1.Nanoengineered cargo with targeted in vivo Foxo3 gene editing modulated mitophagy of chondrocytes to alleviate osteoarthritis.
Manyu CHEN ; Yuan LIU ; Quanying LIU ; Siyan DENG ; Yuhan LIU ; Jiehao CHEN ; Yaojia ZHOU ; Xiaolin CUI ; Jie LIANG ; Xingdong ZHANG ; Yujiang FAN ; Qiguang WANG ; Bin SHEN
Acta Pharmaceutica Sinica B 2025;15(1):571-591
Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.
2.Early efficacy of modified suspended fixation with triple plates and double beams for acroxoclavicular dislocation
Dan WEN ; Wenyong FEI ; Pei ZHANG ; Dan GUO ; Yaojia LU ; Hua WANG
Chinese Journal of Orthopaedic Trauma 2024;26(11):964-971
Objective:To evaluate the early clinical outcomes of modified suspended fixation with triple plates and double beams through a limited incision in the treatment of acroxoclavicular dislocation.Methods:A retrospective study was conducted to analyze the 23 patients with acromioclavicular dislocation who had been treated at Department of Orthopedics, The People's Hospital of Northern Jiangsu from June 2021 to August 2023 by modified suspended fixation with triple plates and double beams through a limited incision. There were 9 males and 14 females with an age of (52.2±10.6) years. The incision length, operation time, intraoperative bleeding and complications were recorded. The visual analogue scale (VAS) pain score, Constant-Murley shoulder score, American Shoulder and Elbow Surgeons (ASES) score, range of shoulder motion (anterior flexion, abduction, lateral rotation) were recorded and compared between preoperation and the last follow-up. The coracoclavicular distance (CCD), clavicle tract width and coracoid tract width were measured and compared between postoperative day 2 and the last follow-up.Results:The patients were followed up for 12 (12, 16) months. The incision length was 5 (4, 5) cm, the operation time 50 (40, 60) min, and the intraoperative bleeding 30 (20, 30) mL. No such complications occurred as incision infection, fracture, or failure of internal fixation. The VAS pain score, Constant-Murley shoulder score, ASES score, anterior flexion, abduction and lateral rotation of the shoulder at the last follow-up were, respectively, 0 (0, 0) point, (92.8±4.9) points, (90.4±5.7) points, 175 °(170°, 180°), 175°(170°, 175°), and 85°(80°, 85°), significantly improved compared with the preoperative values [6 (5, 6) points, (40.4±7.2) points, (39.3±7.1) points, 85°(80°, 85°), 85°(80°, 90°), and 35°(35°, 40°)] ( P<0.05). The CCD was (6.1±1.3) mm at postoperative day 2 and (7.5±1.7) mm at the last follow-up, showing a significant difference ( P<0.05). Compared with postoperative day 2, the CCD widening at the last follow-up was <4mm in all patients, giving an excellent rate of 100% (23/23). The medial clavicle tract widening and the medial coracoid tract widening at the last follow-up were both <2 mm in all patients, giving an excellent rate of 100% (23/23). The lateral clavicle tract widening at the last follow-up was >2 mm in 2 patients, giving an excellent rate of 91% (21/23). Conclusions:In the treatment of acroxoclavicular dislocation, our modified suspended fixation with triple plates and double beams through a limited incision can lead to reliable reduction fixation and good recovery of shoulder function, showing advantages of short surgical time, easy surgical operation, high safety, and minimal postoperative widening of bone tracts.
