1.Dysregulated placental autophagy and preeclampsia
Weichen PAN ; Huaijun FEI ; Guangfeng ZHAO ; Mingming ZHENG
Chinese Journal of Perinatal Medicine 2025;28(7):615-618
Preeclampsia is a placenta-originated disorder closely associated with impaired placental development and immune imbalance at the maternal-fetal interface. As a critical process in the regulation of cellular homeostasis, autophagy plays a pivotal role in trophoblast syncytialization, invasion, and immune tolerance at the maternal-fetal interface. Moderate autophagy enhances trophoblast function and promotes spiral artery remodeling, whereas insufficient or excessive autophagy correlates with placental pathological features of preeclampsia, including impaired syncytialization, protein aggregate accumulation, and immune dysregulation. Although trophoblast-specific autophagy deficiencies in animal models can manifest preeclampsia-like phenotypes, clinical studies reveal tissue-specific variability in autophagy-related protein expression, which may be attributable to placental regional heterogeneity, disease subtypes, and sampling timepoints. Future investigations integrating multi-stage clinical cohorts, multicellular models, and genetically modified animals are warranted to elucidate the dynamic role of autophagy in preeclampsia pathogenesis and establish its causal relationship with disease progression, thereby providing a basis for targeted therapeutic strategies.
2.Impact of Intravascular Ultrasalnd-guided Drug-eluting Stent Implantation on Long-term Outcome of Patients With Coronary Artery Disease and Chronic Kidney Disease
Jingyu ZHAO ; Congfei ZHU ; Ling LIN ; Guangfeng ZUO ; Xiangquan KONG ; Zhen GE ; Xiaofei GAO ; Junjie ZHANG
Chinese Circulation Journal 2025;40(9):898-903
Objectives:To assess the impact of intravascular ultrasound(IVUS)guidance for drug-eluting stent(DES)implantation on the long-term outcomes in coronary artery disease(CAD)patients with chronic kidney disease(CKD).Methods:A retrospective study was conducted on 1 800 CAD and CKD patients who underwent coronary DES implantation at Nanjing First Hospital from January 2018 to December 2022.Patients were divided into IVUS-guided group(IVUS group,n=333)and angiography-guided group(angiography group,n=1 467).Propensity score matching(PSM)was performed at a 1:2 ratio to adjust for differences in baseline clinical and angiographic characteristics between the two groups.Major adverse cardiovascular events(MACE),including cardiac death,target vessel myocardial infarction,and clinically driven target vessel revascularization,were evaluated over a 2-year follow-up.Cox proportional hazards regression was performed to identify independent predictors of MACE.Results:After propensity score matching,333 patients in the IVUS group were matched with 666 patients in the angiography group.Following matching,there were no significant differences in clinical characteristics and angiographic data between the two groups(all P>0.05).Regarding procedural data,IVUS group had a higher number of stents implanted,longer total stent length,larger average stent diameter,more frequent use of post-dilation balloons,larger post-dilation balloon diameter,and greater contrast agent usage(all P<0.05).MACE rate was significantly higher in the angiography group than that in the IVUS group(23.9%vs.18.0%,P=0.037).The difference was mainly attributed to a higher rate of cardiac death in the angiography group(16.1%vs.10.8%,P=0.013).Additionally,patients in angiography group had a significantly higher all-cause mortality rate compared to IVUS group(19.7%vs.13.8%,P=0.022).Multivariate cox regression analysis showed that IVUS guidance(HR=0.73,95%CI:0.55-0.99,P=0.042)was an independent protective factor,while hypertension(HR=1.60,95%CI:1.13-2.26,P=0.008),type 2 diabetes(HR=1.56,95%CI:1.19-2.05,P=0.001),acute coronary syndrome(HR=1.92,95%CI:1.12-3.30,P=0.018),and moderate to severe calcification(HR=1.55,95%CI:1.18-2.04,P=0.002)were independent risk factors for MACE at 2 years after DES implantation in CKD patients.Conclusions:Patients with CAD and CKD,IVUS-guided DES implantation is associated with a reduced risk of MACE and all-cause mortality at 2 years post-procedure compared to coronary angiography-guided implantation.
