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

Deep vein thrombosis(DVT)is a common peripheral vascular disease in clinical practice.The lack of precise and efficient early diagnostic techniques renders it susceptible to being overlooked or misdiagnosed,and therefore,identifying trustworthy biomarkers is a major issue that has to be resolved.In this study,the endogenous metabolites in the urine of DVT rats were screened by metabolomics technology based on gas chromatograph-mass spectrometry(GC-MS)and the characteristic metabolites were identified by multiple feature selection algorithms and multivariate statistical analysis,for the development of a machine learning-based diagnostic model for DVT.The urine samples in metabolic cage in the thrombus development phase(between 48 and 72 h)of rats were collected,which was used as the models for inferior vena cava ligation.The metabolic profiles of the control group and DVT were obtained using the GC-MS method.A total of 176 kinds of endogenous metabolites were identified in rat urine through comparison with the FiehnLib database,26 kinds of differential metabolites associated with DVT were screened through a combination of the Mann-Whitney U test and orthogonal partial least squares discriminant analysis(OPLS-DA),and 13 kinds of significant metabolites strongly correlated with DVT were further evaluated in conjunction with various machine learning feature selection techniques.For DVT diagnosis,machine learning models such as Gaussian Naive Bayes(GNB),support vector machine(SVM),logistic regression(LR),and linear discriminant analysis(LDA)were developed.The diagnostic model constructed using 13 kinds of key metabolites demonstrated excellent accuracy and stability,and surpassed the predictive performance of the models utilizing 176 kinds of metabolites and 26 kinds of differential metabolites,as evidenced by examination and comparison of each model's efficacy.The study showed that the integration of multiple feature selection algorithms for analyzing metabolite information in DVT rat urine was capable of effectively identifying reliable potential markers of DVT.Furthermore,the developed machine learning model offered a novel technical approach for the automated diagnosis of DVT.

Objective:To explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge.Methods:This study was a retrospective cohort study that included 268 children with bacterial meningitis who were discharged from the infectious medicine ward of Beijing Children′s Hospital from September 2018 to September 2023. The children were managed with a multidisciplinary collaborative comprehensive healthcare management model after discharge. Outpatient data at 1 month and 6, 12 and 24 months after discharge were collected, including (height, weight, body mass index, nutritional feeding status, hearing and vision screening results, Gesell developmental assessment results and intervention guidance services. The follow-up interval or frequency was dynamically adjusted or increased according to the child′s situation. The paired sample t-test and chi square test were applied to compare the differences in Gesell developmental quotient (DQ) and developmental delay rate between the first and last assessments to preliminarily explore the effectiveness of the comprehensive healthcare management model for children with bacterial meningitis after discharge. Results:All the 268 children completed their first assessment one month after discharge, and 37 children were found to have abnormal physical growth, mainly obesity (28 children), and another 9 children were malnutrition. Nutritional intervention and feeding guidance services were provided to all the 37 children, and as of the last follow-up, 20 children′s physical growth evaluations had turned normal. A total of 188 children completed at least 2 developmental assessments, with an interval of (14.2±9.4) months between the first and last assessments (range: 3.1-49.5 months). The DQ values of in the energy region of adaptability, gross motor skills, fine motor skills, language, and personal social skills at the last assessment were significantly higher than those at the first assessment [(91.93±13.28) vs (80.73±15.96) points, (91.69±12.96) vs (78.31±16.58) points, (89.32±16.11) vs (80.68±15.63) points, (90.10±16.65) vs (82.04±18.43) points, (92.01±14.05) vs (77.82±17.42) points]; moreover, the rates of developmental delay in each energy region were significantly lower than those at the initial assessment (9.6% vs 35.1%, 9.6% vs 42.0%, 18.1% vs 33.0%, 13.3% vs 31.9%, 9.6% vs 42.0%) (all P<0.05). Among the 200 children who completed the hearing screening, 18 were found with hearing abnormalities, and 2 were diagnosed with hearing loss in the Otolaryngology Department. Among 217 children who completed vision screening, 23 had abnormalities, and 5 were diagnosed with ophthalmic abnormalities in Ophthalmology Department (2 with strabismus, 2 with refractive errors, and 1 with optic nerve injury). Two children were found to have autism-like behavior during monitoring, and were referred to a developmental behavior clinic to be diagnosed with autism spectrum disorder and were given early diagnosis and intervention guidance. Conclusion:The comprehensive healthcare management model for children with bacterial meningitis after discharge can integrate clinical and healthcare resources, which is beneficial for improving the prognosis and enhancing the quality of life for children with special health status.

