1.TYROBP attenuates the progression of diabetic kidney disease by inhibiting the ERK signaling pathway
Liang Li ; Jie Huang ; Xinling Wang ; Liping Yan ; Huiqing Yu ; Zhiguo Li
Acta Universitatis Medicinalis Anhui 2025;60(11):2026-2034
Objective:
To investigate whether TYRO protein tyrosine kinase-binding protein (TYROBP) affects the progression of diabetic kidney disease (DKD) through the extracellular signal-regulated kinase ( ERK) pathway.
Methods:
Key genes in DKD were identified through bioinformatics analysis . Immunohistochemical staining and quantitative real-time PCR (qPCR) were used to validate the expression levels of TYROBP in a DKD mouse model and high glucose-stimulated NRK-52E cells . NRK-52E cell models with stable TYROBP overexpression/knockdown and their corresponding empty vector (ev) /scrambled sequence (ss) controls were established via lentiviral trans- fection . Cells were treated with 5 . 5 mmol/L or 30. 0 mmol/L glucose for 72 hours to mimic normal glucose (NG) and high glucose ( HG) conditions , respectively. High glucose medium containing 3 . 5 μmol/L FR180204 was used for ERK inhibitor intervention . The experiment included seven groups : ev + NG , ev + HG , oe-TYROBP + HG , ss + NG , ss + HG , sh-TYROBP + HG , and sh-TYROBP + HG + ERK inhibitor. Western blot was used to de- tect the expression levels of phosphorylated ERK/total ERK (p-ERK/ERK) , apoptosis-related proteins B-cell lym- phoma-2 (Bcl-2) and Bcl-2-associated X protein ( Bax) , and epithelial-mesenchymal transition ( EMT)-related proteins E-cadherin and α-smooth muscle actin ( α-SMA) . Tetramethylrhodamine ethyl ester (TMRE) staining and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) flow cytometry were performed to as- sess mitochondrial membrane potential and apoptosis levels .
Results:
Bioinformatics analysis identified TYROBP as a key gene in DKD . In vivo and in vitro validation showed increased TYROBP mRNA levels in DKD models . The results from the HG model indicated that , compared to the ev + NG/ss + NG group , the ev + HG/ss + HG group demonstrated increased p-ERK/ERK expression , reduced mitochondrial membrane potential , elevated apoptosis , and enhanced EMT. In TYROBP-perturbed NRK-52E cells , compared to the ev + HG group , the oe-TYROBP + HG group showed decreased p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential (P < 0. 05) , reduced apoptosis (P < 0. 001) , and attenuated EMT; whereas compared to the ss + HG group , the sh- TYROBP + HG group exhibited increased p-ERK/ERK expression ( P < 0. 001) , decreased mitochondrial mem- brane potential (P < 0. 01) , elevated apoptosis (P < 0. 001) , and enhanced EMT. Furthermore , compared to the sh-TYROBP + HG group , the sh-TYROBP + HG + ERK inhibitor group displayed reduced p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential ( P < 0. 001) , decreased apoptosis ( P < 0. 001) , and suppressed EMT. Compared with the scrambled sequence control + high glucose group , the TYROBP knockdown + high glucose group showed elevated p-ERK/ERK expression ( P < 0. 001) , reduced mitochondrial membrane potential (P < 0. 01) , increased apoptosis level (P < 0. 001) , and enhanced EMT. Compared with the TYROBP knockdown + high glucose group , the TYROBP knockdown + high glucose + ERK inhibitor group demonstrated decreased p-ERK/ERK expression (P < 0. 01) , restored mitochondrial membrane potential (P < 0. 001) , reduced apoptosis level (P < 0. 001) , and suppressed EMT.
Conclusion
TYROBP may regulate the ERK signaling path- way to modulate apoptosis- and EMT-related proteins , thereby influencing mitochondrial membrane potential , apop- tosis , and EMT in renal tubular epithelial cells and contributing to DKD progression .
