Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P＜0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P＞0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95％CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

BACKGROUND:Clinical skin wound healing continues to be a significant concern,and tissue repair research has moved to the forefront with the development of biomaterials with immunomodulatory properties.Therefore,it is crucial to research wound dressings that have immunomodulatory properties. OBJECTIVE:To prepare chitosan hydrogels that have been modified by arginine with different configurations and assess their capacity to speed up wound healing in a rat animal model. METHODS:(1)In vitro trial:Chitosan modified by pure L-arginine,pure D-arginine,and L-arginine and D-arginine was synthesized by EDC/NHS system,which was then crosslinked with aldehyde-modified four-arm polyethylene glycol.Different chitosan-based hydrogels(CS-L,CS-D,and CS-DL)were finally formed via the Schiff base reaction.Three kinds of hydrogel extracts were co-cultured with fibroblasts respectively.Hydrogel cytocompatibility was assessed using the CCK-8 assay and live/dead staining.The effect of hydrogel on the migration capacity of fibroblasts was assessed by using a scratch test.Three kinds of hydrogels were incubated with rat erythrocyte suspension respectively to evaluate the hemocompatibility of the hydrogels.The hydrogel extract was co-cultured with RAW264.7 macrophages to test the hydrogels'capacity to enhance macrophage NO generation and polarize macrophage phenotype.(2)In vivo experiment:A total of 36 adult SD rats were divided into 4 groups with 9 rats in each group by the random number table method.Two full-layer skin defect wounds of 2 cm×2 cm were made on the back of each rat.Normal saline was added to the wounds of the control group,and corresponding hydrogel was added to the wounds of the CS-L,CS-D,and CS-DL groups,respectively,and then bandaged and fixed.The wound healing was observed regularly after operation.Hematoxylin-eosin staining was performed at 3,10,and 21 days after operation.The samples were collected 10 days after operation and M2 macrophage immunofluorescence staining was performed. RESULTS AND CONCLUSION:(1)In vitro experiments:Under scanning electron microscopy,the three kinds of hydrogels exhibited obvious interpenetrating network structures with pore sizes ranging from 70-200 μm.The three kinds of hydrogels have good swelling performance,degradation performance,self-healing performance,and suitable mechanical strength.The three kinds of hydrogels had good cytocompatibility and hemocompatibility and could promote the migration of fibroblasts.All three kinds of hydrogels had the ability to promote the polarization of macrophages,and CS-D hydrogels had the strongest ability to promote the polarization of macrophages.CS-L hydrogel could significantly promote the production of NO in macrophages.(2)In vivo experiment:3 and 10 days after operation,the wound healing rate in the CS-L and CS-D groups was higher than that in the control group(P<0.05).After 21 days,the wound healing rate of the three hydrogel groups was higher than that of the control group.Hematoxylin-eosin staining displayed that a large number of inflammatory cells were infiltrated in the wound tissue of rats in all groups,accompanied by neovessels and fibroblasts 3 days after operation.10 days after operation,there was still more inflammatory cell infiltration in the wound of the control group,and the inflammation of the other three groups was improved,especially the decrease of inflammatory cells in the CS-D group was more obvious.21 days after operation,the wound epithelium of each group was well repaired,and there was basically no inflammatory cell infiltration in the CS-L and CS-D groups,while there was still a small amount of inflammatory cell infiltration in the control group.Immunofluorescence staining revealed that the number of M2-type macrophages in the CS-D group was higher than that in the other three groups(P<0.05).(3)The results conclude that chitosan hydrogels modified by different configurations of arginine can promote wound healing through different mechanisms.

Objective To quantitatively assess the influence of various factors on the pharmacokinetic parameters of propofol and to develop a propofol population pharmacokinetic model tailored for Chinese patients.Methods Thirty patients scheduled for selective abdominal surgeries received an anesthesia dose of propofol at 2.0 mg·kg-1.The concentration of propofol in collected venous blood samples was measured using liquid chromatography-tandem mass spectrometry.Polymorphisms in metabolizing enzyme genes were detected through Sanger sequencing technology.Pharmacokinetic parameters were computed,and models were constructed and evaluated using Phoenix Winnonlin software.Results Through software analysis,the drug's in vivo process was best described by a three-compartment model.The population mean values for the central compartment clearance rate(CL),shallow peripheral compartment clearance rate(Q2),deep peripheral compartment clearance rate(Q3),central compartment volume of distribution(V),shallow peripheral compartment volume of distribution(V2),and deep peripheral compartment volume of distribution(V3)were 1.71 L·min-1,1.31 L·min-1,1.51 L·min-1,5.92 L,19.86 L and 99.06 L,respectively.Body weight was identified as a significant covariate affecting CL and V,and was incorporated into the model.Conclusion The evaluation of the final model demonstrates its substantial predictive capability,offering directional guidance for the clinical administration of propofol.

The successful development and application of mRNA COVID-19 vaccine fully illustrated the great potential and application prospect of mRNA technology in the field of biomedicine. Currently, many companies worldwide are developing drugs and vaccines based on mRNA technology for the prevention and treatment of various diseases. It can be foreseen that with the continuous launch of mRNA drugs, commercial GMP production capacity matching them is also urgent. The optimization of production processes, intelligent manufacturing and other risk control strategies, as well as the control of industrialization costs, will help improve the core competitiveness of mRNA innovative drug development. In view of this, this article will provide an overview of the global production process of mRNA drugs and the progress of related GMP production dynamics, sort out the key chain points of the mRNA industry chain, explore the construction of the mRNA pharmaceutical enterprise value chain and the formation of core competitiveness, and provide reference and reference for the research and development of innovative mRNA drugs and high-quality development in China.

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(C_min) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole C_min were analyzed, and the changes of voriconazole C_min after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole C_min and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole C_min was negatively correlated with albumin level (r=-2.673). Voriconazole C_min in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole C_min showed that compared with voriconazole C_min 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole C_min> 5.0 mg/L group was increased (χ²=4.318, P=0.038). CONCLUSION The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole C_min, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole C_min of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.
Humans ; Male ; Female ; Voriconazole/therapeutic use* ; Antifungal Agents/therapeutic use* ; C-Reactive Protein ; Creatinine ; Glucocorticoids ; Retrospective Studies ; Drug Monitoring ; Hematologic Diseases

BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Humans ; Hematoma, Epidural, Spinal

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Camptothecin/therapeutic use* ; Case-Control Studies ; Colorectal Neoplasms/drug therapy* ; Fluorouracil/therapeutic use* ; Humans ; Leucovorin/therapeutic use* ; Liver Neoplasms/drug therapy* ; Prognosis ; Retrospective Studies