3.Construction of a screening system for key intracellular survival proteins of macrophages of Staphylococcus aureus
Yaojia SHI ; Tian TIAN ; Tingrong XIONG ; Yu WANG ; Xiaokai ZHANG ; Quanming ZOU
Journal of Army Medical University 2024;46(8):815-821
Objective To establish a high-throughput screening system to obtain key Staphylococcus aureus (S.aureus)secretory proteins which required for S.aureus survival in macrophages.Methods Based on our validated eukaryotic expression vector library of S.aureus secretory proteins,DNA transfection was used to obtain an RAW264.7 macrophage array expressing S.aureus secretory proteins.After the RAW264.7 cells were infected with S.aureus,the extracellular bacteria were removed to observe the intracellular surviving situation of S.aureus.Finally,the screening results were validated by the overexpression and knockout S.aureus of corresponding secretory proteins.Results The optimal transfection dose (1.0 μg/well)of plasmids for RAW264.7,multiplicity of infection (MOI,1 .0 ),and infection time (4 h after removing extracellular bacteria of S.aureus ) were established respectively.To validate the screening results,the corresponding overexpression and knockout strains were constructed.And hypothetical protein and Serine protease E were found to promote the survival of intracellular S.aureus.Conclusion We successfully construct a screening system for key secreted secretory proteins which required for S.aureus surviving in macrophages,which may advance the study of the intracellular surviving mechanism of S.aureus.
4.Analysis on the characteristics and patterns of work-related musculoskeletal disorders among sonographers in Guangdong Province
Danying ZHANG ; Limin WANG ; Yingheng WU ; Yaojia LIANG ; Huimin WANG ; Hanlin HUANG ; Haichun ZHANG ; Zhongping CHEN ; Jinrong LIU ; Xiaoyan MA
China Occupational Medicine 2023;50(3):255-261
Objective To analyze the characteristics of work-related musculoskeletal disorders (WMSDs) among sonographers in Guangdong Province, and to explore the disease pattern of the cases. Methods A total of 512 sonographers from 31 hospitals in Guangdong Province were selected as the research subjects using stratified cluster sampling method. The prevalence of WMSDs in the past year was investigated using the Musculoskeletal Disorders Questionnaire, and the characteristics of WMSDs were analyzed. Latent class analysis was used to identify the disease pattern of WMSDs. Results The overall prevalence of WMSDs was 94.3%. The top five affected body parts were right shoulder, neck, right hand/wrist, lower back and right forearm/elbow, with the prevalence of 80.3%, 75.4%, 61.1%, 55.5% and 45.3%, respectively. The prevalence of WMSDs was higher on the right side for the shoulder, hand/wrist, forearm/elbow, hip/leg and knee compared with the left side (80.3% vs 31.3%, 61.1% vs 13.9%, 45.3% vs 10.0%, 17.4% vs 8.6%, 13.1% vs 8.4%, all P<0.05). The prevalence of WMSDs increased with work years, as well the prevalence of WMSDs in the top five affected body parts among the sonographers (all P<0.05). However, there were no statistical differences in prevalence of WMSDs between general hospitals and maternal and child health hospitals, tertiary hospitals and non-tertiary hospitals, Pearl River Delta hospitals and non-Pearl River Delta hospitals; there was also no statistical difference between different genders and age groups of the sonographers (all P>0.05). The best-fit latent disease pattern for sonographers WMSDs comprised three categories: symptom of neck-right shoulder, symptom of neck-lower back-right shoulder-right elbow-right hand/wrist, and symptom of multi-parts above the knees, with the latent probabilities of 0.438, 0.427 and 0.135, respectively. Conclusion The prevalence of WMSDs in sonographers is extremely high, with a dose-effect relationship with work years. The most common affected parts are neck, lower back and right shoulder, right hand/wrist, and right forearm/elbow. The prevalence of WMSDs in the right side of limb was higher than that in the left. WMSDs primarily occur in multiple parts simultaneously. The most common symptoms occur in the neck-right shoulder and neck-lower back-right shoulder-right elbow-right hand/wrist.
