OBJECTIVES: To explore the value of serum cystatin C (CysC) levels in evaluating renal prognosis in IgA nephropathy (IgAN) patients. METHODS: We retrospectively collected the clinical data of IgAN patients diagnosed by renal biopsy at Guangdong Provincial People's Hospital from January, 2014 to December, 2018. Based on baseline serum CysC levels, the patients were divided into high serum CysC (>1.03 mg/L) group and normal serum CysC (≤1.03 mg/L) group. The composite endpoint for poor renal prognosis was defined as ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage renal disease (ESRD). Lasso regression, multivariate Cox regression and Kaplan-Meier survival analysis were used to identify the risk factors and compare renal survival rates between the two groups. Smooth curves fitting and threshold effect analysis were used to explore the relationship between serum CysC levels and the outcomes. A nomogram model was constructed and its predictive performance was evaluated using concordance index, calibration curve, receiver operating characteristic (ROC) curve and the area under curve (AUC). RESULTS: A total of 356 IgAN patients were enrolled, who were followed up for 4.65±0.93 years. The composite endpoint occurred in 74 patients. High serum CysC was identified as an independent risk factor for poor renal prognosis in IgAN (HR=2.142, 95% CI 1.222 to 3.755), and the patients with high serum CysC levels had a lower renal survival rate (Log-rank χ²=47.970, P<0.001). In patients with serum CysC below 2.12 mg/L, a higher CysC level was associated with an increased risk of poor renal prognosis (β=3.487, 95% CI: 2.561-4.413, P<0.001), while above this level, the increase of the risk was not significant (β=0.676, 95% CI: -0.642-1.995, P=0.315). The nomogram model based on serum CysC and 3 other independent risk factors demonstrated good internal validity with a concordance index of 0.873 (95% CI: 0.839-0.907) and an AUC of 0.909 (95% CI: 0.873-0.945). CONCLUSIONS Serum CysC levels are associated with renal prognosis in IgAN patients, and high serum CysC an independent risk factor for poor renal prognosis.
Humans ; Glomerulonephritis, IGA/diagnosis* ; Cystatin C/blood* ; Prognosis ; Risk Factors ; Retrospective Studies ; Glomerular Filtration Rate ; Kidney Failure, Chronic ; Male ; Female ; Adult ; Nomograms ; Middle Aged

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

β-hydroxy-β-methylbutyric acid (HMB) is widely applied in sports nutrition, disease prevention and other fields. However, chemical synthesis methods, limited by toxic reagents and violent reactions, can hardly meet the demands of green production. The biosynthesis method mainly utilizes enzymatic catalysis or metabolic engineering techniques for synthesis, and has the advantages of high efficiency, low cost, and sustainability. Therefore, the production of HMB by the biosynthesis method has a good application prospect. In this research, a biosynthesis-based production strategy for HMB was developed. By using L-leucine as the substrate and constructing a dual-enzyme co-expression system, we established an efficient catalytic process. At first, the enzymatic properties of L-amino acid deaminase (PvL-AAD) from Proteus vulgaris and 4-hydroxyphenylpyruvate dioxygenase (Rn4-HPPD) from Rattus norvegicus were characterized. Rn4-HPPD had low relative activity and required an acidic environment for catalysis. Based on the surface charge modification strategy of the enzyme protein, site-directed mutagenesis and combinatorial mutagenesis were conducted on 10 sites of Rn4-HPPD. A double mutant Rn4-HPPD^H18R/N302R was thus obtained, with the enzyme activities being 2.00 times and 2.39 times that of the wild type at pH 5.5 and pH 6.5, respectively. Subsequently, the expression of the two enzymes in Escherichia coli was optimized. After the optimal expression ratio of the two enzymes was determined as 1:3 and under the conditions of OD₆₀₀ of 70, pH 6.0, 35 ℃, Fe²⁺ concentration of 1.5 mmol/L, and feeding of the substrate in batches in a 5 L fermenter, the maximum yield of HMB reached 8.60 g/L. This study not only enhances the optimal pH and activity of Rn4-HPPD but also provides new approaches for the efficient microbial synthesis of HMB.
Escherichia coli/metabolism* ; Valerates/metabolism* ; Recombinant Proteins/biosynthesis* ; Animals ; Metabolic Engineering/methods* ; Rats ; Catalysis

Objective To observe the clinical effect of doing Huatuo five-animal play treating blood-stasis-type silent myocardial ischemia(SMI)and its influence on coronary hemodynamics.Methods Ninety patients diagnosed as silent myocardial ischemia were randomly divided into a five-animal play group(n=45,age:51.56±11.00 years,24 males and 21 females)and a regular exercise group(n=45,age:52.44±7.19 years old,24 males and 21 females)according to a random number table.The five-animal play group practised the traditional five-animal play,while the regular exercise group con-ducted daily 30-minute moderate-intensity treadmill aerobic exercise,five times a week,for 4 weeks.The changes in the number of abnormal ST-T segment occurrences,myocardial oxygen consumption(CMO),coronary ischemia threshold(CIT),and blood smoothness index(BSD)within 24-hour ambu-latory electrocardiogram before and after the intervention were observed in both groups,with the thera-peutic effect and hemodynamic characteristics of both groups evaluated.Results The average number of ST-T segment abnormalities decreased after intervention in both groups(P<0.001),with significantly greater improvement in the five-animal play group than the regular exercise group(P<0.001).More-over,the average CMO decreased significantly,while the average CMR and BSD increased significant-ly in both groups after intervention(P<0.05),with significantly greater improvement in the five-ani-mal play group than the other group.Meanwhile,the total effective rate in the five-animal play group was significantly higher than the regular exercise group(P<0.01).Conclusion Undergoing the five-ani-mal play and moderate intensity treadmill aerobic exercise both are effective in treating silent myocardi-al ischemia.However,the former therapy is superior to the latter in bettering CMO,CIT and BSD.

