Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.
Humans ; Siblings ; Genetic Markers ; Computer Simulation ; Irritable Bowel Syndrome/genetics* ; Reproducibility of Results ; Genotype

The last essential enzyme in the biosynthetic pathway of trilobatin, phloretin-4'-O glycosyltransferase (P4'-OGT), catalyzes the conversion of trilobatin to phloretin in vitro. However, only a few P4'-OGTs have been found in plants. This study used Malus domestica phloretin-4'-O glycosyltransferase (MdPh-4'-OGT) as a query to identify and clone two UDP-glucuronosyltransferase (UGT) genes, designated UGT74L2 and UGT74L3, from the transcriptome of Andrographis paniculata. According to a phylogenetic tree analysis, UGT74L2 and UGT74L3 belonged to the UGT74 family, which has been linked to several activities in other species. The in vitro enzymatic reaction demonstrated that UGT74L2 could particularly catalyze the formation of trilobatin from phloretin, but UGT74L3 had no effects. By using Ni-NTA affinity chromatography to extract the soluble UGT74L2 recombinant protein, the enzymatic kinetics of the activity was investigated using phloretin as the substrate. The results showed that the optimal temperature and pH for UGT74L2 enzymatic reaction were 40 ℃ and 8.0 (Tris-HCl system), respectively. Three metal ions (Ca²⁺, Mn²⁺ and Co²⁺) showed inhibitory effect on the activity of UGT74L2, while Mg²⁺ could improve the activity of UGT74L2. Other tested metal ions have no significant effect on UGT74L2. The results of enzymatic kinetic parameters that the K_m value was 29.84 μmol·L^-1, the k_cat was 0.02 s^-1, and the k_cat·K_m^-1 was 572.6 mol^-1·s^-1. By homology modeling, molecular docking and mutation experiments, we found that multiple amino acids residues around the substrate binding pocket play quite an important role during catalytic process, In summary, we identified a novel P4'-OGT gene from medicinal plant Andrographis paniculata and provided a new efficient catalyst to synthesize trilobatin. Meanwhile, this study provides a reference for mining new efficient glycosylation modules from plants.

Chalcone isomerase is a key rate-limiting enzyme in the biosynthesis of flavonoids in higher plants, which determines the production of flavonoids in plants. In this study, RNA was extracted from different parts of Isatis indigotica and reverse-transcribed into cDNA. Specific primers with enzyme restriction sites were designed, and a chalcone isomerase gene was cloned from I. indigotica, named IiCHI. IiCHI was 756 bp in length, containing a complete open reading frame and encoding 251 amino acids. Homology analysis showed that IiCHI was closely related to CHI protein of Arabidopsis thaliana and had typical active sites of chalcone isomerase. Phylogenetic tree analysis showed that IiCHI was classified into type Ⅰ CHI clade. Recombinant prokaryotic expression vector pET28a-IiCHI was constructed and purified to obtain IiCHI recombinant protein. In vitro enzymatic analysis showed that the IiCHI protein could convert naringenin chalcone into naringenin, but could not catalyze the production of liquiritigenin by isoliquiritigenin. The results of real-time quantitative polymerase chain reaction(qPCR) showed that the expression level of IiCHI in the aboveground parts was higher than that in the underground parts and the expression level was the highest in the flowers of the aboveground parts, followed by leaves and stems, and no expression was observed in the roots and rhizomes of the underground parts. This study has confirmed the function of chalcone isomerase in I. indigotica and provided references for the biosynthesis of flavonoid components.
Isatis/genetics* ; Plant Proteins/metabolism* ; Phylogeny ; Arabidopsis/genetics* ; Flavonoids ; Cloning, Molecular

The lignan glycosyltransferase UGT236(belonging to the UGT71 B family) from Isatis indigotica can catalyze the production of phloridzin from phloretin in vitro. UGT236 shares high identity with P2'GT from apple. In this study, the recombinant plasmid pET28 a-MBP-UGT236 was transferred into Escherichia coli Rosetta(DE3) cells and induced by isopropyl-β-D-thiogalactoside(IPTG). The purified UGT236 protein was used for enzymatic characterization with phloretin as substrate. The results showed that UGT236 had the optimal reaction temperature of 40 ℃ and the optimal pH 8(Na_2HPO_4-NaH_2PO_4 system). The UGT236 activity was inhibited by Ni~(2+) and Al~(3+), enhanced by Fe~(2+), Co~(2+), and Mn~(2+), and did not affected by Mg~(2+), Ca~(2+), Li~+, Na~+, or K~+. The K_m, K_(cat), and K_(cat)/K_m of phloretin were 61.03 μmol·L~(-1), 0.01 s~(-1), and 157.11 mol~(-1)·s~(-1)·L, and those of UDPG were 183.6 μmol·L~(-1), 0.01 s~(-1), and 51.91 mol~(-1)·s~(-1)·L, respectively. The possible active sites were predicted by homologous modeling and molecular docking. By mutagenisis and catalytic activity detection, three key active sites, Glu391, His15, and Thr141, were identified, while Phe146 was related to product diversity. In summary, we found that the lignan glycosyltransferase UGT236 from I.indigotica could catalyze the reaction of phloretin into phloridzin. Several key amino acid residues were identified by structure prediction, molecular docking, and site-mutagenesis, which provided a basis for studying the specificity and diversity of phloretin glycoside products. This study can provide a reference for artificially producing glycosyltransferase elements with high efficiency and specific catalysis.
Glucosyltransferases/genetics* ; Glycosyltransferases/metabolism* ; Isatis ; Lignans/metabolism* ; Molecular Docking Simulation ; Phloretin/metabolism* ; Phlorhizin/metabolism*

