1.Isolation,identification,and biological characterization of enterotoxigenic Escherichia coli from a South China tiger
Jing-ru XU ; Zhi-hao ZHU ; Yu-qi LI ; Si-si FAN ; Ya-li KANG ; Yu-bin ZHUO ; Ling-shan HUANG ; Shu-qi QIU ; XUE-YUXI ; Xiao-ping WU ; Yu-ting LIAO ; Wei-ye LIN ; Xiao-ziyi XIAO ; Xue-jin LI ; Teng-teng CHEN ; Xi-pan LIN ; Kai-xiong LIN ; Ke-wei FAN
Chinese Journal of Zoonoses 2025;41(6):567-573
This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.
2.Analysis of clinicopathological characteristics and prognostic factors in young breast cancer patients
Shujuan JIN ; Xiaojing LIU ; Di MENG ; Si ZUO ; Yan BI ; Xiaowei HAN ; Wei WANG ; Minghua ZHU ; Feng LIANG
Cancer Research and Clinic 2025;37(4):268-272
Objective:To investigate the clinicopathological characteristics and prognostic influencing factors in young breast cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 408 young patients with breast cancer in the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2020 were retrospectively analyzed. The clinical characteristics and prognostic influencing factors of patients were observed. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS) of patients. Univariate analysis of prognostic factors was conducted by using the log-rank test, and multivariate analysis was performed by using Cox proportional risk model.Results:The median age [ M ( Q1, Q3)] of 408 young female patients with breast cancer was 36 (33, 39) years; the 5-year OS and 5-year DFS rates were 89.9%, 84.0% of 387 breast cancer patients in early and middle stage (except for stage Ⅳ). There were statistically significant differences in the 5-year OS and 5-year DFS rates (excluding stage Ⅳ of DFS) of patients with different clinical staging and molecular subtypes (all P < 0.05). The differences were statistically significant in the 5-year DFS rate of patients with different pathological types and histological grades (all P < 0.05). There were no statistically significant differences in the 5-year OS and DFS rates between the patients receiving breast-conserving surgery or mastectomy (all P > 0.05). The results of multivariate Cox regression analysis indicated that clinical staging ( HR = 3.121, 95% CI: 2.301-4.233, P < 0.001) and molecular classification ( HR = 1.441, 95% CI: 1.126-1.845, P = 0.004) were independent prognostic factors for OS. Additionally, clinical staging ( HR = 3.001, 95% CI: 2.174-4.141, P < 0.001) was identified as an independent prognostic factor for DFS. Conclusions:The prognosis of young breast cancer patients is closely related to clinical staging and molecular subtype. The later the clinical stage is, the poorer prognosis is. Luminal-type breast cancer has a better prognosis than other subtypes. For early-stage breast cancer patients who meet the criteria for breast-conserving surgery, breast-conserving surgery is the first-choice alternative.
3.Gender Differences in Depression:Mechanistic Insights from Traditional Chinese and Western Medicine and Advances in Antidepressant Research
Hao-quan TIAN ; Jin PAN ; Lu-si XU ; Xiao-yan XUE ; Qian-cheng MAO ; Liu-xuan HUANG ; Ying-ying ZHU ; Ke MA
Progress in Modern Biomedicine 2025;25(13):2231-2240,2153
Depression is a highly heterogeneous psychiatric disorder with complex pathogenesis influenced by the interplay of biological,psychological,and social-environmental factors.Based on the 2021 edition of the Chinese Guidelines for the Prevention and Treatment of Depressive Disorders,which explicitly identify gender as a significant risk factor for depression onset,this paper systematically reviews the gender-differentiated pathogenesis and therapeutic advances in depression from both traditional Chinese medicine(TCM)and Western medical perspectives.In Western medicine,a large number of studies have demonstrated the sex-specific mechanism of estrogen/testosterone fluctuations and monoamine transmitter system regulation.While in TCM,although the constitution theory proposes that there are significant gender differences in congenital constitution and that qi depression and qi deficiency are associated with susceptibility to depression,current evidence primarily relies on cross-sectional surveys and lacks validation through high-quality RCTs.Compared with Western medicine,the direct research on gender-differentiated antidepressant effects in TCM remains relatively underdeveloped.In future study,it may be possible to deepen and improve the research on anti-depression in TCM from the biological markers of particular constitutions in the gender dimension.This paper advocates establishing a bio-psycho-social integrated intervention model,advancing mechanistic exploration through prospective cohort studies and multi-omics technologies,and promoting precision diagnosis and treatment systems based on gender differences,and to form a three-dimensional diagnosis and treatment and research system that covers biomarkers,social role assessment,and TCM constitution identification,in order to provide a new theoretical framework and a practical pathway for the precise medical treatment of depression.
