Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).

ObjectiveTo explore the characteristics of circadian rhythm of blood pressure in patients with masked hypertension （MH） and its relationship with twelve two-hour peirods， providing a basis for early detection and intervention of MH. MethodsPatients who underwent 24-hour ambulatory blood pressure examination in the ambulatory blood pressure room of Jiangsu Province Hospital of Chinese Medicine from January to December 2022 were enrolled， and according to their outpatient blood pressure measurements， 24-hour ambulatory blood pressure monitoring and follow-up survey results， the MH， essential hypertension （EH） and normal blood pressure groups were classified， with 50 cases in each group. The general data， office blood pressure and 24-hour ambulatory blood pressure monitoring data were collected. The circadian rhythm of blood pressure including 24-hour average systolic blood pressure （24h SBP）， daytime average systolic blood pressure （d SBP）， nighttime average systolic blood pressure （n SBP）， 24-hour average diastolic blood pressure （24h DBP）， daytime average diastolic blood pressure （d DBP）， and nighttime average diastolic blood pressure （n DBP） were compared among the groups， and the nighttime blood pressure dipping percentage was calculated. The type of circadian rhythm was determined based on the nighttime blood pressure dipping percentage. The variability of blood pressure including 24h SBP standard deviation （24h SBP-SD）， d SBP standard deviation （dSBP-SD）， n SBP standard deviation （nSBP-SD）， 24h DBP standard deviation （24h DBP-SD）， d DBP standard deviation （dDBP-SD）， and n DBP standard deviation （nDBP-SD） were compared among groups， and the corresponding coefficient of variation （CV）， that is， 24h SBP-CV， d SBP-CV， n SBP-CV， 24h DBP-CV， d DBP-CV and n DBP-CV， were calculated. Based on the 24-hour ambulatory blood pressure monitoring results， the twelve two-hour average SBP and DBP in each group were calculated and compared. Simultaneously， patients with EH were divided into grades 1， 2， and 3 for further stratified analysis. ResultsThe age of the MH group was significantly higher than that of the EH group and the normal blood pressure group （P＜0.01）. The body mass index （BMI） and the proportion of smoking and alcohol consumption in the MH group and the EH group were significantly higher than those in the normal blood pressure group （P＜0.05 or P＜0.01）. In the normal blood pressure group， there were 49 dipper patterns （98.0%） and one non-dipper pattern （2.0%）； in the MH group， there were two dipper patterns （4.0%）， 29 non-dipper patterns （58.0%） and 19 reverse-dipper patterns （38.0%）； in the EH group， there were 20 dipper patterns （40.0%）， 23 non-dipper patterns （46.0%） and seven reverse-dipper patterns （14.0%）. Compared to the normal blood pressure group， the groups of MH and EH had significantly decreased proportion of dipper pattern and increased proportion of non-dipper and reverse-dipper pattern （P＜0.01）； the proportion of dipper pattern in the MH group was lower than that in the EH group， while the proportion of reverse-dipper pattern was higher （P＜0.01）. Compared to those in the normal blood pressure group， n SBP and n DBP in the MH group， as well as the the average SBP and average DBP at Zi hour （子时， 23：00-1：00）， Chou hour （丑时， 1：00-3：00）， Yin hour （寅时， 3：00-5：00）， Mao hour （卯时， 5：00-7：00） and average SBP at Hai hour （亥时， 21：00-23：00） in the MH group increased，while the average DBP at Si hour （巳时， 9：00-11：00） decreased （P＜0.01）； 24h SBP， 24h DBP， d SBP， d DBP， n SBP， and n DBP，d SBP-SD， n SBP-SD，n DBP-SD increased， as well as the average SBP and average DBP at twelve two-hour periods increased in the EH group，while the 24h SBP-CV， 24h DBP-CV，and d DBP-CV in the EH group decreased（P＜0.05 or P＜0.01）. The EH group had higher 24h SBP， 24h DBP， d SBP， d DBP， n SBP， n DBP， 24h DBP-SD and n DBP-SD ， as well as higher average SBP and DBP at all twelve two-hour periods， and lower d DBP-CV than the MH group（P＜0.05 or P＜0.01）. The EH group had 18 cases of grade 1 （36.0％）， 19 cases of grade 2 （38.0％） and 13 cases of grade 3 （26.0％）， with no significant differences among groups （P＞0.05）. ConclusionThe circadian rhythm of blood pressure in MH patients are mostly non-dipper and reverse-dipper patterns， and the abnormal elevation of blood pressure is obvious at Zi hour， Chou hour， Yin hour and Mao hour （23：00-7：00）.

