1.Plasma metabolites,immune cells,and hip osteoarthritis:causal inference based on GWAS data from European populations
Xiangbin RONG ; Haibo ZHENG ; Xueshen MO ; Kun HOU ; Ping ZENG
Chinese Journal of Tissue Engineering Research 2026;30(4):1028-1035
BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95%confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95%confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5%of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.
2.Plasma metabolites,immune cells,and hip osteoarthritis:causal inference based on GWAS data from European populations
Xiangbin RONG ; Haibo ZHENG ; Xueshen MO ; Kun HOU ; Ping ZENG
Chinese Journal of Tissue Engineering Research 2026;30(4):1028-1035
BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95%confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95%confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5%of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.
3.The World Health Organization Integrated Care for Older People (ICOPE) Framework and the Association with Frailty in Older Adults
Wan-Yun CHOU ; Kun-Pei LIN ; Chiung-Jung WEN ; Ding-Cheng (Derrick) CHAN ; Su-I HOU
Annals of Geriatric Medicine and Research 2026;30(1):41-50
Background:
The World Health Organization published the 2019 Integrated Care for Older People (ICOPE) framework to guide, assess, and promote the intrinsic capacity (IC) of older adults, referring to their physical and mental health. This study aims to investigate the relationship between IC and frailty among older adults.
Methods:
This cross-sectional study was conducted in a medical center in Taiwan in 2021. Two hundred ten patients over 65 admitted to the geriatric ward were invited to participate. The questionnaire included an IC measure, Fried Frailty Scale, and demographic items. The IC measure was ascertained using the six domains of ICOPE (cognition, mobility, nutrition, visual, hearing, and depressive symptoms). The Fried Frailty Scale was used to categorize participants as robust (Fried Frailty Scale=0), prefrail (Fried Frailty Scale=1-2), or frail (Fried Frailty Scale ≥3). Multinomial logistic regression was used to analyze the association between individual ICOPE domains and frailty stages, while adjusting for confounders.
Results:
Among the participants, 39.0% were prefrail, and 28.6% were frail. Limited mobility and depressive symptoms were significantly associated with prefrail (adjusted odds ratio [aOR]=4.44, 95% confidence interval [CI] 1.82–10.82; aOR=8.41, 95% CI 1.75–40.37) and frail (aOR=11.57, 95% CI 3.63–36.93; aOR=13.77, 95% CI 2.62–72.49) individuals, respectively. Malnutrition (aOR=4.01, 95% CI 1.18–13.62) and hearing loss (aOR=4.37, 95% CI 1.09–19.66) were significantly associated with frail older adults.
Conclusion
Limited mobility and depressive symptoms occurring at the prefrail stage could be used as assessment items for early detection of prefrail.
4.From Blood-brain Barrier Penetration to Barrier Functional Remodeling: New Intervention Strategies via Nanodelivery Systems for Alzheimer’s Disease
Xu-Ran WANG ; Chang-Feng YIN ; Huan CHEN ; Hong-Wei HOU ; Yi-Kun WANG
Progress in Biochemistry and Biophysics 2026;53(9):2414-2429
Alzheimer’s disease (AD) is pathologically characterized by cerebral amyloid β‑protein (Aβ) aggregation, neurofibrillary tangles and progressive cognitive deterioration. There is an urgent clinical demand for targeted therapeutic agents against AD, whereas the blood-brain barrier (BBB) acts as a critical physical barrier that blocks over 98% small-molecule drugs and nearly all biomacromolecules from entering brain parenchyma. Nanomedicine-based drug delivery systems (NDDSs) with tunable physicochemical properties can cross the BBB via multiple transcytosis pathways including adsorptive-mediated, receptor-mediated and transporter-mediated routes, opening a promising avenue for targeted AD treatment. A core academic viewpoint proposed herein is that robust in vitro endothelial penetration of nanocarriers cannot guarantee effective accumulation in brain target cells. Comprehensive evaluation of BBB-crossing delivery efficiency should not merely rely on in vitro permeability tests, but cover the full multi-step transcytosis cascade, cellular tropism in brain tissues and in vivo therapeutic outcomes. This review systematically sorts out diverse nanoplatforms applicable to BBB penetration for AD intervention. Inorganic nanomaterials such as gold and ceria nanoparticles possess large specific surface areas and intrinsic antioxidant capacity, which eliminate reactive oxygen species and hinder Aβ fibrillization. Liposomal formulations and solid lipid nanoparticles exhibit superior biocompatibility with biomimetic phospholipid bilayer