1.Treadmill Exercise Improves Cognitive Dysfunction in Diabetic Mice by Regulating PANoptosis Through the p38 MAPK Signaling Pathway
Ke-Yan SHENG ; Yu-Yan CHEN ; Yuan GAO ; Bao-Wen ZHANG ; Meng ZHANG ; Zhi WANG ; Xian-Juan KOU
Chinese Journal of Biochemistry and Molecular Biology 2024;40(7):987-998
Cognitive dysfunction is one of the serious complications of type 2 diabetes.Exercise interven-tion has a certain effect on improving diabetes cognition,but the exact process remains ambiguous.This research aims to explore the impact and molecular processes of treadmill exercises in enhancing cognitive impairments in type 2 diabetic mice.Ten m/m 8-week-old male mice were used as the control group.Forty db/db mice,each 8 weeks old and male,were categorized into four distinct groups with each group containing 10 mice,including the db/db group(model group),db+Exe group(exercise group),db+Exe+SB203580 group(exercise combined with the p38 MAPK inhibitor group),db+SB203580 group(p38 MAPK inhibitor group).db+Exe group and db+Exe+SB203580 group were subjected to treadmill running intervention(40 min/time,5 times/week,a total of 8 weeks).db+Exe+SB203580 and db+SB203580 group were intraperitoneally injected with SB203580(5 mg/kg,5 times/week,8 weeks)2 hours before treadmill exercise.The results of body weights and fasting blood glucose measurement showed that 8-week treadmill exercise could significantly reduce the body mass and fasting blood glucose levels(P<0.01);the results of water maze showed that treadmill exercise improved cognitive dysfunction in diabetic mice(P<0.05).Immunofluorescence staining revealed that treadmill exercise diminished the fluorescence intensity of NLRP3 in hippocampus,and there was a significant difference in CA1 and CA3 regions(P<0.05).Treadmill exercise reduced the fluorescence intensity of PI in the hippocampus,and there was a significant difference in the DG region(P<0.01).The results of qRT-PCR revealed that treadmill exercise decreased IL-1β and IL-18 mRNA levels in hippocampus,with a notable difference in IL-1β mRNA levels(P<0.05).Western blotting analysis revealed that treadmill exercise reduced the concentrations of Caspase3,Caspase9 and Bax in hippocampus(P<0.01),reduced the concentrations of TXNIP,NLRP3,GSDMD-N,IL-1β,IL-18,Cleaved Caspase1 and Caspasel(P<0.05),decreased the levels of p-RIPK1,RIPK1,p-RIPK3 and RIPK3(P<0.05).After adding p38 inhibitors,treadmill ex-ercise combined with p38 inhibitor intervention further inhibited the expression of Caspase3,TXNIP,GS-DMD-N and IL-18(P<0.05),and the expression levels of Caspase9,Bax,NLRP3,IL-1β,Cleaved Caspase 1 and Caspase 1 also showed a downward trend.The expression of RIPK1 and p-RIPK3 in-creased significantly(P<0.05),and the protein expression levels of p-p38,p-RIPK1 and RIPK3 showed an upward trend.In conclusion,treadmill running intervention can effectively improve the cogni-tive dysfunction in type 2 diabetic mice,and its mechanism is partly through the p38 MAPK signaling pathway to regulate PANoptosis.
2.Establishing integrated system-based point-of-care testing method for genotyping of respiratory syncytial virus
Fei DENG ; Liguo ZHU ; Ke XU ; Xian QI ; Huiyan YU ; Shenjiao WANG ; Changjun BAO
Chinese Journal of Microbiology and Immunology 2024;44(8):660-664
Objective:To develop an integrated point-of-care testing (POCT) reagent for genotying respiratory syncytial virus (RSV) and evaluate its performance.Methods:Specific primers and probes were designed based on the conserved sequences of the genomes of RSV A and B as well as ON1 and BA9 genotypes. The PCR reaction system and conditions were optimized. The vitrification technology of reagents and multiplex detection platform were integrated to develop the RSV genotyping POCT reagent. The sensitivity, specificity, reproducibility, and clinical performance of the product were then evaluated.Results:The sensitivity of the developed integrated RSV genotyping POCT reagent reached 500 copies/ml. It exhibited good specificity with no cross-reaction with clinically similar pathogens. The coefficient of variation of Ct values for both inter-batch and intra-batch reproducibility was less than 5%, indicating good reproducibility. In testing 53 clinical samples, the detection results showed high consistency and concordance with the reference reagent, with a positive concordance rate of up to 98.11%.Conclusions:The developed integrated RSV genotyping POCT reagent incorporates nucleic acid extraction, purification, and detection into a single process, achieving a "sample in, result out" workflow. It is simple to operate and provides accurate, reliable, and stable detection results. This product can be used for the genotyping of RSV A and B in POCT, offering support for the prevention, control, and diagnosis of RSV.
