1.Effect of HIF-1α on osteogenic-angiogenic coupling response in BMSCs sheets
ZHANG Dan ; HUANG Yinli ; TENG Yonghui ; HAN Chang
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(9):744-756
Objective:
To explore the effect of HIF-1α on osteogenic-angiogenic coupling response in bone mesenchymal stem cells (BMSCs) and provide new concepts for engineered bone tissue in vitro.
Methods:
With the approval of the hospital’s experimental animal ethics committee, BMSCs were harvested from Wistar rats. The lentivirus carrying hypoxia-inducible factor-1α (HIF-1α) and empty lentivirus were stably transfected into the third generations of BMSCs to form LV-HIF-1α-BMSCs and LV-BMSCs. Meanwhile, BMSCs without transfection of lentivirus were used as a blank control. Then, the effect of HIF-1α transfection was verified by qPCR and Western Blot. LV-HIF-1α-BMSCs were induced to differentiate into endothelium-like cells (iECs). The morphology was observed by optical microscopy, the differentiation rate was detected by cellular flow CD31, and the Transwell test was used to detect the migration ability. At the same time, LV-HIF-1α-BMSCs and LV-BMSCs were continuously cultured to form osteogenic cell sheets (OCTs), which were stained by alkaline phosphatase on day 14 and alizarin red staining on day 21, and counted for mineralization capacity. Finally, iECs were implanted into OCTs to form prevascularized osteogenic cell sheets (P-OCTs), immunofluorescence CD31 was performed to detect the formation of vascular networks, and the results were recorded on days 1, 3, 7, and 14. Meanwhile, osteopontin (OPN) and osteocalcin (OCN) were detected by western blot to verify their ability for osteogenic differentiation on days 1, 7, and 14.
Results:
The optimal multiplicity of infection (MOI) for lentiviral transfection was 30, and the transfection efficiency was >80%. The results of qPCR and western blot showed that compared with the LV-BMSCs group and BMSCs group, the LV-HIF-1α-BMSCs group had stable and high expressions of HIF-1α (P<0.05). LV-HIF-1α-BMSCs showed an enhanced ability to differentiate into endothelial cells, with a differentiation rate as high as 91.81%. Transwell assay verified that HIF-1α could recruit iECs in vitro. Alkaline phosphatase staining and alizarin red staining confirmed that OCTs formed by LV-HIF-1α-BMSCs had a statistically significant osteogenic differentiation ability compared with LV -BMSCs control group (P<0.05). When iECs were implanted into the LV-HIF-1α-BMSCs group OCTs to form P-OCTs, iECs substantially proliferated and rapidly fused, and formation of the progressive lumen was revealed by immunofluorescent CD31 staining. The expressions of OPN and OCN were significantly enhanced compared with those of the LV-BMSCs control group; OCN was the highest on day 7, and OPN was the highest on day 1 (P<0.05).
Conclusion
BMSCs transfected by HIF-1α have good osteogenic-angiogenic effect after induction and differentiation, which provides experimental foundation for optimizing the construction of three-dimensional prevascularized bone tissue.
2.Association of thyroid autoimmunity with thyroid function and gestational diabetes mellitus among pregnant women at first-trimester
Chengcheng HAN ; Xiaofeng WANG ; Jing GAO ; Jing YANG ; Lijuan ZHAO ; Changfang HUANG ; Juanjuan ZHANG ; Jingning XU ; Yinli CAO
Chinese Journal of Perinatal Medicine 2025;28(8):675-681
Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.
