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.

ObjectiveTo investigate the therapeutic effect of Siegesbeckiae Herba water decoction （SWD） at different doses on atherosclerosis （AS） in a mouse model induced by a high-fat diet and analyze its potential mechanism of action. MethodsThirty-six male ApoE^-/- mice were randomly divided into six groups： blank control group， model group， low-dose， medium-dose， and high-dose SWD groups， and positive control group. Firstly， the AS mouse model was created by feeding mice a high-fat diet. After successful modeling， the low-， medium-， and high-dose SWD groups were intragastrically administered with SWD at 0.65， 1.3， 2.6 g·kg^-1， respectively. The positive control group was intragastrically administered with 30 mg·kg^-1 of atorvastatin calcium aqueous solution， while the blank and model groups received an equal volume of 0.9% sodium chloride solution via oral gavage， all administered for 12 weeks. During the administration period， the general condition of the mice was observed and recorded daily. Before sampling， color Doppler ultrasound was performed to observe the pathological changes in atherosclerotic plaques in the aortic wall of mice. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in aortic tissue in mice， and oil red O staining was used to detect the atherosclerotic plaque area in the aorta. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum lipid indices and the levels of interleukins （IL-1β， IL-4， IL-6， and IL-10） and tumor necrosis factor-α （TNF-α） in mice. Protein expression levels of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue were detected by Western blot. ResultsCompared with the blank control group， the model group showed a significant increase in body weight. The results of color Doppler ultrasound showed enhanced vascular wall echo， suggesting the presence of atherosclerotic plaques. HE staining showed foam cell aggregation， fibrous connective tissue proliferation， and vascular intima injury in the aortic tissue. Oil red O staining showed a significant increase in the plaque area in the aortic tissue （P<0.01）. ELISA results indicated significantly elevated levels of IL-1β， IL-6， TNF-α， total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein （LDL） in mouse serum （P<0.01）， as well as significantly decreased levels of IL-4， IL-10， and high-density lipoprotein （HDL） （P<0.01）. Western blot results showed that the expression of IKKα， IKKβ， and NF-κB p65 in mouse aortic tissue increased significantly （P<0.01）. Compared with those in the model group， mice in the middle- and high-dose SWD groups showed significant weight loss. In the high-dose group， the aortic vascular wall echoes were weakened， and the atherosclerotic plaques were reduced. The aortic lesions of mice in the medium- and high-dose SWD groups were significantly alleviated. The plaque area percentage showed an inverse correlation with the administered dose in all groups treated with SWD （P<0.05）. In the medium-dose SWD group， serum levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）， while those of IL-4 and IL-10 were significantly increased （P<0.01）. In the high-dose SWD group， levels of IL-1β， IL-6， TNF-α， TC， TG， and LDL were significantly decreased （P<0.01）， while IL-4， IL-10， and HDL were significantly increased （P<0.01）. The IKKα and IKKβ expression was significantly decreased in the low-dose SWD group （P<0.05）， and IKKα， IKKβ， and NF-κB p65 were significantly decreased in the medium- and high-dose SWD groups （P<0.05， P<0.01）. ConclusionSWD may exert therapeutic effects on AS by regulating the expression of related inflammatory factors through the NF-κB signaling pathway， thereby reducing inflammation， plaque area， and lipid content in the body.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Objective To explore the role and molecular mechanism of Lnc-BM in the occurrence and development of gastric cancer (GC). Methods GC tissues and paired adjacent normal tissues of 36 GC patients were collected, and the expression of Lnc-BM was detected by RT-qPCR. Colony formation and CCK-8 assays were used to investigate the proliferation of GC cells. The migration and invasion properties of GC cells were investigated via Transwell assay. RNA pull-down assay was applied to confirm the interaction between FASTK and Lnc-BM. Western blot assay was used to detect FASTK protein level in Lnc-BM overexpressing or knockdown cells. Mitochondrial respiratory capacity and the related proteins expression levels were detected by Seahorse and Western blot assays, respectively. Lnc-BM stably overexpressing GC cells were constructed and then injected subcutaneously into nude mice. The tumor growth was observed. Results Lnc-BM was highly expressed in GC tissues compared with their paired adjacent normal tissues. Lnc-BM overexpression significantly promoted GC cells proliferation migration and invasion, while Lnc-BM knockdown inhibited GC cells proliferation, migration and invasion (P < 0.05). RNA pull-down experiment demonstrated that Lnc-BM can directly bind to FASTK. Western blot results indicated that overexpression of Lnc-BM increased the protein levels of FASTK, while knockdown of Lnc-BM inhibited the expression of FASTK (P < 0.05). Compared to the control group, overexpression of Lnc-BM increased the levels of mitochondria associated proteins, such as MT-ND6 and TOM20 (P < 0.05). Seahorse results indicated that overexpression of Lnc-BM enhanced mitochondrial respiratory capacity (P < 0.05). Knocking down FASTK in Lnc-BM stably overexpressing cells can reverse the increase in mitochondrial respiratory capacity caused by Lnc-BM overexpression (P < 0.05). In vivo, the results of subcutaneously implanted tumor model in nude mouse showed that Lnc-BM overexpression promoted the tumor growth (P < 0.05). Conclusion Lnc-BM promotes GC progression by regulating mitochondrial respiratory function through the FASTK/MT-ND6 axis.

