1.Generalized Functional Linear Models: Efficient Modeling for High-dimensional Correlated Mixture Exposures.
Bing Song ZHANG ; Hai Bin YU ; Xin PENG ; Hai Yi YAN ; Si Ran LI ; Shutong LUO ; Hui Zi WEIREN ; Zhu Jiang ZHOU ; Ya Lin KUANG ; Yi Huan ZHENG ; Chu Lan OU ; Lin Hua LIU ; Yuehua HU ; Jin Dong NI
Biomedical and Environmental Sciences 2025;38(8):961-976
OBJECTIVE:
Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects.
METHODS:
We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.
RESULTS:
We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity.
CONCLUSION
GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans
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Environmental Exposure/analysis*
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Linear Models
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Nutrition Surveys
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Environmental Pollutants
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Body Mass Index
2.Effects of Fuke Qianjin Formula and its modifications on the sequelae of pelvic inflammatory disease in rats
Jia XU ; Ya-Li TAN ; Zhi-Kui XIAO ; Ji-Lin KUANG ; Li-Mei LIN ; Lei LEI
Chinese Traditional Patent Medicine 2024;46(8):2571-2579
AIM To study the effects and possible mechanism of Fuke Qianjin Formula and its modifications on sequelae of pelvic inflammatory disease(PID)in rats.METHODS The SD rats were randomly divided into the normal group,the sham operation group,the model group,Kangfuyan group(FYK,0.756 g/kg),Fuke Qianjin Formula group(FKQ,2.7 g/kg),Yijun Formula group(YJ,2.7 g/kg),Kangyan Formula group(KY,2.7 g/kg)and Buyi Formula group(BY,2.7 g/kg).After 28 days of corresponding administration by gavage,the rats were put to death to procure their uterus,spleen,thymus and liver for the calculation of the organs indices levels;the observation of the general morphology of uterus and oviduct and histopathological examination of uterus and oviduct;the measurement of.the serum levels of IL-1β,IL-18 and IL-6 by ELISA;the detection of the uterine expressions of TGF-β1,caspase-1,NLRP3,IL-18 and CTGF by Western blot;and the detection of the expressions of CD4+and CD8+in spleen lymphocytes by flow cytometry.RESULTS Compared with the model group,FKQ and YJ group,KY group and BY group displayed decreased indices levels of the uterus,spleen and thymus(P<0.01);FKQ group and KY group displayed reduced uterine swelling,increased endometrial glands,and reduced inflammatory exudation(P<0.01),and lower serum levels of IL-1β,IL-18 and IL-6(P<0.01);FKQ group,KYgroup and BY group displayed decreased protein expressions of TGF-β1 and CTGF(P<0.05,P<0.01);FKQ group and KY group displayed decreased protein expressions of NLRP3,caspase-1 and IL-18(P<0.05,P<0.01);and FKQ group and BY group displayed increased CD4+/CD8+ratio(P<0.01).CONCLUSION Being protective to sequelae of PID rat models,Fuke Qianjin Formula and its modifications may contribute their anti-inflammatory efficacy by inhibiting the activation of NLRP3 body to hinder the activation of caspase-1,reduce the secretion and release of pro-inflammatory factor IL-18,and thus inhibit pyroptosis.