4.Efficacy of the transpubic access in the treatment of female urogenital tract injury
Weidong ZHU ; Jiemin SI ; Chongrui JIN ; Wenxiong SONG ; Xuxiao YE ; Lujie SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(10):774-777
Objective:To explore the application value of transpubic access on female urogenital tract injury.Methods:A retrospective analysis was conducted on 15 female patients with urogenital tract injury caused by trauma admitted to our department from May 2020 to October 2024,all of whom were complicated urethral stricture or atresia,accompanied by urethrovaginal fistula or vaginorectal fistula. All patients underwent suprapubic vesicostomy before surgery,and 1 case underwent sigmoidostomy simultaneously. The mean age of the patients was(29.6 ± 3.2)years old,and the course of disease was 6-24 months. Preoperative urethrography and urethroscope showed the location of urethral stenosis,with proximal urethra stricture in 7 cases and distal urethra stricture in 8 cases. The average length of strictures was(2.8±0.2)cm. The urethral ultrasonography,magnetic resonance and CTU examination showed 8 patients were complicated with urethrovaginal fistula,and 1 patient was complicated with vaginorectal fistula. All patients underwent transpubic access and resection of symphysis pubis. According to the specific conditions of urethral stricture,7 of them underwent end-to-end urethral anastomosis,5 cases underwent bladder wall flap urethroplasty,3 cases underwent vulva flap urethroplasty,8 cases underwent urethral vaginal fistula repair,1 case underwent vagino-rectal fistula repair,and 7 cases underwent vaginoplasty during the operation.Results:All the 15 patients underwent successful operation without complication. After the catheter being removed 4 weeks after surgery,2 patients had urgent urinary incontinence and 3 patients had stress urinary incontinence. The bladder neck was reconstructed 3 months after surgery,the symptoms of urinary incontinence improved in 1 case,urinary incontinence remained in 2 cases,and pharmaceutical or physical therapy were continued. Two patients could not urinate normally after the catheter was removed and still carried the vesicostomy tube,waiting for further treatment. The other 8 patients had unobtrusive voiding after extubating,and were followed up for an average of(22.5±3.2)months. There was no recurrence of urinary fistula,and the average maximum urinary flow rate was(22.8±3.2)ml/s.Conclusions:The transpubic approach is a safe and effective way to treat female genital tract injury by different surgical methods according to specific conditions,especially for patients with severe trauma,poor local tissue conditions,complicated urethrovaginal fistula or vagino-rectal fistula.