3.The correlation between colorectal cancer tissues JAK2 gene mutations and TCF3 protein expression with clinical pathological features and prognosis
Ke-Jin YAN ; Hong-Liang ZHU ; Xian-Qiang XIE ; Dong-Sheng LI ; Zeng-Lu ZHENG ; Ji-Yang LI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(6):675-680,690
Objective To explore the correlation between colorectal cancer tissue Janus kinase 2(JAK2)gene mutations and T cytokine 3(TCF3)protein expression with clinical pathological characteristics and prognosis,and to provide laboratory reference indicators for early evaluation of the illness severity and prognosis of colorectal cancer.Methods A retrospective analysis was conducted on the data of 50 colorectal cancer patients who were admitted from January 2016 to April 2021 and retained colon cancer and adjacent tissue wax blocks.Basic information,clinical and pathological features such as TNM staging,lymph node metastasis,and 3-year survival prognosis of the patients were collected.The wax blocks of colon cancer and adjacent tissues of patients were detected,in which Taqman fluorescence probe method was applied to detect the distribution of JAK2 gene at the rs2230724 locus AA,AG,and GG genotypes in colon cancer tissues,and immunohistochemistry method was applied to detect the positive expression rate of TCF3 protein in colon cancer and adjacent tissues.The basic information,JAK2 rs2230724 gene mutation,and TCF3 protein expression of patients with different clinical and pathological characteristics were compared,and the influencing factors of clinical and pathological characteristics of colon cancer was analyzed by logistic regression model.Kaplan Meier survival curve was applied to compare the survival prognosis of patients with JAK2 gene mutations and TCF3 protein expression in colorectal cancer tissue,and Cox regression model was applied to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The positive expression rate of TCF3 protein in colon cancer tissues was higher than that in adjacent tissues(P<0.05).The age,BMI,proportion of GG genotype at rs2230724 locus of JAK2 gene and positive expression rate of TCF3 protein in TNM stage Ⅲ colon cancer patients were higher than those in TNM stage Ⅰ-Ⅱ patients(P<0.05);The age,BMI,smoking rate,proportion of GG type at the rs2230724 locus of JAK2 gene in colon cancer tissue,and positive expression rate of TCF3 protein in patients with lymph node metastasis were higher than those without lymph node metastasis(P<0.05);The results of the logistic regression model analysis showed that the influencing factors of clinical pathological features such as TNM staging and lymph node metastasis in colon cancer were age,mutation of JAK2 gene rs2230724 site in colon cancer tissue,and positive expression rate of TCF3 protein(P<0.05).The Kaplan Meier survival curve analysis showed that patients with JAK2 gene rs2230724 GG genotype and TCF3 protein positivity in colon cancer tissue had higher cumulative all-cause mortality rates(P<0.05).The results of univariate and multivariate Cox regression model analysis showed that independent risk factors affecting the prognosis of colorectal cancer patients include JAK2 gene rs2230724 site GG type,TCF3 protein positive expression,TNM stage Ⅲ,lymph node metastasis,and age.Conclusion The proportion of JAK2 gene rs2230724 GG type and TCF3 protein expression in colorectal cancer tissues are related to their clinical pathological characteristics and prognosis,and can be used as reference indicators for evaluating clinical pathological characteristics and predicting prognosis of colorectal cancer.