5.Effect of different fertilization methods on pregnancy outcome of unexplained infertility patients
Yaojia ZHANG ; Rui SHI ; Yinfeng ZHANG ; Yunshan ZHANG
Chinese Journal of Reproduction and Contraception 2022;42(7):682-687
Objective:To compare the clinical pregnancy outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) fertilization in patients with unexplained infertility. Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with unexplained infertility from July 2014 to July 2019 in the Assisted Reproductive Center of Tianjin Central Hospital of Gynecology Obstetrics. The patients were divided into IVF group ( n=299) and ICSI group ( n=234) according to the fertilization methods. The general information, fertilization condition, embryo development and pregnancy outcomes were compared between the two groups. Results:There were no statistically significant differences between ICSI group and IVF group in two pronuclei (2PN) fertilization rate, 2PN cleavage rate, and high-quality embryo rate (all P>0.05). Infertility type had a statistically difference between the two groups ( P<0.001). Stratified analysis was conducted according to the primary and secondary infertility. Among patients with primary infertility, 2PN cleavage rate in ICSI group [91.2% (1339/1468)] was higher than that in IVF group [87.8% (1646/1844), P=0.062]. There were no statistically significant differences in 2PN fertilization rate and high-quality embryo rate between the two groups (all P>0.05). The clinical pregnancy rate and the live birth rate in ICSI group [39.8% (74/186), 33.3% (62/186)] were higher than those in IVF group [37.8% (45/119), 31.1% (37/119)] without significant differences (all P>0.05). In the patients with secondary infertility, there were no statistically significant differences in 2PN fertilization rate, 2PN cleavage rate and high-quality embryo rate between the two groups (all P>0.05). The clinical pregnancy rate [20.8% (10/48)] and the live birth rate [18.8% (9/48)] of ICSI group were significantly lower than those of IVF group [49.4% (89/180), P<0.001; 40.0% (72/180), P=0.006]. After adjusting female age, infertility duration, body mass index, basal follicle-stimulating hormone and the number of oocyte retrieved, logistics regression showed that different fertilization methods had similar live birth rate ( OR=1.178, 95% CI=0.686-2.202) in primary infertility patients, and the live birth rate of ICSI group was significantly lower than that of IVF group ( OR=0.408, 95% CI=0.180-0.924) in secondary infertility patients. Conclusion:In patients with unexplained infertility, ICSI could not significantly improve fertilization rate, embryo quality and pregnancy outcome. Especially in patients with secondary infertility, IVF patients had significantly better pregnancy outcome than ICSI patients, and routine IVF fertilization should be preferred.
6.Effect of different fertilization methods on pregnancy outcome of unexplained infertility patients
Yaojia ZHANG ; Rui SHI ; Yinfeng ZHANG ; Yunshan ZHANG
Chinese Journal of Reproduction and Contraception 2022;42(7):682-687
Objective:To compare the clinical pregnancy outcomes of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) fertilization in patients with unexplained infertility. Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with unexplained infertility from July 2014 to July 2019 in the Assisted Reproductive Center of Tianjin Central Hospital of Gynecology Obstetrics. The patients were divided into IVF group ( n=299) and ICSI group ( n=234) according to the fertilization methods. The general information, fertilization condition, embryo development and pregnancy outcomes were compared between the two groups. Results:There were no statistically significant differences between ICSI group and IVF group in two pronuclei (2PN) fertilization rate, 2PN cleavage rate, and high-quality embryo rate (all P>0.05). Infertility type had a statistically difference between the two groups ( P<0.001). Stratified analysis was conducted according to the primary and secondary infertility. Among patients with primary infertility, 2PN cleavage rate in ICSI group [91.2% (1339/1468)] was higher than that in IVF group [87.8% (1646/1844), P=0.062]. There were no statistically significant differences in 2PN fertilization rate and high-quality embryo rate between the two groups (all P>0.05). The clinical pregnancy rate and the live birth rate in ICSI group [39.8% (74/186), 33.3% (62/186)] were higher than those in IVF group [37.8% (45/119), 31.1% (37/119)] without significant differences (all P>0.05). In the patients with secondary infertility, there were no statistically significant differences in 2PN fertilization rate, 2PN cleavage rate and high-quality embryo rate between the two groups (all P>0.05). The clinical pregnancy rate [20.8% (10/48)] and the live birth rate [18.8% (9/48)] of ICSI group were significantly lower than those of IVF group [49.4% (89/180), P<0.001; 40.0% (72/180), P=0.006]. After adjusting female age, infertility duration, body mass index, basal follicle-stimulating hormone and the number of oocyte retrieved, logistics regression showed that different fertilization methods had similar live birth rate ( OR=1.178, 95% CI=0.686-2.202) in primary infertility patients, and the live birth rate of ICSI group was significantly lower than that of IVF group ( OR=0.408, 95% CI=0.180-0.924) in secondary infertility patients. Conclusion:In patients with unexplained infertility, ICSI could not significantly improve fertilization rate, embryo quality and pregnancy outcome. Especially in patients with secondary infertility, IVF patients had significantly better pregnancy outcome than ICSI patients, and routine IVF fertilization should be preferred.