2.Study on the Expression of Integrin αvβ3 and Osteopontin in Decidual Tissues in Missed Miscarriage with Polycystic Ovary Syndrome
Xinling WEN ; Li WANG ; Xuewen YU
Journal of Practical Obstetrics and Gynecology 2025;41(1):48-53
Objective:to investigate the expression of integrin αvβ3 and osteopontin(OPN)in decidual tissues in missed abortion women with polycystic ovarian syndrome(PCOS).Methods:PCOS women with missed abor-tion(PCOS missed abortion group),non-PCOS with missed abortion(non-PCOS missed abortion group)and women with normal early pregnancy induced abortion(normal control group)who were admitted to the First Affili-ated Hospital of Xi'an Jiaotong University from February 2018 to December 2022 were selected as participants,and 20 subjects in each group.The expressions of integrin αvβ3 and OPN in decidual tissues among the three groups were detected.Correlation analysis was conducted between the expression levels of integrin αvβ3 and OPN in PCOS patients with missed abortion.Results:Integrin αvβ3 and OPN were mainly expressed in the epi-thelial cells of the uterus,as well as in decidual cells.There were significant differences in the positive rates and IHC scores of integrin αvβ3 and OPN in decidual tissues among the three groups(P<0.05).The positive rates and IHC scores in PCOS missed abortion group were significantly lower compared with non-PCOS missed abor-tion group and normal control group,and the difference was statistically significant(P<0.05),but there was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The integrin αvβ3 and OPN in decidual tissues were mainly co-located in uterine epithelial cells.There were significant differ-ences in immunofluorescence intensity of integrin αvβ3 and OPN among the three groups(P<0.05).The missed abortion group of PCOS was significantly lower than that of non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).No significant difference was found between non-PCOS missed abortion group and normal control group(P>0.05).There were significant differences in the protein expression levels and mRNA expression levels of integrin αvβ3 and OPN in decidual tissue among the three groups(P<0.05).PCOS missed abortion group was significantly lower than non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).There was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The results of Pearson correlation analysis showed that the protein and mRNA expression levels of integrin αvβ3 and OPN in decidual tis-sue of PCOS patients with missed abortion were significantly positively correlated(r>0,P<0.01).Conclusions:The integrin αvβ3 and OPN were expressed in both epithelial cells of the uterus and decidual cells in early preg-nancy.The expressions of them were significantly decreased in decidual tissues of PCOS patients with missed a-bortion,which might be related to reduced endometrial receptivity.The role of integrin αvβ3 and OPN in the occur-rence of missed abortion needs further study.
3.Study on the Expression of Integrin αvβ3 and Osteopontin in Decidual Tissues in Missed Miscarriage with Polycystic Ovary Syndrome
Xinling WEN ; Li WANG ; Xuewen YU
Journal of Practical Obstetrics and Gynecology 2025;41(1):48-53
Objective:to investigate the expression of integrin αvβ3 and osteopontin(OPN)in decidual tissues in missed abortion women with polycystic ovarian syndrome(PCOS).Methods:PCOS women with missed abor-tion(PCOS missed abortion group),non-PCOS with missed abortion(non-PCOS missed abortion group)and women with normal early pregnancy induced abortion(normal control group)who were admitted to the First Affili-ated Hospital of Xi'an Jiaotong University from February 2018 to December 2022 were selected as participants,and 20 subjects in each group.The expressions of integrin αvβ3 and OPN in decidual tissues among the three groups were detected.Correlation analysis was conducted between the expression levels of integrin αvβ3 and OPN in PCOS patients with missed abortion.Results:Integrin αvβ3 and OPN were mainly expressed in