4.Design and implementation of nuclear emergency medical rescue simulation platform based on VR and AR technologies
Ke-Xian LI ; Hai-Jun WANG ; Ying HE
Chinese Medical Equipment Journal 2024;45(9):50-56
Objective To design a nuclear emergency medical rescue simulation platform to solve the problmes in nuclear accident scenario simulation,fidelity of on-site medical treatment training and training organization.Methords A nuclear emergency medical rescue simulation platform was developed with the technologies of virtual reality(VR),augmented reality(AR),spatial positioning,full-body motion capture,gesture simulation and three-dimensional modeling,Unity3D platform,3D Studio Max software and Visual Studio,which mainly consisted of a hardware system and a software system.The hardware system was composed of the AR training equipment and VR training equipment,of which,the AR training equipment included a surface contamination detector simulator,an individual decontaminator simulator and AR glasses,and the VR training equipment was made up of VR glasses,large-space localization equipment,backpack computers,data gloves and full-body motion capture equipment.The software system involved in several modules for theoretical knowledge teaching and assessment,VR/AR practical teaching training and VR/AR evaluation.Results The system realized simulated collaborative training and evaluation for medical emergency response to nuclear accidents.Conclusion The platform constructed contributes to solving the practical problems in organizing and implementing education and training for nuclear emergency medical rescue,and the education and training are both enhanced greatly.[Chinese Medical Equipment Journal,2024,45(9):50-56]
5.Application Progress of Electrochemical Methods in Quality Control of Traditional Chinese Medicine
Yan-Bing PAN ; IHSAN AWAIS ; Min SHI ; Wen-Wen MA ; MURTAZA GHULAM ; Ke-Fei HU ; Jun LI ; Xian-Ju HUANG ; Han CHENG
Chinese Journal of Analytical Chemistry 2024;52(1):22-34
The quality control of traditional Chinese medicine(TCM)is the core issue to ensure the modernization,industrialization and internationalization of TCM.Compared with other detection methods,electrochemical analysis method has many advantages such as high sensitivity,fast detection speed and low cost,making it an important means of quality control for TCM and having broad development prospects.This article reviewed the research progress of electrochemical methods in quality control of TCM in recent years,discussed the application of electrochemical fingerprinting technique in identification of TCM,and comprehensively summarized the application of electrochemical technology in analyzing effective components and harmful substances in TCM,including flavonoids,alkaloids,quinones,glycosides,heavy metals and pesticide residues.Finally,the development prospects of electrochemical methods in the field of quality control of TCM were discussed.
6.Exploration on the Clinical Application of Ephedrae Herba in Stimulating Yang Qi
Yi-Shan ZHOU ; Xian-Yong LIAO ; Ke-Lang RAO ; Ying PI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):234-239
Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3~9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.
7.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.
8.Exercise Improves Nonalcoholic Fatty Liver Disease in T2DM Mice by Inhibiting Ferroptosis Through p38 MAPK Signaling Pathway
Bao-Wen ZHANG ; Ying LI ; Yuan GAO ; Ke-Yan SHENG ; Zhi WANG ; Xian-Juan KOU
Progress in Biochemistry and Biophysics 2024;51(11):2983-2997
ObjectiveTo explore the mechanism of treadmill exercise against type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) based on the regulator effects of exercise on ferroptosis. MethodsEight 8-week-old male m/m mice were used as control group (Con, n=8), and db/db mice of the matched age were randomly divided into T2DM model group (db/db, n=8), exercise group (db+Exe, n=8), p38 mitogen-activated protein kinase (MAPK) inhibitor group (db+SB203580, n=8) and exercise combined with p38 MAPK inhibitor group (db+Exe+SB203580, n=8). After one-week adaptive feeding, the mice in the db+Exe group and db+Exe+SB203580 group underwent moderate intensity treadmill exercise for 40 min/d, 5 d/week lasting 8 weeks. The db+SB203580 group and db+Exe+SB203580 group were treated with SB203580 (a specific inhibitor of p38 MAPK) with a dose of 5 mg/kg, 5 d/week for 8 weeks. And the exercise intervention was performed 2 h later after the intraperitoneal injection of SB203580. The body weight and fasting blood glucose of mice were measured regularly every week during the experiment. After 24 h of the last intervention, the mice were weighted, the liver tissues were taken, weighted and the liver index was calculated. The pathological changes of liver were determined by Oil Red O and hematoxylin-eosin (HE) staining. The levels of blood lipids, liver function, Fe2+ and oxidative stress markers of liver were measured by enzyme linked immunosorbent assay (ELISA). The related mRNA expression levels of lipogenesis and inflammation were evaluated by quantitative reverse transcriptase-mediated PCR (qRT-PCR). The related protein expression levels of lipogenesis and ferroptosis in liver were determined by immunohistochemical (IHC) staining and Western blot. ResultsThe body weight, fasting blood glucose, liver index, blood lipid and transaminase levels in the db/db group were significantly increased compared with the Con group. HE and Oil Red O staining showed severe lipid accumulation and ballooning change in the liver of db/db mice. Biochemical tests showed that Fe2+ and MDA level of liver constitution homogenate increased, while GSH level decreased significantly. The results of qRT-PCR showed that the mRNA levels of MCP-1, IL-6, SREBF1 and ACC1 in liver tissue of db/db mice were all significantly increased. Western blot results showed that the expression levels of SREBF1, ACC1 increased, ferroptosis relative proteins were significantly decreased. The 8 weeks of exercise significantly reduced the rise in body weight, blood glucose, liver index and blood lipid levels in db/db mice. Exercise intervention also alleviated hepatic steatosis and reduced the expression levels of Fe2+, MDA, MCP-1, IL-6, ACC1 and SREBF1, upregulated the expression levels of GSH, NRF2, HO-1, SLC7A11 and GPX4 in liver tissue of db/db mice. The intervention of exercise combined with SB203580 significantly down-regulated the mRNA expression levels of ACC1, MCP-1, IL-6, reduced the levels of Fe2+ and MDA, and up-regulated the level of GSH in db/db mice. Compared with the db+Exe group, the expression of Fe2+, MDA, MCP-1, and SREBF1 in the liver of the db+Exe+SB203580 group mice significantly increased, while the expression level of GSH and expression levels of ferroptosis relative proteins also significantly decreased. In addition, compared with db+SB203580 group, the iron accumulation and lipid peroxidation in the liver of db+Exe+SB203580 group were significantly improved. ConclusionThe8-week treadmill exercise can effectively alleviate liver injury and steatosis, and its mechanism may be related to the inhibition of hepatocyte ferroptosis through p38 MAPK signal.