7.Effect of body mass index on the assisted reproductive outcome of frozen-thawed embryo transfer in patients with polycystic ovary syndrome
Yinfeng ZHANG ; Haining LUO ; Rui SHI ; Yaojia ZHANG ; Xiaomei TAI ; Xinyu HU ; Junfang MA ; Xinyan WANG ; Yunshan ZHANG ; Pengpeng QU
Chinese Journal of Obstetrics and Gynecology 2021;56(4):257-263
Objective:To investigate the effect of body mass index (BMI) on clinical pregnancy and neonatal outcomes in patients with polycystic ovary syndrome (PCOS) during frozen-thawed embryo transfer.Methods:A total of 650 patients with PCOS who received routine in vitro fertilization or intracytoplasmic sperm injection treatment for frozen-thawed embryo transfer from June 2014 to June 2019 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively analyzed. According to BMI, PCOS patients were divided into group A (18.5≤BMI<23 kg/m 2, n=253), group B (23≤BMI<25 kg/m 2, n=167), and group C (BMI≥25 kg/m 2, n=230). The general information, clinical pregnancy outcomes, pregnancy complications, the incidence of macrosomia and low-birth-weight infants were compared in the three groups, and the influencing factors of neonatal birth weight were analyzed. Results:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate all showed downward trend with the increase of BMI, but the differences were not statistically significant (all P>0.05). The live birth rate in group C [47.0% (108/230)] was significantly lower than those in groups A and B, with statistical significance ( χ2 =7.43, P=0.024). The late miscarriage rate was higher in group C [9.4% (13/139)] than in groups A and B ( χ2 =7.66, P=0.022). The birth rates of macrosomia in groups B [22.2% (16/72)] and group C [21.1% (16/76)] were significantly higher than that in group A, and the difference was statistically significant ( χ2 =14.15, P=0.001). There was no statistically significant difference in the incidence of gestational diabetes between the three groups ( χ2 =3.81, P=0.149). The incidence of hypertension disorders complicating pregnancy increased with the increase of BMI, and the difference was not statistically significant ( P>0.05). Regression analysis showed that macrosomia was significantly associated with maternal pre-pregnancy BMI and gestational weeks, and the risk of macrosomia increased by 15% (95% CI: 3%-28%) for every increase in maternal BMI. Conclusions:The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of PCOS patients in frozen-thawed embryo transfer cycles show downward trend with the increase of BMI. Obese patients with PCOS have a significant increase in late miscarriage rate and a significant decrease in live birth rate. The incidence of hypertension disorders complicating pregnancy in PCOS patients in the obese group has an increasing trend, and the birth rate of macrosomia has increased significantly. Therefore, it is recommended that obese women with PCOS lose weight scientifically before pregnancy to improve pregnancy and neonatal outcomes.
8.Bibliometric analysis of oral motor intervention in premature infants in China from 2010 to 2020
Qian TANG ; Na ZHANG ; Yaojia HU ; Lihui ZHU
Chinese Journal of Modern Nursing 2021;27(21):2832-2836
Objective:To explore the research and development trends of oral motor intervention in premature infants in China, so as to provide an effective reference for further development of oral motor intervention in premature infants.Methods:Chinese literature on oral motor intervention in premature infants included in the China National Knowledge Infrastructure (CNKI) , WanFang, VIP and China Biology Medicine database were searched by computer from January 2010 to October 2020. Quantitative analysis was carried out using Medical Literature King, Excel 2019 and SPSS 25.0.Results:The number of documents that met the requirements was 303, and the number of documents was on the rise. A total of 224 documents were published from 2013 to 2019, accounting for 73.93% of the total number of documents. Guangdong Province had the largest number of published documents, with 53 articles (17.49%) , followed by Jiangsu with 29 articles (9.57%) . The document fund support rate was 16.17% (49/303) , and the co-author rate was 64.03% (194/303) , and the author's collaboration was 1.96 (595/303) . Among the document types, the number of case-control studies was the largest, with 249 (82.18%) , and the second was review literature, with 32 (10.56%) . The contents of the document research were mainly feeding and growth and development, with 182 articles (60.07%) and 34 articles (11.22%) respectively. The evaluation indicators used were mainly oral feeding time, body weight, hospital stay and milk sucking volume.Conclusions:The overall number of the document is on the rise, and the research efforts continue to increase, but the quality of the document, fund support rate, and evidence-based strength still need to be improved, and the research content needs to be further expanded.
