Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Antigens, CD19 ; Chemokine CCL19 ; Immunotherapy, Adoptive ; Interleukin-7 ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Programmed Cell Death 1 Receptor ; Receptors, Chimeric Antigen

Aim To investigate the effect of circRNA- 32011 on myocardial apoptosis induced by arsenic triox- ide (ATO).Methods Primary cardioniyocytes of suckling neonate mouse were treated with ATO ( final concentration 10 (xniol • L_1 ) for 24 h.Then cell via¬bility was measured by M IT assay.The mKNA expres¬sion levels of Bel-2/ Bax and circRNA-3201 I were de¬tected by KT-PCK.Bcl-2/Bax protein expression lev¬els were detected by Western blot.Overexpression and knock down circHNA-32011 respectively by plasmid and siHNA were used to verify its function in ATO-in- duced cardiomyocyte apoptosis.Results Myocardial cell viability decreased, Bel-2 expression significantly decreased while Bax expression increased in ATO group compared with the control group.CircKNA- 32011 was down-regulated in ATO ineuhated cardio¬niyocytes.Ovcrex press ion of circRNA-32011 in ATO- incubated cardioniyocytes increased myocardial cell vi¬ability and Bel-2 expression and decreased the expres¬sion of Bax.Knockdown of circRNA-32011 could fur¬ther reduce cardiomyoevte activity and Bel-2 expression and increase the experssion of Bax induced by ATO.Conclusions CircRNA-32011 protects cardiac myo¬cytes from apoptosis induced by arsenic trioxide, which may provide a new potential therapeutic strategy for ATO-induced myocardial injury.

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
Biomarkers/metabolism* ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Male ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Spermatozoa/metabolism*

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

ObjectiveUltra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） was used to analyze the chemical constituents in the aerial part and roots of Gentiana straminea from different areas of Qinghai province， and the main chromatographic peaks and differential components of different parts were identified. MethodThe chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column （2.1 mm×100 mm， 1.8 μm） with 0.1% formic acid aqueous solution （A）-acetonitrile （B） as the mobile phase for gradient elution （0-1 min， 1%-13%B； 1-5 min， 13%-18%B； 5-7 min， 18%-50%B； 7-9.5 min， 50%-60%B； 9.5-11 min， 60%-99%B； 11-14 min； 99%B； 14-15 min， 99%-1%B； 15-16 min， 1%B）， the column temperature at 40 ℃， and the flow rate of 0.3 mL·min^-1. Electrospray ionization （ESI） and negative ion full scan mode were selected for the mass spectrometric conditions to analyze the samples， and the detection range was m/z 50-1 200. Chemical constituents of the aerial part were qualitatively analyzed with the reference substances， literature information and ChemSpider. Principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） were used to analyze the classification trend， correlation and differential chemical components between aerial part and roots of G. straminea. ResultA total of 68 components， including 24 iridoids， 13 flavonoids， 8 triterpenoids， 6 xanthones， 5 fatty acids， 4 saccharides， 3 phenolic glycosides， 2 alkaloids， 2 sterols and 1 lignan， were preliminarily identified from the aerial part of G. straminea. Among them， 42 components were firstly reported in 4 Gentiana species included in the 2020 edition of Chinese Pharmacopoeia. Eight differential components were screened out， namely sucrose， maltotriose， loganic acid， shanzhiside methyl ester， 6′-O-β-D-glucosylgentiopicroside， swertiamarin， gentiopicrin and isovitexin. ConclusionThe aerial part of G. straminea is rich in chemical constituents and has good medicinal potential. There were significant differences in the chemical components between the aerial part and roots of G. straminea， and the main differential components were iridoids， which could provide a basis for exploring efficacy differences in different parts of G. straminea.

