BACKGROUND:Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels;however,the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear. OBJECTIVE:To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method. METHODS:Five features associated with behavioral correlations in the Oswestry disability index score,including time spent watching TV,time spent on the computer,and light/moderate/vigorous physical activity,were selected from large-scale population-based genome-wide association studies,and instrumental variables were extracted for each of these behaviorally related features.Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database.The results were analyzed using the inverse variance weighted,MR-Egger regression,simple mode,weighted mode,weighted median estimator,and regression model odds ratios(OR)and 95%confidence interval(CI)to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration.Cochran's Q was used to test for heterogeneity,MR-Egger intercept to test for multiplicity,and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration. RESULTS AND CONCLUSION:The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration(OR=1.775,95%CI:1.418-2.221,P<0.001)/(OR=1.384,95%CI:1.041-1.839,P<0.001),an inverse causal association between light physical activity and the risk of intervertebral disc degeneration(OR=1.000,95%CI:0.999-1.000,P=0.020).MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration(P=0.005),while there was no horizontal pleiotropy between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=0.521,P=0.851).Cochran's Q analysis showed that heterogeneity was observed between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=3.33×10-11,P=0.001),and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration(P=0.186).Overall,there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration,i.e.,not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score,but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration.These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration,indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration,and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.

In recent years， the incidence and mortality rates of cancer have been increasing， posing a serious threat to human health. Western medicine mainly uses treatments such as surgical resection， chemotherapy， immunotherapy and targeted therapy， but they are prone to complications， drug resistance and adverse reactions. A growing number of studies have shown that traditional Chinese medicine has obvious advantages in the treatment of cancer， reducing the recurrence rate of cancer and improving the quality of survival of patients. Cellular senescence refers to a state of irreversible cell cycle growth arrest when cells cease to proliferate after a limited number of divisions， resulting in a decline in cell proliferation and differentiation capacities and physiological functions， accompanied by morphological changes such as flattening and multinuclear morphology. At the molecular level， it shows increased expression of DNA damage-related genes， reduced expression of cell cycle-related factors and significant secretory activity. The malignant development of cancer is closely related to cellular senescence. With the increasing number of cancer cell proliferation， cancer-related genes undergo continuous mutations， freeing them from cellular senescence and thus achieving unlimited proliferation. Through recent studies， it has been found that induction of tumor cell senescence， possibly through modulation of cellular DNA damage， cell cycle arrest and senescence-associated secretory phenotype （SASP）， which converts the suppressive immune tumor microenvironment to an activated immune tumor microenvironment and thus reverses the escape of tumor cell senescence， is a promising strategy for cancer therapy. However， the mechanism of cellular senescence in cancer progression is not fully understood， especially the anti-cancer role played by traditional Chinese medicine in regulating cellular senescence. This article summarized and concluded the specific molecular mechanisms of cellular senescence， the role of cellular senescence in cancer progression， and the mechanism of anti-cancer effects of traditional Chinese medicine based on cellular senescence from the perspective of regulating cellular senescence， with a view to providing ideas and methods for the anti-cancer effects of traditional Chinese medicine and the development of new drugs.