3.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
4.Distribution and type characteristics of HPV infection of women in Shiyan , Hubei Region
Man KUANG ; Ya-lin MA ; Gui-juan ZHU
Journal of Public Health and Preventive Medicine 2023;34(1):127-130
Objective To analyze the distribution and type characteristics of human papillomavirus (HPV) infection in women in Shiyan, Hubei region, so as to provide a basis for the prevention and treatment of HPV infection. Methods From January 2019 to December 2020, a sample of 3,180 women in XX region who had sexual intercourse experience were randomly selected, and their HPV genotypes were tested using flow-through hybridization, then the distribution characteristics and types of HPV infection in women of different ages were observed. Results Among of 3 180 patients, HPV infection was predominant in women aged 31-50 years , with 25.85% (822/3 180) aged 31-40 years and 22.08% (702/3,180) aged 41-50 years. HPV infection was the least prevalent in the ≤25 and >60 years age groups, with 428 cases and 289 cases respectively. HPV infection occurred in 1 310 out of 3 180 women , with a positive infection rate of 41.19% (1 310/3 180). HPV infection was most prevalent in the ≤25 years and ≥60 years age groups, accounting for 56.78% and 67.13% respectively. Single infection was the main infection type in all age groups, accounting for 76.03%. Twenty-one HPV genetic subtypes were detected in the subjects, out of a total of 1 918 strains of the virus. The main high-risk subtypes for single infection were HPV16, HPV52 and HPV58, accounting for 13.92%, 13.87% and 12.57% respectively, followed by HPV53 and HPV33, accounting for 7.61% and 5.58% respectively. The predominant low-risk subtypes for single infection were HPV11, HPV8 and HPV6, with accounting for 7.51%, 5.47% and 5.01% respectively. Conclusion HPV infection in women in Shiyan, Hubei region is predominantly in the ≤25 and ≥60 years age groups, and early clinical screening and preventive measures such as vaccination for high-risk HPV typing are of vital importance.
5.Progress in research of long-term protective efficacy of human papillomavirus vaccine.
Xin Hua JIA ; Xue Feng KUANG ; Ya Han CHEN ; Yu Fei LI ; Zhao Feng BI ; Ting WU ; You Lin QIAO
Chinese Journal of Epidemiology 2023;44(5):851-854
The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.
Humans
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Human Papillomavirus Viruses
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Biomedical Research
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Papillomavirus Vaccines
6.Rapid identification of the different constituents in Fructus Schisandrae Chinensis before and after processing by UHPLC-QTOF/MSE combining with metabonomics
Wei LI ; Yong-gui SONG ; Kuang-yi LIU ; Lin-jun YANG ; Ya-li LIU ; Dan SU ; Yu-lin FENG
Acta Pharmaceutica Sinica 2016;51(9):1445-1450
This study was performed to use UHPLC-QTOF/MSE technology to rapidly search and identify variations of chemical ingredients between Fructus Schisandrae Chinensis and its processed products. The present study provides a basis for the study of Chinese herbal medicine processing with a focus on the impact of processing on chemical components. Using a time-dependent data scan mode (MSE) couple with metabolomics technology, we acquired accurate data and identified the potential chemical markers. A total of 12 chemical markers were identified in the crude, vinegar-processed and wine-processed Schisandra chinensis fruit; The results showed that the levels of 6-O-benzoylgomisin O, schisantherin B, schisantherin C, schisantherin D and neokadsuranic acid are the highest in crude Schisandra chinensis fruit; thelevels of schizandrin A, schizandrin B, schizandrin C, gomisin D and gomisin T are the highest in wine-processed Schisandra chinensis fruit; the levels ofschisantherin A and schisandrin are the highest in vinegar-processed Schisandra chinensis fruit. There were significant changes of chemical components between Fructus Schisandrae Chinensis and their processed products, and these findings may offer a reasonable explanation for variation of efficacy and clinical applications in the processed products of Fructus Schisandrae Chinensis.
7. Establishing a clinical pathway for occupational chronic mild lead poisoning
Jian-Zhong CHEN ; Shun-Hua LIANG ; Qian-Ling ZHENG ; Bin LI ; Li-Hua XIA ; Feng-Ling ZHAO ; Ping CUI ; Xing-Ya KUANG ; Han-Lin HUANG
China Occupational Medicine 2016;43(06):677-682
OBJECTIVE: To establish an effective clinical pathway of hospitalization process for occupational chronic mild lead poisoning within the framework of project time; to formulate a rational and effective management model for the diagnosis and treatment. METHODS: Occupational chronic mild lead poisoning was selected as a disease for pilot study based on GBZ 37-2015 Diagnosis of Occupational Chronic Lead Poisoning. According to evidence-based medicine criteria,the clinical procedure was developed,preliminary used and evaluated in clinical practice in several hospitals,with the best treatment scheme of the disease. The principal methods used are literature research,case analysis and expert consultation.RESULTS: Standardized documents relevant to clinical pathway for occupational chronic mild lead poisoning have been formulated,including standardized in-hospital treatment process,Clinical Pathway Forms for medical staff and Consent Documents of Clinical Pathway for Patients. Preliminary clinical research showed that this clinical pathway is conducive to standardizing medical process,improving medical quality,shortening the time in hospital,reducing medical cost and the waste on medical resources. CONCLUSION: The results confirm that the clinical pathway for occupational chronic mild lead poisoning is scientific,rational,normative and practical. It will surely contribute to promote the management of disease diagnosis and treatment.