Objective: To compare the dwelling time and complications of low lying umbilical venous catheterization (UVC) in preterm infants with that of central UVC. Methods: This was a prospective cohort study. A total of 3 020 preterm infants from 44 neonatal intensive care units (NICU) who had UVC inserted from October 2019 to August 2021 were enrolled. Demographic and general baseline data, dwelling time of UVC and reasons for removal, complications and their occurrence time were collected. According to the position of the catheter tip, the preterm infants were divided into low lying UVC group (insertion depth of 3-5 cm) and central UVC group (the catheter tip was close to the entrance of right atrium, or at the 8^th-9^th thoracic vertebra level). The Mann-Whitney U test was used to compare the dwelling time and incidence of complications (cases/1 000 catheter days), and the independent t test and Chi-square test were used to compare the characteristics between the 2 groups. The receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off value of UVC dwelling time. Results: Among the included 3 020 preterm infants, 1 624 (53.8%) were males, the gestational age was 29.9 (28.4, 31.6) weeks, the birth weight was (1 264±301) g, and 2 172 (71.9%) premature babies had central UVC. There were no significant differences in the proportion of males, the gestational age and the birth weight of neonates between the 2 groups (all P>0.05). There were also no significant differences in the rate of maternal history, PPROM>18 hours, chorioamnionitis, antenatal antibacterial angents exposure and antibacterial angents usage through UVC (all P>0.05). The dwelling time of central UVC was longer than that of low lying UVC (7 (6, 10) vs. 4 (3, 7) days, U=23.42, P<0.001). The complication incidence of central and low lying UVC were 20.0 and 70.8 cases/1 000 catheter days, respectively. The top 3 complications of central UVC were occlusion, catheter tip migration, and CLABSI (9.3, 3.5, 3.0 cases/1 000 catheter days). The top 3 complications of low lying UVC were catheter occlusion, CLABSI, and catheter tip migration (45.8, 6.3, 5.4 cases/1 000 catheter days). The ROC curve of UVC dwelling time and complications showed that the cut-off values ​​of central UVC and low lying UVC were 6.5 and 4.5 days, respectively. The 2 groups both showed a trend of increases in the 3 complications with the prolonged dwelling time. Cox regression analysis showed that the overall difference in the proportion of occlusion between the central UVC and low lying UVC groups was statistically significant (χ²=30.18, P=0.024). There were both no significant differences in catheter tip migration and CLABSI (both P>0.05). Conclusions: The most common UVC complication in preterm infants is occlusion. It is not recommended to keep a low lying UVC for longer than 4.5 days. During the whole dwelling period, a close monitoring for UVC complications is required.
Pregnancy ; Male ; Infant, Newborn ; Humans ; Female ; Infant ; Infant, Premature ; Birth Weight ; Prospective Studies ; Catheterization, Central Venous/adverse effects* ; Anti-Bacterial Agents ; Catheterization, Peripheral/adverse effects* ; Retrospective Studies

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

AIM: To observe the effect of eccentricity of the optical treatment zone on retinal defocus after wearing orthokeratology lens for 12mo.METHODS: In this case-control study, a total of 120 myopic patients(120 eyes)who completed the fitting in our hospital from March 2021 to September 2021 and insisted on wearing orthokeratology lenses for 12mo were selected. According to the eccentricity after wearing lenses for 12mo, they were divided into the low eccentricity group(<0.5mm, 58 cases, 58 eyes)and the moderate and high eccentricity group(≥0.5mm, 62 cases, 62 eyes). The optical treatment zone diameter(OTZD), eccentricity, axial length(AL), pupil diameter(PD)and refraction difference value(RDV)were evaluated after 12mo of wearing orthokeratology lenses, and the correlation between RDV and eccentricity was analyzed.RESULTS: After wearing orthokeratology lenses for 12mo, AL growth and RDV at 30°～40° and 40°～53° from the fovea were significantly lower in the moderate and high eccentricity group than in the low eccentricity group(all P<0.05). In all patients, RDV at 40°～53° from the fovea was positively correlated with AL growth and OTZD(rs=0.544, 0.333, both P<0.01), and negatively correlated with eccentricity(rs=-0.224, P=0.014).CONCLUSION: Peripheral retinal defocus is related to eccentricity and OTZD after wearing orthokeratology lenses. The greater eccentricity and the smaller OTZD within a certain range can induce more peripheral retinal myopic defocus, leading to a better control of AL growth.

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.

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.
Antineoplastic Agents/therapeutic use* ; Clinical Trials as Topic ; Humans ; Marketing ; Neoplasms/drug therapy* ; Research Design ; United States ; United States Food and Drug Administration

Decompression, Surgical ; Diskectomy, Percutaneous ; Humans ; Intervertebral Disc Displacement/surgery* ; Laser Therapy ; Lumbar Vertebrae/surgery* ; Robotic Surgical Procedures ; Treatment Outcome

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*