3.Association of thyroid autoimmunity with thyroid function and gestational diabetes mellitus among pregnant women at first-trimester
Chengcheng HAN ; Xiaofeng WANG ; Jing GAO ; Jing YANG ; Lijuan ZHAO ; Changfang HUANG ; Juanjuan ZHANG ; Jingning XU ; Yinli CAO
Chinese Journal of Perinatal Medicine 2025;28(8):675-681
Objective:To analyze the relationship among thyroid autoimmunity (TAI), thyroid function, and gestational diabetes mellitus (GDM) in early pregnant women in Xi'an.Methods:A prospective study included pregnant women who underwent prenatal check-ups at the Northwest Women's and Children's Hospital from November 2020 to October 2021, with a gestational age of 6 to 14 weeks. Thyroid function, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and urinary iodine levels were measured, and the prevalence of thyroid disease and GDM was monitored. The subjects were divided into four groups: TPOAb positive only, TgAb positive only, both TPOAb and TgAb positive, and both TPOAb and TgAb negative, to compare the differences in the prevalence of thyroid disease and GDM among the groups. Statistical analysis was performed using Kruskal-Wallis rank-sum test, Bonferroni correction, Chi-square test, and a multivariate logistic regression model was used to analyze the relationship between TAI, thyroid disease, and GDM. Results:A total of 20 243 early pregnant women were included in this study, among which 1 615 (7.98%) were positive for TPOAb only; 865 (4.27%) were positive for TgAb only; 1 672 (8.26%) were positive for both TPOAb and TgAb (both positive group); and 16 091 (79.49%) were negative for both TPOAb and TgAb (both negative group). The thyroid stimulating hormone levels in the TPOAb positive only group, TgAb positive only group, and both positive group were significantly higher than those in the both negative group, respectively (Bonferroni correction, all P<0.05); the free thyroxine level in the TPOAb positive only group was significantly lower than that in the both negative group ( P<0.05). After adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing hypothyroidism during pregnancy was significantly increased in the both positive group ( OR=11.49, 95% CI: 2.84-46.39); the risk of developing subclinical hypothyroidism during pregnancy was significantly increased in the TgAb positive only group ( OR=1.99, 95% CI: 1.05-3.76) and the both positive group ( OR=3.74, 95% CI: 2.49-5.63); the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.43, 95% CI: 1.04-1.96) and the both positive group ( OR=1.94, 95% CI: 1.53-2.46). Among early pregnant women with normal thyroid function, after adjusting for age, pre-pregnancy body mass index, and urinary iodine levels, multivariate logistic regression analysis showed that compared to the both negative group, the risk of developing GDM was significantly increased in the TgAb positive only group ( OR=1.46, 95% CI: 1.06-2.02) and the both positive group ( OR=1.80, 95% CI: 1.40-2.32). Conclusion:TgAb positive only is a risk factor for subclinical hypothyroidism and GDM. Screening for thyroid autoantibodies, especially TgAb, during pregnancy helps in the early identification of high-risk pregnant women for thyroid dysfunction and GDM.
4.Spatiotemporally responsive cascade bilayer microneedles integrating local glucose depletion and sustained nitric oxide release for accelerated diabetic wound healing.
Yongnian ZENG ; Chenyuan WANG ; Jiapeng LEI ; Xue JIANG ; Kai LEI ; Yinli JIN ; Tianshu HAO ; Wen ZHANG ; Jianying HUANG ; Wei LI
Acta Pharmaceutica Sinica B 2024;14(11):5037-5052
High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H2O2), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H2O2 with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.
