1.Huayu Mingmu Prescription Downregulates PI3K/Akt/mTOR-HIF-1α/VEGFA Signaling Pathway to Intervene in Retinal Angiogenesis of DR Rats
Xiaoqiu MA ; Lei ZHAO ; Huimin ZHOU ; Fanghui ZHENG ; Guoqing YANG ; Tao ZUO ; Xiande MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):78-87
ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR)-hypoxia inducible factor-1α/vascular endothelial growth factor A (HIF-1α/VEGFA) signaling pathway in diabetic retinopathy (DR) rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group, while the remaining 53 rats were fed a high-sugar, high-fat diet combined with low-dose streptozotocin (STZ) intraperitoneal injection to establish a type 2 diabetes mellitus (T2DM) rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model, low-dose, medium-dose, and high-dose groups of Huayu Mingmu prescription (9.29, 18.57, 37.14 g·kg-1), and a calcium dobesilate group (0.16 g·kg-1), with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography, and pathological changes in retinal tissue were evaluated using hematoxylin-eosin (HE) staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff (PAS) staining. Immunofluorescence (IF) was used to detect the expression of VEGFA and angiopoietin-2 (Ang-2) in retinal tissue. Western blot was employed to detect the protein expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue. ResultsCompared with the normal group, the model group exhibited significant pathological changes in retinal tissue, including the appearance of acellular capillaries, as well as significant endothelial cell (E) proliferation and pericyte (P) loss (P<0.01). The E/P was significantly elevated (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly increased (P<0.01), and the expression of Ang-2 protein was significantly elevated (P<0.01). In contrast, retinal tissue in the treatment groups showed alleviated pathological changes, with reduced endothelial cell proliferation and pericyte loss (P<0.05, P<0.01). Among the treatment groups, the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P (P<0.01). Protein and mRNA expression levels of PI3K, Akt, mTOR, HIF-1α, VEGFA, and VEGFR2 in retinal tissue were significantly reduced (P<0.05, P<0.01), and the expression of Ang-2 protein was significantly decreased (P<0.01). ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats, delay the progression of DR, and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.
2.Impact of inhaled corticosteroid use on elderly chronic pulmonary disease patients with community acquired pneumonia.
Xiudi HAN ; Hong WANG ; Liang CHEN ; Yimin WANG ; Hui LI ; Fei ZHOU ; Xiqian XING ; Chunxiao ZHANG ; Lijun SUO ; Jinxiang WANG ; Guohua YU ; Guangqiang WANG ; Xuexin YAO ; Hongxia YU ; Lei WANG ; Meng LIU ; Chunxue XUE ; Bo LIU ; Xiaoli ZHU ; Yanli LI ; Ying XIAO ; Xiaojing CUI ; Lijuan LI ; Xuedong LIU ; Bin CAO
Chinese Medical Journal 2024;137(2):241-243
3.Application of 8-ring traction-assisted endoscopic submucosal dissection for gastric lesions
Dandan ZHU ; Xiaotan DOU ; Huimin GUO ; Min CHEN ; Lei WANG ; Chenggong YU
Chinese Journal of Digestive Endoscopy 2024;41(1):65-67
To evaluate the effectiveness and safety of 8-ring assisted traction in endoscopic submucosal dissection (ESD), a total of 13 patients with 15 gastric lesions who underwent 8-ring traction-assisted ESD in Nanjing Drum Tower Hospital from July 2021 to January 2022 were included in the retrospective cohort study. All patients successfully completed the operation. The median procedure time was 56 min, and the dissected area per unit time was 0.20±0.02 cm 2/min. The en bloc resection rate, the complete resection rate and the curative resection rate were 93.3% (14/15), 80.0% (12/15) and 80.0% (12/15), respectively. There were no ESD-related complications, such as delayed bleeding or intraperative and postoperative perforation. No deaths occurred. As a novel internal traction technology, 8-ring traction method is simple to operate, providing a good field of vision during ESD to improve the dissection efficiency and reduce complications, which is worthy of further clinical research and promotion.