Abstract: Upon monitoring cytoplasmic aberrant double-stranded DNA, cGAS-STING signaling pathway induces the expression of type I interferons and pro-inflammatory cytokines, which activates the host immune response and enhances anti-tumor immune response and resistance to pathogen infection. However, sustained activation of the cGAS-STING signaling pathway drives diseases such as autoimmune diseases, aging-associated inflammation, and neurodegenerative pathologies. Herein, we describe the mechanism by which cGAS-STING signaling pathway participates in regulating the development of various immune-related diseases, with a particular review of the research and development progress of STING agonists, cGAS inhibitors, and STING inhibitors, aiming to provide some theoretical reference for the future development of cGAS-STING modulators.

BACKGROUND:Total knee arthroplasty is one of the effective methods to treat end-stage knee osteoarthritis.However,some patients still experience chronic post-surgical pain.It is significant to find out the influencing factors of chronic post-surgical pain.Demographic factors,social psychological factors and perioperative pain were the focus of previous studies,but muscle factors closely related to the occurrence and development of knee osteoarthritis were rarely reported. OBJECTIVE:To evaluate the value of preoperative quantitative ultrasound analysis of quadriceps femoris in predicting chronic post-surgical pain after total knee arthroplasty. METHODS:A total of 250 patients with knee osteoarthritis who underwent the first unilateral total knee arthroplasty under elective general anesthesia from January to August 2022 in the Affiliated Hospital of Xuzhou Medical University were selected.All patients were treated with the same anesthesia and operative methods.Before the surgery,clinical data were recorded,and the thickness and echo intensity of quadriceps femoris on the operated side were measured by ultrasound imaging,which could quantify the degree of quadriceps femoris atrophy.Multivariate logistic regression was used to analyze the independent factors affecting the occurrence of chronic post-surgical pain,and receiver operating characteristic curves were used to evaluate its predictive value. RESULTS AND CONCLUSION:(1)250 subjects were involved in the result analysis,and 91 of them had chronic post-surgical pain,with an incidence of 36.4%.(2)There were significant differences between the chronic pain and non-chronic pain groups in preoperative pain score during movement,preoperative Western Ontario and McMaster University Osteoarthritis Index,preoperative anxiety and depression scale score,preoperative muscle thickness and echo intensity of quadriceps femoris,and postoperative acute pain score(P<0.05).(3)Multivariate logistic regression analysis showed that preoperative thickness of quadriceps femoris was an independent protective factor for chronic post-surgical pain and preoperative pain score during movement was an independent risk factor for chronic post-surgical pain.(4)Receiver operating characteristic curves showed that the area under the curve of the preoperative thickness of quadriceps femoris was 0.625(95%CI:0.555-0.695),and the critical value was 2.78 cm,sensitivity was 0.802,specificity was 0.415.(5)It is concluded that the preoperative thickness of quadriceps femoris is an independent protective factor for chronic post-surgical pain,but its predictive efficacy is low,and its clinical application needs to be further verified or modified.

