1.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
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.
2.Effects of sodium acetate on lowering uric acid and renal protection in mice with hyperuricemic nephropathy
Xue-Man LIN ; Shi-Qi ZHONG ; Yong-Mei LI ; Xiao-Yi QIN ; He-Yang JIANG ; Jia-Xin ZHOU ; Jian-Xin PANG ; Ting WU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2222-2226
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.
3.Analysis of inorganic elements in different batches of earthworm polypeptides by ICP-MS combined with chemometrics technology
Hong-liu YANG ; Wei-ting ZHONG ; Yu-shi GUO ; Shu-qi LI ; Jin-chai QI ; Yong-gang LIU ; Tao MA
Acta Pharmaceutica Sinica 2024;59(4):1040-1047
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
4.Mechanism of Anti-inflammatory Effects of Bupi Yichang Pills on Inhibiting Glycolytic Metabolic Pathway in Mice with Experimental Colitis
Qiuping XIAO ; Jiaqi HUANG ; Qi WAN ; Min SHI ; Shanshan LI ; Duanyong LIU ; Liling CHEN ; Youbao ZHONG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):1-9
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.
5.Application of HPV semi-quantitative detection in swab of head and neck mucosal lesions
Qijia LI ; Xiaoyan WANG ; Yurong HE ; Rongjia LI ; Xiaoyu SHI ; Shuo DING ; Wei GUO ; Yanming ZHAO ; Jugao FANG ; Qi ZHONG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(6):341-345
OBJECTIVE To compare the consistency between the semi-quantitative detection of HPV E6/E7 mRNA and the detection of p16 IHC and E6/E7RNA ISH in the tissues,and the feasibility of detecting high-risk HPV in head and neck mucosal lesions by HPV E6/E7 mRNA detection in the swabs was discussed.METHODS A total of 100 cases of head and neck mucosal lesions treated by the Department of Head and Neck Surgery,Beijing Tongren Hospital Affiliated to Capital Medical University from September 2022 to August 2023 were collected.Semi-quantitative detection of HPV E6/E7 mRNA was performed in oropharynx,lesion surface swab and lesion tissue specimen,and p16 immunohistochemical staining(IHC)and E6/E7 mRNA in situ hybridization(ISH)were detected in lesion tissue,and the consistency and difference of different detection results were studied.RESULTS Among the 100 patients,83 met the inclusion criteria and were divided into 21 papilloma cases,10 polyps/chronic inflammation cases,19 laryngeal cancer cases,13 oropharyngeal cancer cases,and 20 hypopharyngeal cancer cases according to pathological diagnosis.The HPV E6/E7 mRNA semi-quantitative results of oropharyngeal swab and lesion surface swab showed moderate or near high consistency with p16 IHC results.The results of HPV E6/E7 mRNA semi-quantitative in diseased tissue were highly consistent with those of p16 IHC(Kappa=0.780).In the diagnostic efficacy analysis,both swabs showed high consistency with HPV E6/E7 mRNA ISH(Kappa=0.690 and 0.708).CONCLUSION In the head and neck mucosal lesions,the HPV semi-quantitative detection results of oropharyngeal and lesion surface swab showed good consistency compared with classical p16 IHC and gold standard HPV E6/E7 mRNA ISH.It is a simple and reliable method for clinical high-risk HPV detection,which is helpful for the screening and individualized precise prevention and control of HPV infection in head and neck mucosal lesions.
6.The future directions of artificial intelligence in the biological benefit-dominated diagnosis and treatment of pan-creatic cancer
Zhong QI ; Ying XING ; Shi CHENG
Journal of Surgery Concepts & Practice 2024;29(1):5-9
Pancreatic cancer is a high malignant tumor with insidious onset,early metastasis,and extremely poor prognosis.How to improve the early diagnosis and the prognosis of the patients is the current research focus.Although traditional surgical resection may improve the prognosis of some patients,the long-term effect is still poor.Biological benefit is the new mode of pancreatic cancer treatment,and it is crucial to do the whole process monitoring,precisely make the treatment plan and predict the effect under this mode.Artificial intelligence technology,with its powerful data processing and image recognition functions and high learning efficiency,can help to build relatively perfect prediction models with the cooperation of multidisciplinary experts,assist clinicians to make optimal plans,and make the pancreatic cancer patients benefit from precision medicine and individualized therapy.
