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

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 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.

Objective To sort out and summarize the research hotspots and trends of Chinese medicine nursing technolo-gy at the present stage.Methods We searched the research literature on TCM nursing technology included in China Knowledge,Wanfang,and Wipu build-up to November 30,2023,and used CiteSpace 6.1.R6 software to perform co-occurrence analysis of research institutions and keyword clustering,timeline,and emergence analysis.Results A total of 5 771 documents were in-cluded,with a general upward trend in the number of publications,peaking at 692 publications in 2021.5 206 documents from 673 journals were included in the research literature,of which 19 journals had ≥50 publications(35.47％).2 087 research or-ganizations were involved,of which 27 had ≥20 publications(13.24％).Involving 9 484 authors,there were a total of 8 au-thors ≥5 in the cluster,indicating the existence of stable teamwork in the cluster.The keyword co-occurrence analysis yielded the research hotspots of TCM nursing technology as TCM nursing,training,nursing management,clinical efficacy,complica-tions,and quality of life.Conclusion Based on the econometrics and visualization analysis of the literature on TCM nursing technology,we explored the research hotspots and trends in this field,and provided two theoretical paths for medical institution managers to construct and optimize the management system of TCM nursing technology:to standardize the TCM nursing technology in hospitals and establish a clinical access management system;and based on the multidimensional management method,to inno-vate the training system of TCM nursing technology.

[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.

Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

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.

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.

Objective:To explore the application effect of case-based learning (CBL), teaching mode combined with 3D printing in clinical teaching of sacral tumors.Methods:A total of 108 undergraduate interns and standardized residency training students who studied in our hospital from 2017 to 2018 were divided into the CBL teaching group ( n = 53) and the CBL combined with 3D printing teaching group ( n = 55) according to their study time. The combined teaching group used computer tomography (CT) data to reconstruct and print out a 3D model of sacral tumors based on CBL, and performed preoperative teaching on the invasion of the surrounding tissues of the tumor. The scores of the students in the two groups were evaluated respectively, and the students were surveyed by self-identification questionnaire (learning interest, self-learning ability, teamwork ability, comprehensive analysis ability and clinical thinking ability). The t-test (one-sided) was used for comparison between groups using stata 14.0. Results:The score of CBL teaching group (75.90±6.70) was lower than that of CBL combined with 3D printing teaching group (83.60±7.40). In terms of critical thinking ability evaluation, self-learning ability, learning interest, comprehensive analysis ability and clinical thinking ability, the CBL combined 3D printing teaching group was superior to the CBL teaching group, and the difference was statistically significant ( P<0.001). In terms of teamwork ability, there was no statistical difference between the two groups. Conclusion:The CBL teaching mode combined with 3D printing can improve academic performance, students' learning interest and clinical thinking ability of sacral tumors in the teaching of undergraduate interns and standardized residency training students.

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.