Changes of plasma METTL3, WTAP and FTO levels in patients with systemic lupus erythematosus and their correlation with clinical indicators / 中国医师杂志

Objective:To explore the clinical significance of N6-methyladenine (m6A) in systemic lupus erythematosus (SLE) by comparing the changes in plasma levels of m6A modification related proteins [methyltransferase 3 (METTL3), methyltransferase 14 (METTL14), Wilms tumor 1 associated protein (WTAP), AlkB homologous protein 5 (ALKBH5), and fat mass and obesity-associated protein (FTO)] and m6A between patients with systemic lupus erythematosus (SLE) and healthy controls.Methods:A total of 64 SLE patients admitted to the Seventh Affiliated Hospital of Sun Yat-Sen University from May 2020 to June 2022 and 24 healthy volunteers during the same period were selected to compare and analyze the plasma levels of METTL3, METTL14, WTAP, ALKBH5, FTO and m6A between the two groups. The correlation between METTL3, WTAP, FTO levels and clinical indicators was analyzed.Results:The plasma METTL3 level of SLE patients was significantly higher than that of control group ( P<0.05), and the plasma WTAP and FTO levels were significantly lower than those of control group (all P<0.05). In SLE patients, plasma METTL3 level was negatively correlated with hemoglobin level ( r=-0.344, P<0.05), plasma FTO level was positively correlated with plasma IgM level ( r=0.337, P<0.05), and plasma IgA level was negatively correlated with SLE patients ( r=-0.286, P<0.05). The incidence of renal involvement and positive rate of plasma anti-histone antibody were higher in SLE patients with high METTL3 level (all P<0.05). The positive rates of plasma anti-dsDNA antibody, anti-SM antibody and AuaA antibody were higher in SLE patients with low FTO level (all P<0.05). Conclusions:The plasma METTL3 level in SLE patients are significantly increased, while the plasma WTAP and FTO levels are significantly reduced, which are related to various clinical indicators and may be related to the onset of SLE.

Inhibition of Fatty Acid β-Oxidation by Fatty Acid Binding Protein 4 Induces Ferroptosis in HK2 Cells Under High Glucose Conditions

Background@#Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD. @*Methods@#We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells. @*Results@#In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells. @*Conclusion@#Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.

Analysis of drug use in medical institutions of Guangdong area during 2017-2022 / 中国药房

OBJECTIVE To analyze the situation of drug use in medical institutions of Guangdong area from 2017 to 2022， and to provide reference for the production， sale and procurement of drugs by government departments， medical insurance departments， pharmaceutical enterprises， drug sales enterprises and hospitals. METHODS Using the retrospective analysis method， based on original data from Guangdong hospital information network from 2017 to 2022， statistical analysis was conducted on the drug procurement amount of 118 medical institutions that had been online for the past 6 years， as well as the distribution of 14 major categories of drugs among all purchased drugs by online medical institutions， and sales amount of drug production enterprises. RESULTS The drug procurement amount of 118 medical institutions that had been online in Guangdong area from 2017 to 2022 showed a growth-negative growth-slow growth trend. Among the 14 major categories of drugs， the top 5 drugs in the list of consumption sum were anti-infective drugs， cardiovascular drugs， nervous system drugs， anti-tumor drugs， and digestive system drugs； among the top 200 drugs in terms of procurement amount， three major categories of drugs， namely the anti-infective drugs， anti-tumor drugs and cardiovascular system drugs， occupied the main position. The top 10 drugs in the list of procurement amounts were mainly anti-tumor drugs and cardiovascular system drugs； foreign manufacturers occupied the top 3 places in the list of sales amounts in medical institutions of Guangdong area. CONCLUSIONS In Guangdong area， the growth of drug procurement amount in medical institutions is gradually slowing down， the usage of anti-infective drugs is still abundant， the prevention and treatment of chronic diseases need great attention， and foreign pharmaceutical companies are in a leading position in the sales amount of medical institutions.

