1.Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation
Ziyu YIN ; Yun GAO ; Junjiao WANG ; Weigang XUE ; Xueping PANG ; Huiting LIU ; Yunfang ZHAO ; Huixia HUO ; Jun LI ; Jiao ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):139-145
ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce neuroinflammation. The cells were divided into the normal group, the model group, and the ZH-13 low- and high-dose treatment groups (10, 20 μmol·L-1). The model group was treated with 1 μmol·L-1 LPS. Cell viability was assessed using the cell proliferation and activity assay (CCK-8 kit). Nitric oxide (NO) release in the cell supernatant was measured using a nitric oxide kit (Griess method). The mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins was assessed by Western blot. ResultsCompared with the model group, ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation (P<0.05, P<0.01). In the 20 μmol·L-1 ZH-13 treatment group, the mRNA expression levels of IL-1β, TNF-α, iNOS, and IL-6 were significantly reduced compared to the model group (P<0.05, P<0.01). In both the low- and high-dose ZH-13 groups, the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase (JNK) in the upstream MAPK pathway were significantly reduced (P<0.05). After stimulation with the JNK agonist anisomycin (Ani), both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group (P<0.01). ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.
2.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
3.Prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China
Jingcen HU ; Yinqi DING ; Haiyu PANG ; Canqing YU ; Dianjianyi SUN ; Pei PEI ; Huaidong DU ; Junshi CHEN ; Zhengming CHEN ; Lan ZHU ; Jun LYU ; Liming LI
Chinese Journal of Epidemiology 2024;45(1):11-18
Objective:To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China.Methods:A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described.Results:The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age ( P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area ( P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions:The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.
4.Association between waist circumference and ischemic stroke: a prospective study in adults from Qingdao
Yuhui LI ; Lei LIU ; Dan HU ; Xiaoyan ZHENG ; Jun LYU ; Canqing YU ; Pei PEI ; Haiping DUAN ; Ruqin GAO ; Zengchang PANG ; Xiaocao TIAN ; Dianjianyi SUN
Chinese Journal of Epidemiology 2024;45(2):178-184
Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.
5.An observational and Mendelian randomization study of the associations of body mass index with plasma amino acids and acylcarnitines in Chinese adults
Si CHENG ; Ting WU ; Canqing YU ; Dianjianyi SUN ; Pei PEI ; Huaidong DU ; Junshi CHEN ; Zhengming CHEN ; Yuanjie PANG ; Jun LYU ; Liming LI
Chinese Journal of Epidemiology 2024;45(6):770-778
Objective:To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults.Methods:Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method.Results:Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions:BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.
6.Current status of tuberculosis burden in China
Xinyao WANG ; Meili JIANG ; Yuanjie PANG ; Dianjianyi SUN ; Canqing YU ; Lan WANG ; Jun LYU ; Liming LI
Chinese Journal of Epidemiology 2024;45(6):857-864
Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease that most often affects the lungs. China is still among the high-burden tuberculosis countries in the world. Although the estimated incidence of tuberculosis in China has declined in recent years, the declining rate is slow. It still faces major issues such as a slower rate of decline, a widening gap between estimated and notified incidence, higher risk among middle-aged and older adults, a high number of cases among agriculture and related workers, and a heavier disease burden in the country's western regions. In addition, latent tuberculosis infection, drug-resistant tuberculosis, tuberculosis coinfection with HIV, and extrapulmonary tuberculosis have also exacerbated the disease burden of tuberculosis to some extent. This paper reviewed the epidemic characteristics of tuberculosis, the epidemiological triad, three links and two factors in the transmission process, the disease burden, and other aspects to provide a reference for formulating prevention and control strategies on tuberculosis.
7.An integrated curriculum for epidemiology and medical statistics teaching in undergraduate students majoring in clinical medicine: lesson learned from teaching reform
Yuanjie PANG ; Xue CONG ; Chunxiao LIAO ; Wenjing GAO ; Canqing YU ; Jun LYU ; Tao WU ; Siyan ZHAN ; Liming LI
Chinese Journal of Epidemiology 2024;45(11):1598-1604
Epidemiology and medical statistics are essential courses for undergraduate students majoring in clinical medicine. By studying the two courses, they can obtain the core skills for their future clinical practice. High-level medical schools both at home and abroad have accumulated successful experiences in curriculum, teaching methods and teaching models of the two disciplines. These colleges have also carried out the exploration of the curriculum reform centering on "organ systems integration". This paper summarizes the current status of epidemiology and medical statistics teaching and curriculum integration in representative medical schools both at home and abroad, and puts forward suggestions for deepening teaching reform and optimizing the curriculum system to provide reference for the integration of epidemiology and medical statistics curriculums for undergraduate students majoring in clinical medicine in China.