the epi-thelial cells of the uterus,as well as in decidual cells.There were significant differences in the positive rates and IHC scores of integrin αvβ3 and OPN in decidual tissues among the three groups(P<0.05).The positive rates and IHC scores in PCOS missed abortion group were significantly lower compared with non-PCOS missed abor-tion group and normal control group,and the difference was statistically significant(P<0.05),but there was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The integrin αvβ3 and OPN in decidual tissues were mainly co-located in uterine epithelial cells.There were significant differ-ences in immunofluorescence intensity of integrin αvβ3 and OPN among the three groups(P<0.05).The missed abortion group of PCOS was significantly lower than that of non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).No significant difference was found between non-PCOS missed abortion group and normal control group(P>0.05).There were significant differences in the protein expression levels and mRNA expression levels of integrin αvβ3 and OPN in decidual tissue among the three groups(P<0.05).PCOS missed abortion group was significantly lower than non-PCOS missed abortion group and normal control group,and the difference was statistically significant(P<0.01).There was no significant difference between non-PCOS missed abortion group and normal control group(P>0.05).The results of Pearson correlation analysis showed that the protein and mRNA expression levels of integrin αvβ3 and OPN in decidual tis-sue of PCOS patients with missed abortion were significantly positively correlated(r>0,P<0.01).Conclusions:The integrin αvβ3 and OPN were expressed in both epithelial cells of the uterus and decidual cells in early preg-nancy.The expressions of them were significantly decreased in decidual tissues of PCOS patients with missed a-bortion,which might be related to reduced endometrial receptivity.The role of integrin αvβ3 and OPN in the occur-rence of missed abortion needs further study.
4.Research progress on epidemiologic associations between Epstein-Barr virus infection and risk of gastric cancer
Wang XINLING ; Jin YU ; Pan KAIFENG ; Li WENQING
Chinese Journal of Clinical Oncology 2024;51(15):780-784
Epstein-Barr virus(EBV)is the first virus discovered to be associated with human tumors,and its association with gastric cancer has received widespread attention in recent years.In 2014,The Cancer Genome Atlas initially classified gastric cancer into four subtypes based on molecular characteristics,with EBV positive individuals grouped into a distinct subtype known as EBV-positive gastric cancer,which has unique molecular and clinicopathological characteristics.While EBV infection in malignant gastric epithelial cells and the induction of host genetic mutations and epigenetic abnormalities were generally considered as important bases for EBV carcinogenesis,the mechanisms un-derlying the relationship between EBV infection and gastric cancer risk remain unclear.We here summarize the existing epidemiological data supporting associations between different indicators of EBV infection and gastric cancer and provide an overview of the potential roles and mechanisms of EBV in gastric cancer carcinogenesis,which is expected to offer significant guidance for future studies elucidating the rela-tionship between EBV infection and gastric cancer development.
5.Prevalence of psoriatic arthritis in Chinese population with psoriasis: A multicenter study conducted by experienced rheumatologists.
Hua ZHANG ; Miao CHEN ; Ran CUI ; Xia LI ; Kexiang YAN ; Lihong CHEN ; Zhenghua ZHANG ; Ning YU ; Xinling BI ; Hui DENG ; Yangfeng DING ; Qiong HUANG ; Sheng-Ming DAI
Chinese Medical Journal 2023;136(12):1439-1447
BACKGROUND:
Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis.
METHODS:
Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists.
RESULTS:
A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%).
CONCLUSION
The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.
