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Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target.
Li, HY, Huang, LF, Huang, XR, Wu, D, Chen, XC, Tang, JX, An, N, Liu, HF, Yang, C
Journal of immunology research. 2023;:7625817
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress to lupus nephritis (LN). The pathogenesis of SLE and LN has not yet been fully elucidated, and effective treatment for both conditions is lacking. The endoplasmic reticulum (ER) is the largest intracellular organelle and is a site of protein synthesis, lipid metabolism, and calcium storage. Under stress, the function of ER is disrupted, and the accumulation of unfolded or misfolded proteins occurs in ER, resulting in an ER stress (ERS) response. ERS is involved in the dysfunction of B cells, macrophages, T cells, dendritic cells, neutrophils, and other immune cells, causing immune system disorders, such as SLE. In addition, ERS is also involved in renal resident cell injury and contributes to the progression of LN. The molecular chaperones, autophagy, and proteasome degradation pathways inhibit ERS and restore ER homeostasis to improve the dysfunction of immune cells and renal resident cell injury. This may be a therapeutic strategy for SLE and LN. In this review, we summarize advances in this field.
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Berberine reduces circulating inflammatory mediators in patients with severe COVID-19.
Zhang, BY, Chen, M, Chen, XC, Cao, K, You, Y, Qian, YJ, Yu, WK
The British journal of surgery. 2021;108(1):e9-e11
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Berberine has a long history in traditional Chinese medicine for the treatment of diarrhoea and gastroenteritis owing to its antimicrobial, antimotility and antisecretory properties. The aim of this study was to examine the effect of berberine on laboratory parameters in patients who have been hospitalised due to COVID-19. This study enrolled prospectively 39 patients with severe COVID-19 who were hospitalized, of which 18 patients were allocated to the berberine group and 17 to the control group. Patients in the berberine group were given berberine plus routine therapy within 14 days of admission, and those in the control group received only routine therapy. Results indicate that there wasn’t any significant difference between the two groups in relation to the laboratory parameters namely interleukin-6, tumour necrosis factor-alpha, C-reactive protein, procalcitonin and white blood cells levels within 14 days. In subgroup analyses of patients with diarrhoea, berberine significantly improved the changes in interleukin-6, tumour necrosis factor-alpha and C-reactive protein. Authors conclude that it is unclear whether berberine has any antiviral effect on SARS-CoV-2, and further experiments are needed to clarify this.
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Polymorphisms of rs2483205 and rs562556 in the PCSK9 gene are associated with coronary artery disease and cardiovascular risk factors.
Gai, MT, Adi, D, Chen, XC, Liu, F, Xie, X, Yang, YN, Gao, XM, Ma, X, Fu, ZY, Ma, YT, et al
Scientific reports. 2021;(1):11450
Abstract
PCSK9 plays a crucial role in lipid metabolism. This case-control study explored the associations of novel single nucleotide polymorphisms (SNPs) of the PCSK9 gene with coronary artery disease (CAD) (≥ 1 coronary artery stenosis ≥ 50%) and its risk factors in the Han population in Xinjiang, China. Four tag SNPs (rs11583680, rs2483205, rs2495477 and rs562556) of the PCSK9 gene were genotyped in 950 CAD patients and 1082 healthy controls. The distributions of genotypes in rs2483205 and rs562556 were significantly different between the groups (all p < 0.05). The TT genotype of rs2483205, GG genotype of rs562556, and their H4 (T-G) haplotype were associated with CAD [odds ratio (OR) 0.65, confidence interval (CI) 0.45-0.95, p = 0.024; 0.63, 0.45-0.90, p = 0.011; 0.50, 0.35-0.70, p < 0.001, respectively]. Additionally, the model (TT + CT vs. CC) of rs2483205 was associated with increased risk of obesity, and the G allele of rs562556 was associated with lower low-density lipoprotein cholesterol (LDL-C), blood glucose, body mass index (BMI), and mean platelet volume (MPV) (all p < 0.05). rs2483205, rs562556, and their H4 haplotype of the PCSK9 gene were associated with CAD. Additionally, rs2483205 is associated with obesity, and rs562556 is associated with LDL-C, blood glucose, BMI, and MPV.
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Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury.