9.Application progress of family-centered hospice care service model in pediatrics
Na ZHANG ; Qian TANG ; Lihui ZHU ; Dan LUO ; Muhua CHEN ; Yaojia HU
Chinese Journal of Modern Nursing 2021;27(35):4882-4887
According to the state's relevant policies on the development of hospice care, hospice care has become a social concern, and it is currently one of the key areas of medical development in China. This article elaborates on the current status and necessity of the development of children's hospice care, summarizes the application effects of family-centered child hospice care in the quality of life of children, the degree of grief of family members and the relationship between doctors and patients, and puts forward corresponding suggestions. This article aims at speeding up the standardized construction of the family-centered hospice care model in our country, and promote the development of children's hospice care in our country.
10.Clinical research of sequential embryo transfer in frozen thawed cycles of patients with recurrent implantation failure
Yinfeng ZHANG ; Haining LUO ; Rui SHI ; Yaojia ZHANG ; Junfang MA ; Yunshan ZHANG
Chinese Journal of Reproduction and Contraception 2020;40(11):893-898
Objectives:To investigate the effect of sequential embryo transfer, cleavage stage and blastocyst stage embryo transfer on the clinical outcome of patients with recurrent implantation failure (RIF) and the relationship between the number of sequential transfered embryos and multiple pregnancy.Methods:A retrospective case-control study was conducted and the outcome of 317 patients with a history of RIF were analyzed, of which 50 women underwent sequential embryo transfer of two embryos on Day 3 and Day 5/6 (group A), 61 women underwent sequential embryo transfer of three embryos on Day 3 and Day 5/6 (group B), 124 women underwent Day 3 embryo transfer only (group C) and 82 women underwent Day 5/6 embryo transfer only (group D) at the Reproductive Medical Center of Tianjin Central Hospital of Gynecology and Obstetrics from January 2015 to January 2019. General information, controlled ovarian hyperstimulation outcome and pregnancy outcome were analyzed among four groups.Results:There were no significant differences in age, duration of infertility, body mass index (BMI), and basal hormone levels between the groups. The embryo implantation rate of groups A, B and D (36.0%, 31.1% and 31.3%) was significantly higher than that of group C (17.0%, P<0.001, P<0.001, P=0.026). The clinical pregnancy rate, the ongoing pregnancy rate and the live birth rate of group A (62.0%, 56.0%, 52.0%) and group B (60.7%, 49.2%, 47.5%) were significantly higher than those in group C (28.2%, 20.2%, 17.7%, all P<0.001) and group D (40.2%, 31.7%, 30.5%; group A vs. group D, P=0.015, P=0.006, P=0.014; group B vs. group D, P=0.016, P=0.034 , P=0.037). The early abortion rate of group A (3.2%) was significantly lower than that of group C (25.7%, P=0.028). The multiple pregnancy rate in group B (32.4%) was higher than that in group A (16.1%), group C (14.3%), and group D (21.2%), but the difference was not statistically significant ( P>0.05). The preterm birth rate in group B (34.5%) was higher than that in group A (25.9%), group C (13.0%), and group D (8.0%). The difference in preterm birth rate between group B and group D was statistically significant ( P=0.020). Conclusion:Sequential embryo transfer of frozen-thawed embryo transfer cycle can effectively improve the clinical pregnancy rate of patients with RIF. Especially, the sequential embryo transfer of 2 embryos can significantly improve the clinical pregnancy rate and the live birth rate without increasing the multiple pregnancy rate. Sequential transplantation can be used as an effective treatment for RIF patients.

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