4.Efficacy and safety of endoscopic submucosal dissection for circular superficial esophageal cancer
Xiaotan DOU ; Jianhai WU ; Ting ZHOU ; Huimin GUO ; Min CHEN ; Tian YANG ; Tingsheng LING ; Xiaoqi ZHANG ; Ying LYU ; Lei WANG ; Xiaoping ZOU
Chinese Journal of Digestive Endoscopy 2024;41(2):117-120
Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for circular superficial esophageal cancer.Methods:A retrospective analysis was conducted on 74 consecutive cases of circular superficial esophageal squamous cell carcinoma treated with ESD at Nanjing Drum Tower Hospital from January 2015 to December 2019. The success rate of ESD, curative resection rate, incidence of complications, and additional treatment were mainly observed.Results:One case was transferred to surgery, and the remaining 73 cases successfully completed ESD treatment. The success rate of ESD was 98.6%. Postoperative pathology of ESD revealed that 39 cases achieved curative resection, with a curative resection rate of 53.4% (39/73). Intraoperative muscle layer injury occurred in 15 cases (20.5%), and intraoperative perforation occurred in 1 case (1.4%). Two cases (2.7%) experienced delayed bleeding, and one case (1.4%) experienced delayed perforation. Eleven cases were lost to follow-up, and the remaining 62 cases received follow-up for 36.4±19.0 months. Among the follow-up cases, 12 underwent additional surgery and 5 cases additional chemotherapy and radiotherapy. Among the 57 patients with follow-up data who did not underwent surgery, 49 developed esophageal stenosis after ESD, with an incidence rate of 86.0%.Conclusion:ESD for circular superficial esophageal cancer is generally safe, but it is prone to muscle layer injury during the operation, with a low curative resection rate, a high incidence of postoperative esophageal stenosis, and a high proportion of additional surgical procedures.
5.Surveillance of bacterial resistance in tertiary hospitals across China:results of CHINET Antimicrobial Resistance Surveillance Program in 2022
Yan GUO ; Fupin HU ; Demei ZHU ; Fu WANG ; Xiaofei JIANG ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Yuling XIAO ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Jingyong SUN ; Qing CHEN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yunmin XU ; Sufang GUO ; Yanyan WANG ; Lianhua WEI ; Keke LI ; Hong ZHANG ; Fen PAN ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Wei LI ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Qian SUN ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanqing ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Wenhui HUANG ; Juan LI ; Quangui SHI ; Juan YANG ; Abulimiti REZIWAGULI ; Lili HUANG ; Xuejun SHAO ; Xiaoyan REN ; Dong LI ; Qun ZHANG ; Xue CHEN ; Rihai LI ; Jieli XU ; Kaijie GAO ; Lu XU ; Lin LIN ; Zhuo ZHANG ; Jianlong LIU ; Min FU ; Yinghui GUO ; Wenchao ZHANG ; Zengguo WANG ; Kai JIA ; Yun XIA ; Shan SUN ; Huimin YANG ; Yan MIAO ; Mingming ZHOU ; Shihai ZHANG ; Hongjuan LIU ; Nan CHEN ; Chan LI ; Jilu SHEN ; Wanqi MEN ; Peng WANG ; Xiaowei ZHANG ; Yanyan LIU ; Yong AN
Chinese Journal of Infection and Chemotherapy 2024;24(3):277-286
Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5%were gram-positive and 70.5%were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3%,76.7%and 77.9%,respectively.Overall,94.0%of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8%of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2%in the isolates from children and 95.7%in the isolates from adults.The resistance rate to carbapenems was lower than 13.1%in most Enterobacterales species except for Klebsiella,21.7%-23.1%of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1%to 13.3%.The prevalence of meropenem-resistant strains decreased from 23.5%in 2019 to 18.0%in 2022 in Pseudomonas aeruginosa,and decreased from 79.0%in 2019 to 72.5%in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.
