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 explore the prognostic value of MUC13 expression in gastric cancer(GC)patients and its impact on the biological behavior of GC cells.Methods:Comprehensive anal-ysis of the expression pattern of MUC genes in GC tissues based on the TCGA database to screen for differentially expressed genes.Spearman correlation analysis determined the correlation of ex-pression between MUC genes in GC tissues.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analysis were used to explore the potential biological functions of MUC genes.Univariate COX regression analysis was performed to explore the relationship between all differentially expressed MUC genes and the prog-nosis of GC patients to screen out MUC genes that were significantly related to the prognosis of GC.Clinical GC tissue samples were used to further verify the expression of MUC13 through im-munofluorescence,and its relationship with the clinicopathological characteristics and prognosis of GC was analyzed.siRNA was used to silence the expression of MUC13 in GC cells,and the effect of MUC13 on cell proliferation,migration and invasion was analyzed through CCK-8,colony forma-tion and Transwell experiments.Results:Among all MUC members,the expression levels of MUC1,MUC2,MUC3A,MUC4,MCU5B,MUC12,and MUC13 were significantly upregulated in GC tissues(P＜0.05).There are certain interactions between these MUC genes,and they are mainly en-riched in pathways related to digestive system processes,epithelial structure maintenance,apical plasma membrane,saliva secretion,etc.Importantly,upregulation of MUC13 in GC tissues indicates poor patient prognosis(Log-rank P＜0.05).In addition,MUC13 expression was significantly correlat-ed with the age(P＜0.001)of GC patients and tumor size(P=0.035).Further cell function experiments showed that after silencing MUC13,the proliferation ability of GC cells was significantly reduced(P＜0.05),while their migration and invasion abilities were not significantly affected(P＞0.05).Con-clusions:Highly expressed MUC13 is closely related to the poor prognosis of gastric cancer,par-ticipates in the regulation of tumor progression and is a potential therapeutic target and prognostic marker for gastric cancer.

Objective To investigate the performance of brands and types of high-flow nasal cnnula oxygen therapy(HFNC)devices at different altitudes.Methods Four different models of HFNC devices,including R-80S bi-level non-invasive ventilator integrated with HFNC device,HF-60A HFNC device,HFT-300 HFNC device and H-80A HFNC device,were connected with the gas flow meter,simularted head and QuickLung and then put into a low-pressure chamber.The flow rates of the HFNC devices were set to 10,15,20,25,30,35,40,45,50,55 and 60 L/min,and the simulated altitudes of the low-pressure chamber were set to 6 000,5 000,4 000,3 000,2 000,1 000 and 0 m.The actual output airway flow rates,airway pressure changes and trends of the four HFNC devices were recorded at different setting altitudes and flow rates.SPSS 25.0 software was used for statistical analysis.Results The actual output airway flow rates of the four HFNC devices showed an increasing trend as the altitude rose with the simulated altitude of 6 000 m and the setting flow rate kept constant,which increased slowly and even went to decrease when the altitude and flow rate exceeded some limits.The degree of changes in the flow rate with the increasing altitude varied,and there was no uniform pattern.With the rising of altitude,the actual output airway pressure of the four HFNC devices with the flow rate raning from 10 to 35 L/min also increased gradually,which showed a decreasing trend(turning point)after going up to some certain value when the flow rate exceeded 35 L/min,and the altitude where the turning point appeared was lowered as the flow rate increased.Conclusion The actual output airway flow rates and airway pressure during HFNC rise at a high-altitude environment,and generally considerations have to be taken on required airway pressure,patient comfort and the altitude of the patient's usual place of residence when setting the flow rates of the HFNC device.[Chinese Medical Equipment Journal,2024,45(6):49-58]

Objective To explore the effect of chenodeoxycholic acid(CDCA)on the expression of glucagon-like peptide-1(GLP-1)in the intestine of mice induced by high-fat diet(HFD)through farnesoid X receptor(FXR),and investigate the related mechanism.Methods Forty C57BL/6 mice were divided into control group,HFD group,HFD+CDCA group,HFD+Z-Gug(FXR antagonist)group,and HFD+CDCA+Z-Gug group,with 8 animals in each group.During intervention for 8 weeks,body weight and 24-hour food intake were measured every week.At the 8th week,oral glucose tolerance test(OGTT)and intraperitoneal glucose tolerance test(IPGTT)were conducted.After the mice were sacrificed,the serum levels of GLu,TG,CHO,LDL-C and HDL-C were detected;the expression levels of GLP-1 and FXR in intestinal tissues were detected by immunofluorescence assay;and the mRNA levels of TNF-α,IL-6,IL-1β,Gcg and FXR were detected by RT-qPCR;the serum level of GLP-1 was detected by ELISA,and the proportion of intraepithelial lymphocytes(IELs)subsets and the expression of CD26/DPP4 were detected by flow cytometry.Results Compared with the control group,the HFD group had increased body weight,abnormal serum glucose and lipid metabolism,impaired oral glucose tolerance,and weakened secretion of gastrointestinal hormones(P＜0.05),enhanced FXR expression at mRNA and protein levels,declined Gcg mRNA level and GLP-1 secretion level(P＜0.05),increased mRNA levels of intestinal inflammatory factors TNF-α,IL-6 and IL-1β(P＜0.05),raised proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs,and TCRαβ+CD8αβ+IELs but reduced proportion of TCRγδ+IELs,and increased total CD26/DPP4 expression in IELs(P＜0.05).Compared with the HFD group,HFD+CDCA treatment resulted in significantly increased body weight,impaired oral glucose tolerance,decreased secretion of gastrointestinal hormones,increased FXR mRNA and protein expression,and decreased Gcg mRNA expression and GLP-1 secretion(P＜0.05);decreased proportions of TCRαβ+IELs,TCRαβ+CD8αα+IELs and TCRααβ+CD8αβ+IELs but increased proportion of TCRγδ+ cells in IELs,and increased expression of total CD26/DPP4 in IELs(P＜0.05),which were significantly improved after Z-Gug intervention(P＜0.05).Conclusion CDCA may inhibit the expression and secretion of GLP-1 in intestinal tissue by activating FXR,and reduce the secretion of GLP-1.At the same time,CDCA may inhibit the expression of related inflammatory factors,regulate the proportions of IELs subsets,up-regulate the expression level of CD26/DPP4,promote the degradation of GLP-1 and aggravate insulin resistance.