8.TNF-α and IL-1RA polymorphisms and silicosis susceptibility in Chinese workers exposed to silica particles: a case-control study.
Yong Wei WANG ; Jia Ya LAN ; Lin Yue YANG ; Jun Wang DE ; Jie KUANG
Biomedical and Environmental Sciences 2012;25(5):517-525
OBJECTIVETo assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles.
METHODSCase-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α (-238 and -308) and IL-1RA (+2018) was performed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) and SYBR green-based quantitative polymerase chain reaction (qPCR), respectively. Unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidential intervals (CI) for SNPs.
RESULTSNo significant differences were found between cases and controls in particles exposure length, body mass index (BMI), and status of smoking and alcohol consumption except for age (P=0.001) and blood type (P=0.042). The frequencies of TNF-α (-238) and IL-1RA (+2018) genotypes in cases were significantly different from those in controls, (P=0.001 and P=0.002, respectively), while a borderline significant difference was found in the frequencies of TNF-α (-308) between cases and controls (P=0.063). The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNF-α (-308), TNF-α (-238) and IL-1RA (+2018) were 2.8 (95% CI: 1.1-7.5), 20.9 (95% CI: 1.8-236.4) and 4.0 (95% CI: 1.6-10.1), respectively.
CONCLUSIONIt is suggested that cytokine polymorphisms of TNF-α (-238, -308) and IL-1RA (+2018) are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.
Adult ; Asian Continental Ancestry Group ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin 1 Receptor Antagonist Protein ; genetics ; metabolism ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Genetic ; Silicon Dioxide ; toxicity ; Silicosis ; genetics ; Tumor Necrosis Factor-alpha ; genetics ; metabolism
9.The clinical application of 320-slice Computed Tomography (CT) hepatic artery images in patients with liver transplantation.
Jin WANG ; Lin LUO ; Jian-sheng ZHANG ; Si-dong XIE ; Ling-yun LIU ; Zai-bo JIANG ; Ya-qin ZHANG ; Bing HU ; Hong SHAN ; Yang YANG ; Gui-hua CHEN ; Si-chi KUANG
Chinese Journal of Hepatology 2010;18(4):292-296
OBJECTIVETo evaluate the clinical significance of 320-slice CT hepatic artery images in patients with liver transplantation.
METHODSA total of 58 patients underwent CT scanning by 320-slice scanner after liver transplantation. They were divided into 2 groups according to the concentration of contrast media as follows: Group A (27 cases, 350 mgI/ml iopromide), Group B (31 cases, 370 mgI/ml iopromide). Contrast medium was infused at 6 ml/s, with a total dose of 50 ml. Images were generated by dynamic volume scanning and were processed by 4D digital subtraction angiography (DSA) imaging software. The time-density curve (TDC) of the hepatic artery was delineated. The time to peak, peak contrast enhancement were recorded. The physiological parameters such as body weight and height were analyzed.
RESULTS(1) There were no differences in clinical parameters such as age, sex, height, weight, or BMI between groups. The time to peak of hepatic artery of group A and B was (19.71+/-3.11) s and (20.06+/-3.67) s, and had no significant difference. The maximum peak enhancement of hepatic artery in groups B was higher than that group A (P < 0.05). (2) 4D DSA revealed hepatic artery pseudo-aneurysm (n = 2), and hepatic artery mild stenosis (n = 13), moderate stenosis (n = 5), severe stenosis (n = 9) and occlusion (n = 1), segmental moderate and severe stenosis (n = 4), and compensatory circulation with hepatic artery severe stenosis and occlusion (n = 6). hepatoportal arteriovenous fistulas (HPAVF, n = 12), donor-recipient hepatic artery mismatch (n = 3). Hepatic arterial branch are decreased and opened in 15 cases and 8 cases.