6.Association between cardiovascular health behaviors and hyperuricemia among community residents of different age groups
Jinxiu ZHANG ; Jinli RU ; Jing NING ; Huimin LEI ; Liqin HAN
Chinese Journal of General Practitioners 2024;23(9):928-934
Objective:To explore the association between cardiovascular health behaviors and hyperuricemia (HUA) among community residents of different age groups.Methods:It was a cross-sectional study. A total of 2 138 community residents aged (47.1±11.6) years with 1 012 males (47.3%) were selected by cluster sampling method as study subjects in Taiyuan Nanzhai Community from March to November 2020. There were 104 cases aged 8-18 years (underage group), 868 cases aged 19-44 years (youth group), 625 cases aged 45-59 years (middle-aged group), 375 cases aged 60-74 years (young elderly group), and 166 cases aged≥75 years (elderly group). Blood uric acid was measured and>420 μmol/L was defined as HUA, there were 385 cases with high uric acid level (HUA group) and 1 753 cases with normal uric acid levels (control group). The general information was collected by questionnaires, and general ergonomic indicators were measured on-site by medical personnel. The cardiovascular health behaviors included smoking, exercise, diet, and sleep in study subjects were documented. Multivariate logistic regression model was used to analyze the related factors of HUA.Results:Among 2 138 participants, 1 161 (54.3%) had never smoked (up to standard), and the order of proportion of non-smokers from high to low was underage group, elderly group, young elderly group, young group and middle-aged group ( P<0.001); 486(22.7%) people met the dietary standards, and the order of proportion of meeting the dietary standards from high to low was underage group, elderly group, young elderly group, middle-aged group, and young group ( P<0.001); 554(25.9%) people achieved physical fitness standards, and the order of the proportion of achieving physical fitness standards from high to low was young elderly group, middle-aged group, elderly group, underage group, and young group ( P<0.001); 783 (36.6%) people met the sleep standards, and the order of proportion meeting the sleep standards from high to low was underage group, youth group, middle-aged group, young elderly group, and elderly group ( P<0.001). Among the participants, only 39 (1.8%) met the standards for all 4 types of behaviors; 485 (22.7%), 1 229 (57.5%), and 424 (19.8%) had low, medium, and high total scores for ideal cardiovascular health behaviors, respectively. The total score of ideal cardiovascular health behaviors ranked from high to low was elderly group, young elderly group, underage group, middle-aged group, and young group ( P<0.001). The multivariate logistic regression analysis showed that body mass index (BMI) ( OR=1.125, 95% CI: 1.086-1.165) was positively correlated with HUA, while female ( OR=0.241, 95% CI: 0.182-0.320), total score of cardiovascular health behaviors (compared to lower level, intermediate level: OR=0.186, 95% CI: 0.127-0.273, high level: OR=0.038, 95% CI: 0.020-0.072), and number of achieved healthy behavior items ( OR=0.757, 95% CI: 0.621-0.922) were negatively correlated with HUA. Conclusions:The underage group has the highest number of people who meet the smoking, dietary, and sleep standards, the young and elderly group has the highest number of people who meet the exercise standards, and the elderly group has the highest total score for ideal cardiovascular health behaviors. There is a positive correlation between BMI and HUA, while there is a negative correlation of HUA with female, the total score and number of achieved items of cardiovascular health behaviors.