5.Clinical guideline for diagnosis and treatment of nonunion of osteoporotic vertebral fractures (version 2025)
Haipeng SI ; Le LI ; Junjie NIU ; Wencan ZHANG ; Fuxin WEI ; Jinqiu YUAN ; Qiang YANG ; Hongli WANG ; Guangchao WANG ; Shihong CHEN ; Yunzhen CHEN ; Xiaoguang CHENG ; Jianwen DONG ; Shiqing FENG ; Rui GU ; Yong HAI ; Tianyong HOU ; Bo HUANG ; Xiaobing JIANG ; Lei ZANG ; Chunhai LI ; Nianhu LI ; Hua LIN ; Hongjian LIU ; Peng LIU ; Xinyu LIU ; Sheng LU ; Shibao LU ; Chunshan LUO ; Lvy CHAOLIANG ; Lvy WEIJIA ; Xuexiao MA ; Wei MEI ; Chunyang MENG ; Cailiang SHEN ; Chunli SONG ; Ruoxian SONG ; Jiacan SU ; Honglin TENG ; Hui SHENG ; Beiyu WANG ; Bingwu WANG ; Liang WANG ; Xiangyang WANG ; Nan WU ; Guohua XU ; Yayi XIA ; Jin XU ; Youjia XU ; Jianzhong XU ; Cao YANG ; Maowei YANG ; Zibin YANG ; Xiaojian YE ; Hailong YU ; Xijie YU ; Hua YUE ; Zhili ZENG ; Xinli ZHAN ; Hui ZHANG ; Peixun ZHANG ; Wei ZHANG ; Zhenlin ZHANG ; Jianguo ZHANG ; Tengyue ZHU ; Qiang LIU ; Huilin YANG
Chinese Journal of Trauma 2025;41(10):932-945
Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.
6.Impact of suture configuration and fixation type on biomechanical strength of rotator cuff repair:A factorial design study
Yinzhe CUI ; Zheng YAN ; Jia MA ; Zhefeng JIN ; Jiawen ZHAN ; Minshan FENG ; Guangwei LIU ; Jie YU ; Xu WEI ; Jiangtao SI ; Minghui ZHUANG ; Tao HAN ; Jianguo LI ; ZHANGKAIRUI ; Liguo ZHU
Chinese Journal of Sports Medicine 2025;44(9):729-737
Objective To explore the impact of suture configuration and fixation type on the biome-chanical strength of rotator cuff repair,using a factorial design study.Methods Sixteen fresh-frozen porcine shoulder samples were randomized into an anchorless double-row suture bridge transosseous su-tures(DS)group,an anchored double-row suture bridge transosseous-equivalent(DE)group,an an-chorless X-BOX construct transosseous sutures(XS)group,and an anchored X-BOX construct transos-seous-equivalent(XE)group,each of four,according to suture configuration(double-row suture bridge,traditional X-BOX construct)and fixation type(suture anchors,transosseous sutures).Then,their fatigue resistance(first-cycle excursion,gap length difference ratio,and the percentage of ex-posed footprints)and the failure strength(the maximum failure load and the re-tear type)were mea-sured using a biomechanical material testing machine.Results Different suture configurations affected failure strength(F=39.559,P<0.001),with the double-row suture bridge groups(693.07±58.35 N,746.76±138.57 N)showing significantly higher failure strength,compared to the traditional X-BOX groups(462.90±18.91 N,421.43±90.76 N).However,the fixation type did not significantly im-pact failure strength(F=1.161,P=0.302).Moreover,the suture configuration influenced the gap differ-ence ratio(F=7.781,P=0.016),but had no significant correlation with other fatigue resistance indica-tors(P>0.05).Meanwhile,failure strength and fatigue resistance were not correlated with fixation type,and the interaction between suture and fixation type(P>0.05).The incidence of failure types for the four suture configurations was as follows:Type I tendon tear:XS>XE>DS=DE;type II tendon tear:DS>XE>XS=DE;fixing material-related failure:DE>DS=XE=XS.Conclusion The failure strength and gap formation ratio in rotator cuff repair under fatigue loading are influenced by suture configuration,whereas no significant association has been observed with respect to fixation method,whether using transosseous sutures or suture anchors.
