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.

ObjectiveTo explore the guidance value of “treatment of disease in accordance with three conditions” theory in the prevention and treatment of corona virus disease 2019（COVID-19） based on the differences of syndromes and traditional Chinese medicine（TCM） treatments in COVID-19 patients from Xingtai Hospital of Chinese Medicine of Hebei province and Ruili Hospital of Chinese Medicine and Dai Medicine of Yunnan province and discuss its significance in the prevention and treatment of the unexpected acute infectious diseases. MethodDemographics data and clinical characteristics of COVID-19 patients from the two hospitals were collected retrospectively and analyzed by SPSS 18.0. The information on formulas was obtained from the hospital information system （HIS） of the two hospitals and analyzed by the big data intelligent processing and knowledge service system of Guangdong Hospital of Chinese Medicine for frequency statistics and association rules analysis. Heat map-hierarchical clustering analysis was used to explore the correlation between clinical characteristics and formulas. ResultA total of 175 patients with COVID-19 were included in this study. The 70 patients in Xingtai，dominated by young and middle-aged males，had clinical symptoms of fever， abnormal sweating，and fatigue. The main pathogenesis is stagnant cold-dampness in the exterior and impaired yin by depressed heat， with manifest cold， dampness， and deficiency syndromes. The therapeutic methods highlight relieving exterior syndrome and resolving dampness， accompanied by draining depressed heat. The core Chinese medicines used are Poria，Armeniacae Semen Amarum，Gypsum Fibrosum，Citri Reticulatae Pericarpium，and Pogostemonis Herba. By contrast，the 105 patients in Ruili， dominated by young females， had atypical clinical symptoms， and most of them were asymptomatic patients or mild cases. The main pathogenesis is dampness obstructing the lung and the stomach， with obvious dampness and heat syndromes. The therapeutic methods are mainly invigorating the spleen， resolving dampness， and dispersing Qi with light drugs. The core Chinese medicines used are Poria，Atractylodis Macrocephalae Rhizoma，Glycyrrhizae Radix et Rhizoma，Coicis Semen，Platycodonis Radix，Lonicerae Japonicae Flos， and Pogostemonis Herba. ConclusionThe differences in clinical characteristics， TCM syndromes， and medication of COVID-19 patients from the two places may result from different regions，population characteristics， and the time point of the COVID-19 outbreak. The “treatment of disease in accordance with three conditions” theory can help to understand the internal correlation and guide the treatments.

Adult ; Anastomosis, Surgical ; Constipation/surgery* ; Humans ; Megacolon/surgery* ; Proctocolectomy, Restorative

To analyze the functional change of horizontal semicircular canals after cochlear implantation.Eighteen patients were enrolled in this study.Their vestibular function was evaluated by using the caloric test and video head impulse test before and one week,one month after CI surgery,respectively.The unilateral weakness(UW),slow phase velocity(SPV)in caloric test and gain in video head impulse test(vHIT-G)were observed.Caloric test was abnormal when UW>25% or SPV mean<6°/s,while vHIT was abnormal when vHIT-G<0.8.The SPV of the implanted ear were[(10.36±8.01)°/s;(14.77±14.24)°/s]pre-operatively,[(6.45±7.52)°/s;(5.14±4.67)°/s]1 week post-operatively and[(6.05±3.86)°/s;(6.27±4.17)°/s]1 month post-operatively.Statistically significant difference(<0.05)was found between pre-and post-operative period.The vHIT-G of the implanted ear were(0.73±0.33)pre-operatively,(0.65±0.32)1 week post-operatively and(0.71±0.36)1 month post-operatively.There was no statistically significant difference of vHIT-G between preand post-operative period((pre-operative/1 week post-operative)=0.084,(pre-operative/1 month post-operative)=0.679).Four patients presented with vertigo and one of them manifested slight unsteadiness post-operatively.All symptoms resolved within 7 days.These symptoms had no correlate with age,gender,implantedear and results of vestibular test.Cochlear implantation can affect the horizontal semicircular canal function,and the video head impulse test and caloric test should be used in a complementary fashion.
Caloric Tests ; Cochlear Implantation ; adverse effects ; methods ; Head Impulse Test ; Humans ; Semicircular Canals ; physiopathology ; Vertigo

β3-adrenoceptor (β3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of β3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis assay. Furthermore, we investigated the NE-induced expression of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a β3-AR agonist and antagonist on expression of these marker genes. β3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the β3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti-apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK.
Adrenergic Agonists ; pharmacology ; Adrenergic Antagonists ; pharmacology ; Animals ; Apoptosis ; Cells, Cultured ; Myocytes, Cardiac ; drug effects ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo compare changes of hypothalamus-pituitary-adrenal axis (HPAA) in different rat models of Gan stagnation (GS), Pi deficiency (PD), Gan stagnation Pi deficiency (GSPD) syndromes, and to observe interventional effect of Chaishu Sijun Decoction (CSD, capable of soothing Gan-qi invigorating Pi) on them.