7.Application of single metal clip traction to endoscopic submucosal dissection for duodenal lesions
Dandan ZHU ; Xiaotan DOU ; Huimin GUO ; Min CHEN ; Lei WANG ; Chenggong YU
Chinese Journal of Digestive Endoscopy 2024;41(9):707-711
Objective:To assess the safety and efficacy of single metal clip traction-assisted endoscopic submucosal dissection (ESD) for the treatment of duodenal lesions.Methods:Data of 45 patients with duodenal lesions who underwent ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School between April 2021 and October 2022 were retrospectively recruited. Among them, 19 patients received single metal clip traction- assisted ESD while 26 patients received traditional ESD. The incidence of complications, dissection speed, en bloc resection rate and R0 resection rate of the two groups were mainly observed. Secondary observation indexes included specimen longer diameter, shorter diameter and area.Results:All 45 procedures were successfully completed, with the procedure time of 44.0 (27.0, 67.0) min for the single metal clip traction- assisted ESD group and 34.0 (24.0, 43.5) min for the traditional ESD group ( Z=-1.678, P=0.093). In the single metal clip traction-assisted ESD group, 2 cases (10.5%) had complications, including 1 intraoperative perforation and 1 postoperative bleeding (approximately 20 mL). There were three cases (11.5%) of complications in the traditional ESD group, including 1 case of postoperative bleeding (approximately 50 mL) and 2 cases of postoperative perforation, with no significant intergroup variation ( P=1.000). The dissection speed of the single metal clip traction-assisted ESD group was 16.0 (11.0, 25.8) mm 2/min, significantly larger than that of the traditional ESD group [5.3 (2.2, 21.1) mm 2/min, Z=-2.287, P=0.022]. The en block resection rate and R0 resection rate of the single metal clip traction-assisted ESD group were both 100.0% (19/19). Additionally, the specimen longer diameter, shorter diameter and area of the single metal clip traction-assisted ESD group were 34.0 (22.0, 45.0) mm, 25.0 (20.0, 34.0) mm, and 745.8 (380.0, 1 342.4) mm 2, respectively, significantly larger than those of the traditional ESD group of 20.0 (12.8, 30.3) mm ( Z=-3.119, P=0.002), 14.0 (8.8, 21.3) mm ( Z=-3.417, P=0.001), 190.4 (84.0, 498.7) mm 2 ( Z=-3.275, P=0.001). Conclusion:Single metal clip traction is safe and effective for duodenal ESD, demonstrating a notable improvement in the dissection speed, especially suitable for large duodenal lesions.
8.An evidence-based predictive model for early recurrence risk after hepatocellular carcinoma surgery and external validation study
Wenkao ZHOU ; Fangli ZHAO ; Jiajia CHEN ; Lei CHEN ; Lingyan HUANG ; Yue WANG ; Huimin TANG
Cancer Research and Clinic 2024;36(11):835-842
Objective:To construct an evidence-based prediction model for early recurrence after surgery of hepatocellular carcinoma (HCC) based on Meta-analysis and to do external validation study.Methods:The literatures in Chinese National Knowledge Infrastructure, Wanfang, VIP, Chinese Science Citation Database (CSCD), Chinese Social Science Citation System (CCSCI), PubMed, Web of Science and IEEE databases between January 2019 and December 2023 were searched based on the subject words. According to the inclusion and exclusion criteria, 9 literatures were included to screen the risk factors affecting the early recurrence of HCC. When the same risk factor was found in ≥5 included literatures, Meta-analysis was performed by using Review Manager 5.4.1 software. External validation data were collected from 401 patients with primary HCC who underwent surgery in Liaoning Cancer Hospital between March 2014 and March 2017. The patients were divided into early recurrence group (176 cases) and early non-recurrence group (225 cases) according to whether they relapsed 2 years after surgery. The OR values of all risk factors obtained in the Meta-analysis were converted into modeling, and postoperative early recurrence rate of HCC in the Meta-analysis was used to calculate β 0, and finally the logistic model was obtained. The OR value was incorporated into the logit (P) model, and the morbidity (P) of the external validation data was calculated. Taking the recurrence 2 years after surgery or not as the dependent variable and P as the independent variable, the receiver operating characteristic (ROC) curve was drawn to calculate the area under the curve (AUC). Results:A total of 8 risk factors for early HCC recurrence were screened out from 9 literatures (x 1: alpha-fetoprotein ≥ 400 ng/ml; x 2: tumor number ≥ 2; x 3: the longest tumor diameter ≥ 5 cm; x 4: Barcelona staging B-C; x 5: microvascular invasion; x 6: moderate to low differentiation; x 7: incomplete capsule; x 8: nonanatomic hepatectomy). The Meta-analysis included 1 757 HCC cases, with 960 postoperative early recurrences and an early recurrence rate of 45.36%, finally the β 0 value was -0.201. The predictive model for 2-year recurrence of HCC was constructed and calculated as logit (P) = -0.201+0.835x 1+0.905x 2+0.783x 3+1.008x 4+0.765x 5+0.831x 6+1.533x 7+0.940x 8. Analysis of variance by external validation data showed that the differences in ascites, alpha-fetoprotein, tumor number, tumor diameter, Barcelona staging, microvascular invasion, tumor differentiation degree, capsule invasion, resection type, and systemic inflammation index were statistically significant between early recurrence group and early non-recurrence group (all P < 0.05). ROC curve analysis showed that AUC of postoperative early recurrence of HCC predicted by the model was 0.718, (95% CI: 0.689-0.753), the optimal cut-off value was 3.11, the Yoden index was 0.288, the sensitivity was 69.32%, and the specificity was 69.56%. Conclusions:The evidence-based prediction model constructed based on Meta-analysis for postoperative early recurrence of HCC has a high predictive value. However, further verification and optimization with big data is still needed.
