilepsy that met the inclusion criteria were collected from the establishment of the Chinese Patent Publication Announcement Network until August 21,2023.Excel 2021 was used to establish the database of prescription medication.Python,SPSS Modeler 18.0,Cytoscape 3.10.1,and R language software were used to model prescription data,analyze medication frequency,conduct complex network analysis,association rule analysis,clustering analysis,to explore the prescription law.Results A total of 376 patents meeting the criteria for epilepsy were included,involving 827 kinds of Chinese materia medica,with a total frequency of 4 911 times.Gastrodiae Rhizoma,Acori Tatarinowii Rhizoma,Bombyx Batryticatus,Scorpio,Uncariae Ramulus cum Uncis were among the top five frequently used Chinese materia medica.The high-frequency drug efficacy categories were primarily liver soothing and wind alleviating drugs,tranquilizers,and phlegm resolving,cough suppressing,and asthma alleviating drugs.The predominant medicinal properties were mild,warm and cold,while the predominant tastes were sweet,pungent and bitter.The herbs were classified under the liver,heart,lung and spleen meridians.The core complex network of Chinese materia medica was identified,and the core combination was Gastrodiae Rhizoma-Acori Tatarinowii Rhizoma-Bombyx Batryticatus.The association rule analysis identified 28 commonly used medicinal combinations,with the highest support being observed for Scorpio-Bombyx Batryticatus.Clustering analysis yields four sets of data.Similarity analysis revealed the unique properties of the patented compound in the treatment of epilepsy.Conclusion The high-frequency drugs and commonly used drug combinations of TCM compounds for treating epilepsy,as disclosed on the Chinese Patent Publication Announcement Network,are primarily aimed at calming wind and stopping convulsions,as well as resolving phlegm and opening the orifices,which can provide reference for clinical practice.

Objective:To investigate the effect of preoperative old muscular calf vein thrombosis on the safety and efficacy of total knee arthroplasty (TKA).Methods:A total of 411 patients with end-stage knee osteoarthritis who underwent primary TKA in the First Affiliated Hospital of Nanjing Medical University from September 2021 to March 2023 were retrospectively analyzed. There were 89 males and 322 females, aged 68.05±5.91 years (range, 50-82 years). The body mass index was 26.8±3.7 kg/m 2 (range, 17.4-39.8 kg/m 2). The group was divided into a preoperative thrombosis group (47 cases) and a preoperative none-thrombosis group (364 cases) according to whether or not there was a combination of old muscular calf vein thrombosis before TKA. The clinical characteristics (location and size) and lower limb swelling were observed, and the American Knee Society (AKS) score, visual analogue scale (VAS) and Villalta score were recorded to compare the differences between the two groups. Results:All patients successfully completed the operation and were followed up for 7.4±1.1 months (range, 6-9 months). Postoperative deep venous thrombosis (DVT) occurred in 96% (45/47) of the patients in the preoperative thrombus group, which was greater than the 38.5% (140/364) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=55.184, P<0.001). 29% (13/45) of the patients who developed DVT postoperatively in the preoperative thrombus group had DVT located in the main vein, which was greater than the 9% (12/140) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=12.028, P<0.001). 51% (23/45) of patients with DVT after operation had thrombosis ≥6 mm, which was higher than 34% (47/140) of patients in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=4.454, P=0.035). The rate of thigh swelling on postoperative day 3 was 8.42%±3.50% in the group with preoperative thrombus and 7.80%±4.12% in the preoperative none-thrombus group, and the differences were not statistically significant ( t=-0.995, P=0.320). The rate of calf swelling on postoperative day 3 was 8.14%±3.40% in the preoperative thrombus group, which was greater than the 5.51%±3.45% in the preoperative none-thrombus group, and the difference was statistically significant ( t=-4.923, P<0.001). Postoperative AKS scores were elevated in both groups and were greater than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in AKS score between the two groups before operation ( P>0.05), and the AKS scores in the preoperative thrombus group were smaller than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). Postoperative VAS scores were reduced in both groups and were smaller than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in preoperative VAS scores between the two groups ( P<0.05), and the VAS scores in the preoperative thrombus group were greater than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). The Villalta score of patients with DVT after operation in the preoperative thrombus group was 4.47±2.47 at the last follow-up, which was greater than that of the preoperative none-thrombus group, which was 2.90±1.92, and the difference was statistically significant ( t=-4.395, P<0.001). Conclusion:Preoperative combined old muscular calf vein thrombosis increases the incidence of postoperative DVT and the dangerousness of DVT is higher.