BACKGROUND:It has been found in recent observational studies that assessing localized fat mass is crucial in the evaluation of disc degeneration.Although obesity has been recognized as a risk factor for disc degeneration,the causal relationship between fat mass,which is a key factor in obesity,and intervertebral disc degeneration has been unclear in previous studies. OBJECTIVE:To investigate the causal risk factors of intervertebral disc degeneration associated with different distributions of fat mass,thereby enhancing the understanding of the pathogenesis of intervertebral disc degeneration and contributing to the development of preventive,therapeutic,and prognostic strategies. METHODS:Genetic markers associated with trunk and lower limb fat mass were extracted as instrumental variables from the publicly available IEU Open GWAS under the conditions of strong correlation and fulfillment of linkage disequilibrium.These markers were combined with the Mendelian randomization analysis to investigate the relationship between body fat and intervertebral disc degeneration.We used the latest version 9 database of FinnGen and assessed the results using several regression models,including inverse variance weighting,MR-Egger regression,simple mode,weighted mode,and weighted median estimator.We also assessed the heterogeneity of the genetic markers using Cochran's Q test,and multiplicity was assessed using the MR-Egger intercept test.Additionally,we used the leave-one-out method to determine the sensitivity of individual genetic markers to the causal effect of the exposure and outcome.The results were presented as odds ratios(OR)and 95%confidence intervals(CI). RESULTS AND CONCLUSION:The results from the inverse variance weighting method revealed that there was a positive causal relationship between trunk fat mass and the risk of developing intervertebral disc degeneration(OR=1.25,95%CI:1.15-1.35,P＜0.001).Additionally,there was an inverse causal relationship between bilateral lower limb fat mass and the risk of developing intervertebral disc degeneration(OR=0.7,95%CI:0.63-0.78,P＜0.001;OR=0.69,95%CI:0.62-0.76,P＜0.001).Furthermore,the MR-Egger intercept analysis did not detect any potential horizontal pleiotropy.No bias single nucleotide polymorphisms were detected,while heterogeneity tests were present,and the leave-one-out sensitivity analysis suggested reliable results.The results above demonstrate a positive causal relationship between trunk fat mass and intervertebral disc degeneration.As trunk fat mass increases,the risk of intervertebral disc degeneration rises.With an increase in both lower limb fat mass,the risk of intervertebral disc degeneration decreases.Fat content and distribution affects the risk of developing intervertebral disc degeneration and should be given more attention.

Objective:To evaluate the effect of statins combined with PCSK9 inhibitors on coronary artery atherosclerotic plaque, as well as to verify the lipid-lowering effect of the combined therapy.Methods:A computerized search of PubMed, Embase, Web of Science, Cochrane Library, Wanfang, and CNKI databases was conducted to retrieve published literature from inception to December 20, 2022. The English search terms utilized included "PCSK9 inhibitors," "Alirocumab," "Evolocumab," "plaque," "IVUS," and "OCT." The corresponding Chinese search terms were "PCSK9 inhibitors," "plateau," "intravascular ultrasound," and "optical coherence tomography." The literature that examined the effect of statins alone or in combination with PCSK9 inhibitors on coronary atherosclerotic plaques using intravascular ultrasound or optical coherence tomography was identified. The collected data were subsequently processed using Review Manager (Revman) version 5.4.Results:In the final analysis, nine studies involving 1912 patients were included. The analysis results revealed that compared with statins alone, statins combined with PCSK9 inhibitors significantly reduced the percentage of atherosclerotic volume ( MD: -2.08 mm 3, 95% CI: -2.94 to -1.23 mm 3, P < 0.001), accelerated the regression of atherosclerotic volume ( MD: -1.13 mm 3, 95% CI: -1.49 to -0.77 mm 3, P < 0.001), slightly, but not significantly, reduced the overall atherosclerotic volume ( MD: -6.42 mm 3, 95% CI: -14.34-1.51 mm 3, P = 0.110). Nevertheless, the combined therapy contributed to a significant reduction in atherosclerotic volume ( MD: -5.16 mm 3, 95% CI: -7.09 to -3.23 mm 3, P < 0.001) and significantly increased the fiber cap thickness of thin cap plaques ( MD: 8.46 μm, 95% CI: 5.13-11.79 μm, P < 0.001). Additionally, this combined therapy significantly lowered blood lipid levels. Conclusion:The combination of statins and PCSK9 inhibitors can significantly improve the characteristics and phenotype of atherosclerotic plaques and significantly reduce blood lipid levels. For patients with high cardiovascular risk, it is recommended to initiate treatment with statins combined with PCSK9 inhibitors as soon as possible and maintain it for a long time to ensure more benefits.