OBJECTIVE: To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease. METHODS: The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T₁₀ fracture, 3 cases of T₁₂ fracture, 9 cases of L₁ fractures, 5 cases of L₂ fractures and 2 cases of L₃ fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T₁₀ fracture, 1 case of T₁₁ fracture, 6 cases of T₁₂ fracture, 10 cases of L₁ fracture and 1 case of L₃ fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation. RESULTS: All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison(P<0.05), and there was no statistically difference between the two groups(P>0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant(P<0.05). CONCLUSION Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.
Bone Cements ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty/methods* ; Male ; Osteoporotic Fractures/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Spondylosis ; Treatment Outcome ; Vertebroplasty

OBJECTIVE: To investigate the effects of long-term and low dose ionizing radiation on ocular lens opacities of residents living in areas with high natural radiation background(HNRB) in Yangjiang City, China. METHODS: A total of 483 Han residents from Yangjiang City(HNRB area) and 517 from Enping City(control area) were selected as study subjects using a cluster random sampling method. Questionnaire survey and lens examination were carried out. The risk factors of lens opacity and its severity were analyzed by logistic regression analysis. RESULTS: The prevalence rates of lens opacity, cortical opacity and posterior subcapsular opacity in HNRB area were higher than those in control area(60.7% vs 51.6%, 53.4% vs 46.8%, 21.9% vs 9.3%, all P<0.05). There was no significant difference in karyotype turbidity between HNRB area and control area(52.4% vs 47.6%, P>0.05). After adjusting for confounding factors including age, gender, cardiovascular/metabolic diseases, smoking, alcohol drinking and tea drinking, the unconditional logistic regression analysis results showed that the risk of ocular opacity, cortical opacity and posterior subcapsular opacity in residents of HNRB area was higher than that in control area(all P<0.05). Multivariate disordered logistic regression analysis results showed that residents in the HNRB area had a higher risk of grade two karyotype turbidity than grade one karyotype turbidity(P<0.01). Ordered logistic regression analysis results showed that residents in HNRB area had an increased risk of developing severe cortical turbidity(P<0.01). CONCLUSION: Long-term and low dose ionizing radiation exposure may increase the risk of ocular lens opacity, especially cortical and posterior subcapsular cataract, and affect the severity of the disease.

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. In this study, we aimed to identify the risk factors for severe COVID-19 to improve treatment guidelines. METHODS: A multicenter, cross-sectional study was conducted on 313 patients hospitalized with COVID-19. Patients were classified into two groups based on disease severity (nonsevere and severe) according to initial clinical presentation. Laboratory test results and epidemiological and clinical characteristics were analyzed using descriptive statistics. Univariate and multivariate logistic regression models were used to detect potential risk factors associated with severe COVID-19. RESULTS: A total of 289 patients (197 nonsevere and 92 severe cases) with a median age of 45.0 (33.0, 61.0) years were included in this study, and 53.3% (154/289) were male. Fever (192/286, 67.1%) and cough (170/289, 58.8%) were commonly observed, followed by sore throat (49/289, 17.0%). Multivariate logistic regression analysis suggested that patients who were aged ≥ 65 years (OR: 2.725, 95% confidence interval [CI]: 1.317-5.636; P = 0.007), were male (OR: 1.878, 95% CI: 1.002-3.520, P = 0.049), had comorbid diabetes (OR: 3.314, 95% CI: 1.126-9.758, P = 0.030), cough (OR: 3.427, 95% CI: 1.752-6.706, P < 0.001), and/or diarrhea (OR: 2.629, 95% CI: 1.109-6.231, P = 0.028) on admission had a higher risk of severe disease. Moreover, stratification analysis indicated that male patients with diabetes were more likely to have severe COVID-19 (71.4% vs. 28.6%, χ2 = 8.183, P = 0.004). CONCLUSIONS The clinical characteristics of those with severe and nonsevere COVID-19 were significantly different. The elderly, male patients with COVID-19, diabetes, and presenting with cough and/or diarrhea on admission may require close monitoring to prevent deterioration.
Adult ; COVID-19/pathology* ; China/epidemiology* ; Comorbidity ; Cough ; Cross-Sectional Studies ; Diarrhea ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

Objective To estimate the mortality and years of life lost among youth aged 18-44 in Chongqing from 2011 to