architectures, capable of co-loading hydrophilic nucleic acids for Tau regulation and lipophilic Aβ inhibitors; relying on receptor-mediated transcytosis, they achieve sustained drug retention in the brain. Polymeric nanocarriers including nanogels and polyamidoamine dendrimers enable multi-target combinatorial therapy, and can be engineered to release cargo in response to inflammatory microenvironments, thereby suppressing excessive microglial activation and protecting neuronal mitochondria. Beyond conventional nanocarriers, this work elaborates two cutting-edge BBB-crossing delivery platforms: biomimetic nanosystems and metal-organic frameworks (MOFs). Biomimetic nanoparticles camouflaged with erythrocyte, platelet or macrophage membranes, as well as natural exosomes, evade immune clearance, prolong systemic circulation and inherently home to inflammatory lesions. Serving as “nano-decoys”, they neutralize Aβ neurotoxins and remodel cerebral inflammatory microenvironments simultaneously. MOFs feature high porosity and customizable pore channels for co-delivery of multiple therapeutics, and can be integrated with near-infrared photothermal and photooxidation modalities to facilitate focal brain lesion therapy. This review highlights a transformative paradigm shift in the field of BBB-targeted AD therapy: research focus has shifted from simply maximizing cerebral drug penetration toward active modulation and functional restoration of the BBB. Impaired BBB transporters intrinsically impede endogenous Aβ clearance. Accordingly, BBB-regulating nanocarriers are designed to remodel the low-density lipoprotein receptor-related protein 1 (LRP1) trafficking cascade, redirecting endocytic vesicles from lysosomal degradation to non-degradable transcytosis and restoring the intrinsic Aβ efflux capacity of the BBB. Distinct from conventional strategies that only exert local lesion inhibition, this systemic clearance strategy eliminates cerebral Aβ deposits by accelerating peripheral excretion.
5.A preliminary study on a grading scale for objectively assessing the degree of laxity of upper eyelid skin
Kun MA ; Tuanjie HOU ; Pingsong LI ; Xiao CHEN ; Le MA
Chinese Journal of Plastic Surgery 2025;41(1):26-31
Objective:To investigate the feasibility of a new clinical grading scale for assessing the degree of laxity of upper eyelid skin.Methods:From May 2022 to October 2023, the patients who underwent upper eyelid skin laxity plastic surgery in the Department of Plastic Surgery and Burns-Department of Medical Cosmetology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, were prospectively enrolled. The degree of upper eyelid skin laxity was graded independently by three plastic surgeons who did not participate in the operation according to the grading scale and using facial photographs of the patients.The clinical grading scale categorizes the degree of skin laxity into 4 grades ranging from 0 to 3 degrees, by analyzing the position of the lower edge of the upper eyelid skin relative to the upper eyelid edge and the pupil, and the higher the grade, the more serious the degree of skin relaxation. If bilateral upper eyelid skin laxity were presented, the grade of the side with more severe laxity was taken as the grade of the upper eyelid skin laxity of the patient. The Kendall coefficient (range -1-1) of the three doctors’ grading result before and after operation was calculated respectively. The closer the value was to 1, the better the consistency of the three doctors, and the better the stability of the grading scale. The degree of upper eyelid skin laxity before and after operation was expressed as M ( Q1, Q3), and the paired Wilcoxon signed rank test was used for comparison. Results:A total of 50 female patients aged 32 to 67 years old (mean 45.3 years) who underwent bilateral upper eyelid skin laxity plastic surgery were enrolled. The Kendall coefficients of the grading result of the upper eyelid skin laxity of 50 patients by three doctors before and after operation were 0.975 and 0.882, respectively ( P<0.01). It suggested high consistency among evaluators for the same patient. 50 patients were graded as 2(1, 2) degree and 0(0, 0) degree preoperatively and postoperatively, respectively, indicating that the degree of upper eyelid skin laxity was significantly improved postoperatively. The result of Wilcoxon signed rank test showed that there were significant differences in preoperative and postoperative grading result of the three doctors ( P<0.01). Conclusion:The grading scale of upper eyelid skin laxity is objective and easy to use. Its evaluation result are stable and repeatable, and it can effectively analyze the changes of the degree of upper eyelid skin relaxation before and after surgery.