METHODSSeventy Wistar rats were divided into the normal control group (group 1), the GS group (group 2), the PD group (group 3), the GSPD group (group 4), the GS intervention group (group 5), the PD intervention group (group 6), and the GSPD intervention group (group 7) according to random digit table, 10 in each group. Rats in group 1 received no treatment. Rats in group 2 and 5 were modeled by chronic restraint method. Rats in group 3 and 6 were modeled by excess fatigue plus alimentary abstinence method. Rats in group 4 and 7 were modeled by chronic restraint, excess fatigue, and alimentary abstinence method. At the 2nd weekend of modeling, CSD at 2.86 g/kg was fed to rats in group 5, 6, and 7 by gastrogavage for 2 successive weeks. Equal volume of distilled water was given to rats in the rest 4 groups. On the 29th day, rats were killed, adrenal weight weighed, and adrenal index calculated. Levels of plasma and hypothalamus corticotropin-releasing hormone (CRH), plasma and pituitary adrenocorticotrophic hormone (ACTH), and plasma corticosterone (CORT) were determined using radioimmunity.

RESULTSCompared with group 1, adrenal index significantly decreased in group 2, 3, and 4 (P < 0.05). Of them, plasma and hypothalamus CRH, plasma CORT increased significantly in group 2 and 4 (P < 0.05). Besides, plasma and pituitary ACTH increased in group 4 (P < 0.05). Plasma and pituitary ACTH, as well as plasma CORT decreased significantly in group 3 (P < 0.05). Compared with group 2, 3, and 4, adrenal index increased significantly in group 5, 6, and 7 (P < 0.05). Compared with group 2, plasma CORT, hypothalamus CRH, and pituitary ACTH decreased significantly in group 5 (P < 0.05). Compared with group 3, plasma ACTH and CORT increased significantly in group 6 (P < 0.05). Compared with group 4, plasma CRH, ACTH, CORT, hypothalamus CRH, and pituitary ACTH decreased in group 7 (P < 0.05).

CONCLUSIONSThe function of HPA .axis was damaged to varying degrees in rats of the three models in this experiment. Hyperactivity of HPA axis existed in GS syndrome and GSPD syndrome. Impairment of feedback regulation in hypothalamus and pituitary was accompanied in GSPD syndrome. Hypofunction of HPA axis existed in PDS. CSD, capable of soothing Gan-qi invigorating'Pi, showed improvement on disarranged HPAA, but with optimal effect on GSPD syndrome. CSD had higher correlation with GSPD syndrome.

Adrenocorticotropic Hormone ; metabolism ; Animals ; Corticosterone ; Corticotropin-Releasing Hormone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hypothalamo-Hypophyseal System ; metabolism ; Hypothalamus ; metabolism ; Medicine, Chinese Traditional ; Models, Animal ; Pituitary Gland ; metabolism ; Pituitary-Adrenal System ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo observe changes of gonad functions of Gan-qi stagnation (GS), Pi deficiency (PD), Gan-qi stagnation Pi deficiency (GSPD) model rats, and the effect of Chaishu Sijun Decoction (CSD) on them.

METHODSRats were randomly divided into 7 groups according to romdom digit table, i.e., the normal control group, the GS model group, the GS medication group, the PD model group, the PD medication group, the GSPD model group,and the GSPD medication group, 10 in each group. Rats in the GS model group, the PD model group, and the GSPD model group were treated with chronic restraint, improper diet +excessive fatigue, chronic restraint +improper diet +excessive fatigue. The model was established for 4 successive weeks. Starting from the 15th day of modeling, CSD at the daily dose of 3.57 g/kg was given by gastrogavage to them for 14 successive days. Equal volume of distilled water was given by gastrogavage to rats in each model group and the normal control group for 14 successive days. The blood contents of gonadotrophin releasing hormone (GnRH), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and testosterone (T) were detected in rats of each group.

RESULTSCompared with the normal control group, there was statistical difference in GnRH, T, E,, and FSH in the GS, PD, and GSPD model groups (P < 0.05, P < 0.01). The content of LH was elevated in the GS model group (P < 0.05) and declined in the GSPD model group (P < 0.01). Compared with the GS model group, the contents of FSH, LH, and T decreased and E2 increased in the PD model group (all P < 0.05); the contents of FSH and LH also declined in the GSPD model group (P < 0.05). Compared with the PD model group, the T content increased and FSH decreased in the GSPD model group (all P < 0.05). Compared with each corresponding model group, the FSH content decreased (P < 0.01) and LH increased in the GS medication group; the T content increased, E2 and LH decreased (P < 0.05, P < 0.01) in the PD medication group; the T content decreased (P < 0.01), GnRH, E2, FSH, and LH increased (P < 0. 05, P < 0.01) in the GSPD medication group.

