The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

With three representative types of gynecological diseases (dysmenorrhea, pelvic inflammation, polycystic ovary syndrome) as examples, the application methods of meridian and acupoint diagnosis for gynecological diseases treated with acupuncture and moxibustion are discussed. During clinical diagnosis and treatment, it is recommended to examine the patient's leg segment along the three yin meridians of foot, aiming to explore the positive reactions of the meridians and acupoints (color, shape, skin temperature, sensory abnormalities, etc.). Acupuncture and moxibustion treatment at this positive reaction place can improve the clinical efficacy. Meridian and acupoint diagnosis could provide basis for meridian syndrome differentiation, thus guiding the selection of acupoint prescriptions; it is also helpful to clarify the deficiency, excess, cold and heat of the disease nature, thus guiding the selection of acupuncture and moxibustion methods. In addition, it is an auxiliary method to estimate the prognosis and outcome of the disease.
Female ; Humans ; Moxibustion ; Meridians ; Acupuncture Points ; Acupuncture Therapy ; Foot ; Genital Diseases, Female/therapy*

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Objective: To analyze the prevalence of dry and wet age-related macular degeneration (AMD) in patients with diabetes, hypertension and hyperlipidemia, and to analyze the risk factors for AMD. Methods: A population-based cross-sectional epidemiologic study was conducted involving 14,440 individuals. We assessed the prevalence of dry and wet AMD in diabetic and non-diabetic subjects and analyzed the risk factors for AMD. Results: The prevalence of wet AMD in diabetic and non-diabetic patients was 0.3% and 0.5%, respectively, and the prevalence of dry AMD was 17% and 16.4%, respectively. The prevalence of wet AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 0.5%, 0.3%, 0.2%, and 0.7%, respectively. The prevalence of dry AMD in healthy, hypertensive, hyperlipidemic, and hypertensive/hyperlipidemic populations was 16.6%, 16.2%, 15.2%, and 17.2%, respectively. Age, sex, body mass index, and use of hypoglycemic drugs or lowering blood pressure drugs were corrected in the risk factor analysis of AMD. Diabetes, diabetes/hypertension, diabetes/hyperlipidemia, and diabetes/hypertension/hyperlipidemia were analyzed. None of the factors analyzed in the current study increased the risk for the onset of AMD. Conclusion There was no significant difference in the prevalence of wet and dry AMD among diabetic and non-diabetic subjects. Similarly, there was no significant difference in the prevalence of wet and dry AMD among subjects with hypertension and hyperlipidemia. Diabetes co-existing with hypertension and hyperlipidemia were not shown to be risk factors for the onset of dry AMD.
Cross-Sectional Studies ; Diabetes Mellitus/epidemiology* ; Humans ; Hyperlipidemias/epidemiology* ; Hypertension/epidemiology* ; Macular Degeneration/etiology* ; Risk Factors

Aim To explore the ameliorative effects of Rosa roxburghii Tratt on hyperlipidemia and investigate the underlying mechanism by using experimental validation and network pharmacology.Methods The therapeutic effect of Rosa roxburghii Tratt on hyperlipidemia was investigated by constructing a hyperlipidemic rat model and measuring the serum lipid index and liver pathological changes.The literature search method was used to obtain active ingredients and targets of Rosa roxburghii Tratt,the target gene was collected from GeneCards,OMIM,DrugBank database,then generated herbal-active ingredient-potential target networks and protein-protein interactions(PPI)networks.The target GO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID software.Molecular docking was carried out using AutoDock.Results Rosa roxburghii Tratt could significantly improve dyslipidemia and liver pathological damage in hyperlipidemic rats.Network pharmacology results showed that RXRA,AKT1,ESR1,PIK3R1 were key targets of Rosa roxburghii Tratt to lower blood lipids.Molecular docking showed that Roxburic acid and α-linolenic acid had good binding to RXRA,AKT1,ESR1,and PIK3R1.Conclusions Combined with pharmacodynamic experiments and network pharmacology-molecular docking,the therapeutic effect and possible mechanism of action of Rosa roxburghii Tratt on hyperlipidemia are preliminarily explored,which provides a certain basis for the in-depth study of pharmacodynamic substance basis,mechanism of action and clinical application.