9.Progress on Pharmacological Effect of Terpinen-4-ol: A Review
Qing DU ; Yuxi ZHONG ; Ming YANG ; Lei CHEN ; Huimin ZENG ; Chongwen AI ; Yongmei GUAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(14):265-271
Terpine-4-ol is abundant in nature. As a cyclic monoterpenoid compound, terpine-4-ol is distributed in a variety of natural plants. It is the main component and the key active substance in many traditional Chinese essential oils, such as Melaleuca alba essential oil and coral ginger essential oil. Terpine-4-ol has anti-microbial, anti-tumor, insecticidal, anti-inflammatory, and other effects. It can treat cancer, as well as oral and cardiovascular diseases with great safety. In terms of antibacterial activity, terpine-4-ol can destroy bacterial cell walls, improve membrane permeability, and regulate bacterial migration, reproduction, and other related genes to inhibit bacterial activity. In terms of antifungal activity, terpine-4-ol can bind with ergosterol in fungal cell walls to cause fungal death. In terms of insecticidal activity, terpine-4-ol can inhibit Na+ and K+-ATPase activity and cause the death of the insect. In terms of anticancer activity, terpine-4-ol can regulate the expression of apoptosis-related proteins in cancer cells, so as to control the apoptosis of cancer cells. In this paper, the pharmacological activity and action mechanism of terpine-4-ol were reviewed to provide a reference for further research and utilization of terpine-4-ol.
10.Mechanism of nephrotoxicity induced by chronic exposure of bisphenol A in mice based on oxidative stress and cell apoptosis.
Zhongwei TANG ; Huimin WANG ; Zhuo ZHANG ; Yanbiao KONG ; Xuepei LEI ; Jianqin YUAN
Chinese Journal of Biotechnology 2023;39(1):372-385
Bisphenol A (BPA) is widely used to produce epoxy resin and polycarbonate plastic products. In severe cases, these plastics may release BPA, which then infiltrates into the environment. Various concentrations of BPA have been found in most biological fluid. Its presence has been well shown to be closely related to many chronic diseases, including chronic kidney disease (CKD). However, little is known regarding the adverse effects of BPA exposure and its succedent cellular events on CKD. Hence, in the current in vivo study, we aimed to assess the effects of chronic exposure to BPA on animal nephrotoxicity through investigating oxidative stress and apoptosis. Upon exposure to BPA at 0.01, 0.1, and 1 mg/L via drinking water for four weeks, the mated and pregnant females were continuously exposed to BPA until weaning. Subsequently, three weeks old F1-male neonates were also orally challenged with the same three doses of BPA for ten weeks. The results showed that the kidneys of 0.1 and 1 mg/L BPA-treated mice were seriously damaged; the contents of serum renal function indexes and lipid peroxidation products were significantly increased, including urea nitrogen, creatinine, uric acid, and thiobarbituric acid reactive substances; the morphological structure of mouse kidneys was impaired; the expressions of antioxidant-related genes at mRNA and protein levels from mouse kidneys were markedly diminished, including glutathione-S-transferase, superoxide dismutase, and catalase; the expressions of genes and proteins related to apoptosis index (ratio of Bax/Bcl-1 and Caspase-3) were significantly enhanced. The data manifested that cumulative oxidative stress and apoptosis might play an essential role in the animal nephrotoxicity induced by chronic exposure to BPA.
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Oxidative Stress
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Antioxidants
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Apoptosis
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Renal Insufficiency, Chronic

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