ObjectiveTo observe the effect of bee acupuncture therapy on clinical symptoms and signs， as well as the level of inflammatory cytokine interleukin-6 （IL-6） in synovial fluid of patients with knee osteoarthritis. MethodsThe 94 patients with knee osteoarthritis were divided into the control group and the trial group by the random number table method， with 47 cases in each group. Both groups were given one tablet （60 mg） of etoricoxib orally every morning for 2 weeks. The control group also received microneedle shallow acupuncture therapy， once a day for 5 consecutive times followed 2-day pause， and continued 5 consecutive times， as a course of treatment； the trial group was treated with bee acupuncture therapy once every 2 days， 2 times a week， and 4 times as a course of treatment. Both groups have a course of treatment for 2 weeks. The changes in clinical symptoms and signs of patients in the two groups were observed and evaluated before treatment， after 1- and 2-week treatment， and 12-week follow-up and the differences in Lequesne index scores， HSS scores， Visual Analogue Scale （VAS） scores and IL-6 levels in knee synovial fluid between the two groups of patients were also compared. ResultsNo patients lost to follow up in either group. The Lequesne index scores and VAS scores were lower， and the HSS scores were higher in both groups at all time points after treatment compared with those before treatment （P＜0.05）. Compared at the same time after treatment， the Lequesne index scores and VAS scores of the trial group were lower than those of the control group， and the HSS scores were higher than those of the control group （P＜0.05）. IL-6 in synovial fluid was lower in the trial group at the 12-week follow-up than before treatment （P＜0.05）， but there was no significant difference between two groups at each time point（P＞0.05）. ConclusionBee acupuncture therapy for knee osteoarthritis can significantly improve clinical signs and symptoms， but has no significant effect on the level of IL-6 in knee synovial fluid.

Objective:To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation.Methods:This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis.Results:Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions:The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Objective:To explore the value of baseline PET/CT parameters for predicting prognosis in patients with double-expression lymphoma (DEL).Methods:The clinical and 18F-FDG PET/CT data of 118 patients (66 males, 52 females; age: 28-85 years) with diffuse large B-cell lymphoma (DLBCL) diagnosed in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University and the First Affiliated Hospital of Nanjing Medical University from June 2015 to September 2022 were retrospectively analyzed. The optimal thresholds for SUV max, total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in predicting overall survival (OS) rate were determined using ROC curve analysis. Univariate and multivariate analyses, along with Kaplan-Meier survival analysis were performed to construct a survival prediction model. The effect of the model was evaluated by the calibration curve for the model, the time-dependent ROC curve analysis and decision curve analysis. Results:As of the last follow-up, 25 patients died, and the OS rate was 78.8%(93/118). The AUC of the ROC curve for TMTV was 0.705, with a corresponding optimal threshold of 230.9 cm 3. In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG PS) score (hazard ratio ( HR)=3.886, 95% CI: 1.455-10.375; P=0.007) and TMTV ( HR=4.649, 95% CI: 1.665-12.979; P=0.003) were identified as independent predictors of OS. The combined model of ECOG PS score and TMTV was superior to ECOG PS score model and TMTV model alone in predicting OS. Conclusion:TMTV, a metabolic indicator, and ECOG PS score, a clinical risk factor, are independent predictors of OS in patients with DEL, and their combination can provide more accurate prognostic predictions.

[Objective]To explore the micro-ecological mechanism of soil amendment combined with Trichoderma solution in resolving the replant obstacles of Atractylodes macrocephala through studying their effects on the microbial community structure in the rhizosphere soil.[Methods]In pot experiment and field experiment,different soil amendments and Trichoderma inoculants were applied to Atractylodes macrocephala,the survival rate,physiochemical properties of soil and microbial community were detected,as well as analysis of the microenvironmental changes in the rhizosphere.[Results]The number of leaves and survival rate were significantly increased after the application of lime(mainly composed of calcium oxide)and mixed bacterial solution;the activity of soil-urease(S-UE),soil-phosphatase(S-NP),solid-β-glucosidase(S-β-GC),soil-catalase(S-CAT)in the rhizosphere were also increased,indicating that the replant obstacle was alleviated.Meanwhile,the rhizosphere bacteria and fungi were the highest.The sequencing results showed that the bacteria in the rhizosphere soil after the application of lime and mixed bacterial solution were mainly composed of Gemmatimonadetes,Verrucomicrobia,Firmicutes,Actinobacteria,while the fungi were mainly composed of Ascomycetes,Mortierella,Basidiomycetes and Chytridiomycota,after the application of lime and mixed bacterial solution,the proportion of Fusarium decreased,and the proportion of Penicillium increased.[Conclusion]The combination of lime as a soil amendment and Trichoderma can effectively improve the replant disorder of Atractylodes macrocephala and promote the growth of Atractylodes macrocephala,which may be by improving the structure of the microbial communities in the rhizosphere,increasing the abundance of biocontrol bacteria and reducing the abundance of pathogenic bacteria.