7.Management strategies for vesicovaginal fistula following cervical cancer radiotherapy in women
Jiemin SI ; Weidong ZHU ; Ranxing YANG ; Lujie SONG ; Chongrui JIN ; Jianwen HUANG ; Xuxiao YE ; Zuowei LI ; Wenxiong SONG ; Qiang FU ; Yinglong SA
Chinese Journal of Urology 2025;46(8):587-592
Objective:To investigate the treatment strategies for vesicovaginal fistula(VVF)in women following cervical cancer radiotherapy.Methods:A retrospective analysis was performed on the clinical data of 33 female patients with post-radiotherapy VVF after cervical cancer treatment at Shanghai Sixth People’s Hospital between January 2020 and June 2024. The patients were categorized into three groups based on surgical approaches:Group A(11 patients):Underwent prone-position VVF repair. Mean age:(50.0±9.6)years;mean radiotherapy sessions:(22.6±2.2). All had simple VVF without concurrent intestinal or surrounding soft-tissue fistulas. Among them,1 patient previously received laparoscopic VVF repair,1 transvaginal VVF repair,and 2 gracilis muscle flap packing for VVF repair. One month prior to surgery,the average daily usage of urine pads was 16.7(12.8,25.7)pieces,and the quality of life(QOL)score stood at 4.0(4.0,5.0)points. Preoperative cystoscopy revealed that 8 cases had fistulas located in the trigonal region of the bladder,while 3 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.2(0.8,1.6)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 3 cases of type 1,4 cases of type 2,2 cases of type 3,and 2 cases of type 4;7 cases of type A and 4 cases of type B;as well as 3 cases of typeⅠ,7 cases of type Ⅱ,and 1 case of type Ⅲ.Group B(20 patients):Underwent gracilis muscle flap packing for VVF repair. Mean age:(58.6±8.8)years;mean radiotherapy sessions:(29.8±3.9). Three patients had concurrent rectovaginal fistulas and received colostomy for fecal diversion. History of previous interventions:3 had laparoscopic VVF repair,4 transvaginal VVF repair,and 1 both transvaginal and laparoscopic VVF repair. One month prior to surgery,the average daily usage of urine pads was 19.7(15.8,27.7)pieces,and the QOL score stood at 5.0(5.0,6.0)points. Preoperative cystoscopy revealed that 13 cases had fistulas located in the trigonal region of the bladder,while 7 cases had fistulas on the posterior bladder wall. The diameter of the fistula openings,measured under a microscope,was 1.8(1.0,3.2)cm. Based on the Goh classification criteria for vesicovaginal fistulas,this group included 4 cases of type 1,9 cases of type 2,3 cases of type 3,and 4 cases of type 4;6 cases of type A,11 cases of type B and 3 cases of type C;as well as 1 cases of type Ⅱ,and 19 case of type Ⅲ. Group C(2 patients):Underwent ureterocutaneous diversion. Ages:67 and 73 years;radiotherapy sessions:51 and 60,respectively. Both had concurrent rectovaginal fistulas and bladder soft-tissue fistulas. The patient presented with recurrent thigh abscesses accompanied by fever. One month prior to surgery,the daily usage of urine pads was 29 and 23 pieces,respectively,and the QOL score was 6 points. Cystoscopic examination revealed that the vesicovaginal fistulas were located in the trigone of the bladder,with diameters of 3 cm and 4 cm,respectively. Additionally,partial defects were noted in the ventral wall of the urethra,while no bladder soft tissue fistulas were detected. According to the Goh classification for vesicovaginal fistulas,both cases were categorized as type 4,type C,and type Ⅲ. For Groups A and B,urinary catheters were indwelled for 3 weeks postoperatively,then removed to assess spontaneous urination and incontinence. QOL was evaluated,with a minimum 6-month follow-up. For confirmed postoperative VVF recurrence,re-repair was performed 3?6 months later based on patient preference. For Group C,double-J stents were placed in the ureters,and stoma bags were applied 3 days postoperatively. Stents were replaced every 1?2 months,with QOL assessment. Successful fistula repair in Groups A and B was defined as the absence of vaginal leakage confirmed by cystoscopy after six months of the procedure with no vaginal leakage. For Group C,surgical success was determined by the resolution of perineal urinary leakage and improvement in QOL.Results:All 33 patients completed surgery successfully. Group A:Follow-up duration:16.3(9.6,24.6)months. Surgical repair succeeded in 7 patients,with unobstructed spontaneous urination and no vaginal incontinence. Four patients had VVF recurrence:2 refused further treatment,and 2 underwent repeat gracilis muscle flap packing. One was successfully repaired,while one recurrence case refused further treatment. Group B:Follow-up duration:17.0(9.5,24.8)months(8?32 months). Thirteen