OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To develop a digital intelligent multimodal shift handover system for the intensive care unit (ICU) and evaluate its application effect in ICU shift handovers. METHODS: A research and development team was established, consisting of 1 department director, 1 head nurse, 3 information technology engineers, 3 nurses, and 2 doctors. Team members were assigned responsibilities including overall coordination and planning, platform design and maintenance, pre-application training, collection and organization of clinical feedback, and research investigation respectively. A digital intelligent multimodal shift handover system was developed for ICU based on the Shannon-Weaver linear transmission model. This innovative system integrated automated data collection, intelligent dynamic monitoring, multidimensional condition analysis and visual reporting functions. A cloud platform was used to gather data from multi-parameter vital signs monitors, infusion pumps, ventilators and other devices. Artificial intelligence algorithms were employed to standardize and analyze the data, providing personalized recommendations for healthcare professionals. A self-controlled before-after method was adopted. Before the application of the ICU digital intelligent multimodal shift handover system (from December 2023 to March 2024), the traditional verbal bedside handover was used; from June 2024 to March 2025, the ICU digital intelligent multimodal shift handover system was applied for shift handovers. Questionnaires before the application of the shift handover system were collected in April 2024, and those after the application were collected in April 2025. The shift handover time, handover quality (scored by the nursing handover evaluation scale), satisfaction with doctor-nurse communication (scored by the ICU doctor-nurse scale) before and after the application of the handover system were compared, and nurses' satisfaction with the shift handover system (scored by the clinical nursing information system effectiveness evaluation scale) was investigated. RESULTS: After the application of the ICU digital intelligent multimodal shift handover system, the shift handover time was significantly shorter than that before the application [minutes: 20 (15, 25) vs. 30 (22, 40)], the handover quality was significantly higher than that before the application [score: 84.0 (78.0, 88.5) vs. 71.0 (55.0, 79.0)], and the satisfaction with doctor-nurse communication was also significantly higher than that before the application (score: 84.58±6.79 vs. 74.50±11.30). All differences were statistically significant (all P < 0.05). In addition, the nurses' system effectiveness evaluation scale score was 102.30±10.56, which indicated that nurses had a very high level of satisfaction with the ICU digital intelligent multimodal shift handover system. CONCLUSIONS The application of the ICU digital intelligent multimodal shift handover system can shorten the shift handover time, improve the handover quality, and enhance the satisfaction with doctor-nurse communication. Nurses have a high level of satisfaction with this system.
Intensive Care Units ; Humans ; Patient Handoff ; Artificial Intelligence ; Algorithms

Objective To investigate the clinical effect of lithium disilicate glass ceramic cantilever resin-bonded fixed partial dentures(CRBFPDs)on single anterior tooth loss to provide a reference for the selection of restoration methods for single anterior tooth loss.Methods This study was reviewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Forty-two patients with less than two anterior teeth with monomaxillary loss were included in this study.After 6 months,1 year,2 years,and 3 years,the aesthetic and functional effects of the restorations and the periodontal health status were evaluated,and the visual analog scale(VAS)was used to assess pa-tient satisfaction.Results During the observation period,the connector fractured in one case within 3 months.One case had debonded within 2 years.The aesthetic restoration effect of all lithium disilicate glass ceramic CRBFPDs was categorized as Class A.The periodontal health was good,there was no clinical absorption in the soft and hard tissues of the abutment or subbridge,periodontal status according to the evaluation indices was classified as class A,and the total satisfaction rate of the patient was 100%.Conclusion For single anterior tooth loss patients,lithium disilicate glass ceramic cantilever resin-bonded fixed partial denture can achieve the restoration effect of less invasion,better adhesion,aesthetics,comfort and good biocompatibility.With high patient satisfaction,it can be considered an ideal restoration method for replacing a single anterior tooth.

The structures and activities of enzymes are influenced by pH of the environment. Understanding and distinguishing the adaptation mechanisms of enzymes to extreme pH values is of great significance for elucidating the molecular mechanisms and promoting the industrial applications of enzymes. In this study, the ESM-2 protein language model was used to encode the secreted microbial proteins with the optimal performance above pH 9 and below pH 5, which yielded 47 725 high-pH protein sequences and 66 079 low-pH protein sequences, respectively. A deep learning model was constructed to identify protein acid-base tolerance based on amino acid sequences. The model showcased significantly higher accuracy than other methods, with the overall accuracy of 94.8%, precision of 91.8%, and a recall rate of 93.4% on the test set. Furthermore, we built a website (https://enzymepred.biodesign.ac.cn), which enabled users to predict the acid-base tolerance by submitting the protein sequences of enzymes. This study has accelerated the application of enzymes in various fields, including biotechnology, pharmaceuticals, and chemicals. It provides a powerful tool for the rapid screening and optimization of industrial enzymes.
Deep Learning ; Hydrogen-Ion Concentration ; Amino Acid Sequence ; Enzymes/metabolism* ; Sequence Analysis, Protein ; Proteins/metabolism* ; Bacterial Proteins/metabolism*

Objective:To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B.Methods:175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC).Results:The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion:HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.
Acupuncture Therapy/adverse effects* ; Cerebral Infarction/drug therapy* ; Fibrinogen ; Humans ; Stroke/drug therapy* ; Thrombolytic Therapy/adverse effects* ; Tissue Plasminogen Activator/adverse effects* ; Treatment Outcome