【Objective】 To develop a quick and accurate crossmatching test technology without the power equipment and additional reagents before blood transfusion, so as to improve the timeliness and safety of blood transfusion treatment in sudden situations as war or natural disasters. 【Methods】 The irregular antibodies quickly promote coagulants (QPC) were used as the reaction medium reagent. The 200 μL QPC were wrapped in the bursts bead and preset within different recess of the detection tubes. The bursts beads were squeezed with the reagent left in the well, then the blood samples were dropped in the main(recipient plasma: 200 μL, donor 3%—5% RBC: 100 μL) and secondary(donor plasma: 200 μL, recipient 3%—5% RBC: 100 μL)reaction grooves. The result interpretated by hand wrestling or 1 500 g centrifugation of 15 seconds. Meanwhile, the comparing experiments with the prior methods were implemented to evaluate the method’s reliability. 【Results】 The results of the bursting reagent, being stored at 37℃ for one week, were consistent with those of the freshly prepared cross-matching reagent, indicating that the bursting reagent was practical in the field and had good stability at normal temperature. No statistical difference between the sensitivity and the results of the microcolumn gel method was noticed by paired data t test (P>0.05). The parallel cross matching tests of 50 clinical samples were performed by microcolumn gel method and coagulant-bursting technique; the Kappa value was 0.973 2, and irregular antibodies were detected in 2 cases, with concordance rate at 100%, showing good consistency. 【Conclusion】 The improved method is simple and fast, and also safe and reliable for compatibility testing before blood transfusion, which is especially suitable for the field rescue of the wounded in wartime and sudden natural disasters, and is worthy of popularization.

OBJECTIVE To observe the toxic effects of single administration and repeated administration of Qingzi granules for 13 weeks on rats, and to evaluate their preclinical safety. METHODS For the single dose toxicity experiment, SD rats were randomly divided into two groups, vehicle control group(deionized water) and Qingzi group(18 g·kg-1), which were given in a volume of 30 mL·kg-1 per time, twice in 24 h(interval more than 4 h), and observation was performed for 14 d after administration. The toxicity reaction was evaluated through observation of body weight change and pathological anatomy. For the repeated dose toxicity experiment, juvenile SD rats(postnatal day, PND 4) were randomly divided into vehicle control group (deionized water) and low, medium and high dose of Qingzi groups(1, 2 and 4 g·kg-1). The rats were orally administered twice daily with vehicle or Qingzi for 13 weeks in a volume of 10 mL·kg-1 per time. A recovery period of 4 weeks was followed. Test items included clinical observations, body weight measurement, food intake measurement, hematology test, biochemical test, urinalysis, sex hormone level determination, cellular immune function assay, growth indexes and histopathology test. RESULTS For the single dose toxicity experiment, Qingzi granules were orally administered to SD rats without significant toxicity, and the maximum-tolerated dose was greater than 18 g·kg-1. In the repeated dose toxicity test, juvenile SD rats were given Qingzi granules by gavage and repeated administration for 13 weeks, the no observed adverse effect level was 2 g·kg-1. The target organ of toxicity was the liver and the main toxic effect was inflammatory necrosis of hepatocytes, no dose-dependent relationship. CONCLUSION No overt toxicity of Qingzi granules was observed on the tested animals within the intended clinical dosage range.