Clinical characteristics and risk factors of dialysis catheter-related infection in CRRT patients / 中华肾脏病杂志

Objective To explore the clinical characteristics and risk factors of catheterrelated infection in continuous renal replacement therapy (CRRT) patients.Methods The demographic and clinical data of CRRT patients who inserted with double-lumen non-cuffed dialysis catheter at the First Affiliated Hospital of Sun Yat-sen University from January 1,2016 to December 31,2016 were collected.According to the presence or absence of catheter-related infections,they were divided into infected group and uninfected group.Statistics and analysis of the incidence and pathogenic characteristics of catheter-related infections;Comparison of clinical features of infected and uninfected groups;A multivariate Cox proportional hazard model was used to analyze risk factors for catheter-related infections.Results A total of 364 patients with CRRT (437 cases of central venous catheterization) were enrolled in the study.Catheter-related bloodstream infection (CRBSI) and catheterrelated colonization (CRCOL) rates were 3.565 and 2.228 events per 1000 catheter-days.These catheters were associated with higher proportion of inserted in ICU (P=0.007),immunosuppression (P=0.002),receive catecholamine inotropes therapy (P=0.001) and shock (P=0.030).The infection catheters also had shorter indwelling time (P=0.032) and lower level of blood hemoglobin (P=0.017),serum creatinine (P=0.004),blood brain natriuretic peptide (P=0.005) pericatheter use.The most common pathogens were Gram-negative bacteria,especially Acinetobacter baumannii,which caused 37.5％ CRBSI and 20.0％ CRCOL.Multivariate Cox regression model showed female (P=0.029,HR=2.151),diabetes (P=0.016,HR=2.807),receive catecholamine inotropes therapy (P=0.012,HR=2.655),immunosuppression (P=0.037,HR=2.203) were independent risk factors associated with catheterrelated infection.Conclusions The incidence of CRBSI and CRCOL is 3.565 and 2.228 events per 1000 catheter-days CRRT patients in our hospital.The most common pathogen of catherter-related infection is Gram-negative bacteria.Female,diabetes,received catecholamine inotropic drugs,and immunosuppression were independent risk factors associated with catheter-related infection.

A one-step specific assay for continuous detection of sirtuin 2 activity

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with diverse physiological functions. A variety of small molecules have been developed to interrogate the physiological function of SIRTs. Therefore, it is desirable to establish efficient and convenient assays to screen SIRTs modulators. In this study, we designed a series of fluorescent nonapeptide probes derived from substrates of SIRT1-SIRT3. Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore, which makes this system free of lysine-recognizing protease. Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1-SIRT3 and SIRT6, it was confirmed that this assessment system was the most suitable for SIRT2 activity detection. Thus, SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide. Finally, two specific and efficient fluorescent probes for SIRT2, ne-D9 and ne-K4a, were developed. Evaluation of the results revealed that ne-K4a based assay was more suitable for modulators screening , while the other specific substrate ne-D9 was stable in cell lysate and could detect the activity of SIRT2 in the same. In summary, this study presents a novel strategy for detecting SIRT2 activity and in cell lysate.

Effects of individual health education combined with collective health education for maintenance hemodialysis patients with hyperkalemia / 现代临床护理

Objective To investigate the effects of individual and collective health education on hemodialysis patients with hyperkalemia. Methods Thirty hyperkalemia patients treated with maintenance hemodialysis from Mar. 2013 to Mar. 2014 were set as the control group, in which the patients were given pre-established individual health education by the hemodialysis nurse weekly. Another 30 patients of the same sort, as the experiment group, were treated with individual health education combined with collective health education weekly from Apr. 2014 to Apr. 2015. The two groups were compared in term of serum potassium before and after intervention. Result Serum potassium of the experiment group after the intervention were significantly lower than the control group and the experiment group after the intervention (P<0.001). Conclusion Individual health education combined with collective health education can change traditional indoctrination one-way communication to the two-way communication conversion , make the patients consciously change their incorrect dietary behaviors, and reduce the serum potassium levels in the hemodialysis patients with hyperkalemia.

