1. Gabapentin effectively alleviates pain sensitization and regulates CACNA2D1 expression in postherpetic neuralgia rats
Xing-Zhen LONG ; Zun-Feng MA ; Wen-Yao HUO ; Lin-Bo SUN ; Yang ZHANG ; Sheng-Li YU ; Xue BAI
Chinese Pharmacological Bulletin 2023;39(5):903-909
Aim To identify the molecular target of gabapentin in the treatment of postherpetic neuralgia(PHN). Methods The molecular target of gabapentin for PHN was analyzed by network pharmacology and molecular docking and confirmed by coprecipitation test. Rats were randomly divided into control group, model group, model+50 mg·kg-1 gabapentin group, model+100 mg·kg-1 gabapentin group, and model+200 mg·kg-1 gabapentin group, with nine rats in each group. The pain-related behaviors of the rats were measured at different time points. The mRNA and protein expressions of CACNA2D1, Bax, and Bcl-2 in rat spinal cord were determined by immunofluorescence, Western blot, and qPCR. Results CACNA2D1 was the target gene of gabapentin that determined via network pharmacology, molecular docking, and co-precipitation tests. After modeling, mechanical pain threshold and thermal pain threshold significantly decreased, and the number of apoptotic GABA cells significantly increased. However, after intraperitoneal injection of 50, 100, and 200 mg·kg-1 gabapentin, mechanical pain threshold and thermal pain threshold significantly increased(P<0.05), and the number of apoptotic GABA cells significantly decreased(P<0.01). Immunofluorescence and Western blot results showed that compared with the model group, with the increase of gabapentin concentration, the positive expression rate of Bax significantly decreased, and the positive expression rate of Bcl-2 and CACNA2D1 significantly increased. The mRNA expression levels of Bax, Bcl-2 and CACNA2D1 detected by qPCR were consistent with the results of immunofluorescence and Western blot. Conclusions Gabapentin up-regulates the expression of target protein CACNA2D1, inhibits the proapoptotic protein Bax, and promotes the expression of apoptotic inhibitor Bcl-2.
2.Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men.
Xi Jia TANG ; Lei Jing DUAN ; Wen Li LIANG ; Si CHENG ; Ting Li DONG ; Zhen XIE ; Kang Mai LIU ; Fei YU ; Zi Huang CHEN ; Guo Dong MI ; Liang LIANG ; Hong Jing YAN ; Lin CHEN ; Li LIN ; Dian Min KANG ; Xiao Bing FU ; Mao Feng QIU ; Zhen JIANG ; Jie XU ; Zun You WU
Chinese Journal of Epidemiology 2022;43(1):72-77
Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies
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HIV Infections/epidemiology*
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HIV-1
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Homosexuality, Male
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Humans
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Immunoenzyme Techniques
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Incidence
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Male
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Sexual and Gender Minorities
3.Analysis on distribution and epidemic characteristics of common pathogens of pneumonia among hospitalized children,Suzhou,2011-2018
Xin-xin XU ; Li-ling CHEN ; Jian-mei TIAN ; Jun ZHU ; Yu-zun LIN ; Yin WANG ; Jun-mei GAO ; Xue-jun SHAO ; Tao ZHANG ; Jun ZHANG ; Gen-ming ZHAO
Chinese Journal of Disease Control & Prevention 2020;24(3):264-268
Objective To understand the distribution and epidemic characteristics of common pathogens of pneumonia among hospitalized children in Suzhou. Methods Nasopharyngeal secretions were collected from hospitalized children with clinical pneumonia admitted to the respiratory department of Children's Hospital Affiliated to Suzhou University from April 2011 to March 2018 to detect common viral and bacterial pathogens of children's pneumonia. Results The total positive rate of pathogens was 75. 6% in the 4 765 clinical pneumonia cases. The positive rate of bacterial pathogens was 57. 4%. Streptococcus pneumoniae ( SP) was the highest,followed by Haemophilus influenzae ( H. i) ; The positive rate of viral pathogens was 44. 1%. Respiratory syncytial virus ( RSV) was the highest,followed by Bocavirus ( BoV) . The mixed infection rate of bacteria and virus was 25. 9%,and the most common types were RSV and SP,BoV and Streptococcus viride ( SV) . Conclusions SP,H.i,RSV and BoV are the main pathogens of clinical pneumonia in children. There are statistical differences in different age groups and seasons of hospitalized children's pneumonia in Suzhou. The mixed infection rate of bacteria and virus is high.
4.Clinical study on factor Ⅷ inhibitor in children with hemophilia A.
