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 clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals ; Berberine/therapeutic use* ; Fatty Liver ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Necrosis

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.

Objective To establish a rat model of craniocerebral blast injury caused by the shock wave of cabin explosion.Methods Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups (10 each):3g,5g,8g TNT with vest groups,5g TNT without vest group and control group.Uncased explosives of different equivalent were suspended in the cabin center.After anesthesia,with exception of control group,the rats were placed in prone position about 31 cm below the explosive,facing the explosive with or without vest.After the explosion,the survived rats were observed,serological and pathological examinations were performed at 3h,1d and 3d after the explosion.Results In terms of tissue damage and mortality,compared with the control group,no obvious injury formed in rats of the 3g TNT with vest group,and all of them survived;Rats in 5g TNT with vest group showed mild lung injury,brain tissue edema,enlarged blood vessel,patchy hemorrhage on the brain surface,and with a mortality of 30％;Rats in 8g TNT with vest group showed serious organ damage with a mortality of 80％;Rats in 5g TNT without vest group suffered from severe lung injury,almost all died right after the explosion.Therefore,rats in 5g TNT with vest group were more in line with the experimental needs.Further serum and pathologic examinations showed that the brain water content increased,the serum neuron specific enolase (NSE) and S-100β protein also increased markedly,and necrotic or apoptotic changes happened in the cortex and hippocampus neurons.Conclusion A stable animal model of craniocerebral blast injury may be established with rats in the case of chest and abdomen protected and then exposed to 5g TNT explosion in cabin.

BACKGROUNDThe long-term outcomes of patients with autoimmune hepatitis (AIH) given the immunosuppressive treatment are considered to be preferable. However, little is known about the response of AIH patients with cirrhosis to immunosuppressive treatment. We assessed the effects of immunosuppressive therapy in Chinese AIH patients with cirrhosis from a tertiary hospital.

METHODSPatients with a clinical diagnosis of AIH January 2000 and December 2015 were retrospectively reviewed. Two-hundred and fourteen patients who were followed up and satisfied the simplified AIH criteria were included in the study. Among these patients, 87 presented with cirrhosis when initially diagnosed for AIH. Immunosuppressive treatments were employed in 57 AIH patients who did not present with cirrhosis and 39 patients who presented with cirrhosis. Initial responses to immunosuppressive treatment of patients with and without cirrhosis were analyzed. Independent risk factors were assessed for predicting the prognosis of patients. The t-test and Cox regression statistical analysis were used.

RESULTSIn total, 96 AIH patients including 39 with cirrhosis and 57 without cirrhosis underwent immunosuppressive therapy. The overall complete remission after initial immunosuppressive treatment was achieved in 81/96 patients (84.4%), whereas 9/96 (9.4%) achieved incomplete response, and 6/96 (6.3%) occurred treatment failure. Compared to noncirrhotic patients, patients who presented with cirrhosis responded to treatment to a comparable extent regarding complete response (noncirrhosis 50/57 [87.7%] vs. cirrhosis 31/39 [79.5%], P = 0.275), incomplete remission (noncirrhosis 4/57 [7.0%] vs. cirrhosis 5/39 [12.8%], P = 0.338), and treatment failure (noncirrhosis 3/57 [5.3%] vs. cirrhosis 3/39 [7.7%], P = 0.629). Importantly, the remission rate was comparable (54/57 [94.7%] and 36/39 [92.3%], P = 0.629) for noncirrhotic and cirrhotic patients after immunosuppressive therapy. Compared to patients who maintained remission (n = 19) after drug withdrawal, patients who experienced relapse (n = 17) had significantly higher levels of serum immunoglobulin G at entry (15.0 ± 6.5 g/L vs. 22.3 ± 5.8 g/L, t = 2.814, P = 0.004). Moreover, cirrhosis at presentation significantly increased the risk of disease exacerbation (hazard ratio [HR]: 4.603; P = 0.002). The treatment of immunosuppressant (HR: 0.058; P = 0.005) and the level of aspartate aminotransferase at presentation (HR: 1.002; P = 0.017) also increased the risk of disease progression.

CONCLUSIONSThe efficacy of initial immunosuppressive treatment in AIH patients with cirrhosis is comparable to that in those without cirrhosis. Cirrhotic patients not treated by immunosuppressants have poor long-term outcomes.

Aged ; Asian Continental Ancestry Group ; Azathioprine ; therapeutic use ; Female ; Hepatitis, Autoimmune ; complications ; drug therapy ; Humans ; Immunosuppressive Agents ; therapeutic use ; Liver Cirrhosis ; drug therapy ; etiology ; Male ; Middle Aged ; Multivariate Analysis ; Prednisolone ; therapeutic use ; Proportional Hazards Models ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo analysis the molecular interaction network of 14-3-3 sigma in non small cell lung cancer (NSCLC) cells.

METHODSEstablished stable over-expressed 14-3-3 sigma protein PG cells, MTT assay was used to assess the growth rate of PG cells. Though stable isotope labeling by amino acids in cell culture (SILAC) and Mass spectrometry (MS) technology, to identify difference expressed proteins caused by over expressed 14-3-3 sigma. The protein expressed >2 or <0.5 times was termed as the differential protein. By searching Human protein reference database (HPRD) and Kyoto encyclopedia of genes and genomes (KEGG), established the molecular interaction network of tumor suppressor gene 14-3-3 sigma.