Objective:To explore the progression of diabetic macrovascular disease and the effects of Didangtang at different doses on it. Method:Four-week-old male apolipoprotein-E knockout （ApoE^-/-） mice with diabetic macrovascular disease induced by exposure to high-fat diet combined with streptozotocin （STZ） were randomly divided into the model， simvastatin， as well as high-， medium-， and low-dose Didangtang groups. The age-matched ApoE^-/- mice of the same batch only fed with a high-fat diet were classified into the ApoE^-/- （model control） group， and C57BL/6 mice with the same genetic background receiving a regular diet into the normal group. The sampling was conducted at the 8th and 20th weeks of the experiment for observing the pathological characteristics of the aorta and the proportion of plaque area in mice of each group at different time points， followed by the comparison of blood glucose， blood lipid， and oxidized low-density lipoprotein （ox-LDL） levels. The aortic NOD-like receptor protein 3 （NLRP3） and cysteinyl aspartate-specific proteinase-1 （Caspase-1） protein expression was detected by Western blot assay， and the serum interleukin-1β （IL-1β）， interleukin-18 （IL-18）， interleukin-1α （IL-1α）， and tumor necrosis factor-α （TNF-α） levels by enzyme-linked immunosorbent assay （ELISA）. Result:The comparison with the normal group revealed that the proportions of plaque area in the ApoE^-/- group and the model group were increased （P<0.01）， while the proportion of plaque area in each administration group was significantly reduced in contrast to that of the model group （P<0.05）. The aortic NLRP3 and Caspase-1 protein expression levels as well as the serum IL-1β， IL-18， IL-1α， and TNF-α levels in the ApoE^-/- group and the model group were significantly higher than those in the normal group （P<0.01）. Compared with the model group， each administration group exhibited a significant reduction in aortic NLRP3 and Caspase-1 protein expression and serum IL-1β， IL-18， IL-1α， and TNF-α levels （P<0.05）， with the strongest inhibitory effect detected in the medium-dose Didangtang group （P<0.05）. Conclusion:Didangtang directly alleviates diabetic macrovascular disease possibly by down-regulating NLRP3 and Caspase-1 protein expression and easing the inflammatory cascade.

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

Objective:To investigate the immunogenicity and safety of a boost dose of measles, mumps, and rubella combined vaccine (MMR) for children 4 to 6 years old.Methods:Children, aged 4 to 6 years old, had vaccinated with 1 dose of measles and rubella combined vaccine(MR) at the age of 8 months and 1 dose of MMR vaccine at 18-months, were recruited in Shanxi, Inner Mongolia, and Beijing, respectively. All children were assigned into 4, 5 and 6-year-old group. The children who met inclusion and exclusion criteria were vaccinated with 1 dose MMR vaccine, and were collected blood samples before vaccination and 35 to 42 d after the vaccination. During the study period, adverse events were collected at 30 min, 1 d, 2 d, 3 d, 4-12 d, and 13 to 42 days after vaccination. Serum was tested for IgG antibodies against measles, mumps and rubella. Geometric mean concentrations (GMC) of measles, mumps, and rubella antibodies were compared among groups by analysis of variance or non-parametric test. Seropositive rates and adverse event rates were compared among groups by Chi-square test or Fisher exact test.Results:A total of 500 children were included in immunogenicity analysis and 535 children were included in safety analysis. The overall adverse event rate was 20.37%, the most of severity for adverse events was mild. The rates of local and systemic adverse events were 0.37% and 20.00%, respectively. Symptoms of local adverse events were redness. The main systemic adverse events were fever, followed by cough, rash and runny nose. Received a dose of MMR vaccine for booster immunization, the seropositive rates of measles antibody, mumps antibody and rubella antibody were above 99% for all 3 age groups, and there was no significant difference between groups. There were significant differences in mumps antibody GMC among groups ( P=0.042), but no significant differences in measles and rubella antibodies GMC. Conclusion:The immunogenicity and safety of a boosted MMR vaccintion in children aged 4, 5 and 6 years were all similar good.

The aim of this study was to identify the anti-inflammatory markers of Zhachong shisanwei pills (ZC-13) and characterize their mechanisms. UPLC/Q-TOF-MS combined with an NF-κB dual fluorescence reporter gene system and NO content detection were utilized to identify the anti-inflammatory bioactive substances in ZC-13. Network pharmacology and bioinformatics methods were used to predict the main targets and pathways of these anti-inflammatory markers, and to verify the main anti-inflammatory pathways of costunolide. Results showed that in ZC-13, four kinds of markers related to NF-κB inhibition were identified: gallic acid, ellagic acid, liquiritin apioside, glycyrrhizic acid, and four kinds of markers related to NO release inhibition were found: gallic acid, liquiritigenin, costunolide, and dehydrocostus lactone. The above components exert anti-inflammatory activities mainly through the regulation of PDK1 (3-phosphoinositide-dependent protein kinase 1), MAPK14 (mitogen-activated protein kinase), GSK3β (glycogen synthase kinase-3β) and other anti-inflammatory-related targets, and further adjust the PI3K-AKT (phosphoinositide 3-kinase- protein kinase B), MAPK, mTOR (mammalian target of rapamycin) pathways. Among them, costunolide can inhibit AKT phosphorylation and NF-κB nuclear transfer. The above results identified the anti-inflammatory markers and possible mechanisms of ZC-13, and provide a theoretical basis for standardizing the clinical application and quality of ZC-13.