OBJECTIVE To explore the mechanism of action of Fushao Diqin Decoction in the treatment of colorectal cancer.METHODS In vitro cell experiments were conducted using Fushao Diqin Decoction to treat colorectal cancer CT-26 cells,and the cell proliferation and migration abilities were detected.Flow cytometry was used to detect the levels of reactive oxygen species(ROS)in colorectal cancer CT-26 cells,as well as the levels of iron ions(Fe2+),malondialdehyde(MDA),and the activity of su-peroxide dismutase(SOD).PCR Array and Western blot methods were used to analyze and verify the differential gene expression of ferroptosis.Balb/c mice were randomly divided into a blank control group,a model group,an oxaliplatin group(1.5 mg·kg-1·d-1),a low-dose group of Fushao Diqin Decoction(4.49 g·kg-1·d-1),a medium dose group of Fushao Diqin Decoction(8.97 g·kg-1·d-1),and a high-dose group of Fushao Diqin Decoction(17.94 g·kg-1·d-1)for in vivo animal experi-ments.The effects of Fushao Diqin Decoction on Fe2+,ROS,MDA levels,SOD activity,and Nrf2,Keap1,SLC7A11 and GPX4 ex-pression levels in mouse tumor tissues were tested.RESULTS In vitro cell experiments showed that compared with the blank control group,Fushao Diqin Decoction significantly inhibited the proliferation and migration of colorectal cancer CT-26 cells in a dose-de-pendent manner.Fushao Diqin Decoction could increase the Fe2+content(P＜0.05)and ROS level(P＜0.01)in colorectal cancer CT-26 cells,increase the MDA level in CT-26 cells of colorectal cancer(P＜0.01)and significantly reduce SOD activity(P＜0.01).Iron death PCR array analysis found that compared with the blank control group,after intervention with Fushao Diqin Decoc-tion,the expression of genes GPX4 and SLC7A11 was significantly downregulated,while the expression of GSTA1,HMOX1,Ca9,Chac1,Keap1,Sqstm1,NOX1,FTH1,Tfr1,SAT2,Pparg,and Hamp was significantly upregulated.Western blot analysis revealed that after intervention with Fushao Diqin Decoction,the expression of Keap1 protein was upregulated(P＜0.01),while the expression of Nrf2,SLC7A11,and GPX4 proteins was downregulated(P＜0.01)in colorectal cancer CT-26 cells.The results of in vivo animal experiments showed that Fushao Diqin Decoction significantly inhibited the growth of subcutaneous transplanted tumors in mice(P＜0.05),increased the degree of tumor tissue necrosis,and levels of Fe2+,ROS,and MDA(P＜0.05,P＜0.01),decreased SOD ac-tivity(P＜0.01)and upregulated Keap1 protein expression(P＜0.01),while downregulated Nrf2,SLC7A11,and GPX4 protein ex-pression(P＜0.01).CONCLUSION Fushao Diqin Decoction has an anti-colorectal cancer effect and may promote ferroptosis in colorectal cancer cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway to exert its anti-colorectal cancer effect.

This paper summarized professor LIU Ruifen's clinical experience in treating endometrial hyperplasia. It is believed that the core pathogenesis of endometrial hyperplasia is internal obstruction of uterus and intrauterine collaterals by latent stasis. Based on the clinical manifestations， the menstrual cycle is divided into three stages， that is menstrual period， menstrual leakage period， and clear menstrual period， and the method of “three-staged stasis dispelling” is proposed. During the menstrual period， it is appropriate to move qi and invigorate blood， dissolve stasis and disperse concretions， with self-made Gongqing Formula （宫清方）. For menstrual leakage period， it is suggested to boost qi and clear heat， dispel stasis and stanch bleeding， with self-made Tongyong Zhixue Formula （通用止血方）. In terms of clear menstrual period， the method of dissolving phlegm and dissipating masses， moving qi and dispelling stasis is advised， and self-made Zhitong Tiaoxue Formula （止痛调血方） can be used. Simultaneously， attention should be paid to the combination of syndrome differentiation and disease differentiation， as well as collaborative diagnosis and treatment with traditional Chinese and Western medicine.

【Objective】 To investigate the condition of confidential unit exclusion(CUE) in Guangzhou, so as to ensure blood safety. 【Methods】 The number of CUE donors, demographic characteristics of CUE donors, reasons for CUE, and response time of CUE after blood donation in Guangzhou from 2009 to 2022 were statistically analyzed. 【Results】 From 2009 to 2022, the response ratios of CUE was 0.006 2% (260/4 170 984) and the ratios had statistically significant difference between different years(P<0.05). For the response ratios of CUE, no statistically significant difference was noticed in gender and occupation (P>0.05), but statistically significant differences were found in age, number of blood donations, education background, and marital status (P<0.05). Blood donors aged 18~30 (0.007 3%, P<0.05) and first-time blood donors (0.010 8%, P<0.05) were the main groups of CUE. High risk sexual behavior (28.46%, 74/260) was the primary reason for CUE. The CUE response peak was within 72 hours after blood donation, and the response ratios within 24-72 hours after blood donation was the highest (68.46%, 178/260). 【Conclusion】 CUE is a crucial measure to ensure blood safety. Detailed pre-donation health consultations are suggested for blood donors aged 18-30 and first-time blood donors so as to better excluding high-risk blood donors. Strengthening the publicity of CUE response and process, registering and classifying the reasons for CUE are also important.