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.
Humans ; Antipyretics/therapeutic use* ; Capsules ; Common Cold/diagnosis* ; Double-Blind Method ; Fever/drug therapy* ; Hot Temperature ; Pharyngitis ; Treatment Outcome

Abstract: Objective To detect the polymorphisms of drug resistance-related genes pvcrt-o and pvmdr1 of Plasmodium vivax in lazan city in the China-Myanmar border, in order to guide the treatment plan of Plasmodium vivax. Methods A total of 48 Plasmodium vivax samples were collected from Lazan in the China-Myanmar border in 2007, and fragments of pvcrt-o and pvmdr1 genes were amplified by PCR and sequenced. The sequences were aligned with the Salvador I (Sal-I) strain reference genome sequences to determine the presence of SNPs. Results The target fragments of pvcrt-o gene were amplified from 39 Plasmodium vivax samples, while pvmdr1 genes were amplified from 40 samples. Amongst them, 25 samples had AAG insertion before the 10th amino acid (K10 insertion) of pvcrt-o gene, accounting for 64.1%. Non-synonymous mutations were detected at three loci of pvmdr1 gene (T958M, Y976F, and F1076L), the mutation rates were 100%, 22.5%, and 55.0%, respectively. There were three haplotypes of pvmdr1 gene, of which the triple mutant 958M/976F/1076L accounted for 22.5% (9/40), the double mutant 958M/Y976/1076L accounted for 32.5% (13/40), and the single mutant 958M/Y976/F1076 accounted for 45.0% (18/40). The proportion of strains with pvcrt-o and pvmdr1 gene mutation is 63.16%, which is significantly different from those only with pvmdr1 mutation. Conclusions The proportion of pvcrt-o and pvmdr1 gene mutation of 48 Plasmodium vivax isolates is high in the China-Myanmar border, and there is a certain degree of correlation between the two gene mutations. To assess changes in Plasmodium vivax drug resistance in this region, it is required to improve the surveillance of these two molecular markers.

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.
Animals ; Rats ; Rats, Sprague-Dawley ; NF-kappa B ; NF-KappaB Inhibitor alpha ; NLR Family, Pyrin Domain-Containing 3 Protein ; Galactose ; Interleukin-6 ; Neuroinflammatory Diseases ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha

The efficacy on chronic obstructive pulmonary disease (COPD) at stable stage treated with different methods of acupuncture and moxibustion was evaluated using network Meta-analysis method. The articles of the randomized controlled trial (RCT) on stable COPD treated with acupuncture and moxibustion were searched electronically in CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Web of Science and Cochrane library. The search was conducted from the inception of the databases to March 20th, 2022. Data analysis was performed using R4.1.1, Stata16.0 and RevMan5.3 softwares. A total of 48 RCTs were included, involving 15 kinds of acupuncture and moxibustion interventions and a sample size of 3 900 cases. The results of network Meta-analysis showed that: ① For the forced expiratory volume in one second predicted (FEV₁%), both the governor vessel moxibustion combined with conventional treatment (G+C therapy) and the yang-supplementing moxibustion combined with conventional treatment (Y+C therapy) obtained the better effect than that of the conventional treatment (P<0.05), and the G+C therapy was more effective compared with the thread-embedding therapy combined with conventional treatment (E+C therapy) and warm needling (P<0.05). ② Concerning to COPD assessment test (CAT) score, the results indicated that the Y+C therapy, and the mild moxibustion combined with conventional treatment (M+C therapy) were more effective when compared with the conventional treatment (P<0.05), and the effect of the Y+C therapy was better than that of the E+C therapy (P<0.05). ③ Regarding six-minute walking distance (6MWD), the effect of acupuncture combined with conventional treatment (A+C therapy) was better than that of either the E+C therapy or the conventional treatment (P<0.05). The effect of the G+C therapy was optimal for improving FEV₁%, the Y+C therapy obtained the best effect for improving CAT score, and A+C therapy was the most effective for improving 6MWD. Due to the limitation of the quality and quantity of included studies, this conclusion needs to be further verified through high-quality RCT.
Humans ; Moxibustion ; Network Meta-Analysis ; Acupuncture Therapy ; Databases, Factual ; Pulmonary Disease, Chronic Obstructive/therapy*

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.