Humans
;
Female
;
Male
;
Arthritis, Psoriatic/epidemiology*
;
Rheumatologists
;
Prevalence
;
East Asian People
;
Psoriasis/epidemiology*
6.Prognostic value of pretreatment body mass index in patients with unresectable locally advanced non-small cell lung cancer after chemoradiotherapy
Xinling FAN ; Yin YANG ; Yu WANG ; Jianyang WANG ; Lei DENG ; Xin WANG ; Wenyang LIU ; Wenqing WANG ; Dongfu CHEN ; Zefen XIAO ; Qinfu FENG ; Jima LYU ; Zongmei ZHOU ; Nan BI ; Tao ZHANG
Cancer Research and Clinic 2022;34(7):487-492
Objective:To explore the effect of pretreatment body mass index (BMI) on the prognosis of patients with unresectable locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy.Methods:The clinical data of 711 patients with locally advanced NSCLC treated with radiotherapy, sequential chemoradiotherapy or concurrent chemoradiotherapy from January 2013 to December 2017 in Cancer Hospital of Chinese Academy of Medical Science and Peking Union Medical College were retrospectively analyzed. Radiotherapy was performed with intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT), and the chemotherapy regimens were paclitaxel+carboplatin, pemetrexed+cisplatin or etoposide+cisplatin. The effects of pretreatment BMI and other clinical factors on overall survival (OS) of patients were analyzed. Survival analysis was performed by using Kaplan-Meier method; univariate and multivariate analyses were performed by using Cox proportional hazards model.Results:According to the World Health Organization (WHO) recommended BMI grouping method for Asian, the median OS time of low BMI group (<18.5 kg/m 2, 23 cases), normal BMI group (18.5-23.9 kg/m 2, 293 cases) and high BMI group (≥24.0 kg/m 2, 395 cases) was 17 months (95% CI 11-29 months), 29 months (95% CI 22-36 months) and 30 months (95% CI 27-34 months), respectively. OS in the low BMI group was poorer than that in the normal BMI group and high BMI group ( χ2 = 11.20, P = 0.004). Maximally selected rank statistics was used to determine the optimal cut-off value of BMI for prediction of survival as 21.31 kg/m 2, according to which patients were divided into low BMI group (BMI<21.31 kg/m 2, 130 cases) and high BMI group (BMI≥21.31 kg/m 2, 581 cases), the median OS time of the two groups was 20 months (95% CI 17-27 months) and 32 months (95% CI 28-35 months), respectively. OS in the low BMI group was poorer than that in the high BMI group ( χ2 = 12.30, P < 0.001). Multivariate analysis showed that age ≥ 65 years old, male, Karnofsky score < 80 points, low BMI, smoking, histological type of squamous cell carcinoma and radiotherapy alone were independent risk factors for OS (all P < 0.05). Conclusions:For patients with unresectable locally advanced NSCLC who received chemoradiotherapy, those with low pretreatment BMI have poor prognosis.
7.A case of severe hookworm infection.
Linghui MA ; Dibo NOUHOUM ; Wanni WANG ; Zhishan ZHANG ; Xunya HOU ; Xinling YU ; Weicheng DENG ; Jie GUAN ; Shuaiqin HUANG ; Xiang WU
Journal of Central South University(Medical Sciences) 2022;47(6):814-822
With the improvement of sanitation, the infection rate of hookworm is greatly reduced and the severe infected case is rarely reported. Combined morphological and molecular biological examinations, a severe hookworm infection patient was diagnosed in Department of Laboratorial Examination, Quanzhou First Affiliated Hospital of Fujian Medical University. The morphological methods such as direct fecal smear microscopy, saturated brine flotation and hookworm larvae culture methods were used to identify the eggs and larvae from stool samples of the patient. There were a large number of hookworm eggs in patient's stool samples, and the average count was 60 840 per gram by modified Kato method, which belonged to severe hookworm infection. Meanwhile, to distinguish the hookworm species, the semi-nested RT-PCR assay was employed to detect hookworm internal transcribed spacer series from eggs in patient's stool samples, and the result showed that the hookworm species was confirmed to be Necator americanus.
Ancylostomatoidea/genetics*
;
Animals
;
Feces
;
Hookworm Infections/diagnosis*
;
Humans
;
Necator americanus/genetics*
;
Polymerase Chain Reaction
8.Exploration and practice of improving basic medical teacher's ability from the perspective of medical, teaching and research collaboration
Jiewei LUO ; Xinling YANG ; Shuangzhi YU ; Qi WEI ; Yingping HUANG
Chinese Journal of Medical Education Research 2021;20(9):951-953
The School of Basic Medical Sciences of North Sichuan Medical University explores the reform of the basic medicine teacher's ability cultivation from the following aspects, including the classroom teaching quality, practical teaching skills, the innovation ability of scientific research, the basic and clinical integration and so on. Practice has proved that these reforms have greatly improved the quality of teachers' abilities and also the quality of education and teaching.
