1.Association Between Systemic Inflammatory Response Index and Lung Cancer Prevalence: A Cross-Sectional Study Based on the NHANES Database
Huijuan CHENG ; Shun CHEN ; Weilan LIN ; Cuili LIN ; Feng LU
Medical Journal of Peking Union Medical College Hospital 2026;17(3):689-697
To investigate the association between the systemic inflammatory response index (SIRI) and lung cancer prevalence based on the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study integrated data from 10 consecutive survey cycles of the NHANES database between 1999 and 2018. Multivariable logistic regression models were used to evaluate the association between SIRI and lung cancer prevalence, and a trend test was performed to assess whether there was a linear trend in lung cancer prevalence with increasing SIRI levels. Restricted cubic spline (RCS) analysis was further performed to examine the association and potential nonlinear relationship between SIRI and lung cancer prevalence. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of the results. A total of 35 372 participants were included. With increasing SIRI levels, the mean age of participants showed a significant increasing trend ( Elevated SIRI levels are positively associated with increased lung cancer prevalence, and this association is robust. SIRI, as a simple and cost-effective inflammatory marker, has potential value in risk stratification for lung cancer prevalence.
2.Gentiopicroside Alleviates Atherosclerosis by Suppressing Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation in Vascular Endothelial Cells via SIRT1/Nrf2 Pathway.
Zhu-Qing LI ; Feng ZHANG ; Qi LI ; Li WANG ; Xiao-Qiang SUN ; Chao LI ; Xue-Mei YIN ; Chun-Lei LIU ; Yan-Xin WANG ; Xiao-Yu DU ; Cheng-Zhi LU
Chinese journal of integrative medicine 2025;31(2):118-130
OBJECTIVE:
To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis.
METHODS:
Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role.
RESULTS:
GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors.
CONCLUSION
GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Reactive Oxygen Species/metabolism*
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Iridoid Glucosides/therapeutic use*
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NF-E2-Related Factor 2/metabolism*
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Animals
;
Atherosclerosis/metabolism*
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Inflammasomes/drug effects*
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Male
;
Sirtuin 1/metabolism*
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Signal Transduction/drug effects*
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Humans
;
Endothelial Cells/pathology*
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Mice
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Oxidative Stress/drug effects*
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Apoptosis/drug effects*
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Lipoproteins, LDL
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Mice, Inbred C57BL
3.Relationship between common myositis-specific antibodies and clinical features in children with juvenile dermatomyositis.
Su-Yun CHENG ; Jia-Min LU ; Feng LI
Chinese Journal of Contemporary Pediatrics 2025;27(9):1076-1081
OBJECTIVES:
To investigate the distribution of myositis-specific antibodies (MSA) in juvenile dermatomyositis (JDM) and the relationship between MSA and clinical features of JDM.
METHODS:
Clinical data of 72 children with JDM hospitalized from January 2020 to April 2025 were reviewed retrospectively, all of whom had been tested for MSA. The relationship between common MSA subtypes and clinical features was analyzed.
RESULTS:
Among the 72 children, 45 (62%) were positive for MSA, including 27 anti-NXP2-positive cases (38%), 10 anti-MDA5-positive cases (14%), and 3 anti-cN1A-positive cases (4%). Compared with the MSA-negative group, the anti-MDA5-positive patients showed significantly higher incidence rates of fever, arthritis, and interstitial lung disease (P<0.05). The anti-NXP2-positive patients exhibited significantly higher incidence rates of calcinosis, fever, soft tissue edema, and interstitial lung disease than the MSA-negative patients (P<0.05). Compared with the anti-MDA5-positive group and MSA-negative group, the anti-NXP2-positive group had significantly higher levels of creatine kinase and creatine kinase isoenzyme (P<0.017) and a significantly lower score of the Childhood Myositis Assessment Scale (P<0.017).
CONCLUSIONS
The positive rate of MSA is high in children with JDM, with different subtypes correlating with specific clinical manifestations and organ involvement. Detection of MSA is crucial for diagnosis and clinical management of JDM.
Humans
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Dermatomyositis/immunology*
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Male
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Female
;
Child
;
Retrospective Studies
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Interferon-Induced Helicase, IFIH1/immunology*
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Child, Preschool
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Autoantibodies/blood*
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Adolescent
4.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.