Bao Jun SHANG ; Shi Wei YANG ; Ping Chong LEI ; Rong Jun MA ; Xiang Dong HE ; Xiao Li YUAN ; Li JIANG ; Yu Long LI ; Xiao Yan DONG ; Zhen WANG ; Lin ZHANG ; Zun Min ZHU
Chinese Journal of Hematology 2020;41(2):138-142
Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Child
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Factor VIII/therapeutic use*
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Hemarthrosis
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Hemophilia A/drug therapy*
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Hemorrhage
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Humans
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Retrospective Studies
5.Ampelopsin inhibited apoptosis and migration of SMMC-7721 cells through MAPKs signaling pathway
Shi-mei QI ; Qi JIANG ; Qiang LI ; Zun-yong FENG ; Yu-qing ZHANG ; Shun-li DONG ; Zhi-lin QI ; Yao ZHANG
Acta Pharmaceutica Sinica 2019;54(8):1431-1438
This research is aimed to investigate the effect of ampelopsin on apoptosis and migration of human hepatoma SMMC-7721 cells and explore the molecular mechanism. SMMC-7721 cells were pretreated with different doses of ampelopsin and cells proliferation was detected by CCK8 kit. Cell morphology was observed under an inverted microscope. Nuclear morphology was detected by DAPI staining. Apoptotic rate was detected by Annexin V-FITC/PI flow cytometry. Migration and invasion were detected by Transwell and scratch healing test. Western blotting was used to detect cleavage of poly ADP-ribose polymerase (PARP), expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), E-cadherin, and N-cadherin, and phosphorylation of ERK, P38 and JNK in MAPKs pathway. Our results showed that ampelopsin significantly inhibited proliferation and induced apoptosis of SMMC-7721 cells, with half inhibition dose (IC50) for 24 h was 38.98 μg·mL-1. With 50 μg·mL-1 ampelopsin treatment, typical apoptotic morphological changes occurred, such as cell detachment, shrinkage and nuclear condensation. Apoptotic rate increased from 15% to 55.1%, with PARP cleavage significantly increased. In addition, treatment of ampelopsin reduced scratch healing of cells and transmembrane cells number. The expression levels of MMP-2 and MMP-9 were decreased. Further analysis of EMT-related proteins showed that after ampelopsin treatment, E-cadherin was up-regulated and N-cadherin was down-regulated. During ampelopsin treatment, ERK reached its peak of activation after 1 h, while the maximum activation time of JNK was 12 h. Meanwhile, P38 was activated within 4 h, with the highest point at 2 h. But after 4 h, ampelopsin inhibited phosphorylation of P38. These results indicated that ampelopsin induced apoptosis and reduced migration through activating MAPKs pathway and reversing EMT process in SMMC-7721 cells. This work provides a mechanistic basis for utilizing ampelopsin for anti-hepatocarcinoma treatment.
6.The estimation of influenza-related outpatient rate in children under 5 years in Suzhou from 2011 to 2017
Jun-mei GAO ; Li-ling CHEN ; Jian-mei TIAN ; Jun ZHU ; Yu-zun LIN ; Yin WANG ; Jia YU ; Wei SHAN ; Xue-jun SHAO ; Tao ZHANG ; Jun ZHANG ; Gen-ming ZHAO
Chinese Journal of Disease Control & Prevention 2019;23(1):34-38
Objective To estimate the outpatient rate of influenza-related influenza-like illness (ILI) for children younger than 5 years in Suzhou municipal districts. Methods From October 2011 to March 2017, we conducted a prospective surveillance program on ILI for children under 5 years in outpatient settings of Soochow University Affiliated Children’s Hospital (SCH). The throat swabs were collected and tested for influenza viruses by RT-PCR. Based on the healthcare utilization surveys and population data, the number of visits and the outpatient rate of influenza-related ILI for children younger than 5 years in Suzhou municipal districts were estimated. Results During 2011-2017, in total, there were 45 930 estimated influenza-related ILI cases younger than 5 years in Suzhou municipal districts, which consisted of 7 490 influenza A/H1N1 cases, 17 843 influenza A/H3N2 cases and 20 597 influenza B cases. The estimated outpatient rate of influenza-related ILI was 6.4% in 2011-2017, which was highest in 2011-2012, 20.5%, and the lowest in 2012-2013, 2.4%. Conclusion The number of visits and the outpatient rate of influenza-related ILI in children younger than 5 years was high in Suzhou municipal districts.
7.Correlation between myeloperoxidase expression and gene alterations and prognosis in acute myeloid leukemia.