Chen, XC, Li, ZH, Yang, C, Tang, JX, Lan, HY, Liu, HF
Kidney diseases (Basel, Switzerland). 2021;(4):254-267
Abstract
BACKGROUND Macroautophagy (autophagy) is a cellular recycling process involving the destruction of damaged organelles and proteins in intracellular lysosomes for efficient nutrient reuse. SUMMARY Impairment of the autophagy-lysosome pathway is tightly associated with multiple kidney diseases, such as diabetic nephropathy, proteinuric kidney disease, acute kidney injury, crystalline nephropathy, and drug- and heavy metal-induced renal injury. The impairment in the process of autophagic clearance may induce injury in renal intrinsic cells by activating the inflammasome, inducing cell cycle arrest, and cell death. The lysosome depletion may be a key mechanism triggering this process. In this review, we discuss this pathway and summarize the protective mechanisms for restoration of lysosome function and autophagic flux via the endosomal sorting complex required for transport (ESCRT) machinery, lysophagy, and transcription factor EB-mediated lysosome biogenesis. KEY MESSAGE Further exploring mechanisms of ESCRT, lysophagy, and lysosome biogenesis may provide novel therapy strategies for the management of kidney diseases.
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The Effects of Early Oropharyngeal Administration of Microdosed Colostrum on Feeding Status in Ventilated Extremely Low-Birth-Weight Infants.
Chen, XC, Tong, YF, Han, ZM, Lin, ZL
Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine. 2021;(8):648-653
Abstract
Background: For extremely low-birth-weight infants (ELBWIs), mechanical ventilation and total parenteral nutrition are generally required in the early stages and lose the protective effect of early gastrointestinal nutrition of colostrum. We conducted a prospective randomized controlled trial to explore the effectiveness of early colostrum oropharyngeal administration on the feeding status of ELBWIs on mechanical ventilation. Materials and Methods: We randomly divided mechanically ventilated ELBWIs into an intervention group and a control group. In the intervention group, we provided oropharyngeal administration of colostrum during mechanical ventilation. The first colostrum oropharyngeal administration ended within 24 hours of birth. In the control group, we gave colostrum only for gastrointestinal nutrition, and other interventions were the same as for the intervention group. We collected the 1st and 6th day of life airway secretions and urine specimens from both groups. We recorded feeding status, including corrected gestational age at onset of enteral nutrition, corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, corrected gestational age of sucking began, and corrected gestational age of per oral feeding. We also recorded growth of body mass, the incidence of feeding intolerance, and necrotizing enterocolitis (NEC). Results: On the 6th day of life, concentrations of secretory immunoglobulin A, and lactoferrin in airway secretions and urine of the intervention group were significantly higher than those of the control group (p < 0.05). The intervention group showed younger corrected gestational age of no gastric retention during feeding, corrected gestational age of full enteral nutrition, the corrected gestational age of sucking began and per oral feeding than those in the control group (p < 0.05). The day of recovery to birth weight was earlier than those in the control group (p < 0.05). The rate of feeding intolerance and NEC incidence in the intervention group was significantly lower than in the control group (p < 0.05). Conclusions: Early oropharyngeal administration of colostrum improves immune function of the gastrointestinal tract and the systemic anti-infective capability in ELBWI on mechanical ventilation, promoting the maturity of gastrointestinal function, improving feeding condition, and reducing the risk of feeding intolerance and NEC.
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Apolipoprotein A1 is associated with SYNTAX score in patients with a non-ST segment elevation myocardial infarction.
Chen, BD, Chen, XC, Yang, YN, Gao, XM, Ma, X, Huang, Y, Li, XM, Gai, MT, Liu, F, Pan, S, et al
Lipids in health and disease. 2019;(1):159
Abstract
BACKGROUND The study was designed to investigate lipid profile and SYNTAX score in patients with non-ST segment elevation myocardial infarction (NSTEMI). METHODS 311 patients with NSTEMI were enrolled. The demographic, clinical data, blood samples and SYNTAX score were documented. The Pearson linear correlation was used to detect confounding factors linearly correlated with SYNTAX score. The significantly correlated confounding factors were put into the multiple linear regressions. RESULTS The Pearson linear correlation showed that high-density lipoprotein- cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) were significantly correlated with Syntax Score (r = - 0.119, P = 0.044 and r = - 0.182, P = 0.002, respectively). The multiple linear regressions for Syntax Score were built using HDL-C and ApoA1, respectively. After the adjustment of other significantly correlated confounding factors such as white blood cell count (WBC), myohemoglobin (MB), glutamic-oxalacetic transaminase (AST) and creatinine, the ApoA1 still showed significant association with Syntax Score (β = - 0.151, P = 0.028). The area under curve was (AUC) 0.624 and the optimal cutoff value is 1.07 g/L when using ApoA1 to predict moderate and severe coronary artery lesions. The patients with ApoA1 ≥ 1.07 g/L and < 1.07 g/L have the Syntax Scores of 12.21 ± 11.58 and 16.33 ± 11.53, respectively (P = 0.001). CONCLUSIONS The ApoA1 is the only lipid factor significantly associated with complexity of coronary artery lesion in patients with NSTEMI, the patients with ApoA1 < 1.07 g/L may have more complex coronary artery lesions.
