Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.

Atrial functional mitral regurgitation (AFMR) is mitral regurgitation in patients with atrial fibrillation (AF), whose left atrium (LA) is enlarged, the left ventricle is not enlarged or only slightly enlarged, the left ventricular ejection fraction is preserved, and the mitral valve itself has no apparent lesion. At present, the etiology, pathophysiology and mechanism of this disease have not been completely clear yet. Existing studies have found that the causes of AFMR mainly include AF, enlargement of LA and mitral annulus, destruction of mitral annular shape, inability of mitral valve remodeling to compensate for mitral annular expansion, and hamstringing of the posterior mitral leaflet by atriogenic tethering. AFMR is demonstrated to be associated with an increased risk of mortality and readmission due to heart failure. Therefore, it serves as a primary therapeutic target for patients with heart failure and AF. However, the optimal treatment of AFMR still remains controversial. Therefore, this article will mainly expound the current definition, etiology, pathophysiological mechanism, treatment, and prognosis of AFMR.

Objective To explore the characteristics of blood lipid metabolism indicators and risk factors of prognosis in children with systemic lupus erythematosus (SLE). Methods A total of 54 children who were diagnosed with SLE and hospitalized in Chengdu Women and Children’ s Central Hospital from January 2013 to August 2022 were selected. Clinical data of all children were collected and blood lipid metabolism indicators and biochemical indicators were detected , and binary logistic regression was used to analyze the prognosis risk factors in children with SLE. Results Among the 47 cases (87.04%) had abnormal blood lipid metabolism at admission, and is mainly manifested as elevated levels of LDL-C, TG and TC and decreased level of HDL-C. The proportion of cardiovascular system damage, hematological system damage, urinary protein positivity, and SLEDAI-2000 score in the group with good prognosis were lower than those in the group with poor prognosis, while the proportion of dsDNA positivity was higher in the group with poor prognosis. Binary Logistic regression analysis showed that the cardiovascular system damage and positive urinary protein were risk factors for poor prognosis, with statistically significant differences (P<0.05). Conclusion Abnormal blood lipid metabolism is common in children with SLE, and cardiovascular system damage and positive urinary protein may increase the risk of poor prognosis in young children.

Objective To analyze the prevalence and risk factors of sleep apnea syndrome (SAS) in patients with Alzheimer&#39;s disease (AD), and to provide theoretical basis for the prevention of SAS in AD patients. Methods A total of 130 AD patients admitted to the Department of Neurology of Guang&#39;an People&#39;s Hospital of Sichuan Province from January 2019 to September 2022 were selected and divided into control group (without SAS) and observation group (with SAS) according to whether the patients were complicated with SAS{AHI ≥5 times/h}. Snoring, waking at night, dry mouth in the morning, AHI and SaO2 values were compared between the two groups. Clinical data of AD patients, including age, gender, body mass index (BMI), AD course, tobacco and alcohol history, and neurodegenerative diseases, were collected by self-made questionnaire and consulting the patient&#39;s electronic medical record bed. Univariate analysis and logistic regression were used to analyze the independent risk factors for SAS in AD patients. Results Among 130 AD patients, 43 cases (33.08%) of SAS occurred. The proportion of snoring, awakening at night, dry mouth in the morning and AHI value in the observation group were significantly lower than those in the control group (P<0.05). SaO2 value in observation group was significantly lower than that in control group (P<0.05). There were significant differences in age, duration of AD, BMI, smoking history, combined hypertension, neurodegenerative disease, PSQI score and PSQI score between the two groups (P<0.05). Multivariate logistic regression analysis showed that BMI≥28 kg/m², PSQI score >16 points and CDR score ≥2 points were independent risk factors for SAS in AD patients (P<0.05). Conclusion The incidence of SAS associated with AD is higher, and the main risk factors are BMI≥28 kg/m², PSQI score >16 and CDR score. Polysomnosis monitoring should be performed regularly to prevent SAS.

OBJECTIVE To summarize the strategies and potential drugs that can improve the oxygen affinity of red blood cells in the hypobaric and hypoxic environment in the current research. METHODS The retrieved literatures were screened, extracted and summarized by referring to the literature on the relationship between hypobaric hypoxic environment and erythrocyte oxygen affinity in CNKI database, Web of Science database and Pubmed database. RESULTS Under the hypobaric and hypoxic environment, the body’s oxygen uptake capacity and oxygen utilization efficiency decreased, resulting in the body being in a state of hypoxia. Improving the oxygen affinity of red blood cells could help the body adapt to and get used to the hypobaric and hypoxic environment, and many improvement methods had been applied in other diseases. CONCLUSION Improving the oxygen utilization rate of red blood cells by increasing the oxygen affinity of erythrocytes under hypobaric and hypoxia environment is the starting point and focus of the current research on preventing the damage of high altitude hypobaric and hypoxic environment to the human body.

Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

[摘 要] 目的：设计并制备一种分别靶向B细胞表面抗原CD19和CD22的CAR-T细胞，检测其对肿瘤细胞的体内外杀伤效果。方法：将含有人源化 CD19 ScFv的二代CAR分子和带有CD3ε链作为共刺激结构域的CD22 ScFv CAR分子以P2A自剪切肽连接，序列连接于慢病毒载体pLTR-CMV-MCS中，以HEK-293T细胞包装相应的慢病毒载体，感染健康志愿者提供的T细胞制备CAR-19-22-T细胞，同时以相同二代结构分别构建单靶向CAR-T细胞作为参照。构建表达荧光素酶、CD19和/或CD22的前列腺癌3M细胞（靶细胞）。将各种CAR-T细胞与靶细胞共同培养，采用荧光素酶化学发光法和ELISA法检测其对靶细胞的杀伤能力和细胞因子的分泌水平。通过尾静脉注射Raji-Luc细胞构建NOD-SCID免疫缺陷小鼠白血病模型，分别注射各组CAR-T细胞进行治疗并评估其疗效。结果：培养7 d的CAR-19-22-T细胞的CAR-19表达率为13.7%，CAR-22表达率为14.3%。CAR-19-22-T细胞在10∶1效靶比时，对3M-CD19-Luc、3M-CD22-Luc和3M-CD19-CD22-Luc细胞的杀伤率均显著高于T细胞[（78.1±14.4）% vs （11.1±4.3）%、（46.7±10.7）% vs （12.4±2.7）%、（90.5±4.3）% vs （14.3±3.7）%，均P<0.01]；与3M-CD19-Luc、3M-CD22-Luc、3M-CD19-CD22-Luc靶细胞共培养后，CAR-19-22-T细胞IFN-γ、TNF-α和IL-2水平均显著低于CAR-19-T和CAR-22-T细胞（P<0.05或P<0.01）。CAR-19-22-T细胞对移植Raji-Luc细胞模型小鼠治疗效果明显，其生存期显著长于T细胞组（P<0.01），与CAR-19-T组和CAR-22-T组荷瘤小鼠比较差异均无统计学意义（均P>0.05）。结论：成功设计并制备了一种双靶点CAR-19-22-T细胞，其能够有效杀伤表达CD19和/或CD22抗原的肿瘤细胞，对Raji-Luc细胞的白血病模型小鼠有显著的治疗效果。

AIM: To evaluate the visual function and visual quality of patients with diabetic macular edema treated with conbercept injection.

METHODS: The average change of contrast sensitivity(CS), best corrected visual acuity(BCVA), central retinal thickness(CRT)and NEIVFQ-25 score were observed for 3mo after intravitreal injection of conbercept in 43 eyes of 38 patients with diabetic macular edema.

RESULTS: The mean CS increased from(1.060±0.14)units to(1.47±0.31)units at 12wk after intravitreal injection of conbercept(P<0.05). The average LogMAR BCVA decreased significantly from 0.535±3.32 to 0.333±0.11 at 12wk(P<0.05), and the average CRT decreased significantly from 369.45±36.42μm to 226.53±39.48μm at 12wk(P<0.05). There is not a correlation between the changes in CRT and BCVA and the improvement of CS. The NEIVFQ-25 score improved in 30 cases(79%)from baseline to 12wk. 6 cases(16%)had no change in the NEIVFQ-25 score, and 2 cases(5%)declined in the NEIVFQ-25 score.

CONCLUSION: The treatment of conbercept injection for diabetic retinal macular edema can significantly improve the visual function and the quality of life.

Anti-vascular endothelial growth factor(VEGF)drugs have been used to treat various ophthalmic diseases, especially in the treatment of vascular proliferative ophthalmopathy. Anti-VEGF drugs can significantly inhibit the formation of new blood vessels and reduce retinal edema, thereby improving the patient&#39;s vision. However, their long-term therapeutic effect and safety require longer-term follow-up and research. This article reviews the application and research progress of anti-VEGF drugs in ophthalmology and provides references for clinical application and further research.

AIM: To compare the efficacy and safety of intravitreal conbercept and ranibizumab in the treatment of macular edema secondary to retinal vein occlusion(RVO-ME)in order to provide basis for clinical guidance.

METHODS: The Cochrane Library, Embase, Web of Science, and CNKI, Wanfang data, and VIP database were comprehensively searched for studies comparing conbercept versus ranibizumab in patients with RVO-ME. Best-corrected visual acuity(BCVA), central macular thickness(CMT), intraocular pressure(IOP), mean number of intravitreal injections and adverse events were extracted from the final eligible studies. RevMan 5.3 software was used for relevant index data analysis. Random and fixed effect models were employed to evaluate heterogeneity and the publication bias.

RESULTS: A total of 14 randomized controlled trial(RCT)studies, involving 1 350 eyes. There was no significant difference in BCVA improved between the two groups after treatment 2wk, 2mo, 3mo and 6mo, but there was significant difference in BCVA improved after treatment 1wk [WMD=-0.03; 95% CI(-0.05, -0.02); P<0.0001] and 1mo [WMD=-0.03; 95% CI(-0.04, -0.01); P=0.001]. The conbercept treatment group had higher CMT reduction compared with ranibizumab treatment group after 6mo treatment, and there was a significant difference [WMD=-28.77; 95% CI(-54.23, -3.31); P=0.03], and there were no significant difference between two groups in others period of time. There were no significant difference in intraocular pressure(IOP)and adverse events between the two groups [OR=0.95; 95% CI(0.57, 1.57); P=0.84]. However, the use of conbercept had a fewer mean number of injections.

CONCLUSION: CMT and BCVA were improved significantly both in the conbercept and ranibizumab groups. Compared with ranibizumab, conbercept group did not have greater improved BCVA, but with a more CMT reduction after 6mo. The advantage of conbercept is fewer injections and maybe it is better for treatment of RVO-ME.