Xiao Yan DONG ; Yu Long LI ; Li JIANG ; Cheng Ye WU ; Bao Jun SHANG ; Lin ZHANG ; Wei CHENG ; Zun Min ZHU
Chinese Journal of Hematology 2019;40(1):40-45
Objective: To analyze the percentage of myeloperoxidase (MPO)-positive acute myeloid leukemia (AML) blast cells, and to explore the correlation of MPO expression with the clinical features, gene alterations, therapeutic response and prognosis of AML. Methods: The expressions of MPO in BM blasts cells of 233 newly diagnosed AML were retrospectived analyzed, they were divided into two groups using the percentage of MPO-positive blast [low (≤70%) and high (>70%)], clinical features, gene alterations, chemotherapy efficacy and prognosis were compared between the two groups. Results: ①Of the 233 patients, 121(51.9%) were in the low MPO group, and the rest 112(48.1%) in the high MPO group. Favorable-risk group according NCCN guidelines of AML was always MPO-high (χ(2)=32.773, P<0.001), while MPO-low was closely related to poor-risk (χ(2)=7.078, P=0.008); ②DNMT3A mutation (χ(2)=6.905, P=0.009), spliceosome genes mutation (SF3B1/SRSF2/U2AF1) (χ(2)=5.246, P=0.022), RUNX1 mutation (χ(2)=4.577, P=0.032), ASXL1 mutation (χ(2)=7.951, P=0.005) and TP53 mutation (P=0.004) were more likely to be seen in the low MPO group, while C-KIT mutation (χ(2)=8.936, P=0.003) and CEBPA mutation (χ(2)=12.340, P<0.001) were more frequent in the high MPO group, especially CEBPA double mutation; ③The rates of first complete remission in the low MPO group were significantly lower than that in the high MPO group (38.8% vs 68.1%, χ(2)=15.197, P<0.001). Multivariate analysis showed that low MPO positivity significantly affected the CR(1) unfavourably. ④The overall survival (OS) and the progression-free survival (PFS) were significantly worse in the low MPO group (18.0% vs 89.4% for OS, and 11.5% vs 56.7% for PFS, P<0.001). Multivariate analysis disclosed that the low number of MPO was significantly unfavourable prognostic factor. ⑤The low MPO group still showed a worse survival even when restricted to the patients with normal karyotype, the OS and the PFS were 31.1% and 18.8% respectively. Conclusions: AML with different MPO expression percentage had a unique gene mutation spectrum. Low expression of MPO was an independent risk factor for CR(1), OS and PFS in AML patients, which may be a simple and highly significant factor for AML patients when evaluating the therapeutic efficacy and prognosis.
Humans
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Leukemia, Myeloid, Acute
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Mutation
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Peroxidase
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Prognosis
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Remission Induction
8.Therapy-related acute myeloid leukemia with t(9;22)(q34;q11) and t(16;21)(q24;q22) double translocation: a case report and literature review.
Xiao Yan DONG ; Yu Long LI ; Cheng Ye WU ; Wei CHENG ; Bao Jun SHANG ; Lin ZHANG ; Lin Na CHENG ; Zun Min ZHU
Chinese Journal of Hematology 2019;40(11):956-958
10.Study on incidence of HIV infection among heroin addicts receiving methadone maintenance treatment in Dehong prefecture, Yunnan province
Song DUAN ; Yue-Cheng YANG ; Jing HAN ; Shun-Sheng YANG ; Ying-Bo YANG ; Yu-Cun LONG ; Guo-Qiang LI ; Jin-Song YIN ; Li-Fen XIANG ; Run-Hua YE ; Jie GAO ; Ren-Hai TANG ; Lin PANG ; Ke-Ming ROU ; Zun-You WU ; Na HE
Chinese Journal of Epidemiology 2011;32(12):1227-1231
Objective To determine the incidence and risk factors of HIV infection among heroin addicts receiving methadone maintenance treatment(MMT)in Dehong prefecture,Yunnan province.Methods All heroin addicts who were HIV negative at the initiation of MMT in June 2005 and through June 2011,in Dehong prefecture were included in the cohort analysis.HIV incidence was calculated and related risk factors determined by using Cox proportional hazard regression model.Results A total of 3154 MMT clinic attendants were qualified for this cohort study.By June 2011,1023(32.4%)of them had never received any follow-up HIV testing so were thus referred as loss to follow-up.The other 2131(67.6%)members had received at least one follow-up HIV testing and were observed for a total of 4615.86 person-years.During the period,22 new HIV infections or seroconverters were identified,making the overall HIV incidence as 0.48/100 person-years.The HIV incidence was higher among those who were unemployed,never married,self-reported being injecting drug users(IDUs)and HCV positive at entry into the MMT program.None of those who were always negative on follow-up-urine-testing of morphine was discovered as HIV newly infected during the follow-up period.Data from multiple regression analysis under Cox proportional hazard model indicated that after controlling for confounding variables,non-IDUs at the entry point for the MMT program,were less likely to be HIV newly-infected or seroconverted than IDUs(HR=0.29,95%CI:0.11-0.76).Conclusion MMT prograqm in Dehong prefecture was demonstrated to be fairly effective in reducing HIV transmission through drug use.Those HIV negative attendants at the MMT clinic who were IDUs or keep using drugs during the treatment,were at higher risk of HIV seroconvertion.More efforts were needed to improve the follow-up and HIV testing programs for the MMT clinic attendants.

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