1.Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion
Yanhong YANG ; Jianliang ZHANG ; Dongxiao LI ; Cuiping LIU ; Rong GUO ; Yi XIAO ; Ling ZHOU ; Lingxia TONG ; Hong ZHANG
Journal of Sichuan University (Medical Sciences) 2024;55(3):542-551
Objective Kisspeptin,a protein encoded by the KISS1 gene,functions as an essential factor in suppressing tumor growth.The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway,which assumes a central role in maintaining cellular homeostasis.In the specific context of this investigation,the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization.This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway,aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion(RSA).Methods We enrolled a cohort comprising 45 individuals diagnosed with RSA,who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020.On the other hand,an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included.To comprehensively assess the molecular landscape,Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin(and its gene KISS1),IGFBP1(an established marker of decidualization),Notch1,Akt,and Foxo1 within the decidua.Human endometrial stromal cells(hESC)were given targeted interventions,including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10(the bioactive fragment of kisspeptin),and were subsequently designated as the siKP group or the KP10 group,respectively.A control group comprised hESC was transfected with blank siRNA,and cell proliferation was meticulously evaluated with CCK8 assay.Following in vitro induction for decidualization across the three experimental groups,immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups.Furthermore,RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1,Notch1,Akt,and Foxo1 across the three cell groups.Subsequently,decidualization was induced in hESC by adding inhibitors targeting Notch1,Akt,and Foxo1.The expression profiles of the aforementioned proteins and genes in the four groups were then examined,with hESC induced for decidualization without adding inhibitors serving as the normal control group.To establish murine models of normal pregnancy(NP)and RSA,CBA/J×BALB/c and CBA/J×DBA/2 mice were used.The mice were respectively labeled as the NP model and RSA model.The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234(acting as a blocker)and were designated as RSA-KP10 and NP-KP234 groups.On the other hand,the control groups received intraperitoneal injections of normal saline(NS)and were referred to as RSA-NS and NP-NS groups.Each group comprised 6 mice,and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes.Results The analysis revealed that the expression levels of kisspeptin,IGFBP1,Notch1,Akt,and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP(P<0.01 for kisspeptin and P<0.05 for IGFBP1,Notch1,Akt,and Foxo1).After the introduction of kisspeptin10 to hESC,there was an observed enhancement in decidualization capability.Subsequently,the expression levels of Notch1,Akt,and Foxo1 showed an increase,but they decreased after interference with KISS1.Through immunofluorescence analysis,it was observed that proliferative hESC displayed a slender morphology,but they transitioned to a rounder and larger morphology post-decidualization.Concurrently,the expression of Notch1 increased,suggesting enhanced decidualization upon the administration of kisspeptin10,but the expression decreased after interference with KISS1.Further experimentation involved treating hESC with inhibitors specific to Notch1,Akt,and Foxo1 separately,revealing a regulatory sequence of Notch1/Akt/Foxo1(P<0.05).In comparison to the NS group,NP mice administered with kisspeptin234 exhibited increased fetal absorption rates(P<0.001)and decreased expression of IGFBP1,Notch1,Akt,and Foxo1(P<0.05).Conversely,RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates(P<0.001)and increased expression levels of the aforementioned molecules(P<0.05).Conclusion It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade.A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization,which in turn might contribute to the development or progression of RSA.
2. Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia
Yun LING ; Yixiao LIN ; Zhiping QIAN ; Dan HUANG ; Dandan ZHANG ; Tao LI ; Min LIU ; Shuli SONG ; Jun WANG ; Yuyi ZHANG ; Shuibao XU ; Jun CHEN ; Jianliang ZHANG ; Tongyu ZHU ; Bijie HU ; Sheng WANG ; Enqiang MAO ; Lei ZHU ; Hongzhou LU
Chinese Journal of Infectious Diseases 2020;38(0):E023-E023
Objective To analyze the clinical features of patients with coronavirus disease 2019 (COVID-19) in Shanghai and to investigate the risk factors for disease progression to severe cases. Methods The clinical data of 292 adult patients with COVID-19 hospitalized in Shanghai Public Health Clinical Center from January 20, 2020 to February 10, 2020 were retrospectively analyzed, including 21 severe patients and 271 mild patients. The demographic characteristics, epidemiological history, history of underlying diseases and laboratory examinations were compared between the two groups. Measurement data were compared using t test or Mann-Whitney U test. The count data were compared using hi-square test. The binary logistic regression equation was used to analyze the risk factors for the progression of patients to severe cases. Results Among the 292 patients, 21 were severe cases with the rate of 7.2% (21/292). One patient died, and the mortality rate was 4.8% in severe patients. The severe patients aged (65.0±15.7) years old, 19 (90.5%) were male, 11 (52.4%) had underlying diseases, 7 (33.3%) had close relatives diagnosed with COVID-19. The mild patients aged (48.7±15.7) years old, 135 (49.8%) were male, 74 (27.3%) had underlying diseases, 36 (13.3%) had close relatives diagnosed with COVID-19. The differences between two groups were all significant statistically ( t =-4.730, χ 2 =12.930, 5.938 and 4.744, respectively, all P <0.05). Compared with the mild patients, the levels of absolute numbers of neutrophils, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatinine, serum cystatin C, C reactive protein (CRP), procalcitonin , D -dimer, pro-B-type natriuretic peptide (proBNP), serum myoglobin, creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum troponin I (cTnI) in severe patients were all significantly higher ( U =2 091.5, 1 928.0, 1 215.5, 729.0, 1 580.5, 1 375.5, 917.5, 789.5, 1 209.0, 1 434.0, 638.0, 964.5, 1 258.0 and 1 747.5, respectively, all P <0.05), while the levels of lymphocyte count, albumin, transferrin, CD3 + T lymphocyte count, CD8 + T lymphocyte count and CD4 + T lymphocyte count in severe patients were all significantly lower ( U =1 263.5, t =4.716, U =1 214.0, 962.0, 1 167.5 and 988.0, respectively, all P <0.05). Further logistic regression analysis showed that the albumin (odds ratio ( OR )=0.806, 95% CI 0.675-0.961), CRP ( OR =1.016, 95% CI 1.000-1.032), serum myoglobin ( OR =1.010, 95% CI 1.004-1.016), CD3 + T lymphocyte count ( OR =0.996, 95% CI 0.991-1.000) and CD8 + T lymphocyte count ( OR =1.006, 95% CI 1.001-1.010) at admission were independent risk factors for the progression of COVID-19 patients to severe illness (all P <0.05). Conclusions Severe cases of patients with COVID-19 in Shanghai are predominantly elderly men with underlying diseases. Albumin, CRP, serum myoglobin, CD3 + T lymphocyte count and CD8 + T lymphocyte count could be used as early warning indicators for severe cases, which deserve more clinical attention.
3.Shanghai community-based practice of early lung cancer screening with low-dose spiral computed tomography
Xiaoyang LUO ; Quan LIU ; Shengping WANG ; Yuan LI ; Lei SHEN ; Guodong LI ; Wentao LI ; Yanping ZHAO ; Huilin XU ; Hong FANG ; Guiqiang SHAO ; Jizhi CHU ; Junlei SUN ; Hongqi ZHU ; Zhiyong LI ; Lianghua JIANG ; Jianliang LING ; Weizhong ZHAO ; Jing WANG ; Xiaohua LIU ; Bin LI ; Yiliang ZHANG ; Ting YE ; Yunjian PAN ; Hong HU ; Rui WANG ; Yihua SUN ; Haiyan YANG ; Su XU ; Haiquan CHEN
China Oncology 2016;26(12):996-1003
Background and purpose:As one of the most fatal malignant tumors in China, the morbidity and mortality of lung cancer remain high. Early diagnosis and normative treatment is the key to improve the prognosis of lung cancer. The aim of this study was to explore the practice of early lung cancer screening with low-dose spiral computed tomography (CT) based on the current situation in community health service, with integration of superior resources of med-ical institutions at all levels in Shanghai.Methods:From Aug. 2013 to Aug. 2014, we screened high-risk population in selected communities of Minhang District, Shanghai, for early diagnosis of lung cancer with low-dose spiral CT combined with multidisciplinary comprehensive treatment models including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation and follow-up.Results:Screening population is 11 332 (male 7 144, female 4 188); Twenty-nine cases with pathological diagnosis of malignant tumor, including 27 cases of pri-mary lung cancer, 1 case of lung metastasis, 1 case of breast cancer. The morbidity of primary lung cancer is 238.26×10-5. There were 22 cases of Stage 0-Ⅰ lung cancer accounting for 81.48% of all diagnosed primary lung cancer.Conclusion:Based on community health service, screening with low-dose spiral CT could improve the early diagnosis rate of lung can-cer with feasibility and validity, which could be applicable in qualified eligible medical center and community in China.