5.Risk factors for acute kidney injury after off-pump coronary artery bypass grafting: A systematic review and meta-analysis
Jing PAN ; Yunlan JIANG ; Yue ZHANG ; Yaxin LIU ; Xiaoxing HUANG ; Yinli SHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):1048-1054
Objective To analyze the risk factors for acute kidney injury (AKI) after off-pump coronary artery bypass grafting (OPCABG). Methods The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang data, CBM, VIP, CNKI were searched by computer for researches on risk factors associated with the development of AKI after OPCABG from the inception to March 2022. The meta-analysis was performed using RevMan 5.4 software. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. Results A total of 18 researches were included, involving 9 risk factors. The NOS score of all included studies was≥6 points. Meta-analysis results showed that age [OR=1.03, 95%CI (1.01, 1.06), P=0.020], body mass index (BMI) [OR=1.10, 95%CI (1.05, 1.15), P<0.001], history of hypertension [OR=1.45, 95%CI (1.27, 1.66), P<0.001], history of diabetes [OR=1.50, 95%CI (1.33, 1.70), P<0.001], preoperative serum creatinine level [OR=2.05, 95%CI (1.27, 3.32), P=0.003], low left ventricular ejection fraction [OR=4.51, 95%CI (1.39, 14.65), P=0.010], preoperative coronary angiography within a short period of time [OR=2.10, 95%CI (1.52, 2.91), P<0.001], perioperative implantation of intra-aortic balloon pump [OR=3.42, 95%CI (2.26, 5.16), P<0.001], perioperative blood transfusion [OR=2.00, 95%CI (1.51, 2.65), P<0.001] were risk factors for AKI after OPCABG. Conclusion Age, BMI, history of hypertension, history of diabetes, preoperative serum creatinine level, low left ventricular ejection fraction, preoperative coronary angiography within a short period of time, perioperative implantation of intra-aortic balloon pump, perioperative blood transfusion are risk factors for AKI after OPCABG. Medical staff should focus on monitoring the above risk factors and early identifying, in order to prevent or delay the onset of postoperative AKI and promote early recovery of patients.
6.Risk Factors and Pregnancy Outcome in Women with a History of Cesarean Section Complicated by Placenta Accreta
Yingyu LIANG ; Lizi ZHANG ; Shilei BI ; Jingsi CHEN ; Shanshan ZENG ; Lijun HUANG ; Yulian LI ; Minshan HUANG ; Hu TAN ; Jinping JIA ; Suiwen WEN ; Zhijian WANG ; Yinli CAO ; Shaoshuai WANG ; Xiaoyan XU ; Ling FENG ; Xianlan ZHAO ; Yangyu ZHAO ; Qiying ZHU ; Hongbo QI ; Lanzhen ZHANG ; Hongtian LI ; Lili DU ; Dunjin CHEN
Maternal-Fetal Medicine 2022;04(3):179-185
Objective::To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta (PA).Methods::This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. According to the intraoperative findings after delivery, the study population was divided into PA and non-PA groups. We compared the pregnancy outcomes between the two groups, used multivariate logistic regression to analyze the risk factors for placental accreta.Results::For this study we included 11,074 pregnant women with a history of cesarean section; and of these, 869 cases were in the PA group and 10,205 cases were in the non-PA group. Compared with the non-PA group, the probability of postpartum hemorrhage (236/10,205, 2.31% vs. 283/869, 32.57%), severe postpartum hemorrhage (89/10,205, 0.87% vs. 186/869, 21.75%), diffuse intravascular coagulation (3/10,205, 0.03% vs. 4/869, 0.46%), puerperal infection (33/10,205, 0.32% vs. 12/869, 1.38%), intraoperative bladder injury (1/10,205, 0.01% vs. 16/869, 1.84%), hysterectomy (130/10,205, 1.27% vs. 59/869, 6.79%), and blood transfusion (328/10,205,3.21 % vs. 231/869,26.58%) was significantly increased in the PA group ( P < 0.05). At the same time, the neonatal birth weight (3250.00 (2950.00-3520.00) g vs. 2920.00 (2530.00-3250.00) g), the probability of neonatal comorbidities (245/10,205, 2.40% vs. 61/869, 7.02%), and the rate of neonatal intensive care unit admission (817/10,205, 8.01% vs. 210/869, 24.17%) also increased significantly ( P < 0.05). Weight (odds ratio ( OR)= 1.03, 95% confidence interval ( CI): 1.01-1.05)), parity ( OR= 1.18, 95% CI: 1.03-1.34), number of miscarriages ( OR= 1.31, 95% CI: 1.17-1.47), number of previous cesarean sections ( OR= 2.57, 95% CI: 2.02-3.26), history of premature rupture of membrane ( OR= 1.61, 95% CI: 1.32-1.96), previous cesarean-section transverse incisions ( OR= 1.38, 95% CI: 1.12-1.69), history of placenta previa ( OR= 2.44,95% CI: 1.50-3.96), and the combination of prenatal hemorrhage ( OR= 9.95,95% CI: 8.42-11.75) and placenta previa ( OR= 91.74, 95% CI: 74.11-113.56) were all independent risk factors for PA. Conclusion::There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section, and this required close clinical attention. Weight before pregnancy, parity, number of miscarriages, number of previous cesarean sections, history of premature rupture of membranes, past transverse incisions in cesarean sections, a history of placenta previa, prenatal hemorrhage, and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section. These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.