CONCLUSION320-slice CT hepatic artery images is safe, noninvasive, and accurate technique to evaluate hepatic arterial complications after liver transplantation.
Adolescent ; Adult ; Aged ; Female ; Hepatic Artery ; diagnostic imaging ; Humans ; Liver Diseases ; diagnostic imaging ; etiology ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Tomography, X-Ray Computed ; methods ; Young Adult
10.Diagnostic value of multislice spiral CT and MRI in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma.
Jin WANG ; Bing-jun HE ; Zai-bo JIANG ; Ya-qin ZHANG ; Hong SHAN ; Ru XIAO ; Jian-sheng ZHANG ; Lin LUO ; Si-chi KUANG ; Gui-hua CHEN ; Yang YANG
Chinese Journal of Oncology 2009;31(9):691-696
OBJECTIVETo investigate the manifestation and diagnostic value of multislice spiral CT (MSCT) and MRI imaging in detection of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC).
METHODSThe clinical data of 161 consecutive HCC patients who underwent orthotopic liver transplantation were retrospectively reviewed. Twenty-nine HCC patients were classified by pTNM according to the "Pittsburgh criteria". MSCT and MRI findings of tumor recurrence after liver transplantation were evaluated retrospectively in 29 stage II-IVb HCC patients. The recurrence site and relapse interval between liver transplantation and recurrence were analyzed.
RESULTSLung tumor recurrence were found in 21 cases, presented as cotton-like lesions in a diameter of 2 - 3 cm, with a clear margin and homogeneous density. Pleural tumor recurrence was detected in 4 cases. Liver tumor recurrence were found in 9 cases, which can be divided into four subtypes: multinodular in 4 cases, diffuse lesion in 2 cases, huge mass in 2 cases, and uninodular in 1 case. Two cases showed tumor thrombus in the inferior vena cava and portal vein. Lymph node tumor recurrence was found in 9 cases, presented as multiple nodules at hepatic hilum, lesser peritoneal sac, posterior mediastinum, retroperitoneum, or around pancreatic head, and accompanied with merging and necrosis in one case. Bone tumor recurrence were found as osteolytic destruction in 4 cases, and accompanied with adjacent soft-tissue mass in 2 cases. The recurrence sites of the 29 cases were as following: lung (21 cases, 72.4%), liver (9 cases, 31.0%), lymph nodes (9 cases, 31.0%), bone (4 cases, 13.8%) and other sites (3 cases, 10.3%). Lung tumor recurrence was found in all the 10 stage IVb patients with tumor recurrence after liver transplantation, significantly more frequent than that in stage IVa patients (P = 0.023). After liver transplantation, all 25 patients with stage III approximately IVb HCC developed recurrence within one year, but in the 4 cases with stage II HCC at one year later (P = 0.009).
CONCLUSIONThe results of our study show that in hepatocellular carcinoma patients after liver transplantation, the lung and pleura are the most frequent site of recurrence, followed by liver, lymph node and bone as the second and third sites. The Stage IVb hepatocellular carcinoma should be regarded as a contradiction for liver transplantation due to rapid recurrence. Tumor recurrence occurs later in stage II HCC than in stage III approximately IVb patients. MSCT and MRI are of significant importance in diagnosis and formulating operation plan in HCC patients with recurrence after liver transplantation.
Adult ; Carcinoma, Hepatocellular ; diagnosis ; diagnostic imaging ; secondary ; surgery ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; surgery ; Liver Transplantation ; Lung Neoplasms ; diagnosis ; diagnostic imaging ; secondary ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; diagnosis ; diagnostic imaging ; Neoplastic Cells, Circulating ; Pleural Neoplasms ; diagnosis ; diagnostic imaging ; secondary ; Retrospective Studies ; Tomography, Spiral Computed ; methods


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