1.Targeting farnesoid X receptor as aging intervention therapy.
Lijun ZHANG ; Jing YU ; Xiaoyan GAO ; Yingxuan YAN ; Xinyi WANG ; Hang SHI ; Minglv FANG ; Ying LIU ; Young-Bum KIM ; Huanhu ZHU ; Xiaojun WU ; Cheng HUANG ; Shengjie FAN
Acta Pharmaceutica Sinica B 2025;15(3):1359-1382
Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr -/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.
2.Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia
Guochang XUE ; Huali ZHANG ; Xuexing DING ; Fu XIONG ; Yanhong LIU ; Hui PENG ; Changlin WANG ; Yi ZHAO ; Huili YAN ; Mingxing REN ; Chaoying MA ; Hanming LU ; Yanli LI ; Ruifeng MENG ; Lingjun XIE ; Na CHEN ; Xiufang CHENG ; Jiaojiao WANG ; Xiaohong XIN ; Ruifen WANG ; Qi JIANG ; Yong ZHANG ; Guijuan LIANG ; Yuanzheng LI ; Jianing KANG ; Huimin ZHANG ; Yinying ZHANG ; Yuan YUAN ; Yawen LI ; Yinglin SU ; Junping LIU ; Shengjie DUAN ; Qingsheng LIU ; Jing WEI
Chinese Journal of Pediatrics 2024;62(6):535-541
Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).
3.Postoperative Patient-controlled Analgesia: Thirty Years of Clinical Experience in Peking Union Medical College Hospital
Lin ZHAO ; Liying REN ; Weihua NIE ; Yaqi CHEN ; Jie ZHANG ; Shengjie ZHANG ; Yingli WANG ; Cuicui DIAO ; Huiying MA ; Zheng ZHANG ; Li ZHOU ; Le SHEN ; Huizhen WANG ; Yuguang HUANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):239-245
Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.
4.Syndrome surveillance and early warning technology for acute respiratory infectious diseases: current status and future development
Jin YANG ; Luzhao FENG ; Shengjie LAI ; Libing MA ; Ting ZHANG ; Xingxing ZHANG ; Qing WANG ; Weizhong YANG ; Chen WANG
Chinese Journal of Epidemiology 2023;44(1):60-66
Human still has limited understanding of respiratory infectious diseases, especially emerging acute respiratory infectious diseases. Once the pandemic of this kind of infectious disease occur, it would be a serious challenge to health, political security, the economic development, and social stability. People hope to detect the changes in infectious diseases in early phase through surveillance and give early warning in time. In the field of public health, more attention has been paid to syndrome surveillance as an effective supplement to traditional surveillance. This paper summarizes the current surveillance system of infectious diseases abroad, introduces the syndrome surveillance system of acute respiratory infectious disease and its application in China, and discusses the development of syndrome surveillance and early warning technology for acute respiratory infectious diseases in the future.
5.Efficacy and safety of anlotinib monotherapy and combinated therapy in the treatment of advanced pheo-chromocytoma/paraganglioma
Xianda CHEN ; Nan MA ; Shengjie GUO ; Zhenhua LIU ; Kai YAO
The Journal of Practical Medicine 2023;39(23):3106-3110
Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma.Methods Nine patients with advanced pheochromo-cytoma/paraganglioma(PPGL)who were admitted to the Department of Urology,Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected.Patients were divided into four groups according to different treatments:anlotinib monotherapy group(3 patients),anlotinib combined with PD-1 monoclonal antibody immuno-therapy group(3 patients),anlotinib combined with immunotherapy and chemotherapy group(2 patients),and anlotinib combined with chemotherapy group(1 patients).The effectiveness and safety of different treatment regiments of anlotinib were analyzed.Results Objective response rate(ORR):(44%),Partial response(PR):(44%),Stable disease(SD):(44%),Progressive disease(PD):(11%),Disease control rate(DCR):(89%).The ORR of 2 patients with SDH gene mutation,SDHB and SDHD respectively,was 100%.Median overall survival time(OS)was 16.3 months(IQR:11.3~21.8 months).Median progression-free survival(PFS)was 16.3 months(IQR:9.8~20.8 months).There were 2 patients with adverse events grade≥3/4,all of which were hypertension.Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma.