9.MEI Guoqiang's Experience in Treating Lung Cancer with Modified Xiaoxianxiong Decoction (小陷胸汤)
Shuo HUANG ; Songlin LIU ; Xian ZHOU ; Lesi XU ; Kaizheng ZHAO ; Youlan KE ; Huiyi LU
Journal of Traditional Chinese Medicine 2024;65(17):1753-1756
This article summarized the clinical experience of MEI Guoqiang in treating lung cancer of phlegm-heat obstructed in the lung syndrome with modified Xiaoxianxiong Decoction (小陷胸汤). It is believed that the key pathogenesis of lung cancer with phlegm-heat obstructed in the lung syndrome is the phlegm-heat toxin accumulation. According to the different pathogenic effects of qi stagnation, blood stasis, pathogenic toxin, phlegm-damp, qi deficiency, yin deficiency in the occurrence and development of the disease, it is advocated to clear heat and resolve phlegm, and additionally the methods of diffusing the lung and relieving cough, resolving toxins and dissipating masses, rectifying qi and activating blood, dispelling dampness, supplementing and boosting qi and yin are used if necessary. Multiple methods are used together and flexibly matched. In clinical practice, Xiaoxian-xiong Decoction with the function of clearing heat and relieving phlegm is recommended as the basic formula for further modification. For patients with mild lung symptoms, modified Xiaoxianxiong Decoction is commonly used, while for those with obvious symptoms, self-made Maxing Xianxiong Decoction(麻杏陷胸汤) in modifications is suggested. For patients with Shaoyang (少阳) diseases, modified Chaihu Xianxiong Decoction (柴胡陷胸汤) is often used.
10.Analysis on related factors for internal fixation failure in proximal femoral nail antirotation for treating intertrochanteric fracture
Xian WANG ; Ke SUN ; Zhenhua LIN ; Bin LIANG
Chongqing Medicine 2024;53(8):1226-1230
Objective To investigate the risk factors of internal fixation failure in proximal femoral nail antirotation (PFNA) for treating intertrochanteric fracture.Methods The imageological data of 179 patients with intertrochanteric fracture receiving PFNA internal fixation were analyzed retrospectively.The univariate analysis was adopted to analyze the influence of the gender,degree of osteoporosis,AO/OTA fracture type,top apex distance (TAD),postoperative coxa vara,lateral wall state,fracture reduction situation and screw blade position on the internal fixation failure.The logistic regression model was constructed.The risk factors of internal fixation failure were analyzed.Results Among 179 patients,the internal fixation failure occurred in 16 cases.The univariate analysis showed the AO/OTA fracture type,TAD,postoperative coxa vara,lateral wall state,fracture reduction effect and screw blade location were related with the internal fixation failure (P<0.05).The logistic regression analysis prompted that postoperative coxa vara (OR=6.97,95%CI:2.24-21.68,P=0.001) and the lateral wall breakage (OR=3.08,95%CI:1.03-9.22,P=0.045) were the risk factors of internal fixation failure in femoral intertrochanteric fracture.Conclusion Coxa vara and lateral wall breakage are the risk factors of internal fixation failure in PENA for treating femoral intertrochanteric fracture,and the operation reduction should avoid the coxa vara appearance.

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