3.Impact of Intravascular Ultrasalnd-guided Drug-eluting Stent Implantation on Long-term Outcome of Patients With Coronary Artery Disease and Chronic Kidney Disease
Jingyu ZHAO ; Congfei ZHU ; Ling LIN ; Guangfeng ZUO ; Xiangquan KONG ; Zhen GE ; Xiaofei GAO ; Junjie ZHANG
Chinese Circulation Journal 2025;40(9):898-903
Objectives:To assess the impact of intravascular ultrasound(IVUS)guidance for drug-eluting stent(DES)implantation on the long-term outcomes in coronary artery disease(CAD)patients with chronic kidney disease(CKD).Methods:A retrospective study was conducted on 1 800 CAD and CKD patients who underwent coronary DES implantation at Nanjing First Hospital from January 2018 to December 2022.Patients were divided into IVUS-guided group(IVUS group,n=333)and angiography-guided group(angiography group,n=1 467).Propensity score matching(PSM)was performed at a 1:2 ratio to adjust for differences in baseline clinical and angiographic characteristics between the two groups.Major adverse cardiovascular events(MACE),including cardiac death,target vessel myocardial infarction,and clinically driven target vessel revascularization,were evaluated over a 2-year follow-up.Cox proportional hazards regression was performed to identify independent predictors of MACE.Results:After propensity score matching,333 patients in the IVUS group were matched with 666 patients in the angiography group.Following matching,there were no significant differences in clinical characteristics and angiographic data between the two groups(all P>0.05).Regarding procedural data,IVUS group had a higher number of stents implanted,longer total stent length,larger average stent diameter,more frequent use of post-dilation balloons,larger post-dilation balloon diameter,and greater contrast agent usage(all P<0.05).MACE rate was significantly higher in the angiography group than that in the IVUS group(23.9%vs.18.0%,P=0.037).The difference was mainly attributed to a higher rate of cardiac death in the angiography group(16.1%vs.10.8%,P=0.013).Additionally,patients in angiography group had a significantly higher all-cause mortality rate compared to IVUS group(19.7%vs.13.8%,P=0.022).Multivariate cox regression analysis showed that IVUS guidance(HR=0.73,95%CI:0.55-0.99,P=0.042)was an independent protective factor,while hypertension(HR=1.60,95%CI:1.13-2.26,P=0.008),type 2 diabetes(HR=1.56,95%CI:1.19-2.05,P=0.001),acute coronary syndrome(HR=1.92,95%CI:1.12-3.30,P=0.018),and moderate to severe calcification(HR=1.55,95%CI:1.18-2.04,P=0.002)were independent risk factors for MACE at 2 years after DES implantation in CKD patients.Conclusions:Patients with CAD and CKD,IVUS-guided DES implantation is associated with a reduced risk of MACE and all-cause mortality at 2 years post-procedure compared to coronary angiography-guided implantation.
4.Dysregulated placental autophagy and preeclampsia
Weichen PAN ; Huaijun FEI ; Guangfeng ZHAO ; Mingming ZHENG
Chinese Journal of Perinatal Medicine 2025;28(7):615-618
Preeclampsia is a placenta-originated disorder closely associated with impaired placental development and immune imbalance at the maternal-fetal interface. As a critical process in the regulation of cellular homeostasis, autophagy plays a pivotal role in trophoblast syncytialization, invasion, and immune tolerance at the maternal-fetal interface. Moderate autophagy enhances trophoblast function and promotes spiral artery remodeling, whereas insufficient or excessive autophagy correlates with placental pathological features of preeclampsia, including impaired syncytialization, protein aggregate accumulation, and immune dysregulation. Although trophoblast-specific autophagy deficiencies in animal models can manifest preeclampsia-like phenotypes, clinical studies reveal tissue-specific variability in autophagy-related protein expression, which may be attributable to placental regional heterogeneity, disease subtypes, and sampling timepoints. Future investigations integrating multi-stage clinical cohorts, multicellular models, and genetically modified animals are warranted to elucidate the dynamic role of autophagy in preeclampsia pathogenesis and establish its causal relationship with disease progression, thereby providing a basis for targeted therapeutic strategies.