4.Vestibular rehabilitation combined with cognitive behavioral therapy relieves chronic dizziness and the associ-ated anxiety
Tianyi YUAN ; Ling QIN ; Jianliang TANG ; Chaolang TANG ; Jinlong ZHAO
Chinese Journal of Physical Medicine and Rehabilitation 2016;38(12):938-941
Objective To assess the efficacy of combining vestibular rehabilitation with cognitive behavioral therapy in treating chronic subjective dizziness ( CSD) and the associated anxiety. Methods A total of 98 anxious CSD patients were randomly divided into an experimental group ( n=50) and a control group ( n=48) . All of the pa-tients′scores on the Hamilton anxiety scale ( HAMA) were no less than 14 and their scores on the Hamilton depres-sion scale ( HAMD) were less than 18. Systematic vestibular rehabilitation was given to the patients in the control group, while this was combined with cognitive behavioral therapy for the patients in the experimental group. All pa-tients were evaluated using a dizziness handicap inventory ( DHI) and the HAMA before treatment and in the 4th and 8th week of the treatment. Results Before the treatment there was no significant difference between the 2 groups in any of the assessments. After 3 weeks of treatment, the average HAMA score, DHI total score and its factor scores had decreased significantly. Four weeks later, the average HAMA score, DHI total score and its factor scores for som-atization, emotion and function had improved significantly in both groups compared with before treatment and the scores after 3 weeks. After 3 and 7 weeks of treatment, the average HAMA score, DHI total score and its factor scores of the experimental group were significantly lower than those of the control group. Conclusion Cognitive behavioral therapy amplifies the effects of vestibular rehabilitation in treating persons with CSD, in part by significantly relieving their anxiety.
5.Evaluation of radiation dose to working operator in three types of interventional fluoroscopic procedures
Jianliang PENG ; Yun LOU ; Zechen FENG ; Ling WAN ; Shuhua WANG ; Haiwei ZHOU ; Xinming WANG
Chinese Journal of Radiological Medicine and Protection 2011;31(4):395-397
Objective To assess the level of radiation exposures of operators in three typical types of interventional fluoroscopic procedures.Methods Alderson Radiation Therapy (ART) phantom was used to stimulate the practices of diagnosis and therapy using TLDs for dose measurement.The radiation exposures of eye lens, neck, and breast were measured when the lead shielding of machine was on/off and the equivalent dose and effective dose to the eye lens were estimated.Results Radiation exposure of head was obviously reduced by 85% -90% when the lead shielding was on.The doses in different procedures were different.In cerebral angiography the dose equivalent of eye len was the highest in the three procedures.The annual effective dose for the operators was smaller in peripheral vascular interventions than that in cardiovascular interventional therapy and that in cerebral angiography.Conclusions The operators involved in intervention will receive an annual effective dose of less than 20 mSv as recommended by the ICRP under the protection conditions provided by the current study, except for eye lens.Attention should be paid to the protection of the eyes of operators.

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