Decreased Neuroplasticity May Play a Role in Irritable Bowel Syndrome: Implication From the Comorbidity of Depression and Irritable Bowel Syndrome

No abstract available.

Analysis of associated factors in secondary hyperparathyroidism of continuous ambulatory peritoneal dialysis patients / 中华肾脏病杂志

Objective To study the prevalence and associated factors of secondary hyperparathyroidism (SHPT) in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods A cross-section study was performed.A total of 639 eligible participants undergoing CAPD treatment more than three months in our peritoneal dialysis center from July 2011 to January 2012 were recruited in the study.All the patients were divided into SHPT group and non-SHPT group according to the intact parathyroid hormone (iPTH) level,and the associated factors of SHPT were investigated through Logistic regression analysis.Results The prevalence of SHPT was 46.95％ (300/639).Logistic regression analysis demonstrated that lower hemoglobin,hypocalcemia,hyperphosphatemia,higher alkaline phosphatase,higher Scr,higher nPCR and low calcium dialysate were independent influencing factors of SHPT.Conclusions The prevalence of SHPT is quite high in CAPD patients.Abnormal calcium-phosphorus metabolism,renal anemia,high protein diet and low calium dialysate may affect the SHPT.

Studies of mutations and polymorphism of PINK1 gene in patients with Parkinson' s disease in littoral of Zhejiang Province / 中华神经科杂志

Objective To study deletion mutations and polymorphism of PINK1 gene exons in patients with Parkinson' s disease (PD) in the littoral of Zhejiang Province,and analyze the association between these changes and the etiology of PD.MethodsAll exons of PINK1 gene in 200 PD patients( 112early-onset PD and 88 late-onset PD) and 220 controls (68 young controls and 152 old controls ) were amplified by polymerase chain reaction (PCR). All the positive PCR products were sequenced,and genotypes were detected by dot blot allele and genotype frequencies of PINK1 were compared by the Chisquare test.ResultsNo deletion mutations of the exons were found in all patients and controls.However,a known heterozygote point mutation G12169A in exon 5 was identified in 2 patients with early-onset PD.And G12164A polymorphism and G12101A polymorphism were located on PINK1 gene of exon 5. There were G/G and G/A genotypes in G12164A polymorphism,no A/A genotype.There were G/A and A/A genotypes in G12101A polymorphism,no G/G genotype. The chain relation polymorphism A/A genotype frequency was significantly higher in the PD group 84/200 (42.0％ ) than the control group (52/220,23.6％,x2 =4.034,P =0.045 ).The frequency was also significantly higher in the late-onset PD (40/88,45.5％ ) than the old control (32/152,21.1％,x2 =3.951,P =0.047 ).There were no significant differences in alleles frequencies of other groups.ConclusionThe deletion mutation and point mutation are rare in PD patients in littoral of Zhejiang Province.Chain relation polymorphism at G12164A and G12101A in PINK1 gene might be a susceptible factor for PD patients.

Investigation of sleep quality and its influencing factors in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the sleep quality of maintenance hemodialysis (MHD) patients and analyze its associated factors. Methods The convenience sample method was used to choose 424 MHD patients from 7 hospitals.A set of questionnaires were used in this investigation,including demographic data form,Pittsburgh sleep quality index (PSQI),restless legs syndrome (RLS),social support rate scale (SSRS),subjective global assessment (SGA),family APGAR index (APGAR) and family burden scale of disease (FBS). Results PSQI score of 395 MHD patients (93.2％) was ≥5.APGAR and social support total points were negatively correlated with sleep quality (r=-0.133,P=0.006; r=-0.105,P=0.031).Family burden total point was positively correlated with sleep quality (r=0.215,P=0.000).Nutrition (F=46.123,P=0.000),restless legs syndrome (F=9.392,P=0.000) and sleep apnea syndrome (F=5.645,P=0.001) were closely associated with sleep index scores. Conclusions Incidence of poor sleep quality in MHD patients of our study is quite high.Sleep quality of MHD patients is correlated with lots of factors,such as family concern,social support.