5.Expression of TFDP2 in placentas of women with preeclampsia and its effect on apoptosis of trophoblast cells
Chenrui CAO ; Dan LIU ; Zhiyin WANG ; Guangfeng ZHAO ; Zhongrui PEI ; Yali HU
Chinese Journal of Perinatal Medicine 2024;27(2):133-142
Objective:To investigate the expression level of transcription factor dimerization partner 2 (TFDP2) in the placentas of women with preeclampsia, and analyze its effect on the apoptosis of trophoblast cells.Methods:Placental tissues from thirty puerperae with preeclampsia who gave birth by cesarean section in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between January 2018 and December 2022 (preeclampsia group) and 30 healthy puerperae undergoing cesarean section during the same period (control group) were retrospectively selected. Immunohistochemistry was used to localize TFDP2 in the placental tissues. Real-time quantitative-polymerase chain reaction (qRT-PCR) and Western blot were used to detect the differences in expression of TFDP2 at mRNA and protein levels in placental tissues between the two groups. Forskolin-exposed BeWo cells were transfected with small interfering RNA (siRNA) to knockdown TFDP2 and the changes in the expression of apoptosis-related indicators, B cell lymphoma 2 (Bcl2) and Bcl2 associated X (Bax), at protein and mRNA levels were analyzed by Western blot and qRT-PCR, respectively. Besides, the change in the apoptosis level of BeWo cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry. Downstream signaling pathways were analyzed to understand the involved molecular mechanisms. Two independent samples t-test, Wilcoxon rank-sum test, and Chi-square test were used for statistical analysis. Results:TFDP2 was mostly localized in the syncytiotrophoblasts and the extravillous trophoblasts in the normal placentas. TFDP2 expression in the syncytiotrophoblasts was lower in the preeclampsia group than in the control group at both mRNA (0.722±0.239 vs. 1.000±0.348, t=3.61, P=0.001) and protein (0.728±0.185 vs. 1.000±0.206, t=2.41, P=0.037) levels. Comparing the group without knockdown of TFDP2, the knockdown of TFDP2 in BeWo cells elevated the Bax/Bcl2 ratio (mRNA: 1.755±0.452 vs. 1.000±0.279, t=3.48, P=0.006; protein: 3.206±0.922 vs. 1.000±0.290, t=3.95, P=0.017), and increased cell apoptosis both in number and ratio (TUNEL staining: 4.556±1.740 vs. 2.444±1.130, t=3.05, P=0.008; flow cytometry: 21.37%±1.66% vs. 12.61%±0.38%, t=8.92, P=0.001). Furthermore, following TFDP2 knockdown, a decrease in the phosphorylation activity of catalytic subunit of protein kinase A (PKAc) at the Thr197 site was observed in the cytoplasm of BeWo cells (0.466±0.035 vs. 1.000±0.075, t=11.19, P<0.001) and a reduction in the expression of β-catenin in the cell nucleus was also detected (0.250±0.093 vs. 1.000±0.269, t=4.57, P=0.010). Conclusion:The expression of TFDP2 decreased significantly in the placentas of patients with preeclampsia, which may promote the apoptosis of syncytiotrophoblasts by inhibiting the PKAc/β-catenin signaling pathway.
6.Application of laparoscopic single-incision triangulated umbilical surgery technique in urology
Yuhao YU ; Zhiguang ZHAO ; Gen LI ; Xuexing FAN ; Zhiguo LU ; Guangfeng ZHU ; Xiaoliang DOU ; Xiaopeng CHEN ; Bo ZHAO ; Yong WANG
Chinese Journal of Urology 2024;45(3):238-240
The pursuit of cosmetic effects in post-surgical wounds has led to the development of ultra-minimally invasive techniques in surgery. Minimal invasive surgery has replaced open surgery and has become the new gold-standard for treating diseases. One such technique is the single incision triangulated umbilicus surgery (SITUS), which offers several advantages over traditional laparoscopic and other scarless surgeries, including reduced trauma, faster recovery, and better cosmetic outcomes. SITUS also has a short learning curve, aligns with conventional instrumentation operating habits, and can be used for whole abdominal surgeries. Chinese scholars have made further improvements to the SITUS technology, including expanding its applicability in intra-abdominal surgery and refining its incision closure methods to achieve superior cosmetic results. Currently, SITUS technology is experiencing rapid development in urology applications and has demonstrated satisfactory results in both domestic and international reports. This review aims to discuss the effectiveness and development of the SITUS technique in urology.