8.Recent advances in organ-system-specific biological age
Shuyao SONG ; Zhiyu WU ; Dianjianyi SUN ; Canqing YU ; Jun LYU ; Liming LI ; Yuanjie PANG
Chinese Journal of Epidemiology 2024;45(12):1751-1760
Biological age (BA) is a marker to accurately assess aging, facilitating the prediction of age-related diseases and promoting healthy aging. In recent years, first- and second-generation organ-system-specific BA has been developed using chronological age (CA) or aging-related outcomes (mortality) as training phenotypes and data from questionnaires, physical examinations, clinical biochemistry, imaging, and multi-omics to investigate the specificity of organ systems aging. Here, we review the methodologies for constructing BA, current efforts to assess organ system-specific BA, and related genome-wide association studies (GWAS). Previous studies predominantly used the first-generation BA method, using CA as training phenotypes. Organ-system-specific BA can accurately predict the disease risk of corresponding organ systems. We propose the development of organ system-specific BA through second-generation BA models and conducting GWAS and Mendelian randomization studies to explore organ system-specific aging processes, which will provide a theoretical foundation for the clinical application of organ system-specific BA.
9.Predictive value of serum Fbg and PTX3 levels for perioperative major adverse cardiovascular events in elderly patients undergoing hip replacement surgery
Huaiqian LI ; Tongtao PANG ; Jun LI ; Lei FAN ; Xubin ZHANG
International Journal of Laboratory Medicine 2024;45(21):2638-2641,2646
Objective To explore the predictive value of serum fibrinogen(Fbg)and pentaxin-3(PTX3)levels for perioperative major adverse cardiovascular events(MACE)in elderly patients undergoing hip re-placement surgery.Methods A total of 201 patients who underwent hip replacement surgery in the Qilu Hos-pital of Shandong University,Dezhou Hospital(the hospital)from January 2022 to December 2022 were re-garded as the study group,and based on the presence or absence of MACE during the perioperative period,pa-tients were separated into the non MACE group(183 cases)and the MACE group(18 cases).Another 150 healthy examinees from the hospital were selected as the control group.Fully automated biochemical analyzer and enzyme linked immunosorbent assay(ELISA)were applied to detect serum Fbg and PTX3 levels in re-search objects.Multivariate Logistic regression was applied to analyze the influencing factors of perioperative MACE in elderly patients undergoing hip replacement surgery.Receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of serum indicators for perioperative MACE in elderly patients un-dergoing hip replacement surgery.Results Compared with the control group,the serum Fbg and PTX3 levels in the study group were obviously increased,and the differences were statistically significant(P<0.05).There were 18 cases who had MACE in elderly patients undergoing hip replacement surgery,with an incidence rate of 8.95%.Compared with the non MACE group,the serum Fbg and PTX3 levels in the MACE group were obviously increased,and the differences were statistically significant(P<0.05).Elevated serum Fbg,PTX3,cardiac troponin I(cTnI),brain natriuretic peptide(BNP)levels,and decreased left ventricular ejection fraction were independent risk factors for perioperative MACE in elderly patients undergoing hip arthroplasty(P<0.05).The area under the curve(AUC)of single and combined detection of serum Fbg and PTX3 levels for predicting the occurrence of perioperative MACE in elderly patients undergoing hip arthroplasty was 0.824,0.809,and 0.917,respectively.The combined prediction value of the two was higher than that of indi-vidual prediction(Z combination-Fbg=2.333,P=0.019;Z combination-PTX3=3.110,P=0.001).Conclusion The periop-erative serum Fbg and PTX3 levels in elderly patients undergoing hip replacement surgery are elevated,and the combination of the two has good predictive value for the occurrence of perioperative MACE.
10.A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020
Cai-Yun WANG ; Hong-Mei XU ; Gang LIU ; Jing LIU ; Hui YU ; Bi-Quan CHEN ; Guo ZHENG ; Min SHU ; Li-Jun DU ; Zhi-Wei XU ; Li-Su HUANG ; Hai-Bo LI ; Dong WANG ; Song-Ting BAI ; Qing-Wen SHAN ; Chun-Hui ZHU ; Jian-Mei TIAN ; Jian-Hua HAO ; Ai-Wei LIN ; Dao-Jiong LIN ; Jin-Zhun WU ; Xin-Hua ZHANG ; Qing CAO ; Zhong-Bin TAO ; Yuan CHEN ; Guo-Long ZHU ; Ping XUE ; Zheng-Zhen TANG ; Xue-Wen SU ; Zheng-Hai QU ; Shi-Yong ZHAO ; Lin PANG ; Hui-Ling DENG ; Sai-Nan SHU ; Ying-Hu CHEN
Chinese Journal of Contemporary Pediatrics 2024;26(2):131-138
Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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