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.
Mice ; Animals ; Antioxidants/analysis* ; Plant Extracts/pharmacology* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Paeonia/chemistry* ; Glutathione/analysis*

Objective: The docking and superantigen activity sites of staphylococcal enterotoxin-like W (SElW) and T cell receptor (TCR) were predicted, and its SElW was cloned, expressed and purified. Methods: AlphaFold was used to predict the 3D structure of SElW protein monomers, and the protein models were evaluated with the help of the SAVES online server from ERRAT, Ramachandran plot, and Verify_3D. The ZDOCK server simulates the docking conformation of SElW and TCR, and the amino acid sequences of SElW and other serotype enterotoxins were aligned. The primers were designed to amplify selw, and the fragment was recombined into the pMD18-T vector and sequenced. Then recombinant plasmid pMD18-T was digested with BamHⅠand Hind Ⅲ. The target fragment was recombined into the expression plasmid pET-28a(+). After identification of the recombinant plasmid, the protein expression was induced by isopropyl-beta-D- thiogalactopyranoside. The SElW expressed in the supernatant was purified by affinity chromatography and quantified by the BCA method. Results: The predicted three-dimensional structure showed that the SElW protein was composed of two domains, the amino-terminal and the carboxy-terminal. The amino-terminal domain was composed of 3 α-helices and 6 β-sheets, and the carboxy-terminal domain included 2 α-helices and 7 antiparallel β-sheets composition. The overall quality factor score of the SElW protein model was 98.08, with 93.24% of the amino acids having a Verify_3D score ≥0.2 and no amino acids located in disallowed regions. The docking conformation with the highest score (1 521.328) was selected as the analysis object, and the 19 hydrogen bonds between the corresponding amino acid residues of SElW and TCR were analyzed by PyMOL. Combined with sequence alignment and the published data, this study predicted and found five important superantigen active sites, namely Y18, N19, W55, C88, and C98. The highly purified soluble recombinant protein SElW was obtained with cloning, expression, and protein purification. Conclusions: The study found five superantigen active sites in SElW protein that need special attention and successfully constructed and expressed the SElW protein, which laid the foundation for further exploration of the immune recognition mechanism of SElW.
Humans ; Enterotoxins/genetics* ; Superantigens/genetics* ; Catalytic Domain ; Selenoprotein W/metabolism* ; Receptors, Antigen, T-Cell

Humans ; Extremities ; Ultrasonography, Interventional

OBJECTIVE: To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses. CONCLUSION The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.
Adult ; Humans ; Aspirin/therapeutic use* ; Cardiovascular Diseases/epidemiology* ; Gastrointestinal Hemorrhage ; Myocardial Infarction/prevention & control* ; Primary Prevention/methods* ; Middle Aged ; Aged

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

OBJECTIVE: To assess the methodological quality, report quality and evidence quality of the Meta-analysis and systematic reviews of acupuncture and moxibustion for children with cerebral palsy, aiming to provide decision-making basis for clinical treatment. METHODS: The systematic reviews and Meta-analysis of acupuncture and moxibustion for children with cerebral palsy were searched in CNKI, Wanfang, VIP, SinoMed, Cochrane Library, PubMed and EMbase. The retrieval time was from the database establishment to June 30th, 2022. AMSTAR 2 (a measurement tool to assess systematic reviews) was used to evaluate the methodological quality， and PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 14 systematic reviews were included, including 37 primary outcome indexes. According to AMSTAR 2 evaluation results, there were 4 low quality studies, 10 very low quality studies, and low scores on items 2, 4, 7, 10 and 16. PRISMA scores ranged from 15 to 25, and the main reporting problems reflected in structured abstracts, program and registration, retrieval, and funding sources, etc. According to the GRADE classification results, there were 3 high quality evidences, 7 medium quality evidences, 10 low quality evidences and 17 very low quality evidences. The main downgrading factors were limitations, imprecision and publication bias. CONCLUSION Acupuncture and moxibustion has a certain effect for cerebral palsy in children, but the quality of methodology, reporting and evidence in the included literature is poor, and the comparison of curative effect between different acupuncture and moxibustion methods is unclear.
Child ; Humans ; Acupuncture Therapy/methods* ; Cerebral Palsy/therapy* ; Moxibustion/methods* ; Publication Bias ; Research Report ; Systematic Reviews as Topic ; Meta-Analysis as Topic

Humans ; Osteoma, Osteoid/surgery* ; Bone Neoplasms/surgery* ; Tomography, X-Ray Computed

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.
Rats ; Animals ; Frankincense ; Acetic Acid ; Powders ; Triterpenes ; Anticoagulants/pharmacology* ; Technology