1.Mechanisms of Gut Microbiota Influencing Reproductive Function via The Gut-Gonadal Axis
Ya-Qi ZHAO ; Li-Li QI ; Jin-Bo WANG ; Xu-Qi HU ; Meng-Ting WANG ; Hai-Guang MAO ; Qiu-Zhen SUN
Progress in Biochemistry and Biophysics 2025;52(5):1152-1164
Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.
2.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.
4.Clinical Features and CT Imaging Findings of Melioidosis Pneumonia
Sheng-shi MAI ; Hong-zhang ZHU ; Guang-qiang ZHAO ; Hai CHEN ; Meng ZHANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(6):1038-1045
ObjectiveTo summarize and analyze the clinical features and CT imaging findings of melioidosis pneumonia in order to increase awareness of this disease. MethodsA retrospective study was done on clinical and CT imaging data of 68 cases with melioidosis pneumonia diagnosed from January 1, 2012 to April 1, 2023. ResultsOf the 68 cases, 62 presented with acute infection and 6 chronic infection, 88.2% were male, 85.3% were native residents of Hainan, 85.3% were farmers, 77.9% had onset in summer and autumn, 66.2% had diabetes, 100% had fever as the first clinical symptom, and 88.2% were confirmed positive by blood culture. In most patients, white blood cell count, neutrophil ratio, C-reactive protein and calcitonin levels increased, while lymphocyte ratio decreased, but no statistical difference was found between acute and chronic infection groups (P > 0.05). Of the patients, 36.8% recovered, 42.6% got better, 11.8% patients became therapy-resistant and 8.8% died. CT image showed pathomorphological changes including nodules/masses, patchy ground-glass attenuation or large patchy consolidation or all of these at the same time. Acute and chronic infection groups had significant difference in pathomorphological changes (P = 0.01), but no statistical difference in other imaging findings. Moreover, 36.8% of the patients developed extrapulmonary infections, 8.8% of which multi-site abscess formation. ConclusionsMelioidosis Pneumonia should be considered if the patient is the sojourner from epidemic area, or has diabetes, high fever and rapid-developing disease, with additional presence of multiple inflammatory lesions in lung CT.
5.Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population.
Meng Fan LIU ; Rui Xia MA ; Xian Bao CAO ; Hua ZHANG ; Shui Hong ZHOU ; Wei Hong JIANG ; Yan JIANG ; Jing Wu SUN ; Qin Tai YANG ; Xue Zhong LI ; Ya Nan SUN ; Li SHI ; Min WANG ; Xi Cheng SONG ; Fu Quan CHEN ; Xiao Shu ZHANG ; Hong Quan WEI ; Shao Qing YU ; Dong Dong ZHU ; Luo BA ; Zhi Wei CAO ; Xu Ping XIAO ; Xin WEI ; Zhi Hong LIN ; Feng Hong CHEN ; Chun Guang SHAN ; Guang Ke WANG ; Jing YE ; Shen Hong QU ; Chang Qing ZHAO ; Zhen Lin WANG ; Hua Bin LI ; Feng LIU ; Xiao Bo CUI ; Sheng Nan YE ; Zheng LIU ; Yu XU ; Xiao CAI ; Wei HANG ; Ru Xin ZHANG ; Yu Lin ZHAO ; Guo Dong YU ; Guang Gang SHI ; Mei Ping LU ; Yang SHEN ; Yu Tong ZHAO ; Jia Hong PEI ; Shao Bing XIE ; Long Gang YU ; Ye Hai LIU ; Shao wei GU ; Yu Cheng YANG ; Lei CHENG ; Jian Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):579-588
Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female
;
Humans
;
Adolescent
;
SARS-CoV-2
;
Smell
;
COVID-19/complications*
;
Cross-Sectional Studies
;
COVID-19 Vaccines
;
Incidence
;
Olfaction Disorders/etiology*
;
Taste Disorders/etiology*
;
Prognosis
6.Clinical application value of Huanglian Jiedu Pills in improving syndrome of excess heat and fire toxin based on phase Ⅱ clinical trial study on plasma ATP, 4-HNE, and ACTH levels.