Objective:To explore the safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy in the treatment of cystic renal masses.Methods:The 19 patients with cystic renal masses undergoing laparoscopic microwave ablation combined with partial nephrectomy from November 2017 to December 2019 were retrospectively analyzed. There were 13 males and 6 females. The average age was 46.2 years. The mean body mass index was (25.8±3.1) kg/m 2. The masses located in the left kidney in 7 cases and the right kidney in 12 cases. The ECOG scores were 0. The mean maximum diameter of the tumors was (2.8±1.3) cm. Five cases were diagnosed with Bosniak Ⅲ and 14 cases with Bosniak Ⅳ. According to R. E.N.A.L. scoring, 11 cases were of low difficulty (4-6 points), 7 cases of medium difficulty (7-9 points) and 1 case of high difficulty (10-12 points). The cystic renal masses were ablated by laparoscopic microwave ablation, then followed by partial nephrectomy. Postoperative complications were observed and the prognosis was assessed by CT or MRI. Results:The mean duration of operation was (84.0±20.8) min. The median intraoperative blood loss was 20 (10-50) ml. The median duration of postoperative hospitalization was 3 (2-6) d, and no complications such as bleeding, infection, gross hematuria or urine leakage were observed. According to the malignant degree of cystic renal masses, the patients were divided into low-risk group and high-risk group. The patients with benign cystic kidney tumors or with low biological malignancy were considered as the low-risk group, while the patients with high malignant pathology were considered as the high-risk group. In the low-risk group, there were 4 patients, including 1 patient with papillary adenoma, 1 patient with renal angiomyolipoma, 1 patient with low-grade malignant potential multilocular cystic renal tumor, and 1 patient with renal chromophobe carcinoma (stage T 1a). In the high-risk group, there were 15 cases, including 14 cases of clear cell renal cell carcinoma (AJCC pathological stage: T 1a stage 11 cases, T 1b stage 3 cases; WHO/ISUP classification: 7 cases in grade 1, 6 cases in grade 2, and 1 case in grade 3); 1 case of Type 2 papillary renal cell carcinoma (stage T 1b, grade 2). The median follow-up was 20 months (12-37 months). Both groups survived, and no signs of tumor recurrence, implantation or metastasis were found in chest and abdomen imaging. Blood tests were performed regularly, and no significant abnormalities occurred. Conclusions:The safety and efficacy of laparoscopic microwave ablation combined with partial nephrectomy for the treatment of cystic renal masses is satisfactory, and postoperative pathology is clear, providing a potential option for cystic renal masses treatment.

Objective: To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma. Methods: The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome. The mean age of the entire cohort was 62(40-87)years, with 74 males and 22 females. There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma), 83 cases of bladder carcinoma, and 12 cases of lymph node metastasis. There were 77 cases of primary onset and 19 cases of recurrence. 68 cases in single focus group and 28 cases in multiple group. There were 29 cases in non infiltrative T_a stage, 42 cases in infiltrative lamina propria T₁ stage, 16 cases in infiltrative muscle T₂ stage, and 9 cases in extra-muscular≥T₃ stage. At least 3ml of peripheral blood was collected after fasting for at least 8 hours, After cleavage and centrifugation, immunomagnetic beads were added, folate probe was added, and then amplification was carried out. Then the copy number of CTCs in each ml of blood was calculated. Logistic linear regression was used to analyze the risk factors of lymph node metastasis. Results: The mean CNC of all patients was 12.3±7.3; the mean CNC of ≤62 years old group was 10.8±4.2; the mean CNC of >62 years old group was 13.7±9.2; the mean CNC of initial cases was 11.5±5.3; the mean CNC of recurrent cases was 15.5±12.2. Age (P=0.135) and frequency of onset (P=0.087) had no effect on the number of CTCs. The average CNC of single focus group was 10.5±5.2, multiple focus group was 16.5±9.7, T_a stage group was 8.2±2.3, T₁ stage group was 12.0±4.4, T₂ stage group was 16.4±6.8, and ≥T₃ stage group was 19.5±16.6. The number of lesions (P<0.001) was significantly correlated with pathological T stage (P<0.001) and the number of CTCs. Univariate regression analysis showed that T stage (P<0.001) and the number of CTCs (P=0.02) might be correlated with lymph node metastasis; multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P=0.002). Conclusions CTCs can be used to predict lymph node metastasis of urothelial carcinoma.