BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

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 study the medication law of Professor Piao Bingkui, a national renowned TCM doctor, in treating lung cancer.Method:Medical records and TCM prescriptions of Professor Pu Bingkui for the treatment of lung cancer patients at Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine were retrieved from the hospital information system from January 1, 2013 to December 30, 2023. Database was established with Excel 2019. Drug frequency and drug attribute statistics, association rule analysis, clustering analysis, factor analysis, and complex network analysis were conducted through the ancient and modern medical record cloud platform 2.3.7.Result:Totally 5 768 prescriptions were included, involving 193 kinds of Chinese materia medica. Seven kinds of Chinese materia medica' usage frequency exceeded 90%, which were Astragali Radix, Pseudostellariae Radix, Glehniae Radix, Platycodonis Radix, Citri Reticulatae Pericarpium, Angelicae Sinensis Radix and Coicis Semen. The main properties were neutral and warm, the main tastes were sweet and pungent, and the main meridians were lung, spleen, liver, stomach and kidney meridians. Three cluster groups were obtained by high-frequency medicine clustering. Eight factors were obtained by factor analysis. 48 medicinal pairs were obtained by association rule analysis, from which 6 core medicinal combinations were obtained. Complex network analysis showed that the core prescription was Astragali Radix, Pseudostellariae Radix, Angelicae Sinensis Radix, Glehniae Radix, Platycodonis Radix, Citri Reticulatae Pericarpium and Glycyrrhzzae Radix et Rhizoma.Conclusion:Professor Piao's clinical experience in treating lung cancer with TCM is based on the principle of strengthening healthy qi and eliminating pathogenic factors timely by flexible application of TCM methods as tonifying qi and lung, strengthening spleen and kidney, removing blood stasis and phlegm, clearing heat and detoxifying.

Fibroblast growth factor 19(FGF19)is a postprandial regulatory hormone secreted by human ileum,which participates in the regulation of bile acid,improves glucose tolerance,and has the functions of improving insulin sensitivity and regulating energy metabolism.This article reviews the research progress of FGF19 on glucose metabolism.

AIM:To investigate the effect of Ganoderma leucocontextum extract(GLE)on mice with cisplatin-induced acute kidney injury(AKI)and lipopolysaccharide(LPS)-induced cellular inflammation.METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,AKI group,low-dose(100 mg/kg)GLE group,high-dose(300 mg/kg)GLE group,and quercetin(100 mg/kg)group,with 6 mice in each group.The AKI model was es-tablished by intraperitoneal injection of a 20 mg/kg cisplatin solution.After GLE intervention for 3 d,serum creatinine(SCr)and blood urea nitrogen(BUN)levels were measured.Renal pathology was observed using HE and PAS staining.The expression of β-catenin and Axin2 protein in each group was detected by immunohistochemistry.The expression lev-els of interleukin-1β(IL-1β),IL-6,β-catenin and Axin2 in each group were detected by Western blot and RT-qPCR.The TCMK1 cells were stimulated with 2 mg/L LPS to simulate cellular inflammatory injury.After GLE treatment(0.2,0.4,0.6 and 0.8 g/L)for 24 h,the expressions of IL-1β,IL-6,β-catenin and Axin2 in each group were detected.Fur-ther overexpression of Axin2 was used to verify the changes in the above-mentioned indices.RESULTS:High doses of GLE significantly reduced SCr(P<0.01)and BUN(P<0.05)levels compared with the AKI mice.AKI mice showed re-nal tubule dilatation,tubular epithelial cell necrosis,vacuolation,and other pathological manifestations,which were im-proved after GLE intervention.Immunohistochemistry showed increased expression of Axin2 and β-catenin protein in the kidneys of AKI mice,which was reduced by GLE intervention.Western blot and RT-qPCR results in vitro and in vivo showed that GLE intervention significantly inhibited the expression and mRNA levels of IL-1β,IL-6,Axin2 and β-catenin(P<0.05).Overexpression of Axin2 antagonized the effect of GLE on IL-1β,IL-6,Axin2 and β-catenin,resulting in sig-nificantly up-regulated expressions of these proteins and mRNAs(P<0.01).CONCLUSION:GLE significantly allevi-ates the inflammatory response in AKI mice and LPS-induced cells,and protects against cisplatin-induced kidney injury in mice by inhibiting the Axin2/β-catenin signaling pathway.

Hereditary hemochromatosis(HH) is relatively rare in the Chinese population, and the disease can involve multiple systems. It is easy to be missed and misdiagnosed due to nonspecific clinical manifestations. We report on a case with diabetes as the first diagnosis and being confirmed HH later. In addition to abnormal liver function, this patient also developed a variety of endocrine and metabolic diseases such as hypogonadism and osteoporosis. Included with this case report is a literature based discussion of clinical features, management of HH along with its relationship with endocrine dysfunction to improve disease understanding.

Objective To study the genetic toxicity of carbon tetrachloride for male mice and assess the potential genetic toxic effect on mankind. Methods Micronucleus test and sperm malformation test were used respectively to determine the change of micronucleus cell frequencies (MNCF) and the rate of sperm deformity of germ cell induced by carbon tetrachloride in male mice. Carbon tetrachloride was given through intraperitoneal injection at does of 5,15,25 mg/kg respectively for 24 h and 48 h, the rates of micronucleus in the bone marrow cell and sperm deformity of germ cell of male mice were investigated by counting the number of micronucleus cells per 5 000 polychromatic erythrocyte (PCE) in bone marrow and sperm deformity cells per 5 000 germ cells from male mice. Results The micronucleus rates of PCE in bone marrow and sperms deformity frequencies in carbon tetrachloride treated groups were much higher than the control group (P