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Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.
Jiang, Q, Tang, XP, Chen, XC, Xiao, H, Liu, P, Jiao, J
BMC complementary and alternative medicine. 2017;(1):444
Abstract
BACKGROUND Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF). METHODS This study will be an 8-week double-blinded, randomized, placebo-controlled clinical trial conducted at Guang'anmen Hospital in Beijing, China, and 168 patients with moderately active RA will be randomly assigned with a 1:1 ratio to apply a topical gel preparation containing TwHF or placebo. The primary outcome variable will be the proportion of subjects, by study group, to achieve a 20% improvement in the American College of Rheumatology criteria (ACR20) by week 8. Secondary outcome measures to be assessed at weeks 4 or 8 will include: measurement of ACR20 response rate at week 4, ACR50 response rate, the changes in DAS28 score, and joint synovitis classification assessment monitored by musculoskeletal ultrasound. Safety evaluations conducted at weeks 4, 8 and 12 will be based on spontaneous complaints by the study subjects, but special emphasis will be focused on cutaneous allergy and alterations of menstruation in premenopausal female participants. Statistical analyses will be performed using the intention to treat analysis data set. DISCUSSION This proposed clinical trail is designed to evaluate the efficacy and safety of CET based on a single topically-applied agent in a relatively large patient population with RA. This study protocol gives a detailed description of the usage and dosage of the topical compound TwHF gel and the methodology of this study. In addition, it is hoped that the outcomes of this study will be viewed as supporting the generalizability of CET in the setting of inflammatory rheumatic diseases. The results of this study are expected to have important public health implications for Asian RA patients that currently utilize CET as a complimentary treatment. TRIAL REGISTRATION Clinical trial gov Identifier: NCT02818361 . Registrated on Jun. 15, 2016.
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[Treatment of cerebral palsy children by integrative medical sequential method: a clinical efficacy observation].
Wang, LF, Zhang, J, Chen, XC, He, L, Zhao, XY
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2014;(4):431-4
Abstract
OBJECTIVE To observe the efficacy of integrative medical sequential method in treating cerebral palsy (CP) children's intelligence development, muscular tension, serum interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). METHODS Totally 111 CP children were randomly assigned to the control group (50 cases) and the treatment group (61 cases). All patients received comprehensive rehabilitation training and intravenous dripping of Monosialotetrahexosylganglioside Sodium Injection for 10 days. But those in the treatment group additionally received Chinese medical enema for brain resuscitation, relieving rigidity of muscles and activating collaterals for 14 days. Then they started another medication cycle and lasted for a total of 6 cycles. Serum IL-6 levels and TNF-alpha contents were determined before treatment. Scoring for muscular tension, Gesell score for intelligence development, contents of serum IL-6 and TNF-alpha were assessed before and after treatment in the two groups. RESULTS Compared with before treatment in this group, muscular tension, Gesell scores for intelligence development all decreased in the two groups (P < 0.05). As for inter-group comparison, the decrement was more obvious in the treatment group than in the control group (P < 0.05). The total effective rate was 86.9% in the treatment group and 76.0% in the control group (P < 0.05). The contents of IL-6 and TNF-alpha were obviously reduced in the treatment group and the control group after treatment (P < 0.01). The decrement was more obvious in the treatment group (P < 0.05). CONCLUSION The two treatment methods were effective for CP children, but the efficacy was superior in the treatment group than in the control group, indicating integrative medical methods could play a synergistic effect and optimize the treatment program for CP.