6.Construction and effect of auricular acupressure in patients with cough with different syndrome types
Yanli HOU ; Zhentao LU ; Jing GUO ; Haiqing LIN ; Xinyu TANG ; Jiaomei ZHOU ; Kun WANG ; Yang CHEN
Chinese Journal of Nursing 2025;60(12):1427-1433
Objective To construction and investigate the application effect of auricular acupressure technology in patients with cough with different syndrome types.Methods From December 2022 to March 2023,the Delphi method was used to consult experts to form a technical scheme for auricular pressure in patients with cough with different syndrome types in the early and middle stages.122 patients with stage Ⅰ and stage Ⅱ lung cancer cough from the oncology department of 3 tertiary hospitals of Traditional Chinese Medicine in Beijing between July 2023 to January 2024 were randomly divided into an experimental group(61 cases)and a control group(61 cases).The experimental group referred to the constructed auricular acupressure technique program to identify and take acupoints,and the control group used the original auricular acupressure program for 7 d of continuous intervention.The changes in the scores of the Visual Analog Scale(VAS)and the scores of The MD Anderson Symptom Inventory for lung cancer(MDASI-LC)were observed in the 2 groups before and after the intervention.Results The final scheme included 3 first-level items,12 second-level items,and 14 third-level items.The 2 rounds of expert authority coefficients were 0.88,indicating a high degree of authority,and the Kendall harmony coefficients of the 2 rounds of correspondence were 0.170 and 0.130(P<0.001),respectively,and the results tended to be consistent.A total of 122 patients completed the study.After intervention,the VAS score of cough severity in the experimental group was 3.0(2.0,3.0)points,which was lower than 3.0(3.0,4.0)points in the control group.The MDASI-LC score of the experimental group was 17.0(9.5,31.5)points,which was lower than 28.0(15.5,47.5)points in the control group,and the difference was statistically significant(P<0.05).Conclusion The constructed auricular acupressure technique program has certain scientificity,and it can effectively relieve cough symptoms of stage Ⅰ~Ⅱ lung cancer patients,and the severity of symptom clusters has been improved,which provides the basis for TCM nursing intervention in cough symptoms of lung cancer patients.
7.Prediction of Preterm Labor Using Uterine Electromyography in Women with Threatened Preterm Labor after Tocolytic Therapy
Qiang HUANG ; Feizhou JIANG ; Wenjie HOU ; Leilei HE ; Kun YU ; Li CHEN ; YIhui GU ; Jingtong ZHANG ; Yueming ZHANG
Journal of Practical Obstetrics and Gynecology 2025;41(4):346-350
Objective:To investigate the predictive value of transabdominal uterine electromyography for pre-term labor after tocolysis in women with threatened preterm labor.Methods:A total of 48 pregnant women at 28-34 weeks of gestation diagnosed with threatened preterm labor and admitted to The Fourth Affiliated Hospital of Soo-chow University from January to September 2023 were included.According to the response to tocolysis and whether the pregnancy was prolonged for at least 48 h,women were divided into two groups:non-preterm birth within 48 h(n=35)and preterm birth within 48 h(n=13).Uterine electromyography parameters and difference were compared before and after tocolytic therapy in two groups.Univariate Logistic regression was performed to predict the related factors of preterm birth within 48 h after the using of tocolysis in pregnant women with threat-ened preterm birth by uterine electromyography,and receiver operating characteristic(ROC)curve was per-formed to evaluate their performance.Results:Compared to before treatment with tocolysis,after therapy,in the non-preterm birth within 48 h group,significant reductions in contraction frequency,area,duration and amplitude were observed(P<0.05).In the preterm birth within 48 h group,only contraction frequency decreased significant-ly(P<0.05).Univariate Logistic regression indicated that contraction frequency,contraction duration,and contrac-tion area were predictive factors for premature birth within 48 h after tocolysis(P<0.05).When the duration of u-terine contractions lasting for 104.55 s or more the sensitivity and specificity of predicting premature birth within 48 h are 92.3%and 68.6%,respectively.Conclusions:Uterine electromyography may predict the premature birth within 48 h after tocolytic treatment in preterm labor,which may provide reference for subsequent corticosteroid therapy or transfer of high-risk pregnant patients.