Short-term efficacy of sevelamer hydrochloride on hyperphosphatemia in patients undergoing maintenance hemodialysis / 中华肾脏病杂志

Objective To evaluate the short-term efficacy and safety of sevelamer hydrochloride in treating maintenance hemodialysis (MHD) patients with hyperphosphemia.Methods A multicenter,open-labeled,self-control study was performed.Phosphate binders were discontinued during a two-week washout period.Patients with more than 1.78 mmol/L serum phosphorus after two-week washout period were eligible for the trial.The dose was adjusted every two weeks as necessary to achieve serum phosphorus control. Sevelamer hydrochloride was administered to 138 MHD patients for 10 weeks and a second two-week washout period followed.Results A total of 111 from 138 patients fulfilled the whole 14-week study. Mean serum phosphorus and calcium-phosphate products starte to decline after two-week sevelamer hydrochloride treatment. By the end of 10-week sevelamer hydrochloride treatment, mean serum level of phosphorus [(1.85±0.50) vs (2.57±0.54) mmol/L,P＜0.01],calcium-phosphate product [(4.16± 1.72) vs (5.79 ± 1.50) mmol2/L2,P＜0.01 ] and low density lipoprotein [(1.64±0.76) vs (2.31 ±0.87) mmol/L,P＜0.01] were significantly decreased,while the adjusted serum level of calcium and serum intact parathyroid hormone kept steady.Both serum phosphorus and calcium-phosphrus product increased after the second washout period, but the levels were still lower as compared to pre-treatment [(2.26±0.71) vs (2.57±0.54) mmol/L; (5.12±1.63) vs (5.79±1.50) mmol2/L2,P＜0.01].Of the 138 patients involved,214 episodes in 106 patients and 121 episodes in 89 patients were reported as adverse events and adverse drug reaction respectively. Gastrointestinal symptoms,of which most were mild or moderate,happened to 68.1％ (94/138) patients. Conclusions Sevelamer hydrochloride can control serum phosphorus and reduce the levels of calcium-phosphorus product and cholesterol.Slight gastrointestinal symptoms like constipation are common during the treatment.

Influence of hemodialysis and peritoneal dialysis on complications and outcomes after renal transplantation / 中华肾脏病杂志

Objective To investigate the effects of hemodialysis (HD) and peritoneal dialysis (PD) on the complications and outcomes after renal transplantation. Methods Clinical data of 402 renal transplant recipients maintained on dialysis for more than 3 months were retrospectively studied and divided into 2 groups: HD group(n=303)and PD group(n=99). Among them, 345 recipients were followed up for an average of (30.2±15.2) months. The impact of HD and PD on the acute rejection, delayed graft function (DGF), infection, chronic rejection and the graft and patient survival rates were analyzed. Results The mean dialysis duration was significantly longer in PD group and the hepatitis B infection rate was significantly higher in HD group. There were no signiticant differences between the HD and PD groups in regarding to primary disease for end-stage renal disease, age, gender, blood pressure, hemoglobin, HLA match, hot and cold ischemia time, and hepatitis C vires infection. The incidence of DGF, acute and chronic rejection, and cytomegalovirus and other infections between HD and PD groups were not significantly different. However, the graft loss happened more frequently in hepatatis B patients than that in non hepatitis B patients (19.23% vs 8.86%, P=0.021), and the post-transplant infection ocurred less in non hepatits B patients with PD. The acute rejection episodes were higher in HD patients who received pretransplant dialysis for more than 12 months (P<0.05). The overall recipients survival rates of HD and PD groups were similar (1-year: HD 94.34%, PD 91.25%;5-year: HD 92.83%, PD 90%), and the same as the graft survival rates in HD and PD groups (1-year: HD 93.21%, PD 96.25%;5-year: HD 87.17%, PD 91.25%). Conclusions The influences of PD and HD on the complications after renal transplantaton, 1-year and S-year recipients and graft survival rates are similar, so both HD and PD can be chosen as the pretransplant dialysis modality. As the incidence of acute rejection increases with time in HD, it is better to shorten the time of pretransplant dialysis to decrease the complication.

