AIM To investigate the effects of Zhuangyao Shuanglu Tongnao Formula on neuronal apoptosis in rats with cerebral ischemia-reperfusion injury based on the study of oxidative stress and inflammatory response.METHODS The rats were randomly divided into the sham operation group,the model group,the edaravone group(3.0 mg/kg),the low,medium and high dose groups(9.0,18.0,36.0 g/kg)of Zhuangyao Shuanglu Tongnao Formula,with 18 rats in each group.The middle cerebral artery occlusion/reperfusion was conducted by thread embolism method to simulate cerebral ischemia reperfusion injury in rats followed by 6 days corresponding drugs administration.Subsequently,the rats had their neurological function deficit scored by Zeal Longa scoring method;their sizes of cerebral infarction areas measured by TTC staining;their pathological damage and apoptosis of neurons in hippocampal CA1 area of ischemic penumbra of the brain tissue detected by HE staining and TUNEL staining;their SOD activity and levels of GSH,MDA,IL-6,IL-1β,TNF-α in brain tissue detected by kits;and their protein expressions of Bax,Bcl-2,caspase-3,cleaved-capase-3,TLR4,NF-κB p65,Nrf2,HO-1 in rat brain tissue determined by Western blot.RESULTS Compared with the model group,the groups intervened with edaravone,medium and high dose of Zhuangyao Shuanglu Tongnao Formula displayed improvements in the scores of nerve function defects,the rate of cerebral infarction,the rate of neuronal apoptosis,the levels of IL-6,IL-1β,TNF-α and MDA in the ischemic penumbra of brain tissues,the protein expressions of Bax and TLR4,the ratio of cleaved-capase-3/caspase-3 and p-NF-κB p65/NF-κB p65(P＜0.05),the levels of GSH,the activity of SOD and the protein expressions of Bcl-2,Nrf2 and HO-1(P＜0.05).CONCLUSION Being an inhibitor of oxidative stress and inflammatory response,Zhuangyao Shuanglu Tongnao Formula can alleviate brain injury in rats with cerebral ischemia reperfusion injury through the inhibition of neuronal apoptosis and improvement of neural function mediated by the inhibition of TLR4/NF-κB signal pathway and activation of Nrf2/HO-1 signal pathway.

Objective:To clarify the causal relationship between obesity and male infertility through Mendelian randomization(MR)study.Methods:We assessed the causal effect of genetically predicted body mass index(BMI)on the risk of male infertility via a two-sample MR analysis,with the BMIs of 99 998 cases and 12 746 controls as the exposure factor and genetic information on male infertility obtained from a genome-wide association study of 73 479 Europeans.In the univariable MR(UVMR)analysis of the causal relationship,we mainly used inverse variance weighting(IVW),with MR-Egger regression and weighted median filtering as the supplementary methods.Sensitivity analyses including the Cochran's Q test,Egger intercept test,MR-PRESSO,leave-one-out analysis and funnel plot were performed to verify the robustness of the MR results.To evaluate the direct causal effects of BMI on MI risk,mult-ivariable MR(MVMR)was performed.Results:UVMR indicated a causal relationship between genetically predicted BMI and an in-creased risk of male infertility(OR:1.237,95%CI:1.090-1.404,P=0.001).Sensitivity analysis revealed little evidence of bias in the current study(P>0.05).With such risk factors as type 2 diabetes,alcohol consumption and smoking adjusted,MVMR confirmed a direct causal effect of genetically predicted BMI on the risk of male infertility(P<0.05).Conclusion:Genetically pre-dicted BMI may be associated with an increased risk of male infertility.Further studies are expected to explore the underlying mecha-nisms of this association and provide some new strategies for the prevention and treatment of BMI-related male infertility.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Network Pharmacology ; Data Mining ; Gastroesophageal Reflux/drug therapy*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.

OBJECTIVE: To investigate the types and laboratory characteristics of non-Hodgkin lymphoma(NHL) with bone marrow invasion as the first manifestation. METHODS: 81 non-Hodgkin lymphoma patients with bone marrow invasion as the first manifestation treated in our hospital from January 2010 to July 2019 were selected. The clinical features, blood routine, lactate dehydrogenase (LDH), EB virus results, bone marrow features, immunophenotyping, gene and genetic characteristics of all patients were analyzed retrospectivel. RESULTS: Among 81 patients, 73 cases(90%) were B-cell lymphoma, 5 cases(6%) were T-cell lymphoma and 3 cases(4%) were NK/T-cell lymphoma, while the mantle cell lymphoma and diffuse large B-cell lymphoma were the highest, which accounted for 21%(17 cases) and 19.7%(16 cases), and lymphoma accounted for 8.6%(7 cases). There were 44 cases(54.3%) showed B symptoms, 65 cases (80.2%) showed abnormal blood routine. The MYD88 gene was detected in 5 of 17 cases. 25 cases of patients underwent chromosome examination, the result showed that 5 cases were t(8; 14) (q24; q32), 3 cases were complex karyotype and 17 cases were normal karyotype. 23 cases(23.4%) were EB virus positive, 42 cases(51.9%) were LDH increased. The proportion of bone marrow lymphoma cells was 1%-92%. Among them, 32 cases were diagnosed as lymphoma leukemia, and 6 cases of bone marrow lymphoma cells showed mass distribution similar to extramedullary tumor cells with bone marrow metastasis. CONCLUSION B-cell lymphoma is the predominant NHL with bone marrow invasion as the first manifestation, while mantle cell lymphoma and diffuse large B-cell lymphoma are the most common pathological types with blood routine abnormalities. Bone marrow lymphoma cells can also present clusters of bone marrow metastasis, different types of lymphoma cells can make directional diagnosis.
Adult ; Bone Marrow ; Humans ; Laboratories ; Lymphoma, Large B-Cell, Diffuse ; Lymphoma, Mantle-Cell ; Lymphoma, Non-Hodgkin

Objective:To investigate the status of cardiac rehabilitation after percutaneous coronary intervention (PCI) in rural areas. Methods:A total of 2264 patients after PCI in our hospital from January, 2016 to December, 2019 were selected. The awareness rate of patients on cardiac rehabilitation knowledge was investigated through WeChat, telephone and questionnaire. Patients were divided into rehabilitation group (n = 326) and non-rehabilitation group (n = 1809) according to whether they participated in cardiac rehabilitation. Results:There were 2135 valid questionnaires. The awareness rate of cardiac rehabilitation in PCI patients with coronary heart disease in rural areas was 44.9%, the participation rate was 15.2%, and the participation rate of outpatient heart rehabilitation was only 0.56%. The scores of the MOS Item Short Form Health Survey (SF-36) were higher in the rehabilitation group than in the non-rehabilitation group (t > 4.65, P < 0.05). Conclusion:In rural areas, the knowledge of cardiac rehabilitation is poor for patients after PCI, the participation rate is low, the control rate of risk factors is low, and most patients do not return to farm work. It is important to take a way to improve the awareness and participation of cardiac rehabilitation for patients after PCI, to ensure the exact control of cardiovascular risk factors of patients.