7.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
8.Effect and significance of Wenyang Qudu formula on serum inflammatory factors and immune index in patients with severe infections
Zhijing XU ; Congmei WANG ; Yu'an GEN ; Lu QI ; Yangang SHI ; Huiming ZHANG ; Ying ZHANG ; Yihang ZHONG ; Ruifang LIU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):20-23
Objective To explore effect of Wenyang Qudu formula on serum inflammatory factors and immune index in patients with severe infections.Methods A total of 86 severe infection patients admitted to the Third People's Hospital of Henan Province from January to December 2023 were selected as the research subjects.According to the patient file order,odd numbers were the study group,and even numbers were the control group,with 43 cases in each group.The control group was treated with cefoperazone sulbactam sodium,while the study group was treated with Wenyang Qudu formula in addition to the control group[drug composition:Prepared aconite(first decocted)30 g,Poria cocos 30 g,White peony 15 g,Red peony 15 g,Stir fried atractylodes macrocephala 30 g,Dried ginger 9 g,Roasted licorice 9 g,Cassia twig 15 g,Semen lepidii 15 g,Dragon's bone 15 g,Raw oyster 15 g,Codonopsis pilosula 12 g,Angelica sinensis 12 g,Asarum 3 g,Schisandra chinensis 6 g,and Jujube 12 g].Brew in water,and took one dose daily,once in the morning and once in the evening,for a continuous period of 7 days.The differences in the scores of traditional Chinese medicine symptoms such as fever,dyspnea,frequent urination,urgency,and degree of sputum production,serum levels of interleukin-10(IL-10),C-reactive protein(CRP),eosinophils(EOS),and immune function indicators[immunoglobulin E(IgE),CD3+,CD4+,CD8+,CD4+/CD8+]were compared between two groups after treatment,and observed the occurrence of adverse reactions.Results After treatment,the traditional Chinese medicine symptom scores(fever,dyspnea,frequent urination and urgency,degree of sputum production),as well as IL-10,CRP,EOS levels,IgE,and CD8+ were significantly reduced in both groups compared to before treatment,CD3+,CD4+,and CD4+/CD8+ were significantly increased compared to before treatment.In addition,the study group had significantly lower scores of fever,dyspnea,frequent urination and urgency,degree of sputum production,IL-10,CRP,EOS levels,IgE,and CD8+ compared to the control group(fever score:1.36±0.30 vs.2.57±0.46,dyspnea score:1.22±0.31 vs.2.26±0.75,urinary frequency and urgency score:1.30±0.39 vs.2.33±0.82,degree of sputum production:1.19±0.77 vs.2.51±0.85,IL-10(ng/L):9.03±1.67 vs.10.51±2.40,CRP(mg/L):4.68±1.33 vs.7.82±2.53,EOS(×109/L):0.30±0.04 vs.0.46±0.10,IgE(mg/L):104.62±10.73 vs.135.68±14.64,CD8+:0.228±0.016 vs.0.258±0.020,all P<0.05],the levels of CD3+,CD4+,and CD4+/CD8+ were significantly higher than those in the control group(CD3+:0.636±0.044 vs.0.567±0.055,CD4+:0.537±0.054 vs.0.397±0.045,CD4+/CD8+:1.76±0.51 vs.0.55±0.39,all P<0.05].After treatment,it was discovered that the study group had not experienced any adverse reactions,while the control group had 1 case of nausea and vomiting and 1 case of chest tightness.There was no statistically significant difference in the incidence of adverse reactions between the study group and the control group[0(0/43)vs.0.05%(2/43),P>0.05].Conclusion The Wenyang Qudu formula can reduce the serum factor levels of IL-10,CRP,and EOS in critically infected patients,and improve immune function with good safety.
9.Allyl isothiocyanate exacerbates acute toxoplasmosis through inhibition of inflammatory cytokines
Qiu-Mei LIN ; Hong-Bin LONG ; Jun-Ting HE ; Zhi-hao ZHANG ; Ho-Woo NAM ; Fu-Shi QUAN ; Qi ZHONG ; Xu-Qing LIU ; Zhao-Shou YANG
Parasites, Hosts and Diseases 2024;62(4):476-483
Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.
10.Allyl isothiocyanate exacerbates acute toxoplasmosis through inhibition of inflammatory cytokines
Qiu-Mei LIN ; Hong-Bin LONG ; Jun-Ting HE ; Zhi-hao ZHANG ; Ho-Woo NAM ; Fu-Shi QUAN ; Qi ZHONG ; Xu-Qing LIU ; Zhao-Shou YANG
Parasites, Hosts and Diseases 2024;62(4):476-483
Allyl isothiocyanate (AITC) is a natural product commonly used in food preservation and pharmaceutical applications. Toxoplasmosis, caused by the protozoan pathogen Toxoplasma gondii, is prevalent globally while the impact of AITC on toxoplasmosis is unclear. We explored the effect of AITC on acute toxoplasmosis. We infected C57BL/6 mice with T. gondii type I RH strain following AITC administration. On the 4th day after infection, which corresponds to the initial stage of infection, we collected serum for the determination of inflammatory cytokine levels. The mice serum of the AITC-administered group contained significantly lower levels of granulocyte colony-stimulating factor, interferon-gamma, interleukin (IL)-23 subunit p19, IL-4, IL-6, and monocyte chemoattractant protein-1. The lifespan of the mice in the AITC-administered group was significantly reduced. In vitro experiments showed that AITC promoted the proliferation of intracellular T. gondii accompanied by the inhibition of IL-4, IL-1β, and IL-6 production in RAW264.7 macrophages. Our results showed that AITC facilitated T. gondii infection in the early stage by inhibiting the production of several inflammatory cytokines.

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