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[Prevention of hospital-acquired pneumonia with Yupingfeng Powder in patients with acute cerebral vascular diseases: a randomized controlled trial].
Yan, L, Chen, XC, Guo, J, Qi, LL, Qian, YM, Zhou, XG
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine. 2010;(1):25-9
Abstract
BACKGROUND An increase in the incidence rate of hospital-acquired pneumonia (HAP) has a direct influence on prognosis and survival of patients with acute cerebral vascular diseases (ACVD), and how to prevent HAP is a growing concern to clinicians. OBJECTIVE To study the efficacy of Yupingfeng Powder, a compound traditional Chinese herbal medicine, in preventing HAP in patients with ACVD. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS Sixty ACVD patients with lung qi deficiency syndrome without concurrent infections were randomly divided into prevention group (28 cases) and control group (32 cases). The 60 cases were all from Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Tough measures were taken to prevent cross-infection based on treatment of the primary diseases, well nutrition and support therapy. Yupingfeng Powder was used in the prevention group to prevent HAP. The patients were treated for 10 days. MAIN OUTCOME MEASURES The clinical symptoms, physical signs, body temperature, and chest X-ray were observed. The changes of blood immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and interleukin-6 (IL-6) were detected before and after treatment. RESULTS The total response rate in the prevention group was higher than that in the control group (P<0.05), and the total response rates were 78.57% (22/28) and 31.25% (10/32) respectively. The incidence rate of HAP in the prevention group was lower than that in the control group. There were no significant differences in white blood cell count, neutrophilic granulocyte count, and the levels of IgA, IgG, IgM and IL-6 between the two groups before treatment. The white blood cell count and neutrophilic granulocyte count in the control group increased after treatment, and there was a significant difference between the two groups (P<0.05). There was no significant difference in IgA level in the two groups after treatment, and the IgM levels in the two groups were higher than those before treatment (P<0.05), however there was no significant difference in IgM level between the two groups. In the prevention group, there were significant differences in values of IgG and IL-6 between before and after treatment (P<0.01), and after treatment there were differences in values of IgG and IL-6 between the two groups (P<0.05). CONCLUSION Yupingfeng Powder has a good clinical effect in prevention of HAP in patients with ACVD, and it can improve the immunological function and relieve the lung qi deficiency symptoms. So the prevention effect of Yupingfeng Powder on HAP is worth being further investigated.
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[Color Doppler ultrasound evaluation of a Chinese herbal formula in treating lower limb arteriosclerosis: a randomized controlled trial].
Tong, XJ, Xiang, XY, Cheng, ZH, Chen, L, Chen, XC, Chen, JX
Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine. 2009;(6):518-21
Abstract
OBJECTIVE To observe the effects of a Chinese compound herbal medicine for reinforcing qi, activating blood circulation, expelling phlegm and dredging collaterals in treatment of lower limb arteriosclerosis. METHODS The outpatients and inpatients with lower limb arteriosclerosis from Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine were randomly divided into control group and treatment group after color Doppler ultrasound inspection, and there were 30 cases in each group. The patients in the treatment group were treated with simvastatin and a Chinese compound herbal medicine for reinforcing qi, activating blood circulation, expelling phlegm and dredging collaterals, and the patients in the control group were treated only with simvastatin. The color Doppler ultrasound imaging of lower limb arteries including inside diameter, intima-media thickness, and plaque area in all the patients were examined after 6-month treatment. The levels of serum total cholesterol (TC) and low-density lipoprotein (LDL) were detected too. RESULTS After the treatment, the lower limb artery intima-media thickness and artery plaque area in the treatment group decreased obviously as compared with those in the control group (P < 0.05). Color Doppler flow imaging showed that the percentage of patients with uniphase wave decreased from 26.67% (8/30) to 6.67% (2/30) in the treatment group (P < 0.05), and from 26.67% (8/30) to 16.67% (5/30) in the control group (P < 0.05) as compared with those before the treatment, and there was also a significant difference between the two groups (P < 0.05). The concentrations of serum TC and LDL in the treatment group were lower than those in the control group (P < 0.05). CONCLUSION Color Doppler ultrasound showed that the Chinese compound medicine for reinforcing qi, activating blood circulation, expelling phlegm and dredging collaterals has positive effects on lower limb arteriosclerosis.