Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q₁, Q₃) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.
Aged ; Humans ; Aged, 80 and over ; Frailty/epidemiology* ; Sleep Duration ; Prospective Studies ; Sleep/physiology* ; China/epidemiology*

Peptides have been extensively used in the fields of gene/drug delivery and disease targeting therapy. However, natural peptides are sensitive to protease digestion with short circulatory half-lives in vivo. Many studies on structural modifications of peptides have been reported to improve the delivery or therapeutic effect. In this review we focus on the recent literature on peptide stability in accordance with different structural modifications and summarize the methods and influential factors that are involved in the improvement of stability and half-life in vivo. This review will provide the scientific basis and theoretical references for further investigations and applications in vivo.

OBJECTIVE: From the perspective of clinical application to analyze the effectiveness and reliability of CPC/PMMA bone cement in percutaneous kyphoplasty (PKP) for the treatment of elderly patients with osteoporotic thoracolumbar fractures. METHODS: A retrospective analysis was performed on 62 patients with osteoporotic compression fracture of single-vertebral thoracic or lumbar segment who underwent PKP surgery and had a bone density less than or equal to -3.0 SD from February 2016 to December 2016. Among them, 23 patients were in CPC/PMMA group, with an average age of (77.6±2.2) years old, 39 patients in PMMA group, with an average age of (77.1±1.1) years old. The indexes between two groups were compared, including the visual analogue scale (VAS), height ratio of anterior vertebra (AVHR), local Cobb angle, cement leakage, new adjacent vertebral fracture(NAVF). RESULTS: There were no significant difference in gender, age, follow-up time and preoperative VAS, AVHR, local Cobb angle between two groups (>0.05), at the 1 day after operation, VAS, AVHR, local Cobb angle in all patients got obvious improvement (<0.05), which was no significant difference at 1 day after operation and final follow-up (>0.05). At the same time, there was no statistically significant difference in the incidence of new adjacent vertebral fracture and cement leakage (>0.05). The pain in both groups continued to improve at follow up after operation (<0.05), the local Cobb angle increased (<0.05) and AVHR decreased slightly (<0.05). However, the images of conventional methods (X-ray or CT) could not find signs about CPC degeneration and new bone ingrowth. CONCLUSION CPC/PMMA composite bone cement is safe and reliablein PKP for treatment of elderly patients with osteoporotic thoracolumbar fractures, which can effectively relieve pain and maintain vertebral body stability. It has the same curative effect as PMMA bone cement. It was worthy to research more in future, although no direct evidences support the CPC/PMMA composite bone cement can reduce the incidence of adjacent vertebral fracture, CPC degeneration or new bone ingrowth.
Aged ; Bone Cements ; Dinucleoside Phosphates ; Fractures, Compression ; Humans ; Kyphoplasty ; Osteoporotic Fractures ; Polymethyl Methacrylate ; Reproducibility of Results ; Retrospective Studies ; Spinal Fractures ; Treatment Outcome ; Vertebroplasty

Objective To investigate the spatio-temporal distribution characteristics of Oncomelania hupensis snail habitats in three cities of Suzhou, Wuxi and Changzhou along the Taihu Lake region, so as to provide technical supports for establishing a sensitive and highly effective surveillance and forecast system for schistosomiasis. Methods Snail distribution data were collected from Suzhou, Wuxi and Changzhou cities from 1950 to 2018, and the changing trend for snail habitats were described over years. In addition, the clusters of snail habitats were detected using Kernel density analysis and SaTScan space-time scan analysis. Results The number of snail habitats appeared a single-peak distribution in Suzhou, Wuxi and Changzhou cities from 1950 to 2018, which peaked in 1970 and then declined rapidly. There were 62.68% of snail habitats eliminated within 10 years after identification, of which 38.24% were eliminated at the year of identification. Kernel density analysis and SaTScan space-time scan analysis revealed that high-density clusters of snail habitats were mainly distributed in Kunshan City, Wuzhong District and Xiangcheng District from 1970 to 1980, and in Yixing City in 1990; since then, the clusters gradually shrank, and overall appeared a move from northeast to west of Taihu Lake. A total of 4 new clusters were detected after 1970, as revealed by space-time scanning of snail habitats. In current snail habitats, emerging snail habitats are mainly identified in Huqiu District (Dongzhu Town), Wuzhong District (Guangfu Town), Taicang City (Shaxi Town) and Jintan District, and re-emerging snail habitats are scattered in 7 districts. Conclusions The distribution of snail habitats are spatio-temporal aggregation in Suzhou, Wuxi and Changzhou cities. The monitoring and prediction of emerging and re-emerging snail habitats are the key points in the future.