Ke-Ke LUO ; Hai-Yu ZHAO ; Nan SI ; Bao-Lin BIAN ; Wen XIA ; Yun-Qin CHEN ; Meng-Xiao WANG ; Xiao-Lu WEI ; Xing LI ; Guang-Yuan QIN ; Jian YANG ; Yan-Yan ZHOU ; Hong-Jie WANG
China Journal of Chinese Materia Medica 2023;48(4):1124-1131
A randomized, double-blind, placebo-controlled, multi-center phase Ⅱ clinical trial design was used in this study to recruit subjects who were in line with the syndrome of excess heat and fire toxin, and were diagnosed as recurrent oral ulcers, gingivitis, and acute pharyngitis. A total of 240 cases were included and randomly divided into a placebo group and a Huanglian Jiedu Pills group. The clinical efficacy of Huanglian Jiedu Pills in treating the syndrome of excess heat and fire toxin was evaluated by using the traditional Chinese medicine(TCM) syndrome scale. Enzyme-linked immunosorbent assay(ELISA) was used to determine and evaluate the levels of adenosine triphosphate(ATP), 4-hydroxynonenal(4-HNE), and adrenocorticotropic hormone(ACTH) in plasma of the two groups before and after administration and to predict their application value as clinical biomarkers. The results showed that the disappearance rate of main symptoms in the Huanglian Jiedu Pills group was 69.17%, and that in the placebo group was 50.83%. The comparison between the Huanglian Jiedu Pills group and the placebo group showed that 4-HNE before and after administration was statistically significant(P<0.05). The content of 4-HNE in the Huanglian Jiedu Pills group decreased significantly after administration(P<0.05), but that in the placebo group had no statistical significance and showed an upward trend. After administration, the content of ATP in both Huanglian Jiedu Pills group and placebo group decreased significantly(P<0.05), indicating that the energy metabolism disorder was significantly improved after administration of Huanglian Jiedu Pills and the body's self-healing ability also alleviated the increase in ATP level caused by the syndrome of excess heat and fire toxin to a certain extent. ACTH in both Huanglian Jiedu Pills group and placebo group decreased significantly after administration(P<0.05). It is concluded that Huanglian Jiedu Pills has a significant clinical effect, and can significantly improve the abnormal levels of ATP and 4-HNE in plasma caused by the syndrome of excess heat and fire toxin, which are speculated to be the effective clinical biomarkers for Huanglian Jiedu Pills to treat the syndrome of excess heat and fire toxin.
Humans
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Adrenocorticotropic Hormone
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Hot Temperature
;
Medicine, Chinese Traditional
;
Adenosine Triphosphate
7. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
8.Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study.
Yang YANG ; Ke-Yu LU ; Rui CHENG ; Qin ZHOU ; Guang-Dong FANG ; Hong LI ; Jie SHAO ; Huai-Yan WANG ; Zheng-Ying LI ; Song-Lin LIU ; Zhen-Guang LI ; Jin-Lan CAI ; Mei XUE ; Xiao-Qing CHEN ; Zhao-Jun PAN ; Yan GAO ; Li HUANG ; Hai-Ying LI ; Lei SONG ; San-Nan WANG ; Gui-Hua SHU ; Wei WU ; Meng-Zhu YU ; Zhun XU ; Hong-Xin LI ; Yan XU ; Zhi-Dan BAO ; Xin-Ping WU ; Li YE ; Xue-Ping DONG ; Qi-Gai YIN ; Xiao-Ping YIN ; Jin-Jun ZHOU
Chinese Journal of Contemporary Pediatrics 2022;24(3):240-248
OBJECTIVES:
To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.
METHODS:
A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.
RESULTS:
Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).
CONCLUSIONS
This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use*
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Citrates
;
Humans
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Infant
;
Infant, Newborn
;
Infant, Premature
;
Respiration, Artificial
;
Retrospective Studies
9.Chemical pattern recognition of Atractylodes chinensis from different producing areas and establishment of quantitative analysis of multi-components by single marker (QAMS) method for four components.