8.A Sensitive Ion Chromatography-Inductively Coupled Plasma Mass Spectrometry Method for Analysis of Iodine Speciation in Environmental Water Samples
Huan JIANG ; Ning CHEN ; Yan-Yun WANG ; Yu-Kun FAN ; Meng-Ting ZHANG ; Lu-Yuan ZHANG ; Xiao-Lin HOU
Chinese Journal of Analytical Chemistry 2025;53(2):278-288
Iodine speciations in aquatic environments are affected by dissolved oxygen,redox potential,microbial activity,organic matter decomposition,light reaction,etc.Accurate quantification of iodine speciation can not only help to understand the geochemical cycle of iodine,but also help to trace and study environmental processes.Based on the combination of ion chromatography(IC)and inductively coupled plasma mass spectrometry(ICP-MS),a rapid and sensitive method was established for determining the speciations of iodine in environmental water samples including seawater,river water,lake water,rainwater,groundwater,etc.The results presented here showed that IO3?and I?in seawater were quickly separated and measured within 120 s when using guard column AG22 and 8 mmol/L(NH4)2CO3 as the mobile phase.While for lake water,river water and precipitation samples with high soluble organically bond iodine(SOI),an AS22 separation column(250 mm×4 mm)connected with a guard column and using 50 mmol/L(NH4)2CO3 as mobile phase could effectively separate unknown SOI from IO3? to achieve accurate quantification of IO3?.For accurate correction of iodine measurement signal fluctuations,133Cs was directly added to the(NH4)2CO3 mobile phase as an internal standard.The SOI content was calculated by the total iodine concentrations minus the sum of IO3?and I?.The precision of the established iodine speciation analytical method was better than 3.5%,and the standard addition experiment showed that the analytical method was accurate.When the injection volume was 25 μL,the detection limits were 0.011?0.025 μg/L for IO3? and 0.023?0.031 μg/L for I?,respectively.The method was successfully used to analyze IO3?,SOI and I? in environmental water samples,such as seawater,river water,rainwater and groundwater.
9.Highly Sensitive Mass Spectrometric Analysis of Trace Iodine in Environmental Samples
Huan JIANG ; Yan-Yun WANG ; Yu-Kun FAN ; Ning CHEN ; Xiao-Lin HOU
Chinese Journal of Analytical Chemistry 2025;53(9):1536-1545
The cycling of iodine in the atmosphere and ocean plays a critical role in climate and environmental change.Ice cores and tree rings,as ideal climate archives,can provide essential data for paleoclimate reconstruction through accurate iodine analysis.However,iodine concentrations in ice core samples are as low as 0.01 μg/L,and as low as 0.01 μg/g in tree rings.Most currently reported analytical methods face challenges in accurately quantifying such low levels.In this study,a highly sensitive analytical method for trace iodine in environmental samples was developed based on inductively coupled plasma mass spectrometry(ICP-MS),incorporating a collision/reaction cell under the optimized collision/reaction gas conditions.Collision/reaction cell mode was employed to evaluate potential interferences in determination of trace iodine by ICP-MS.The results indicated that peak tailing from adjacent mass-to-charge ratios and polyatomic ion interferences could be considered negligible.However,residual iodine in ultrapure water constituted the major source of background,highlighting the need for strict control of sample pretreatment and procedural blanks in trace-level iodine analysis.By utilizing collision focusing effect of helium,the measurement sensitivity of iodine was enhanced to 3.5×105 cps(counts per second)/(μg/L),and the detection limit was reduced to 0.002 μg/L.The developed method exhibited a deviation of less than 2.3%in measurement of low-concentration standard solutions,indicating good accuracy.For actual samples and blanks,the precision of repeated measurements within 2 h was better than 1.6%,demonstrating excellent repeatability.No significant memory effect was observed during the measurements.The established method was successfully applied to determination of trace iodine in ice cores,tree rings,and other environmental samples,providing a robust technical foundation for investigating the role of iodine in climate and environmental change.
10.Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.
Yan-Jun WANG ; Zi-Hou ZHAO ; Shuai-Kun LU ; Guo-Liang WANG ; Shan-Jin MA ; Lin-Hu WANG ; Hao GAO ; Jun REN ; Zhong-Wei AN ; Cong-Xiao FU ; Yong ZHANG ; Wen LUO ; Yun-Fei ZHANG
Chinese Journal of Traumatology 2025;28(4):241-251
PURPOSE:
We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery.
METHODS:
A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics.
RESULTS:
Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%.
CONCLUSION
Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
Humans
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Surgical Wound Infection/epidemiology*
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Male
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Female
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Risk Factors
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Retrospective Studies
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Middle Aged
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Adult
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Case-Control Studies
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Fractures, Bone/surgery*
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Aged
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Drug Resistance, Bacterial
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Logistic Models
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Anti-Bacterial Agents/therapeutic use*
;
Incidence
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Bacteria/drug effects*

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