In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective To analyze the research status of in situ simulation in the medical field and explore its hotspots and trends. Methods Relevant literature was searched in China National Knowledge Infrastructure and Web of Science core collection from the inception to February 2024.CiteSpace 6.3.R1 was used to analyze the authors,institutions,and keywords and draw visual knowledge maps. Results A total of 25 Chinese articles and 438 English articles were included.Only 14 English articles were from China.In Chinese articles,the authors with the largest number of articles were Dai Hengmao and Liu Shangkun,and the institution with the largest number of articles was Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.There was little cooperation between the authors and institutions.In English articles,the author and institution with the largest number of articles was Auerbach Marc and Yale University,respectively,and the cooperation between authors and institutions was close.Emergency medicine,emergency event handling,and on-the-job training were the keywords with high frequency in Chinese articles.Patient safety,medical education,and cardiac arrest were the keywords with high frequency in English articles.A total of 4 clusters were generated for Chinese keywords and 13 clusters for English keywords. Conclusions The application of in situ simulation in the medical field is still in the initial stage,and the development is not balanced at home and abroad.The number of articles published and the cooperation between authors and institutions in China obviously lags behind those abroad.Treatment and care of emergency critical patients,emergency event handling and skill training,identification of latent safety threats,improvement of readiness,and promotion of medical quality improvement are the future research hotspots and research trends in this field.
Bibliometrics ; Humans ; China ; Simulation Training ; Education, Medical ; Emergency Medicine/education*

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. ¹³C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.

Coronary perforation is when a contrast agent or blood flows outside a blood vessel through a tear in a coronary artery.In this case,we reported a case of percutaneous coronary intervention for coronary calcified lesions,which led to iatrogenic coronary perforation and cardiac tamponade after the use of Shockwave balloon to treat intracoronary calcified nodules,and the management of PCI-related CAP was systematically reviewed through the literature.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation.Methods:Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma(PRP),the key technical parameters(DMSO addition,incubation time,centrifugation conditions,etc.)of the preparation process were optimized,and the quality of the frozen platelets was evaluated by routine blood tests,apoptosis rate,platelet activation rate and surface protein expression level.Results:In the preparation protocol of novel frozen human platelets,the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing,and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800 xg for 8 min.In addition,platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing.The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation.Conclusion:The preparation technique of novel frozen human platelets was established and the protocol was formulated.It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800 ×g for 8 min in the preparation of novel frozen human platelets.

Aim To explore the protective effects of Xiyanping injection against lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice,and investi-gate the underlying mechanism.Methods In the LPS-induced ALI mouse model,the protective effect of Xiyanping injection against ALI was evaluated by ob-serving the pathological indicators of lung tissue.Net-work pharmacology and molecular docking were used to explore its mechanism.Western blot method was used to validate the predicted target proteins.Results Xiy-anping injection significantly improved the pathological injury and alleviated inflammatory reactions in lungs of ALI mice.Four active ingredients were identified in Xiyanping injection,namely,14-deoxy-11-oxo-an-drographolide,14-deoxyandrographolide,14-deoxy-12-methoxyandrographolide,and andrographolide-19-β-D-glucoside.A total of 288 corresponding drug targets and 4 960 ALI-related targets were obtained,with 192 genes overlapping.The ten core targets associated with Xiyanping injection were identified as STAT3,EGFR,PIK3R1,MAPK1,PIK3CA,NFKB1,ESR1,MAPK8,JAK2,and FYN.GO enrichment analysis re-vealed 310 biological processes(BP),65 cellular components(CC),and 80 molecular functions(MF)associated with the overlapping genes.KEGG pathway enrichment analysis identified 141 pathways related to ALI,with the top 20 pathways including MAPK,TNF-α,VEGF,cAMP,mTOR,AMPK,NOD,JAK-STAT,IL-17,and NF-κB.Molecular docking results demonstrated strong binding affinity between core tar-gets(MAPK1,MAPK8,NFKB1)and active ingredi-ents(14-deoxy-12-methoxyandrographolide and 14-de-oxyandrographolide).Western blotting showed that medium and high doses of Xiyanping injection signifi-cantly downregulated p38,JNK,ERKl/2,NF-κB p65 protein expression in lung tissue of ALI mice(P＜0.01).Conclusions Xiyanping injection has a cer-tain protective effect against ALI,and the mechanism is related to regulating MAPK and NF-κB signaling pathways.