Research progress on the relationship between serum uric acid and sarcopenia / 公共卫生与预防医学

Objective With the deepening of population aging, sarcopenia has become an important public health problem affecting the health and quality of life of the elderly population. As the end-product of purine metabolism in human body, uric acid has dual effects of anti-oxidation, pro-oxidation and pro-inflammatory reaction , which affects the occurrence and development of sarcopenia to a certain extent. This paper reviews the research progress of serum uric acid and sarcopenia. Methods PubMed database, Web of Science core collection database, Embase database, China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for literatures on the relationship between serum uric acid (SUA) level and sarcopenia up to February 7, 2022, and then reviewed. Results A total of 4 epidemiological studies were found on serum uric acid levels and the risk of sarcopenia. Among them, 3 studies found that SUA within a certain level range was a protective factor for sarcopenia, and 1 study suggested that the risk of sarcopenia increased with the increase of SUA levels. There was a gender difference between serum uric acid level and sarcopenia risk. Conclusion At present, the results of studies on the relationship between serum uric acid levels and the risk of sarcopenia are still controversial, which may be caused by the different effects of uric acid in human body. In the future , more extensive and in-depth studies are needed to investigate the relationship between the two.

Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway / 中国中药杂志

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.

Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis / 中国中药杂志

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease / 中国中药杂志

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Mechanisms of Classical Prescriptions and Their Active Components in Immunosenescence Regulation： A Review / 中国实验方剂学杂志

As the body ages， the immune system will undergo a series of changes， which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils， monocytes/macrophages， myeloid-derived suppressor cells， dendritic cells， natural killer cells， etc.， and the underlying mechanisms involve the regulation of cell number， phagocytosis， chemotaxis， adhesion， the function of toll-like receptor （TLR）， antigen presentation， macrophage polarization， cytotoxicity， migration， etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes， and the underlying mechanisms involve the regulation of cell development， proliferation， differentiation， cell number， telomerase activity， self-reactive antibodies， etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years， scholars have found some classical prescriptions and their active components （such as Dushentang and total saponins in Panax ginseng leaves， and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves） can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition， the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration， Dahuang Zhechongwan， can delay D-galactose-induced renal aging in mice， and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore， exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.

Clinical Efficacy of Modified Xiao Chengqitang Combined with Acupoint Catgut Implantation in Treating Diet-induced Obesity Syndrome of Stomach Heat Dampness Obstruction / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and safety of modified Xiao Chengqitang combined with acupoint catgut implantation in treating diet-induced obesity （DIO） syndrome of stomach heat dampness obstruction. Method:One hundred and seventy-two patients were randomly divided into control group（84 cases） and observation group（88 cases）. Both groups of patients received diet and exercise lifestyle adjustments， and acupoint catgut implantation was performed， 10 days for 1 time， 5 days intervals and then catgut implantation again， for a total of 6 times. Patients in observation group took modified Xiao Chengqitang granular powder， 10 g/time， with lukewarm boiled water in morning and evening. Patients in control group took modified Xiao Chengqitang granular powder simulant， 10 g/time， with lukewarm boiled water， 2 times/day. The treatment courses continued 4 months in two groups. Then the body mass index （BMI）， fat percentage （F%）， obesity， waist to hip ratio （WHR） were measured before and after treatment. Color Doppler ultrasonography was used to measure abdominal fat thickness， prehepatic fat thickness （AHF）， perirenal fat thickness （PRF）， and visceral fat index （UVI）. Fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein-cholesterol （HDL-C）， low-density lipoprotein-cholesterol （LDL-C）， fasting insulin （FINS）， leptin （LP）， and adiponectin （APN） were detected before and after treatment， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. In addition， safety evaluation was also conducted. Result:The BMI， F%， obesity degree and WHR in observation group were all lower than those in control group （<italic>P</italic><0.05 or <italic>P</italic><0.01）. Subcutaneous fat thickness， AHF， PRF and UVI in observation group were lower than those in control group （<italic>P</italic><0.01）. The TG， TC， LDL-C and FINS levels in observation group were lower than those in control group （<italic>P</italic><0.01）. The LP and HOMA-IR were also lower than those in control group （<italic>P</italic><0.01）， while the APN was higher than that in control group （<italic>P</italic><0.01）. The total effective rate in clinical application was （71/80） 88.75% in the observation group， higher than （57/75） 76.00% in the control group （<italic>χ</italic>²=4.374，<italic> P</italic><0.05）. Conclusion:Modified Xiao Chengqitang combined with acupoint catgut implantation in treating DIO syndrome of stomach heat dampness obstruction can adjust LP， APN and other factors， improve energy metabolism such as sugar and fat， and effectively control obesity with high safety， so it is worthy of clinical use.

Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease / 中国中药杂志

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.

Adherence to Cancer Prevention Guidelines and Endometrial Cancer Risk: Evidence from a Systematic Review and Dose-Response Meta-analysis of Prospective Studies / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. @*Materials and Methods@#The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger’s and Begg’s tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. @*Results@#Five prospective studies (four cohort studies and one case‑cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No significant publication bias was detected. @*Conclusion@#This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.

Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine / 中国中药杂志

The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.

Effect of Xintong Oral Liquid in Improving Cardiac Function of Patients with Heart Failure and Syndrome of Qi Deficiency and Phlegm and Blood Stasis Caused by Acute Myocardial Infarction / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Xintong oral liquid on heart failure with syndrome of Qi deficiency， phlegm and blood stasis caused by acute myocardial infarction （AMI） and the effect on inflammatory factors. Method:One hundred patients were randomly divided into observation group （50 cases） and control group （50 cases） by random number table. Both groups got comprehensive treatment of western medicine. Patients in control group got simulated medicine of Xintong oral liquid， 20 mL/time， 3 times/day. Patients in observation group got Xintong oral liquid， 20 mL/time， 3 times/day. The treatment lasted for 4 weeks. Before the treatment， and at the second week and forth week after treatment， levels of cardiac troponin I （cTnI）， cardiac troponin T （cTnT）， heart type fatty acid binding protein （H-FABP）， left ventricular ejection fraction （LVEF）， cardiac output （CO）， cardiac output per stroke （SV） and left ventricular end diastolic diameter （LVEDd）， N-terminal B-type natriuretic peptide （NT-proBNP）， lipoprotein phospholipase A2 （Lp-PLA2）， high sensitive C-reactive protein （hs-CRP）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected. The 6-minute walking test was performed to record the 6-minute walking distance and the ratio of 6 min walking distance to estimated value. Scores of traditional Chinese medicine （TCM） syndromes， minnesota Heart Failure quality of life questionnaire （MLHFQ） and Killip classification of cardiac function were recorded. During the 2 months' follow-up， adverse cardiovascular events （MACE） were recorded， and the safety was evaluated. Result:At the second and fourth week， levels of cTnI， cTnT， H-FABP， NT-proBNP， Lp-PLA2， hs-CRP， IL-6 and TNF-α were lower than those in control group （P<0.01）， and levels of LVEF， CO and SV were higher than those in control group （P<0.05， P<0.01）. NT-proBNP was lower than control group （P<0.01）. The 6-minute walking distance and the ratio of 6-minute walking distance to estimated value were all more than those in control group （P<0.01）. Scores of TCM syndrome integral， MLHFQ， Killip heart function grading were lower than those in control group （P<0.05， P<0.01）. Cumulative incidence of MACE was 12.0% （6/50）， which was lower than 28.0% （14/50） in control group （χ2=4.251， P<0.05）. Levels of Lp-PLA2， hs-CRP， IL-6 and TNF-α in observation group were lower those in control group （P<0.01）.And there was no adverse reactions related to Xintong oral liquid. Conclusion:Based on the comprehensive treatment of Western medicine， Xintong oral liquid can reduce the degree of myocardial injury， protect myocardium， improve cardiac function， reduce inflammatory reaction， reduce the occurrence of mace， effectively control clinical symptoms， and improve exercise tolerance and quality of life.

Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways / 中国中药杂志

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Multi-targeted therapeutic effects of Huangkui Capsules on insulin resistance and urine microalbumin in early diabetic kidney disease patients / 中国中药杂志