CONCLUSIONSThere exist different degrees of abnormal function of the gonad axis in the GS, PD, and GSPD models. CSD had certain regulatory effect on the 3 syndromes. Of them, it showed a more comprehensive role in improving the gonad function axis. Results of this experiment had provided the experimental evidence for higher correlation between CSD and GSPD syndrome.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Gonadal Steroid Hormones ; blood ; Gonads ; drug effects ; Male ; Rats ; Rats, Wistar

Humans ; Immunoglobulin M ; Lung ; pathology ; Multiple Myeloma ; diagnosis ; pathology

OBJECTIVETo investigate whether homocysteine (Hcy) participates the proliferation of the spontaneously hypertensive rat(SHR) vascular smooth muscle cell (VSMCs) and the molecular mechanism.

METHODSThe rat's arota were removed. The primary SHR VSMCs were isolated and cultured in vitro, then the SHR VSMCs were divided into four groups: (1) control group, (2) Hcy group, (3) 18alpha-glycyrrhetinic acid (GA) group, (4) Hcy + 18alpha-GA group. We detected proliferation of the SHR VSMCs by MTT and flow cytometry. The expression and co-localization of the connexin (Cx) 43 and Cx40 proteins in the SHR VSMCs were deteced by immunofluorescence. The expression of the Cx43 and Cx40 proteins in SHR VSMCs were detected by Western blot. The molecular dye transfer method (scrape dye transfer method) was applied to detect the gap junction function in the SHR VSMCs.

RESULTS(1) The Cx43 and Cx40 proteins expression in the SHR VSMCs were positive, confocal microscopy supported the co-localization of Cx43 and Cx40 in the cytoplasm. (2) The S value deteced by cell cycle and A value detected by MTT in the Hcy group were increased obviously compared with those in the control group (P < 0.05), decreased in 18alpha-GA group (P < 0.05). Compared with the Hcy group, the S and A value in the Hcy + 18alpha-GA group were significantly decreased, respectively (P < 0.05). (3) The expression of Cx43 and Cx40 proteins in Hcy group were increased compared with the control group (P < 0.05), decreased in 18alpha-GA group (P < 0.05). Compared with the Hcy group, the expression of Cx43 and Cx40 proteins in the Hcy + 18alpha-GA group were significantly decreased, respectively (P < 0.05). (4) The function of gap junction detected by scrape dye transfer method in the Hcy group were enhanced compared with the control group (P < 0.05), weakened in the 18alpha-GA group (P < 0.05). Compared with the Hcy group,the function of gap junction in the Hcy + 18alpha-GA group was significantly weakened (P < 0.05).

CONCLUSIONHcy can enhance the function of gap junctional to stimulate the proliferation of SHR VSMCs through the expression of Cx43 and Cx40 proteins promoted.

Animals ; Cell Proliferation ; Cells, Cultured ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Gap Junctions ; metabolism ; Glycyrrhetinic Acid ; analogs & derivatives ; pharmacology ; Homocysteine ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Rats ; Rats, Inbred SHR

Objective Through a two-year follow up program,this study was to analyze the urinary iodine frequency of a cohort in the intervention trial,concerning different doses of salt iodization,so as to explore the selection of appropriate concentration of salt iodization.Methods A multistage cluster sampling method was used to select three townships in two countries for community intervention with different doses [ ( 15 ± 5 ) mg/kg,(25 ± 5 ) mg/kg,( 35 ± 5 ) mg/kg ] of salt iodization.Results After intervention,the median of urinary iodine was reduced among the population.The urinary iodine frequencies of (15 ± 5) mg/kg and (25 ± 5) mg/kg among groups of children were mainly concentrated in 100-200 μg/L and 200-300 μg/L paragraphs in A county.While the 300 μg/Lparagraph had an overall decline in B county,the 100 μtg/L and 200 μg/L paragraph ratio increased but the trend seemed to be slow.The 100-300 μg/L paragraph of the four treatment groups took a larger proportion and kept smooth in a more ideal state.However,the control group still maintained at above 250 μg/L level.Conclusion The iodine supplementation should be gradually implemented in Chongqing.The doses of salt iodization should be reduced from the current (35 ± 15)mg/kg to (25 ± 5) mg/kg in the economically developed areas.At the same time,we need to continuously follow the changes of the condition.