7.Efficiency of preeclampsia screening based on biomarkers of aneuploidy screening in first trimester
Yuan WANG ; Ya WANG ; Huirong TANG ; Honglei DUAN ; Ying ZHANG ; Jie LI ; Yan ZHANG ; Xiaodong YE ; Zhiyin WANG ; Guangfeng ZHAO ; Yali HU ; Mingming ZHENG
Chinese Journal of Perinatal Medicine 2022;25(8):601-608
Objective:To evaluate the performance of biomarkers in aneuploidy screening in the first trimester-pregnancy associated plasma protein A(PAPP-A) combined with Fetal Medicine Foundation (FMF)'s competing risk model in screening preeclampsia among our population.Methods:This study was based on a prospective cohort of singleton pregnant women who underwent aneuploidy screening in the first trimester in Nanjing Drum Tower Hospital from January 2017 to September 2020. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and PAPP-A were converted into multiples of median (MoM) using the algorithm disclosed on the website of the FMF (fetalmedicine.org). The predictive outcomes of maternal factors alone or in combination with MAP, UtA-PI, and PAPP-A (alone or in combination) were calculated. Chi-square test, Fisher's exact test or rank sum test were used for comparison among groups and Bonferroni method for pairwise comparisons. Receiver operating characteristic (ROC) curve was used to evaluate the screening efficiency and to calculate the sensitivities of predicting preeclampsia, term and preterm preeclampsia at false-positive rates of 5% and 10%. The predictive performance of this model was further compared to the screening strategy that was recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China (2020). Results:Among the 5 144 singleton pregnancy women who were recruited in the cohort, 4 919 cases were included and analyzed in this study. A total of 223 cases were diagnosed as preeclampsia (4.5%), including 55 preterm (1.1%) and 168 term preeclampsia (3.4%). The median of MoM values of MAP, UtA-PI, and PAPP-A in the non-preeclampsia group were around 1.0±0.1. Statistical significance was observed in the difference of MAP, UtA-PI, and PAPP-A Mom between women with preterm preeclampsia and those without preeclampsia [1.061 (0.999-1.150) vs 0.985 (0.935-4.043), 1.115 (0.873-1.432) vs 1.039 (0.864-1.236), 0.820 (0.493-1.066) vs 1.078 (0.756-1.508)], which was also seen in the difference of MAP and PAPP-A Mom between women with term preeclampsia and those without preeclampsia [1.065 (1.002-1.133) vs 0.985 (0.935-4.043), 1.007 (0.624-1.393) vs 1.078 (0.756-1.508)] (all P<0.025). The combination screening with maternal factors+MAP+UtA-PI+PAPP-A was noted for the best efficiency. In predicting preeclampsia preterm and term preeclampsia at the false-positive rate of 10%, the sensitivity of the model was 53.0%, 76.4% and 44.6% respectively. Using the screening method recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020), the proportion of people at high risk of preeclampsia was 5.9% (290/4 919), and the sensitivity for predicting preterm preeclampsia was 25.5% (14/55), which was significantly lower than the combination screening with maternal factors+MAP+UtA-PI+PAPP-A [65.5% (36/55)] when using the same proportion of high-risk population. Conclusion:The preeclampsia screening model based on aneuploidy screening biomarkers in the first trimester--PAPP-A in combination with materral factors, MAP, UtA-PI, can effectively screen preterm preeclampsia in the local population without increasing the laboratory costs.
8.Clinical research of Qingfei-Xiaoyan Decoction combined with conventional western medicine in patients with acute exacerbation of chronic obstructive pulmonary disease
Cunming LI ; Zhenqin ZHENG ; Guangfeng ZHAO ; Ziwei LIN
International Journal of Traditional Chinese Medicine 2020;42(4):343-346
Objective:To observe the clinical efficacy of Qingfei-Xiaoyan Decoction combined with conventional western medicine in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD). Methods:Eighty-two patients with acute exacerbation of COPD were selected in Bozhou People's Hospital from January 2017 to June 2018 and randomly divided into a control group and a treatment group (41 in each group) using randomized number table method. Patients in the control group were treated with conventional western medicine and those in the treatment group with Qingfei-Xiaoyan Decoction on the basis of the control group for 2 weeks. Dyspnea of patients was evaluated with the modified British Medical Research Council dyspnea questionnaire (mMRC). Impact of the disease was measured with the COPD Assessment Test (CAT). The serum levels of C-reactive protein (CRP) and procalcitonin (PCT) were measured by ELISA. Results:The total efficacy rate in trementat group 95.1% (39/41) was significantly higher than that in the control group 73.2% (30/41) ( χ2=4.999, P=0.025). After the treatment, the scores of mMRC (0.63 ± 0.07 vs. 0.95 ± 0.12; t=7.921, P<0.01) and CAT (9.18 ± 0.12 vs. 14.01 ± 1.56; t=11.359, P<0.01) in the treatment group were significantly lower than those in the control group. After the treatment, the forced expiratory volume in one second (FEV1) percentage predicted (51.05% ± 5.63% vs. 45.77% ± 5.31%; t=10.453, P<0.01) and FEV1/forced vital capacity (FVC) (59.15 ± 6.44 vs. 54.24 ± 6.02; t=5.621, P<0.01) in the treatment group were significantly higher than those in the control group. After the treatment, the serum levels of CRP (8.06 ± 0.87 mg/L vs. 10.55 ± 1.21 mg/L; t=10.216, P<0.01) and PCT (4.20 ± 0.48 μg/L vs. 6.33 ± 0.69 μg/L; t=7.004, P<0.01) in the treatment group were significantly lower than those in the control group. Conclusions:Qingfei-Xiaoyan Decoction can inhibite inflammation, improve symptoms and lung function, increase the efficacy in patients with acute exacerbation of COPD.