To observe the multi-targeted therapeutic effects of Huangkui Capsules(HKC)on insulin resistance(IR)and urine microalbumin in the early diabetic kidney disease(DKD)patients. The case data from the 83 DKD patients at G2 and A2 stage were collected respectively and analyzed retrospectively. According to the different treatment,all patients were divided into the control(A)group(40 cases)and the treated(B)group(43 cases). Among them,the A group patients were received "routine basic treatment";the B group patients were received "routine basic treatment+HKC". For the 2 group patients,firstly,the baseline parameters before receiving the treatment were compared respectively,and then,the changes of the total scores of traditional Chinese medicine(TCM) syndromes and the indicators of IR,urine protein,renal function,blood lipids and safety after receiving the treatment for 8 weeks were compared,respectively. Furthermore,for the all patients,the correlation analysis between IR and urine protein or IR and the total scores of TCM syndromes was carried out,respectively. The results showed that,for the B group patients received "routine basic treatment",their total scores of TCM syndromes,urine protein indicators including urine microalbumin(micro-UAlb) and urine microalbumin/urinary creatinine(UACR),IR indicators including fasting serum insulin(FIN)and homeostasis model assessment of insulin resistance(HOMA-IR)were significantly improved,respectively. For the all DKD patients,before and after the treatment,the main IR indicators(FIN and HOMA-IR)were positively correlated with urine protein indicators(micro-UAlb and UACR). The main IR indicators(FIN and HOMA-IR) were also positively correlated with the total scores of TCM syndromes. In addition,2 treatments had no significant effects on renal function,blood lipids and safety indicators in the all DKD patients. Overall, "routine basic treatment+HKC" can ameliorate IR and reduce urine microalbumin in the early DKD patients. Its therapeutic targets may be not only proteinuria,but also IR,which is the upstream risk factor of proteinuria.

Triptolide inhibits NLRP3 inflammasome activation and ameliorates podocyte epithelial-mesenchymal transition induced by high glucose / 中国中药杂志

The aim of this paper was to explore the effects of triptolide( TP),the effective component of Tripterygium wilfordii on improving podocyte epithelial-mesenchymal transition( EMT) induced by high glucose( HG),based on the regulative mechanisms of Nod-like receptor protein 3( NLRP 3) inflammasome in the kidney of diabetic kidney disease( DKD). The immortalized podocytes of mice in vitro were divided into the normal( N) group,the HG( HG) group,the low dose of TP( L-TP) group,the high dose of TP( HTP) group and the mannitol( MNT) group,and treated by the different measures,respectively. More specifically,the podocytes in each group were separately treated by D-glucose( DG,5 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) or HG( 30 mmol·L~(-1)) + TP( 5 μg·L~(-1))or HG( 30 mmol·L~(-1)) + TP( 10 μg·L~(-1)) or DG( 5 mmol·L~(-1)) + MNT( 24. 5 mmol·L~(-1)). After the treatment of HG or TP at 24,48 and 72 h,firstly,the activation of podocyte proliferation was investigated. Secondly,the protein expression levels of the epithelial markers in podocytes such as nephrin and ZO-1,the mesenchymal markers such as collagen Ⅰ and fibronectin( FN) were detected,respectively. Finally,the protein expression levels of NLRP3 and apoptosis-associated speck-like protein( ASC) as the key signaling molecules of NLRP3 inflammasome activation,as well as the downstream effector proteins including caspase-1,interleutin( IL)-1β and IL-18 were examined,severally. The results indicated that,for the cultured podocytes in vitro,HG could cause the low protein expression levels of nephrin and ZO-1,induce the high protein expression levels of collagen Ⅰ and FN and trigger podocyte EMT. Also HG could cause the high protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 and induce NLRP3 inflammasome activation. On the other hand,the co-treatment of TP( L-TP or H-TP) and HG for podocytes could recover the protein expression levels of nephrin and ZO-1,inhibit the protein expression levels of collagen Ⅰ and FN and ameliorate podocyte EMT. Also the co-treatment of TP( L-TP or H-TP) and HG could down-regulate the protein expression levels of NLRP3 and ASC,inhibit NLRP3 inflammasome activation and reduce the protein expression levels of the downstream effector molecules including caspase-1,IL-1β and IL-18. On the whole,HG could activate NLRP3 inflammasome and induce podocyte EMT in vitro. TP at the appropriate dose range could inhibit NLRP3 inflammasome activation and ameliorate podocyte EMT,which may be one of the critical molecular mechanisms of TP protecting againstpodocyte inflammatory injury in DKD.

Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine / 中国中药杂志

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

Pirfenidone inhibits TGF-β/Smad signaling pathway to alleviate hepatic cirrhosis induced by carbon tetrachloride / 中国免疫学杂志