7.Risk Factors and Pregnancy Outcome in Women with a History of Cesarean Section Complicated by Placenta Accreta
Yingyu LIANG ; Lizi ZHANG ; Shilei BI ; Jingsi CHEN ; Shanshan ZENG ; Lijun HUANG ; Yulian LI ; Minshan HUANG ; Hu TAN ; Jinping JIA ; Suiwen WEN ; Zhijian WANG ; Yinli CAO ; Shaoshuai WANG ; Xiaoyan XU ; Ling FENG ; Xianlan ZHAO ; Yangyu ZHAO ; Qiying ZHU ; Hongbo QI ; Lanzhen ZHANG ; Hongtian LI ; Lili DU ; Dunjin CHEN
Maternal-Fetal Medicine 2022;04(3):179-185
Objective::To explore the risk factors and pregnancy outcomes in women with a history of cesarean section complicated by placenta accreta (PA).Methods::This case-control study included clinical data from singleton mothers with a history of cesarean section in 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. According to the intraoperative findings after delivery, the study population was divided into PA and non-PA groups. We compared the pregnancy outcomes between the two groups, used multivariate logistic regression to analyze the risk factors for placental accreta.Results::For this study we included 11,074 pregnant women with a history of cesarean section; and of these, 869 cases were in the PA group and 10,205 cases were in the non-PA group. Compared with the non-PA group, the probability of postpartum hemorrhage (236/10,205, 2.31% vs. 283/869, 32.57%), severe postpartum hemorrhage (89/10,205, 0.87% vs. 186/869, 21.75%), diffuse intravascular coagulation (3/10,205, 0.03% vs. 4/869, 0.46%), puerperal infection (33/10,205, 0.32% vs. 12/869, 1.38%), intraoperative bladder injury (1/10,205, 0.01% vs. 16/869, 1.84%), hysterectomy (130/10,205, 1.27% vs. 59/869, 6.79%), and blood transfusion (328/10,205,3.21 % vs. 231/869,26.58%) was significantly increased in the PA group ( P < 0.05). At the same time, the neonatal birth weight (3250.00 (2950.00-3520.00) g vs. 2920.00 (2530.00-3250.00) g), the probability of neonatal comorbidities (245/10,205, 2.40% vs. 61/869, 7.02%), and the rate of neonatal intensive care unit admission (817/10,205, 8.01% vs. 210/869, 24.17%) also increased significantly ( P < 0.05). Weight (odds ratio ( OR)= 1.03, 95% confidence interval ( CI): 1.01-1.05)), parity ( OR= 1.18, 95% CI: 1.03-1.34), number of miscarriages ( OR= 1.31, 95% CI: 1.17-1.47), number of previous cesarean sections ( OR= 2.57, 95% CI: 2.02-3.26), history of premature rupture of membrane ( OR= 1.61, 95% CI: 1.32-1.96), previous cesarean-section transverse incisions ( OR= 1.38, 95% CI: 1.12-1.69), history of placenta previa ( OR= 2.44,95% CI: 1.50-3.96), and the combination of prenatal hemorrhage ( OR= 9.95,95% CI: 8.42-11.75) and placenta previa ( OR= 91.74, 95% CI: 74.11-113.56) were all independent risk factors for PA. Conclusion::There was an increased risk of adverse outcomes in pregnancies complicated by PA in women with a history of cesarean section, and this required close clinical attention. Weight before pregnancy, parity, number of miscarriages, number of previous cesarean sections, history of premature rupture of membranes, past transverse incisions in cesarean sections, a history of placenta previa, prenatal hemorrhage, and placenta previa were independent risk factors for pregnancies complicated with PA in women with a history of cesarean section. These independent risk factors showed a high value in predicting the risk for placentab accreta in pregnancies of women with a history of cesarean section.