Objective To explore the sensitivity of Culex pipiens pallens to common chemical insecticides in the southwestern region of Shandong Province, so as to provide a theoretical basis for the development of reasonable and effective mosquito control measures. Methods The resistance of Cx. pipiens pallens larvae to 5 chemical insecticides, such as cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate were tested by using the WHO biological test method in 2018, and the co-toxicity coefficients after compounding the above-mentioned insecticides were tested by using a drug compounding method. Results The resistance indexes of Cx. pipiens pallens to cypermethrin, deltamethrin, DDVP, propoxur, and acetofenate in 3 cities were 144.43–557.54, 118.17–445.33, 6.44–19.00, 2.37–8.10, and 0.88–2.98, respectively, and expect the difference between the DDVP resistances of Cx. pipiens pallens in Jining City and Heze City was not statistically significant (P > 0.05), all the other differences were statistically significant (all P < 0.05). The synergistic coefficients of cypermethrin + DDVP, cypermethrin + propoxur, DDVP + acetofenate, and propoxur + acetofenate were 199.58 – 456.95, 190.56 – 292.37, 123.32 – 319.24, and 192.31 – 367.32, respectively. The lower synergism was observed by using the mixture of DDVP + propoxur (synergistic coefficient: 99.87–108.36) . Conclusions After decades of chemical control, Cx. pipiens pallens in the southwestern region of Shandong Province has produced different degrees of resistance to common chemical insecticides. Therefore, comprehensive control measures should be taken to control mosquito breeding and prevent the development of insecticide resistance.

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.

OBJECTIVE: To study effects of postoperative regular training of core muscle strength guided by the concept of enhanced recovery after surgery (ERAS) on the rehabilitation of elderly patients with osteoporotic lumbar vertebral compression fracture after vertebroplasty (PVP) and kyphoplasty(PKP). METHODS: Ninety-four elderly patients with osteoporotic lumbar compression fractures who underwent PKP or PVP from January 2016 to January 2018 and met inclusion criteria were divided into observation group and control group. All the patients were treated with routine anti osteoporosis therapy after operation. There were 47 patients in the observationgroup, including 18 males and 29 females, with an average age of (62.62±3.21) years old;in the control group, there were 47 cases, including 17 males and 30 females, with an average age of (62.38±2.84) years old. The patients in the control group were trained by traditional way, and the patients in observation group were instructed to conduct regular training of core muscle strength according to ERAS concept. The patients were followed up for 1, 3 and 6 months after operation. Patients' conditions were quantitatively evaluated according to Barthel scale, JOA low back pain score and Oswestry Disability Index, and the differences in treatment effects between two groups were statistically analyzed and compared. RESULTS: All the patients were followed up, and the Barthel scale, JOA low back pain score and Oswestry Disability Index score of the observation group were all better than those of the control group on the 1st and the 3rd months after surgery( CONCLUSION Early regular core strength training has a positive effect on early functional recovery and improvement of life ability after PKP or PVP for elderly patients with osteoporotic lumbar compression fractures, which is in line with the concept of accelerated rehabilitation surgery.
Aged ; Enhanced Recovery After Surgery ; Female ; Fractures, Compression/surgery* ; Humans ; Kyphoplasty ; Male ; Middle Aged ; Osteoporotic Fractures/surgery* ; Spinal Fractures/surgery* ; Treatment Outcome ; Vertebroplasty