Objective: This research aimed to explore the therapeutic effect and its mechanism of pirfenidone in liver cirrhosis induced by carbon tetrachloride in mice. Methods: Sixty male C57 BL/6 mice were randomly divided into the control group, model group and different doses of pirfenidone group, twelve rats in each group. Mice were intraperitoneally injected with 20％ CCl4 soybean oil solution ( 5 ml/kg), twice a week for 7 weeks. And these mice were free to drink 20％ ethanol solution in the third week after building the model. The low, medium and high dose groups were respectively given 50, 100 and 200 mg/kg of pirfenidone solution according to the body weights, while the model group and control group were given equal volume of blank solvent after building the model, once a day for 2 weeks. The serum level of ALT and AST, liver index, spleen index, the gene or protein expression level of TGF-β1 and Smad3 were analyzed before and after the treatment of pirfenidone. Results: The serum level of ALT, AST increased significantly in the model group ( P＜0. 05), while decreased significantly in different doses of pirfenidone group ( P＜0. 05). The liver and spleen index in the model group was significantly higher than that in the control group ( P＜0. 05). However, after treating with pirfenidone, the liver and spleen index were significantly lower than that in the model group ( P＜0. 05). The number of TGF-β1 positive cells in the model group was significantly more than that in the control group, but it was significantly decreased in the pirfenidone group. The gene expression level of Smad3 in the model group was significantly higher than that in the control group ( P＜0. 05). The gene expression level of TGF-β1 and Smad3 in different doses of pirfenidone group were significantly lower than that in the model group ( P＜ 0. 05). Meanwhile, the protein level of TGF-β1 and Smad3 were significantly increased in the model group, while decreased in the pirfenidone group. Conclusion: Pirfenidone relieves liver cirrhosis caused by carbon tetrachloride in mice by inhibiting the TGF-β1/Smad3 signaling pathway.

Effect of TLR gene polymorphisms on primary immune response to hepatitis B vaccine in Han children of Guangxi / 中华疾病控制杂志

Objective To explore the association between Toll-like receptors(TLR) gene polymorphisms and the primary immune response level to Hepatitis B Vaccine in Han children in Guangxi. Methods A total of 513 Han children aged 8-9 months were collected from the department of pediatrics in the Maternal and Child Hospital of Guangxi Zhuang Autonomous Region and Nanning Maternal and Child Health Hospital from 2014 to 2016. Peripheral venous blood of each study object was collected to detect HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc and HBV DNA. The polymorphisms of 10 sites of TLR gene were detected by SNPscanTM multiple SNP typing techniques. The association between allele, genotype of TLR gene and anti-HBs levels were analyzed by non-conditional logistic regression. Results The genetic polymorphism of TLR3 gene rs13126816 was related to immune response after primary Hepatitis B immunization in Han children in Guangxi (OR=1.79，95% CI: 1.11-2.89, P=0.018). The anti-HBs level of children with A/A genotype［238.04(519.75) mIU/L］and G/A genotype［347.96(619.68) mIU/L］were significantly lower than those with G/G genotype［489.08(854.76) mIU/L］, and the differences were statistically significant (all P0.05). Conclusions The allele A of TLR3 gene rs13126816 may be the influencing factor for the low response of primary immune response to Hepatitis B Vaccine in Han children.

Association of platelet count, fibrosis-4, and aspartate aminotransferase-to-platelet ratio index with the development and severity of esophageal varices in patients with liver cirrhosis / 临床肝胆病杂志

Objective To investigate the clinical value of platelet count (PLT), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) in predicting the development and classification of esophageal varices (EVs) . Methods A retrospective analysis was performed for the clinical data of 163 patients with liver cirrhosis who visited Department of Hepatology in The First Hospital of Jilin University from January 2012 to December 2015. All patients underwent upper gastrointestinal endoscopy within one week after admission. According to PLT, the patients were divided into PLT ≤50 × 109/L group with 27 patients, PLT 50 × 109/L-≤100 × 109/L group with 84 patients, PLT 100 × 109/L-≤150 × 109/L group with 26 patients, and PLT＞ 150 × 109/L group with 26 patients. The Child-Pugh score, FIB-4, and APRI were recorded, and the association of PLT, FIB-4, and APRI with EVs was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the LSD-t test was used for further comparison between any two groups; the Kruskall-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn-Bonferroni test was used for further comparison between any two groups. The chi-square test was used for comparison of categorical data between groups, and the Fisher's test was used for the data which did not meet the conditions of the chi-square test. Spearman rank correlation was used to investigate the correlation of PLT, FIB-4, and APRI with EVs. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the values of PLT, FIB-4, and APRI in the diagnosis of EVs. Results Of all 163 patients with liver cirrhosis, 114 developed EVs and 49 did not experience EVs. There was a significant difference in the incidence rate of EVs between the cirrhotic patients with different PLTs (χ2= 27. 36, P ＜ 0. 001) . Compared with those with PLT≤150 × 109/L, the cirrhotic patients with PLT＞ 150 × 109/L had a significantly lower proportion of patients with EVs (34. 6％ vs 76. 6％, P ＜ 0. 001) or severe EVs (3. 8％ vs 46. 7％, P ＜ 0. 001) . There were significant differences in FIB-4 and APRI between the patients with different PLTs (χ2= 102. 58 and 57. 02, both P ＜ 0. 001) . PLT was negatively correlated with the degree of EVs (r =-0. 491, P ＜ 0. 001), and FIB-4 and APRI were positively correlated with the degree of EVs (r = 0. 460 and 0. 325, both P ＜0. 001) . PLT had an AUC of 0. 739 and an accuracy of 75. 4％ in predicting the presence or absence of EVs, while FIB-4 had an AUC of 0. 732 and an accuracy of 71. 2％ and APRI had an AUC of 0. 651 and an accuracy of 72. 4％ . PLT had an AUC of 0. 763 and an accuracy of 69. 3％ in predicting the presence or absence of severe EVs, while FIB-4 had an AUC of 0. 742 and an accuracy of 67. 5％ and APRI had an AUC of 0. 676 and an accuracy of 66. 3％ . Conclusion Cirrhotic patients with PLT＞ 150 × 109/L have a significant reduction in the risk of EVs or severe EVs. PLT, FIB-4, and APRI are correlated with the degree of EVs in cirrhotic patients, but they cannot fully replace gastroscopy.

