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.

Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9％NaCl+0.5％carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5％carboxymethyl cellulose sodium),model group(0.9％NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P＜0.05,P＜0.01,P＜0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

To establish a method for determining 26 inorganic elements in earthworm polypeptide and determine the elemental content in different batches of earthworm polypeptide, microwave digestion method was used to pre-treat the samples, and ICP-MS method was used to determine the content of 26 elements in different batches of earthworm polypeptide. The linear relationships of 26 elements were good in the range of 0-1 000 μg·L^-1, with R² greater than 0.999, precision RSD 0.21%-2.71%, repeatability RSD 0.19%-4.69%, stability RSD 0.11%-4.24%, and recovery rates of 82.41%-116.16%. The data was plotted using Origin 2022 software to characterize the distribution of elements content. SPSS 27.0 was used for principal component analysis, and SIMCA 14.1 software was used for OPLS-DA analysis. The results showed that among the 26 elements, the higher content of earthworm polypeptide was K, Na, and Ca, followed by Zn, Fe, Al, B and other trace elements, In, Sc, Co, Pb, Bi and other elements had little or no detectable content, and there were differences in the content of polypeptide in different batches. This study provides a theoretical basis for the production quality control, quality evaluation and drug efficacy application of earthworm polypeptide through the determination and analysis of the elements and content of earthworm polypeptide.

An integrated evaluation model based on the combination of traditional trait identification and modern chemical analysis was used for the identification of key indexes of grade classification and the establishment of grade quality standard of Lycium barbarum fruits (LBF) from Ningxia genuine producing area. Under the guidance of herbal examination and market survey, particle size, skin color and imperfection were taken as the external trait indicators; focusing on the comprehensiveness and validity of the quality evaluation, 2-O-β-D-glucopyranosyl-L-ascorbic acid (AA-2βG), zeaxanthin dipalmitate (ZD) and volatile ether extractives were used as important parameters involving in quality evaluation in addition to the pharmacopoeia test items and determination indicators such as moisture, ash, water-soluble extractives, Lycium barbarum polysaccharide (LBP) and betaine. The quality differences between different traits and grades of LBF as well as the relevance between character and quality were further investigated by mathematical and statistical means such as t-test analysis, correlation analysis and principal component analysis (PCA). Furthermore, the activities of extractives from different grades of LBF were compared at cellular level. The results showed that LBF were mainly preferred for large and red ones; except for betaine, the other index components were relatively high (moisture and ash were low) in the first-grade and samples with bright-red skin color. Besides, there was a significant correlation between skin color and moisture, water-soluble extractives, LBP, AA-2βG and ZD contents. Considering the results of the study and the market situation, the present study took the grain size and skin color of LBF as the core of evaluation, and at the same time introduced the multi-indicator components including LBP, AA-2βG, ZD, water-soluble extractives and moisture to further guide the grading, and established the quality standard of LBF grades combining the trait indexes and the chemical composition. More importantly, in vitro cell models both preliminarily confirmed that the first-grade LBF played a more significant "nourishing liver and kidney" effect, which provided an experimental basis for the quality control of LBF and promoted the realization of high quality and good price.

Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.

Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.

OBJECTIVE To investigate the in vitro anti-inflammatory effects and mechanisms of oblongifolins A （OA） extracted from Garcinia oblongifolia. METHODS RAW264.7 cells were used as the research subject and divided into control group （0.5% DMSO）， lipopolysaccharide （LPS） group （1 μg/mL）， DEX group （10 µmol/L DEX+1 μg/mL LPS）， and low-， medium-， and high-concentration groups of OA （7.5， 15， 30 µmol/L OA+1 μg/mL LPS）. Except for the control group， the remaining groups were first stimulated with LPS for 1 hour and then mixed with drugs for 24 hours. The morphological changes of cells were observed in each group. The contents of nitric oxide （NO）， reactive oxygen species （ROS）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， IL-4 and IL-10 were detected in cells of each group； mRNA expression levels of TNF-α， IL-6 and IL-1β were measured. The expression of key proteins in the nuclear factor κB （NF-κB） and nuclear factor-erythroid 2-related factor 2 （Nrf2） signaling pathways in each group， as well as the nuclear translocation of NF-κB p65 and Nrf2 proteins in control group， LPS group and OA high-concentration group， were detected. RESULTS Compared to the LPS group， the number of spindle-shaped and irregular cells gradually decreased in OA groups， the contents of NO， ROS （except for OA low-concentration group）， TNF-α， IL-6 and IL-1β， the mRNA expressions of TNF-α， IL-6 （except for OA low-concentration group） and IL-1β as well as the protein expressions of phosphorylated NF-κB p65 （p-NF-κB p65）， p-IκBα， and Kelch-like ECH-associated protein 1 （Keap1） were decreased significantly （P＜0.05）. The contents of IL-4 and IL-10， protein expressions of IκBα， Nrf2 （except for OA low- and medium-concentration groups）， HO-1 （except for OA low-concentration group） and NQO1 were all increased significantly （P＜0.05）. OA of high concentration could inhibit NF-κB p65 protein nuclear translocation and promote Nrf2 protein nuclear translocation. CONCLUSIONS OA can suppress LPS-induced inflammation in RAW264.7 macrophages. The underlying molecular mechanism likely entails the inhibition of the NF-κB signaling pathway， the activation of the Nrf2 signaling pathway and the reduction of ROS and inflammatory factor release.

【Objective】 To explore the effectiveness of an image recognition system based on artificial intelligence (AI) in diagnosing benign and malignant endometrial cell clumps. 【Methods】 We selected endometrial cytological specimens from The First Affiliated Hospital of Xi’an Jiaotong University and Xi’an Daxing Hospital from August 2021 to February 2023; histopathology was used as the gold standard. We compared and analyzed the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and diagnostic time of AI image recognition system (AI diagnosis) and professional pathologists’ manual diagnosis (manual diagnosis) of benign and malignant endometrial cell clumps. 【Results】 Among the 126 patients included in the analysis, the overall coincidence rate of AI diagnosis and histological diagnosis was 92.1% (116/126), which was highly consistent with histopathological results (Kappa=0.841). The overall coincidence rate of manual diagnosis and histological diagnosis was 94.4% (119/126), which was highly consistent with histopathological results (Kappa=0.889). There was no statistically significant difference between AI diagnosis and manual diagnosis methods (χ²=0.568, P=0.451). The sensitivity, specificity, positive predictive value, and negative predictive value of AI diagnosis were 91.8%, 92.3%, 91.8%, and 92.3%, respectively. There were 126 cytology sections, each of which required 6.67 minutes for manual diagnosis and 5.00 minutes for AI diagnosis. 【Conclusion】 The AI image recognition system has high diagnostic accuracy, sensitivity and specificity, which is equivalent to the manual diagnosis level of professional pathologists. Therefore, this system has application value in the diagnosis of benign and malignant endometrial cell clumps.