Objective To observe the clinical effect of doing Huatuo five-animal play treating blood-stasis-type silent myocardial ischemia(SMI)and its influence on coronary hemodynamics.Methods Ninety patients diagnosed as silent myocardial ischemia were randomly divided into a five-animal play group(n=45,age:51.56±11.00 years,24 males and 21 females)and a regular exercise group(n=45,age:52.44±7.19 years old,24 males and 21 females)according to a random number table.The five-animal play group practised the traditional five-animal play,while the regular exercise group con-ducted daily 30-minute moderate-intensity treadmill aerobic exercise,five times a week,for 4 weeks.The changes in the number of abnormal ST-T segment occurrences,myocardial oxygen consumption(CMO),coronary ischemia threshold(CIT),and blood smoothness index(BSD)within 24-hour ambu-latory electrocardiogram before and after the intervention were observed in both groups,with the thera-peutic effect and hemodynamic characteristics of both groups evaluated.Results The average number of ST-T segment abnormalities decreased after intervention in both groups(P<0.001),with significantly greater improvement in the five-animal play group than the regular exercise group(P<0.001).More-over,the average CMO decreased significantly,while the average CMR and BSD increased significant-ly in both groups after intervention(P<0.05),with significantly greater improvement in the five-ani-mal play group than the other group.Meanwhile,the total effective rate in the five-animal play group was significantly higher than the regular exercise group(P<0.01).Conclusion Undergoing the five-ani-mal play and moderate intensity treadmill aerobic exercise both are effective in treating silent myocardi-al ischemia.However,the former therapy is superior to the latter in bettering CMO,CIT and BSD.

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

IgA nephropathy (IgAN) is the most common primary glomerular disease and main reason of progression to end-stage renal disease in patients with kidney diseases. Various clinical, pathological, demographic and new factors discovered by researchers in recent years play important roles in the prognosis assessment of IgAN. Furthermore, developing prognostic evaluation models based on several different factors to identify patients at high risk of progression in the early disease stage is clinically significant. This article reviews the researches progress of influencing factors and relevant evaluation models for prognosis of IgAN.

Rheumatoid arthritis is a common clinical autoimmune disease characterized by persistent synovitis and pannus formation. In late stage， irreversible destruction and deformation of bone and joint may occur. In this paper， the authors believe that kidney deficiency and essence deficiency is the core mechanism of rheumatoid arthritis bone destruction， and its disease evolution law is summarized as "marrow reduction， flesh flaccid， collaterals blocked". On the basis of modern medical understanding of bone destruction in rheumatoid arthritis， it is considered that the mechanism in Chinese medicine of "marrow reduction， flesh flaccid， collaterals blocked" ultimately leads to bone destruction， is similar to that in the western medicine of abnormal differentiation of osteoclasts， high expression of nuclear factor-κB receptor activator of ligand， and abnormal expression of inflammatory factors. This point of view may provide a more comprehensive and scientific understanding of the key pathogenic mechanism of bone destruction in rheumatoid arthritis.

[Objective]To explore the occurrence of gasdermin D(GSDMD)-mediated pyroptosis and its effect on cell proliferation,migration and tubular formation abilities of synovial vascular endothelial cells(VEC)in rheumatoid arthritis(RA).[Methods]Synovium tissues from knee joints of 22 RA patients and 18 orthopaedic arthropathies(Orth.A)patients were collected.The level of activated GSDMD-NT segment in synovium was detected by Western blot.The clinical characteristics of RA patients were compared between high and low synovial GSDMD-NT groups.The cell localization of GSDMD in RA synovium was detected by immunofluorescence staining.RA synovial fluid was added to the culture of human umbilical vein endothelial cells(HUVEC)in vitro,and the level of apoptosis and expression of pyroptosis pathway proteins were detected.The effects of GSDMD on apoptosis,proliferation,migration and tubule formation of HUVEC cells were analyzed.[Results]GSDMD expression in RA synovium was significantly higher than that in Orth.A,and more severe joint destruction and higher microvascular count score were found in RA patients with high GSDMD-NT expression.Synovial VEC had positive expression of GSDMD.Stimulation with RA synovial fluid could induce GSDMD-mediated pyroptosis in HUVEC,increased the secretion of vascular endothelial growth factor(VEGF)and their abilities of proliferation,migration and tubule formation.Knockdown of GSDMD could reverse the above effects.[Conclusion]GSDMD-mediated pyroptosis of partial synovial VEC aggravates RA joint destruction through VEGF secretion that promotes proliferation,migration and angiogenesis of the remaining VEC,which may be a new target to block neovascularization and inhibit joint destruction in RA.

Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.