Effects of alcohol on benign prostate hyperplasia induced by testosterone propionate in mice / 中国应用生理学杂志

OBJECTIVE@#To study the effects of alcohol administration on benign prostate hyperplasia(BPH) and the reproductive toxicity during development of benign prostate hyperplasia.@*METHODS@#Seventy adult male Kunming mice were randomly divided into seven groups:control (group CON), negative control (group NC, injected subcutaneously with soybean oil, 25 mg/(kg·d), intragastric administration of distilled water, 7.5 ml/(kg·d)), alcohol for 7 and 21 days (group AL7 and AL21, intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)), testosterone propionate for 7 and 21 days (group TP7 and TP21, injected subcutaneously with testosterone propionate, 25 mg/(kg·d)), testosterone propionate+alcohol for 7 days (group TP+AL7, injected subcutaneously with testosterone propionate, 25 mg/(kg·d), and intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)),10 mice in each groups. Twenty-four hours after the last administration, mice were sacrificed. The indexes of prostate and testis and the parameters of sperm were determined in mice. The levels of free radicals, antioxidation and histopathological changes in testis and prostate were determined.@*RESULTS@#Compared with the control, TP7d group, AL7 and AL21d groups, the prostate coefficient of TP + AL7d group was increased significantly and the quantity and quality of sperm were decreased significantly (0.05).@*CONCLUSIONS@#The typical BPH state could be induced after 7-day treatment of testosterone propionate and alcohol. The testicular and sperm were damaged which enhanced the oxidative stress in reproductive system. The results indicated that alcohol could significantly promote the prostate hyperplasia induced by testosterone propionate in mice.

Effect of major chronic diseases on probability of premature death rate and life expectancy in Tongxiang / 预防医学

Objective To analyze the premature death rate and life expectancy caused by cancer, cardiovascular disease, chronic respiratory disease and diabetes and to provide the basis for the government to formulate residents' health promotion measures. Methods The data of deaths of permanent residents in Tongxiang in 2016 were derived from"Zhejiang Chronic Disease Surveillance Information System" . The mortality, premature death rate, years of potential life loss and life expectancy of four chronic diseases were descriptively analyzed. Results In 2016, a total of 5104 deaths were reported in Tongxiang, with a crude death rate of 738.77 / 100, 000 and a standardized mortality rate of 480.40 / 100, 000, 23.59％ were premature deaths. The mortality rate of the four types of chronic diseases was 8.44％ , malignant tumors, cardiovascular and cerebrovascular diseases, chronic respiratory diseases, diabetes were 5.68％, 2.06％, 0.65％ and 0.24％. Residents' life expectancy was 81.40 years, removal of cardiovascular and cerebrovascular diseases, cancer, chronic respiratory diseases, diabetes, the life expectancy increased 3.69, 2.78, 1.43 and 0.16 years, respectively. The four types of chronic diseases had a potential life-loss loss of 15, 239 person-years, with an average life-saving year of 4.25 years and a life-saving rate of 22.06 ‰. Mortality rate, premature death rate, years of potential loss of life, average life expectancy and longevity rate were higher in males than in females. Conclusion The probability of premature death of four types of chronic diseases in Tongxiang was 8.44％, and male residents were more likely to be affected.