patients restored spontaneous urination without recurrence. Seven had recurrence:5 refused further surgery,and 2 underwent re-repair. One repair succeeded without incontinence,while one recurrence case refused treatment. Group C:Follow-up durations were 6 and 22 months. Perineum remained dry without incontinence(no urine pads needed),and no recurrence of thigh soft-tissue redness/infection occurred. QOL scores were 2 and 3,respectively.Conclusions:Post-radiotherapy VVF in women after cervical cancer presents complex and variable conditions. The primary goal of treatment should be to improve patients’ quality of life. Treatment approaches should be selected based on the complexity of urinary fistulas and local tissue conditions. In general,patients who are younger,have received lower doses of radiation therapy,present with smaller fistula diameters,have well-vascularized and elastic perifistular tissues,and have no concurrent tissue fistulas are candidates for prone-position VVF repair. Patients who do not meet the criteria for transvaginal repair,have a history of at least two previous repair attempts,or have concurrent vaginorectal fistulas require gracilis muscle flap packing for VVF repair. Patients with three or more types of concurrent tissue fistulas,extensive pale and inelastic perifistular tissues,and who are not amenable to repair surgery undergo ureterocutaneous diversion.
8.One-year seedling cultivation technology and seed germination-promoting mechanism by warm water soaking of Polygonatum kingianum var. grandifolium.
Ke FU ; Jian-Qing ZHOU ; Zhi-Wei FAN ; Mei-Sen YANG ; Ya-Qun CHENG ; Yan ZHU ; Yan SHI ; Jin-Ping SI ; Dong-Hong CHEN
China Journal of Chinese Materia Medica 2025;50(4):1022-1030
Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination
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Seedlings/genetics*
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Water/metabolism*
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Seeds/metabolism*
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Polygonatum/genetics*
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Temperature
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Plant Proteins/genetics*
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Plant Dormancy
9.Identification and expression analysis of B3 gene family in Panax ginseng.
Yu-Long WANG ; Ai-Min WANG ; Jing-Hui YU ; Si-Zhang LIU ; Ge JIN ; Kang-Yu WANG ; Ming-Zhu ZHAO ; Yi WANG ; Mei-Ping ZHANG
China Journal of Chinese Materia Medica 2025;50(16):4593-4609
Panax ginseng as a perennial herb of Araliaceae, exhibits pharmacological effects such as central nervous system stimulation, anti-tumor properties, and cardiovascular and cerebrovascular protection. The B3 gene family plays a crucial role in growth and development, antioxidant activity, stress resistance, and secondary metabolism regulation of plants and has been extensively studied in various plants. However, the identification and analysis of the B3 gene family in P. ginseng have not been reported. In this study, a total of 145 B3 genes(PgB3s) with complete open reading frames(ORF) were identified from P. ginseng and classified into five subfamilies based on domain types. Through correlation analysis with ginsenoside content, SNP/InDels analysis, and interaction analysis with key enzyme genes, 15 PgB3 transcripts were found to be significantly correlated with ginsenoside content and exhibited a close interaction network with key enzyme genes involved in ginsenoside biosynthesis, which indicated that these genes may participate in the regulation of ginsenoside biosynthesis. Additionally, this study found that PgB3 genes exhibited induced expression in response to methyl jasmonate(MeJA) stress, which aligned with the presence of abundant stress response elements in their promoters, confirming the important role of the B3 gene family in P. ginseng in stress resistance. The results of this study revealed the potential functions of PgB3 genes in ginsenoside biosynthesis and stress response, providing a significant theoretical basis for further research on the functions of PgB3 genes and their regulatory mechanisms.
Panax/metabolism*
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Gene Expression Regulation, Plant
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Plant Proteins/metabolism*
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Ginsenosides/biosynthesis*
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Multigene Family
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Phylogeny
10.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

Result Analysis
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