8.The osteogenesis ability of human umbilical cord Wharton's Jelly-derived mesenchymal stem cells and periodontal mesenchymal stem cells
Yinli HUANG ; Hong ZHOU ; Xiaoxia SU ; Tianyu ZHONG
Journal of Practical Stomatology 2017;33(5):669-673
Objective:To compare the osteogenesis ability between human umbilical cord Wharton's Jelly-derived mesenchymal stem cells(hUCWJMSCs) and human periodontal ligament mesenchymal stem cells (hPDLSCs) in vitro.Methods:hUCWJMSCs and hPDLSCs were in vitro cultured.The cell proliferation capacity was examined by MTT assay.After osteogenesis induction culture,ALP activity of the cells was determined,minerialization was observed by alizarin red staining,OPN and Runx2 mRNA expression was analyzed by Real-time PCR.Results:hUCWJMSCs grew faster than hPDLSCs.After osteogenic differentiation induction,hPDLSCs group showed higher ALP level,more mineralized nodule formation and higher Runx2 expression compared with hUCWJMSCs group (P < 0.05);while the OPN expressed higher in hUCWJMSCs than in hPDLSCs (P < 0.05).Conclusion:hUCWJMSCs and hPDLSCs have osteogenesis differentiation potential,hPDLSCs are more osteogenetic.
9.Effect of Rhodioloside on PI3-K/AKT signaling pathway on cerebral ischemia-reperfusion injury in rats
Yinli LUO ; Xiaosong HUANG ; Lihong TAN ; Chunyan YU ; Liuqing LIU
Journal of Chinese Physician 2014;(6):734-738
Objective To explore the mechanism of protective effect of Rhodioloside in cerebral ischemia-reperfusion rats and its relevance to phosphatidylinositol 3-kinases ( PI3-K)/protein serine-threonine kinases ( AKT) signaling pathway .Methods Forty eight Sprague-Dawley rats were randomly divided into four groups: sham-operation group , ischemia-reperfusion group , and Rhodiolo-side treatment groups (5 and 10 mg/kg).The model of right middle cerebral artery occlusion was established with thread ligation meth -od.The score of the neurological deficit was estimated 2 h followed by 24 h reperfusion.Histopathological changes were observed by hematoxylin-eosin(HE) staining.The infarct volume was measured with triphenyltetrazolium chloride (TTC) staining.Apoptotic cells were assessed with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method.The expressions of PI3-K and p-AKT were evaluated with immunohistochemistry .Results The score of the neurological deficit was decreased more ob-viously, the number of apoptotic were decreased more significantly , the expressions of PI3-K and p-AKT were increased more signifi-cantly in the Rhodioloside treatment groups (5 and 10 mg/kg) than in the ischemia-reperfusion group ( P <0.05).The score of the neurological deficit was decreased , the number of apoptotic was decreased , and the expressions of PI 3-K and p-AKT were increased in the Rhodioloside treatment group (10 mg/kg) than the Rhodioloside treatment group (5 mg/kg) ( P <0.05).Conclusions The protective mechanism of Rhodioloside therapy against cerebral ischemia r-eperfusion injury might be associated with activating the PI 3-K/AKT signaling pathway and then inhibiting neuronal apoptosis .


Result Analysis
Print
Save
E-mail