6.Expressions of P53 and Ki-67 in prostate cancer and the clinicopathological significance
Pengjie WU ; Wei ZHANG ; Shengjie LIU ; Gang ZHU ; Hong MA ; Lingfeng MENG ; Zheng ZHANG ; Yaoguang ZHANG ; Dong WEI ; Ze YANG ; Ben WAN ; Jianye WANG
Journal of Modern Urology 2023;28(5):421-423
【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.
7.Clinical value of esophageal-jejunal Orvil TM anastomosis and Overlap anastomosis in laparos-copic radical total gastrectomy of adenocarcinoma of esophagogastric junction
Shengjie MA ; Yinquan ZHAO ; Mingjie XIA ; Liang HE ; Weihua TONG ; Yuchen GUO ; Shuang LI ; Quan WANG
Chinese Journal of Digestive Surgery 2023;22(3):383-390
Objective:To investigate the clinical value of esophageal-jejunal OrVil TM anas-tomosis and Overlap anastomosis in laparoscopic radical total gastrectomy of adenocarcinoma of esophagogastric junction (AEG). Methods:The retrospective cohort study was conducted. The clinicopathological data of 112 patients with AEG who were admitted to the First Hospital of Jilin University from July 2017 to August 2022 were collected. There were 87 males and 25 females, aged (64±8)years. All 112 patients underwent laparoscopic total gastrectomy and D 2 lymphadenectomy, in which 61 cases with esophageal-jejunal OrVil TM anastomosis were divided into the OrVil TM group, 51 cases with esophageal-jejunal Overlap anastomosis were divided into the Overlap group. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. Results:(1) Surgical situations. The esophageal invasion length and tumor diameter was 1.0(0.7,2.0)cm and (6.3±2.7)cm in patients of the OrVil TM group, versus 0.2(0.1,0.5)cm and (4.7±2.2)cm, respectively, in patients of the Overlap group, showing significant differences in the above indicators between the two groups ( Z=?6.14, t=3.26, P<0.05). (2) Postoperative complications. Cases with complications ≥Ⅲa grade of Clavien-Dindo classification, cases with respiratory system complications, cases with hydrothorax were 13, 17, 13 in the OrVil TM group, versus 4, 5, 4 in the Overlap group, showing significant differences in the above indicators between the two groups ( χ2=3.91, 5.74, 3.91, P<0.05). Cases underwent readmission within postoperative 30 days were 3 and 1 in the OrVil TM group and the Overlap group, respectively, and all patients recovered after symptomatic treatment. There were 2 cases died after operation in the OrVil TM group and none of patients died after operation in the Overlap group. (3) Influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Results of multivariate analysis showed that esophageal invasion length was an independent factor influencing for patients undergoing esophageal-jejunal OrVil TM anastomosis ( odds ratio=8.25, 95% confidence interval as 3.41?19.96, P<0.05). Conclusions:Compared with esophageal-jejunal Overlap anastomosis, choosing the esophageal-jejunal Orvil TM anastomosis during laparoscopic radical total gastrectomy can take benefit to the proximal margin of patients with AEG. However, the ratios of complications ≥ Ⅲa grade of Clavien-Dindo classification, respiratory system complications and hydrothorax associated to OrVil TM anastomosis are relatively increased. Esophageal invasion length is an independent influencing factor for patients undergoing esophageal-jejunal OrVil TM anastomosis.