OBJECTIVE: To analyze the problems existing in the on-site quality inspection of occupational medical examination(OME) institutions in Guangdong Province. METHODS: A total of 96 OME institutions in Guangdong Province were selected as the research subjects using the random number table method. On-site quality inspections were carried out and the results were analyzed. RESULTS: The OME institutions participating in the on-site quality inspection in 2020 accounted for 49.0%(96/196) of total OME institutions in Guangdong Province. Among them, occupational disease prevention and control hospitals/institutions, Centers for Disease Control and Prevention(CDC), public hospitals, and private hospitals accounted for 8.3%, 9.4%, 42.7% and 39.6%, respectively. They were distributed in 17 prefecture-level cities. The registered OME qualifications include dust, chemical factors, physical factors, radiological factors and other categories. Some institutions have registered two or more OME qualifications. The non-qualified rate of the on-site quality inspections in six assessment modules of the 96 OME institutions from high to low were quality management work, equipment(instruments and vehicles) allocation, quality management system, medical and health technical personnel allocation, information report, and on-site professional assessment module, with the non-qualified rate of 24.1%, 22.4%, 20.7%, 15.9%, 15.6% and 1.1% respectively(P<0.01). The problems were mostly concentrated in the CDC, public and private hospitals, and rarely in occupational disease prevention and treatment hospitals/institutes. In addition to the on-site professional assessment module, a total of 696 non-qualified items were detected in the remaining five modules of the 96 OME institutions, with an average of seven items per institution. Occupational disease prevention and treatment hospitals/institutions, CDC, public hospitals, and private hospitals had an average of 2, 9, 8, 7 non-qualified items respectively. CONCLUSION: In the on-site quality assessment of OME institutions in Guangdong Province, there are relatively few problems in all aspects of occupational disease prevention and treatment hospitals/institutes. CDC has certain inadequacies. The public and private hospitals have more prominent problems in aspects of equipment(instruments and vehicles) allocation, quality management system and quality management work.

Objective:To establish and validate a prognostic model of a contrast-enhanced ultrasound scoring(CEUS)system for evaluating renal artery stenosis(RAS)in the elderly.Methods:This was a single-center retrospective study.A total of 324 elderly RAS patients admitted to Beijing Hospital from October 2017 to July 2020 were randomly assigned into the model group(n=174)and the validation group(150)in a 1∶1 ratio.Clinical and imaging data of patients on admission including general conditions, previous medical history, blood pressure, blood creatinine, renal artery stenosis and cortical blood perfusion in the affected kidney and renal function(GFR)at 1-year follow-up were collected.Univariate and multivariate logistic regression was used to establish a model of the CEUS scoring system.The receiver operating characteristic(ROC)curve and area under the ROC curve(AUC)were used to evaluate prediction accuracy.Clinical application value of the CEUS scoring system model was evaluated via decision curve analysis using a nomogram.Results:Baseline clinical and radiomic data had no significant difference between the model group and the validation group( P>0.05). Multivariate logistic regression analysis results showed that age( OR=1.242, 95% CI: 1.081-1.427, P<0.01), diabetes( OR=1.545, 95% CI: 1.107-2.156, P<0.05), blood pressure( OR=1.328, 95% CI: 1.056-1.670, P<0.05), renal function( OR=2.374, 95% CI: 1.216-3.887, P<0.01)and cortical blood perfusion parameter( OR=2.646, 95% CI: 1.553-6.369, P<0.01)were risk factors for the deterioration of renal function during 1 year follow-up.Based on these results, a nomogram for the CEUS scoring system model was drawn, and its consistency index, the C-Index, was 0.725(95% CI: 0.653-0.776). The AUC of the CEUS scoring system was 0.824 and the Youden index was 0.711 in the model group, with a specificity of 0.774 and a sensitivity of 0.837.The AUC of the CEUS scoring system was 0.853 and the Youden index was 0.715 in the validation group, with a specificity of 0.684 and a sensitivity of 0.889.There was no significant difference in ROC curve between the two groups( D=1.387, P>0.05). In addition, calibration charts of the two models showed that the calibration curve of the CEUS scoring system was close to the standard curve, with no statistically significant difference( P>0.05). Conclusions:The CEUS scoring system model can be used to predict the risk of worsening renal function in elderly RAS patients during 1-year follow-up.

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(
Child ; DMF Index ; Dental Caries/epidemiology* ; Female ; Humans ; Oral Health ; Oral Hygiene ; Prevalence ; Schools ; Students ; Surveys and Questionnaires