Ying-Na CHEN ; Jie-Ya LU ; Cheng-Feng GAO ; Zhi-Ruo FANG ; Yan ZHOU
Journal of Integrative Medicine 2025;23(2):195-208
OBJECTIVE:
Aloin, the main active component in Aloe vera (L.) Burm. f., has shown promising anti-tumor effects. This study investigated the impact of aloin in lung squamous cell carcinoma (LUSC) and explored its functional mechanism.
METHODS:
We analyzed the viability, migration, invasion, proliferation, and apoptosis of two LUSC cell lines after treatment with aloin. Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2 (NR3C2) were predicted by bioinformatics. The biological functions of NR3C2 and metallothionein 1 M (MT1M) in the malignant properties of LUSC cells were determined. A co-culture system of LUSC cells with monocyte-derived macrophages was constructed. Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.
RESULTS:
Aloin suppressed malignant properties of LUSC cells in vitro. However, these effects were negated by the silencing of NR3C2. NR3C2 was found to activate MT1M transcription by binding to its promoter. Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing. Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages, whereas NR3C2 silencing led to reverse trends. Consistent findings were reproduced in vivo.
CONCLUSION
This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization. Please cite this article as: Chen YN, Lu JY, Gao CF, Fang ZR, Zhou Y. Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis. J Integr Med. 2025; 23(2): 195-208.
Lung Neoplasms/metabolism*
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Humans
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Animals
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Cell Line, Tumor
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Carcinoma, Squamous Cell/metabolism*
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Mice
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Macrophages/drug effects*
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Emodin/analogs & derivatives*
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Metallothionein/genetics*
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Cell Proliferation/drug effects*
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Cell Movement/drug effects*
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Apoptosis/drug effects*
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Receptors, Glucocorticoid/genetics*
5.Association between Per and Polyfluoroalkyl Substance and Abdominal Fat Distribution: A Trait Spectrum Exposure Pattern and Structure-Based Investigation.
Zhi LI ; Shi Lin SHAN ; Chen Yang SONG ; Cheng Zhe TAO ; Hong QIAN ; Qin YUAN ; Yan ZHANG ; Qiao Qiao XU ; Yu Feng QIN ; Yun FAN ; Chun Cheng LU
Biomedical and Environmental Sciences 2025;38(1):3-14
OBJECTIVE:
To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles.
METHODS:
Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk.
RESULTS:
Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk.
CONCLUSION
PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans
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Fluorocarbons/blood*
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Female
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Adult
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Middle Aged
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Male
;
Environmental Pollutants/blood*
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Abdominal Fat
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Nutrition Surveys
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Alkanesulfonic Acids/blood*
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Obesity
;
Environmental Exposure
6.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
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Body Mass Index
;
China/epidemiology*
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Male
;
Female
;
Middle Aged
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Prospective Studies
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Rural Population/statistics & numerical data*
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Aged
;
Follow-Up Studies
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Adult
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Mortality
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Cause of Death
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Obesity/mortality*
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Overweight/mortality*
7.Multi-center clinical study on the efficacy and safety of combined lienal polypeptide injection therapy in children with Mycoplasma pneumoniae pneumonia
Qi CHENG ; Yunxiao SHANG ; Han ZHANG ; Jiujun LI ; Ning CHEN ; Lishen SHAN ; Nan YANG ; Lihua NING ; Xuemei BAI ; Jianhua LIU ; Yuling HAN ; Jichun WANG ; Jing LI ; Yong FENG ; Liyun LIU ; Li CHEN ; Si LIU ; Qinzhen ZHANG ; Jia ZHENG ; Fengchao LI ; Sukun LU ; Yun ZHANG ; Xiaoyi CHAI
International Journal of Pediatrics 2025;52(3):204-210
Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia(MPP)in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized,controlled,multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1,2023 to January 31,2024 were included.According to the severity of pneumonia,they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP(SMPP/RMPP)group with 160 cases,and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1,using the random number table method.After screening,subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin,while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT,length of hospital stay,duration of fever,cough score,whether mild cases developed into severe or refractory cases,duration of hormone use,use of intravenous immunoglobulin(IVIG),bronchoscopy treatment,and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication,vital signs,blood routine,urine routine,liver function,myocardial enzymes,renal function,and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals,including 118 cases in the experimental group and 113 cases in the control group.Main observation index:the rate of lung CT aggravation in the experimental group was lower than that in the control group(2.6% vs 15.3%, P<0.01),and the difference was statistically significant.Secondary indexes:there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).However,the rate of cases of plastic bronchitis(PB)found under bronchoscopy in the experimental group was lower than that in the control group(0 vs 18.8%, P=0.03),and the difference was statistically significant.Among the mild MPP(72 cases),there were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and the improvement rate of lung CT between the two groups(all P>0.05).However,compared with the control group,the rate of cases developing into SMPP/RMPP in the experimental group was less(24.3% vs 48.6%, P=0.03),and the difference in IgG before and after treatment was small[0.53(-0.04,1.18)g/L vs 1.33(0.48,2.25)g/L, P=0.01].Among the SMPP/RMPP cases(159 cases),the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group(0 vs 20%, P=0.04),and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group(1.3% vs 19.5%, P<0.01),and the improvement rate of lung CT in the experimental group was higher than that in the control group(88.8% vs 75.3%, P=0.03),with statistically significant differences.There were no statistically significant differences in the length of hospital stay,duration of fever,cough score,duration of hormone use,whether IVIG treatment was used,the number of bronchoscopy treatment cases,and immunoglobulin between the two groups(all P>0.05).Two cases in the experimental group developed rashes,which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine,liver function,myocardial enzymes,renal function,electrocardiogram,and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP,reduce the rate of aggravation of the image findings,promote the absorption of lung inflammation,reduce the rate of PB found under bronchoscopy,and has good safety.
8.Progress in the application of lung transplantation in pulmonary lymphangioleiomyomatosis
Hanzhou HUANG ; Yongqi CHENG ; Jiaji ZHOU ; Rongguo LU ; Feng LIU ; Mingfeng ZHENG
Organ Transplantation 2025;16(2):309-314
Pulmonary lymphangioleiomyomatosis is a rare disease characterized by the abnormal proliferation of pulmonary lymphatic smooth muscle cells. It is common in women and often accompanied by recurrent pneumothorax, chylothorax and progressive dyspnea, imaging characterized by diffuse cystic lesions in both lungs. Pulmonary lymphangioleiomyomatosis progresses aggressively and has a very poor prognosis, with a lack of effective medical treatment options in the advanced stages. Lung transplantation is a safe and effective method for the treatment of advanced pulmonary lymphangioleiomyomatosis, which may significantly improve the survival rate and quality of life of patients. The median survival period after surgery can reach 12 years. This article reviews the pathogenesis, diagnosis, treatment of pulmonary lymphangioleiomyomatosis, and the current status and existing problems of lung transplantation in pulmonary lymphangioleiomyomatosis, aiming to provide a reference for the clinical treatment and subsequent research of pulmonary lymphangioleiomyomatosis.
9.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
10.The efficacy and safety of dapagliflozin in non-diabetic patients with chronic kidney disease
Yuhua FENG ; Jingyu DOU ; Zhen ZHANG ; Lu WEN ; Qianqian LI ; Yan SU ; Genyang CHENG
Chinese Journal of Nephrology 2025;41(11):855-858
A total of 269 non-diabetic chronic kidney disease (CKD) patients were enrolled in this study. Among them, 175 patients (65.1%) were assigned to the control group and received conventional therapy with maximally tolerated doses of renin-angiotensin-aldosterone system inhibitors, while 94 patients (34.9%) were assigned to the dapagliflozin group and received oral dapagliflozin 10 mg/day in addition to the conventional therapy. The results showed that the urine protein quantity in the dapagliflozin group was lower than those in the control group at 3, 6, 12, 18, and 24 months of follow-up (all P<0.05), and the blood albumin level was higher than those in the control group at 18 and 24 months of follow-up (all P<0.05). The Kaplan-Meier survival curve analysis results showed that the cumulative renal survival rate of the dapagliflozin group was significantly higher than that of the control group (Log-rank test, χ2=5.078, P=0.024). Multivariable Cox regression analysis results revealed that using dapagliflozin was independently associated with a reduced risk of the composite endpoint in non-diabetic CKD patients ( HR=0.400, 95% CI 0.163-0.983, P=0.046). There was no statistical difference in adverse reactions between the two groups (all P>0.05). It is indicated that dapagliflozin has a renal protective effect independent of hypoglycemic action and good safety.

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