9.Estrogen Promotes cAMP Production in Mesenchymal Stem Cells by Regulating ADCY2
Guangfeng ZHAO ; Xiujun LI ; Huishuang MIAO ; Shiwen CHEN ; Yayi HOU
International Journal of Stem Cells 2020;13(1):55-64
Background and Objectives:
The maternal-fetal interface is an important source of mesenchymal stem cells (MSCs), and it is influenced by high levels of estradiol (E2) during pregnancy. It is highly important to study the role of E2 in MSCs for both clinical application and understanding of the mechanisms underlying pregnancy related diseases.
Methods:
and Results: In this study, differently expressed genes (DEGs) were found in the MSCs after exposure to E2. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was performed and the integrated regulatory network of DEGs-miRNA was constructed. A total of 390 DEGs were found in the MSCs exposed to E2, including 164 upregulated DEGs (e.g. ADCY2, VEGFA and PPY) and 226 downregulated DEGs (e.g. KNG1, AGT and NPY). Additionally, 10 miRNAs (such as miR-148A/B, miR-152, miR-182) identified the integrated regulatory network of DEGs-miRNAs. Among them, the expression of ADCY2 was significantly upregulated, and this was associated with multiple changed genes. We confirmed that the expression of ADCY2 is significantly promoted by E2 and subsequently promoted the production of cAMP in MSCs. We also found that E2 promoted ADCY2 expression by inhibiting miR-152 and miR-148a.
Conclusions
E2 promotes the expression of cAMP through miR-148a/152-ADCY2 in MSCs. It is suggested that E2 plays a key role in the growth and function of MSCs.
10.Pneumothorax in critically ill neonates: diagnosis using bedside ultrasonography
Xueyun REN ; Jing ZHAO ; Fenghai NIU ; Fang YOU ; Guangfeng QIANG ; Na LIU
Chinese Journal of Neonatology 2019;34(6):439-442
Objective To study the value of lung ultrasonography (LUS) in the diagnosis of pneumothorax in critically ill neonates.Method The neonates admitted to our NICU and suspected to have pneumothorax were prospectively enrolled from June 2017 to December 2018.All eligible infants received both LUS examination and chest X-ray.The characteristics of LUS imaging was analyzed based on the chest X-ray which was used as the golden standard for the diagnosis of pneumothorax.The sensitivity,specificity,positive predictive value and negative predictive value of LUS is computed.The duration of LUS and chest X-ray were compared.The outcome and complications were also observed.Result Fifty neonates with suspected pneumothorax were collected.Among them,pneumothorax was confirmed with chest X-ray in 31 neonates (62.0%).Ultrasound signs of pneumothorax included absence of lung sliding (100%),absence of B lines (100%),stratosphere sign (100%) were observed in all of the 31 neonates.Presence of lung point was also observed in 90.3% of the patients.The sensitivity,specificity,positive predictive value,negative predictive value and X-ray coincidence rate of LUS in the diagnosis of pneumothorax were 100%.LUS and chest X-ray examination took (5.6 ±5.1) min and (20.1 ± 12.2) min,respectively,the difference was statistically significant (P < 0.05).All 31 infants with pneumothorax survived.15 infants underwent closed thoracic drainage after emergency thoracic puncture or aspiration assisted by LUS.No postoperative complications occurred.Conclusion LUS showed high accuracy,sensitivity and specificity in detecting pneumothorax in critically ill neonates.It is simple to operate and can guide clinical rescue more promptly and quickly.

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