9.Correlation between levator hiatus area, pelvic organ prolapse quantification and prolapse symptoms
Manli WU ; Xin LIN ; Xudong WANG ; Yuanchun FU ; Haiyan CHEN ; Shuliang NAN ; Weijun HUANG ; Yu CHEN ; Li WANG ; Chunli JING ; Wenjuan CHEN ; Jiawei TIAN ; Xinling ZHANG
Chinese Journal of Ultrasonography 2020;29(8):700-705
Objective:To investigate the association between levator hiatus area, pelvic organ prolapse quantification (POP-Q) examination and prolapse symptoms.Methods:The prospective multicenter study enrolled 996 female patients between January 2017 and January 2019. All enrolled patients underwent a standard clinical interview, POP-Q examination and transperineal ultrasound examination. Volume data of pelvic floor ultrasound examinations were obtained at rest, during contraction and during maximal Valsalva maneuver. The association between levator hiatus area, POP-Q examination and prolapse symptoms was analyzed. The performance of levator hiatus area on maximal Valsalva for assessing significant POP(POP-Q stage≥2) and prolapse symptoms were also evaluated.Results:There were significant differences of levator hiatus area at rest, during contraction and during maximal Valsalva among patients with different POP-Q stages (all P<0.001). Levator hiatus area during maximal Valsalva showed the highest correlation with abdominal dragging sensation ( r=0.277, P<0.001). The area under the ROC curve (AUC) of levator hiatus area during maximal Valsalva for significant POP (POP-Q stage≥2) was significantly higher than that for prolapse symptoms (AUC: 0.77 vs 0.69, P<0.001). Conclusions:Levator hiatus area on transperineal has moderate correlation with POP-Q examination and their association is stronger than the correlation between ultrasound findings and prolapse symptoms.
10.Feasibility of transperineal ultrasound in quantitative assessment of posterior compartment prolapse
Xin LIN ; Manli WU ; Zeping HUANG ; Jing XU ; Xudong WANG ; Ying CHEN ; Shuangyu WU ; Yuanchun FU ; Haiyan CHEN ; Shuliang NAN ; Weijun HUANG ; Yu CHEN ; Li WANG ; Chunli JING ; Wenjuan CHEN ; Jiawei TIAN ; Xinling ZHANG
Chinese Journal of Ultrasonography 2020;29(9):771-776
Objective:To investigate the feasibility of transperineal ultrasound in quantitative assessment of posterior compartment prolapse among Chinese women.Methods:The prospective multicenter study enrolled 485 women between January 2017 and January 2019. All patients underwent a standard clinical interview, pelvic organ prolapse quantification (POP-Q) examination and transperineal ultrasound examination. Volume data of transperineal ultrasound examinations were obtained at rest and in maximal Valsalva maneuver.Results:The higher POP-Q stage of posterior compartment, the lower rectal ampulla position in maximal Valsalva maneuver (POP-Q stage=0 vs POP-Q stage=1, P<0.001; POP-Q stage=1 vs POP-Q stage≥2, P<0.001), and the greater rectal ampulla hypermobility (POP-Q stage=0 vs POP-Q stage=1, P<0.001; POP-Q stage=1 vs POP-Q stage≥ 2, P=0.007). The rectal ampulla position at rest and in maximal Valsalva maneuver and rectocele depth were correlated with prolapse symptoms ( r=-0.200, P<0.001; r=-0.252, P<0.001; r=0.086, P=0.045). The corresponding cut-off values of rectal ampulla position in maximal Valsalva in diagnosing posterior compartment prolapse (POP-Q stage ≥1) and clinical significant posterior compartment prolapse (POP-Q stage ≥2) were 7.32 mm below the symphysis pubis and 12 mm below the symphysis pubis, respectively, with the area under the ROC curve as 0.75 and 0.85, respectively. Conclusions:The ultrasonic measurements by transperineal ultrasound is significantly associated with POP-Q examination in posterior compartment, and it is demonstrated as a useful tool in quantitative assessment of the severity of posterior compartment prolapse.


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