RESULTSThe growth rate of over-expressed 14-3-3 sigma PG cell was obviously slower down compared to vector PG cells. A database including 147 differential protein was established. And a molecular interaction network of 14-3-3 sigma containing 26 protein was constructed.In this network, the expression of CSNK2A1 (casein kinase II subunit alpha), involved in numerous cellular processes, such as cell cycle progression, apoptosis and transcription, was the most significantly increased. A DNA repair protein, MEN1 (Menin) which functions as a transcriptional regulator was the most significantly decreased.

CONCLUSIONAfter stable transfected with 14-3-3 sigma gene, growth rate of PG cells was inhibited, the proteins associated with cell cycle, DNA damage repair mechanisms were significantly changed, and constructed the molecular interaction network.

14-3-3 Proteins ; genetics ; Amino Acids ; Biomarkers, Tumor ; genetics ; Carcinoma, Non-Small-Cell Lung ; genetics ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Exoribonucleases ; genetics ; Humans ; Isotope Labeling ; methods ; Lung Neoplasms ; genetics ; Mass Spectrometry ; Transfection

Adenomatous Polyps ; pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Endoscopy, Digestive System ; Female ; Gastric Fundus ; pathology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Stomach Neoplasms ; pathology

Objective To analyze the characteristics of urinary iodine and edible iodized salt,and to provide suitable iodine concentration in iodized salt.Methods Sample testing was carried out to detect iodine concentration in marketed salt and child urine before salt iodization (1994).After salt iodization (2001-2010),sample testing was carried out to detect salt iodine level in manufacture,market(2001-2010) and resident household(1997-2010).Urine of children aged 8 to 10 were sampled by PPS method from 1997 to 2005.In 2009,urinary iodine of 20 children was determined in each of 5 schools,which were sampled from 5 counties located at North,South,East,West and center of Chongqing.Based on the urinary iodine and salt iodine levels before salt iodization,the relationship of urinary iodine and consumption of iodized salt was calculated.Suitable iodine concentration in iodized salt was put forward.x2 test and trend analyze approach(F-test) were used for statistical analysis.Results Before salt iodization,salt iodine level was not tested in 204 edible salt samples; the median of urinary iodine was 53.14 μg/L in 1374 children.After salt iodization,form 2001 to 2010,the average iodine levels in manufacture and wholesale salt were between 29.72-36.25 mg/kg and 30.65-36.13 mg/kg,respectively,both of them decreased significantly(F =35.35,140.59,all P ＜ 0.01),and show a downward trend.Batch quality passing rate of industry iodized salt was 100％ except in 2001,which was 92.86％.Batch quality passing rate of market iodized salt were between 88.68％-99.77％,specifically in 2001 (88.68％),in 2002(92.57％) and in 2003 (96.22％).There was no significant difference in other years (all P ＞ 0.05).The median of urinary iodine were between 238.80-328.00 μg/L,more than 35％ fall into ＞ 300 μg/L; while salt iodine increased 1 mg/kg,urinary iodine increased 5.51 μg/L-7.40 μg/L; The medium of urinary iodine of children were between 140.05-383.00 μg/L in 40 counties or districts in 2009.Reducing the iodine concentration in edible iodized salt to 20 mg/kg,the median of urinary iodine can be kept at 163.34 μg/L to 201.14 μg/L.Conclusions Iodine in iodized salt is above sufficient in Chongqing.Salt iodine should be reduced to 20 mg/kg,which will meet various population's need.

Objective To find out the current thyroid volume of school children and its influencing factors in Chongqing.Methods Probability sampling method(PPS) was used to select 30 counties in Chongqing in 2011.Forty children aged 8-10of 1 randomly selected school from every county chosen were enrolled in the study.Thyroid volume of children was examined by B-ultrasonograghy.Body height and body weight were measured.The relationship between gender,age,height and weight and thyroid volume was analyzed,respectively.Results One thousand three hundred and twenty-two children aged 8-10 were investigated.The median of thyroid volume was 3.53 ml.The goiter rate was 5.52％ (73/1322).Thyroid volume of female and male was 3.55 and 3.51 ml,respectively.There was no significant difference of thyroid volume between female and male (H =0.68,P ＞ 0.05).Thyroid volume of children aged 8,9 and 10 was 3.30,3.53 and 3.76 ml,respectively.There was a significant difference of thyroid volume among different age groups(H =52.49,P ＜ 0.01).Thyroid volume of children height (110-,120-,130-and ≥140 cm,respectively) was 2.96,3.22,3.59 and 4.13 ml.There was a significant difference of thyroid volume among different height groups (H =149.23,P ＜ 0.01).Thyroid volume of children weight(17-,20-,30-and ≥40 kg,respectively) was 2.71,3.31,3.91 and 4.74 ml.There was a significant difference of thyroid volume among different weight groups(H =138.44,P ＜ 0.01).For the coefficients of simple and partial correlation,there was a significant correlation between thyroid volume and age,height and weight (P ＜ 0.05).The Spearman coefficient was 0.2411,0.3950 and 0.4285,respectively.The partial correlation coefficient was 0.0640,0.1154 and 0.2319,respectively.The standard partial coefficient of age,height and weight was 0.640,0.1154 and 0.3410,respectively.The proportion of the standard partial coefficients was 1 ∶ 1.8 ∶ 5.3.The function of body weight to thyroid volume was 5.3 times that of age and 3.0 times that of body height.Conclusions The goiter rate of schoolchildren in Chongqing is relatively high.Thyroid volume is affected by age,body height and body weight.The relationship between thyroid volume and iodine nutrition needs further study.