Yan-Yun ZHAO ; Jian-Yun ZHANG ; Kai-Yan ZHENG ; Xian GU ; Qian WANG ; Long GUO ; Hai-Shuo REN ; Yu-Guang ZHENG ; Min-Hui LI ; Hui-Yong FANG
China Journal of Chinese Materia Medica 2022;47(16):4395-4402
This study established the fingerprint and combined it with chemical pattern recognition to evaluate the quality of Atractylodes chinensis samples from different producing areas and then employed the quantitative analysis of multi-components by single marker(QAMS) method to verify the feasibility and applicability of the established method in the quality evaluation of A. chinensis. The fingerprints of A. chinensis samples were constructed via high performance liquid chromatography(HPLC) to evaluate the inter-batch consistency. With the quality control component atractylodin as the internal reference, the relative correction factors(RCFs) were established for atractylenolide Ⅰ, atractylenolide Ⅲ, and β-eudesmol and the content of the four components was calculated. The external standard method was used to verify the accuracy of QAMS method. The quality of A. chinensis was further evaluated by similarity analysis, clustering analysis, and principal component analysis. The fingerprints of 13 batches of samples were calibrated with 21 common peaks, and 4 common peaks were identified with the similarities all above 0.9. The RCFs established with atractylodin as the internal reference represented good reproducibility under different experimental conditions. Specifically, the RCFs of atractylenolide Ⅰ, atractylenolide Ⅲ, and β-eudesmol in A. chinensis were 2.091, 4.253, and 6.010, respectively. QAMS and ESM showed no significant difference in the results, indicating that the QAMS method established in this study was stable and reliable. Thus, HPLC fingerprint combined with QAMS can be used for the quality evaluation of A. chinensis, providing a basis for comprehensive and rapid quality evaluation of A. chinensis.
Atractylodes
;
Chromatography, High Pressure Liquid/methods*
;
Drugs, Chinese Herbal/chemistry*
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Quality Control
;
Reproducibility of Results
10.Comparison of minimally invasive and traditional Chevron osteotomy in treating patients with mild to moderate hallux valgus.
Bing LI ; Wen-Bao HE ; Jiang XIA ; Hai-Chao ZHOU ; You-Guang ZHAO ; Yun-Feng YANG ; Guang-Rong YU
China Journal of Orthopaedics and Traumatology 2022;35(9):818-824
OBJECTIVE:
To compare minimally invasive and traditional Chevron osteotomy in treating patients with mild to moderate hallux valgus.
METHODS:
Clinical data of 36 patients (36 feet) with mild to moderate hallux valgus from January 2019 to February 2021 were retrospectively analyzed, and divided into minimally invasive osteotomy(minimally invasive group) and traditional Chevron osteotomy(traditional group). There were 16 patients in minimally invasive group, including 1 male and 15 females, aged from 36 to 60 years old with an average of(49.0±9.5) years old;9 were mild and 7 were moderate according to Mann classification;treated with minimally invasive osteotomy with hollow screw fixation. There were 20 patients(20 feet) in traditional group, including 2 males and 18 females, aged from 38 to 65 years old with an average of(50.0±9.2) years old;11 were mild and 9 were moderate according to Mann classification;treated with traditional Chevron osteotomy. Hallux valgus angle (HVA), intermetatarsal angle (IMA) before and after operation at 12 months bewteen two groups were observed and compared, and American Orthopedic Foot and Ankle Society (AOFAS) forefoot score and visual analogue scale (VAS) before and after operation at 6 weeks and 12 months between two groups were compared.
RESULTS:
Thirty-six patiens were followed up from 14 to 30 months with an average of (21.00±5.77) months. All incisions were healed well at stageⅠwithout infection. There were no significant differences in HVA, IMA, AOFAS forefoot scores and VAS before and after operation at 12 months between two groups(P>0.05). However, AOFAS forefoot scores and VAS of minimally invasive group was significantly better than that of traditionl group at 6 weeks after operation (P<0.05). Postoperative HVA, IMA, AOFAS forefoot scores and VAS at 12 months bewteen two groups were improved better than that of preoperation(P<0.05).
CONCLUSION
Compared with traditional Chevron osteotomy, minimally invasive osteotomy has less trauma and quicker recovery. Both of them has similar clinical effects, and could receive satisfactory clinical effects, while treatment of minimally invasive osteotomy should pain attention to learning curve.
Adult
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Aged
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Bunion
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Female
;
Hallux Valgus/surgery*
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Humans
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Male
;
Middle Aged
;
Osteotomy
;
Retrospective Studies
;
Treatment Outcome

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