Effects of antibiotic treatment on the inflammatory mediator expression in peritoneum and the peritoneal transport function in the rat with acute bacterial peritonitis / 中国病理生理杂志

AIM: To observe the effect of antibiotic treatment on the inflammatory mediator expression in peritoneum and the peritoneal transport function in rats with acute peritonitis, and explore its mechanisms. METHODS: Eighty-six SD rats were randomly divided into three groups. Control group (n=28) were treated with PBS (ip), peritonitis group (n=28) and treatment group (n=28) were challenged with the E.coli (ip), but at 3 h and 9 h gentamicin was given (ip) in treatment group. Seven rats of every group were randomly sacrificed at 24 h, 48 h, 72 h and 7 d. Peritoneal equilibration test (PET) was did before they were killed. Leukocyte count, pathological changes and the expression of CD45, NF-?B, IL-1?, TNF-? in peritoneum were examined. RESULTS: (1)The blood leukocytes in peritonitis group decreased strikingly, but did not change obviously in other two groups. The peritoneal fluid leukocytes in peritonitis group increased significantly from 24 h to 72 h, while in treatment group, it enhanced more strikingly than peritonitis group at 24 h, and recovered earlier. (2) Both in peritonitis group and treatment group, the expression of activated NF-?B, IL-1?, TNF-? and CD45 increased significantly, but the treatment group was lower than model group at 48 h and 72 h. The mRNA level of IL-1? and TNF-? had the same trend as their protein expression. (3) Compared with the control group, UF and D/D_0 Glu decreased significantly in model group and treatment group, and D/PTP increased dramatically. The D/P TP in treatment group lowered obviously compared with peritonitis group, while the net UF and D/D_0 Glu had not significant difference between treatment group and model group. CONCLUSION: Antibiotic treatment can partly decrease the expression of inflammatory mediators in peritoneum of rats with acute peritonitis and also can improve the protein transport ability to some extent, but can not improve the peritoneal ultrafiltration and the glucose transport function.

Orthogonal Test for Optimization of Rhubarbs Extraction Process and Pharmacodynamic Studies the Extracts / 中药新药与临床药理

Objective To optimize the solvent extraction of Rhubarbs. Methods With different concentrations of alcohol as the solvent, the amount of solvent, the extracting time and the extracting frequencies were assayed by orthogonal test to detect their influences on the extraction rate of rhubarb anthraquinone. And the extracts were analyzed and their pharmacodymamic effects were studied. Results Indicated by the content of total anthraquinones, the best conditions was: reflux extraction with 5- fold 50 % alcohol for 3 times, 0.5 h per time. The purgative activity of the extracts was stronger than that in the positive control group. Conclusion Optimization of the extracting conditions can promote the purgative activity of the extracts. 

Gene expression pattern of periphery blood mononuclear cells in patients with active lupus nephritis / 中国病理生理杂志

AIM: To find new gene function associate with active lupus nephritis (LN) through study on the difference in gene expression of peripheral blood mononuclear cells between LN patients and healthy controls by gene chip. METHODS: The CSC-GE-80 chip containing 8 000 spots of cDNAs were used to investigate the difference of the expression. Both the total RNA from peripheral blood mononuclear cells of active LN patients and healthy donors were reversely transcribed to cDNA with the incorporation of fluorescent( cy3 and cy5) labeled dCTP to prepare the hybridization probes. After hybridization, the gene chip was scanned for the fluorescent intensity. The differentially expressed genes were screened. We repeated that in three groups of LN patients and healthy controls, respectively, and only the genes that have differential expression in all three chips were considered associated with LN. RESULTS: 75 genes were identified to be differently expressed in all three groups of LN patients as compared with healthy controls, including 42 up-regulated genes and 33 down-regulated ones. CONCLUSION: The present study represents a global view of gene expression of LN and provides important clues for further study of LN related genes. And it also suggests defensin ? 1, S100A8, S100A9 may be involved in the pathogenesis of LN.