8.Construction of a predictive model based on columnar maps for factors influencing lesion residuals after minimally invasive rotary mastectomy for breast masses
Changxin LYU ; Zejie SHAO ; Li LI ; Liyong FENG ; Shengjie MA ; Cuili LIU
Chinese Journal of Endocrine Surgery 2023;17(1):84-89
Objective:To investigate the influencing factors associated with lesion residual after minimally invasive rotary mastectomy for breast masses and to construct a predictive model using columnar plots.Methods:Two hundred and twenty-eight patients with Breast lumps in Linyi People’s Hospital from Jun. 2018 to Jun. 2020 were selected as study subjects, all of whom underwent minimally invasive rotational resection, and the influencing factors of postoperative lesion residual were analyzed using univariate and multifactorial analysis, and a column line graph risk warning model was constructed and given for evaluation and validation.Results:228 patients were followed up for 6 months after surgery, 3 cases were lost, 225 cases completed postoperative follow-up, among which 185 cases (82.22%) had successfully resected lesions; 40 cases (17.78%) had residual lesions. Univariate, logistic regression analysis showed that tumor diameter ( t=15.52, P<0.001) , lesion morphology ( t=15.52, P<0.001) , lesion boundary ( χ2=7.71, P=0.006) , ultrasound guidance ( χ2=12.69, P<0.001) , and minimally invasive spinotomy system ( χ2=10.64, P=0.001) were the factors influencing lesion residual after minimally invasive spinotomy of breast masses. Based on the above factors to construct a column line graph model of lesion residual after minimally invasive rotational mastectomy for breast lumps, the area under the working characteristic curve (ROC) for model subjects was 0.974 (95% CI: 0.954-0.994) , indicating that the calibration curve basically matched the actual curve; external validation of the model showed that the area under the obtained ROC was 0.962 (95% CI: 0.933-0.991) , indicating that the model has a high degree of calibration. Conclusion:Tumor diameter, lesion morphology, lesion boundary, ultrasound guidance, and minimally invasive spinotomy system are the influencing factors of lesion residual after minimally invasive spinotomy for Breast lumps, and the column line graph model prediction of lesion residual occurring after surgery constructed based on the above factors has good confidence.
9.Changes of vaginal microecology and related research progress in postmenopausal women
Shengjie XU ; Yibing LAN ; Linjuan MA ; Jianhong ZHOU
Chinese Journal of Geriatrics 2021;40(3):401-405
Pathophysiological changes, such as the vulvovaginal atrophy, reduction in the proportion of lactobacilli, unbalance of the vaginal flora and impaired vaginal immune barrier, can result in a series of symptoms, signs and diseases affecting the health and quality of life in postmenopausal women.This article reviews the change characteristics and related mechanisms of the microbial flora in postmenopausal women in terms of the type, quantity and proportion of vaginal flora, and clarifies efficacy and its mechanisms of systemic and topical estrogen therapy on the improvement of intravaginal environment and urogenital symptoms, in order to improve the quality life in postmenopausal women.
10.Immunogenicity and safety of Sabin IPV vaccine in Banna mini pigs
Yina CUN ; Wei CAI ; Shaohui SONG ; Jian ZHOU ; Shengjie OUYANG ; Wenzhu HU ; Weidong LI ; Guoyang LIAO ; Lei MA
Acta Laboratorium Animalis Scientia Sinica 2018;26(3):331-334
Objective To evaluate the immunogenicity and safety of inactivated poliovirus vaccine derived from Sabin strain (sIPV) in Banna mini pigs, and to provide experimental evidence for the new animal model. Methods sIPV vaccines which are listed at Institute of Medical Biology at Chinese Academy of Medical Sciences were used in this study. The groups of intramuscular sIPV and the wild strain IPV injections (IPV derived from wild strain, wIPV) were designed, and the saline group was used as a negative control group. The Banna mini pigs in various groups were immunized at 0, 1 and 2 months. Blood samples were collected before immunization and on days 30 after each immunization. Levels of neutralizing antibodies were tested for evaluating immunogenicity. The safety was evaluated by observation of the status and weight of mini pigs. Results After the three dose immunization schedules in the Banna mini pigs, the seroconversion rates of type Ⅰ,Ⅱ and Ⅲ sIPV experimental groups and wIPV group were all up to 100%. The neutralizing antibody levels in all the three types were much higher than the protective titer 1: 8. The weight of mini pigs increased after vaccination. Conclusions The sIPV vaccine has good immunogenicity and safety in Banna mini pigs. Banna mini pigs could be a new animal model for evaluation of sIPV vaccine.

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