[Research progress on the mechanism of -lactam resistance in group A Streptococci in vivo]. / Aæ—é“¾çƒèŒä½“å† è€å—-å† é °èƒºç±»è¯ç‰©çš„æœºåˆ¶ç ”ç©¶è¿›å±•.

-lactams, including penicillin, have been used for over 80 years in the treatment of group A Streptococcus (GAS) infections. Although -lactam-resistant GAS strains have not been identified in vitro tests, clinical treatment failures have been reported since the 1950s. The mechanism underlying the clinical failure of -lactam treatment in GAS infections remains unclear. Previous research has suggested that -lactam resistance in GAS in vivo is associated with reduced drug susceptibility of strains, bacterial inoculation effects, biofilm formation, the effect of coexisting bacteria, bacterial persistence, and bacterial internalization into host cells. This article reviews the main reports on -lactam treatment failure in GAS infections and analyzes the possible mechanisms of -lactam resistance in vivo. The findings aim to contribute to future research and clinical approaches in the field.

[Recent research on the epidemiology and preventive strategies of neonatal group B Streptococcus infection in the latest decade]. / 新生儿Bæ—é“¾çƒèŒæ„ŸæŸ“æµè¡Œç— å­¦å’Œé¢„é˜²ç­–ç•¥è¿‘åå¹´æ¥çš„ç ”ç©¶è¿›å±•.

Currently, the main strategy for preventing neonatal group B Streptococcus (GBS) infection is prenatal screening combined with intrapartum antibiotic prophylaxis, which has effectively reduced the incidence of neonatal GBS early-onset disease. However, the burden of GBS infection is still significant. The intrapartum antibiotic prophylaxis strategy has limitations such as inducing antibiotic resistance and inability to effectively prevent GBS late-onset disease. It is crucial to develop and evaluate other prevention strategies, while paying close attention to assessing penicillin allergy in pregnant women and how to prevent GBS infection in neonates with negative maternal GBS screening. In recent years, there has been some progress in GBS vaccines and related immunological research, and the use of specific vaccines is expected to significantly reduce GBS infection in neonates.

[Paying attention to the epidemic of group A Streptococcus infections in multiple European and American countries]. / å ³æ³¨æ¬§ç¾Žå¤šå›½Aæ—é“¾çƒèŒæ„ŸæŸ“ç–«æƒ .

At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.

The dynamic change of serotype distribution and antimicrobial resistance of pneumococcal isolates since PCV13 administration and COVID-19 control in Urumqi, China.

Objective: This study aims to analyze the serotype distribution and drug resistance of Streptococcus pneumoniae isolated from children aged 8 days to 7 years in Urumqi, China, between 2014 to 2021, during which PCV13 was introduced in the private sector's immunization program and COVID-19 control was administrated in the last 2 years. Methods: Serotypes of S. pneumoniae isolates were determined by Quellung reaction, and their susceptibility against 14 antimicrobials were tested. According to the start year of PCV13 administration (2017) and COVID-19 control (2020), the study period was divided into three stages: 2014-2015, 2018-2019, and 2020-2021. Results: A total of 317 isolates were involved in this study. The most common serotypes were type 19F (34.4%), followed by 19A (15.8%), 23F (11.7%), 6B (11.4%), and 6A(5.0%). The coverage rate of both PCV13 and PCV15 was 83.0%. The coverage of PCV20 was a little higher at 85.2%. The resistance rate against penicillin was 28.6% according to the breakpoints of oral penicillin, which would reach up to 91.8% based on the breakpoints of parenteral penicillin for meningitis. The resistance rates to erythromycin, clindamycin, tetracycline, and sulfamethoxazole-trimethoprim were 95.9%, 90.2%, 88.9%, and 78.8%, respectively. The PCV13 isolate was more resistant to penicillin than the non-PCV13 ones. There was not any significant change found in the serotype distribution since the PCV13 introduction and the COVID-19 control. The resistance rate against oral penicillin slightly elevated to 34.5% in 2018-2019 from 30.7% in 2014-2015 and then decreased significantly to 18.1% in 2020-2021 (χ 2 = 7.716, P < 0.05), while the resistance rate to ceftriaxone (non-meningitis) continuously declined from 16.0% in 2014-2015 to 1.4% in 2018-2019 and 0% in 2020-2021 (Fisher = 24.463, P < 0.01). Conclusion: The common serotypes of S. pneumoniae isolated from children in Urumqi were types 19F, 19A, 23F, 6B, and 6A, which we found to have no marked change since the PCV13 introduction and the COVID-19 control However, the resistance rate to oral penicillin and ceftriaxone significantly declined in the COVID-19 control stage.

Identification of Lysosome-Associated Protein Transmembrane-4 as a Novel Therapeutic Target for Osteosarcoma Treatment.

OBJECTIVE: The aim of the study is to evaluate the expression of lysosome-associated protein transmembrane-4 (LAPTM4B) in human osteosarcoma tissue samples collected in our hospital, and to explore the possible correlations between the clinical pathological features of osteosarcoma patients and LAPTM4B expression. METHODS: Immunohistochemical (IHC) assays were performed to detect the expression levels of LAPTM4B in 62 tissue samples of osteosarcoma tissues and corresponding non-tumor tissues. According to LAPTM4B staining intensity in tumor tissues, osteosarcoma patients were classified into LAPTM4B high expression and low expression groups. In addition, the potential correlations between LAPTM4B expression levels and clinical pathological features were evaluated. In addition, we detected the effects of LAPTM4B on the proliferation and invasion of esteosarcoma cells through colony formation assay and transwell assay, respectively. We further explored the potential effects of LAPTM4B on tumor growth and metastasis using in vivo animal model. RESULTS: We revealed that LAPTM4B was highly expressed in human osteosarcoma tissues. We determined the significance between LAPTM4B and clinical features, including the tumor size (P = 0.004*) and the clinical stage (P = 0.035*) of osteosarcoma patients. Our results further demonstrated that ablation of LAPTM4B obviously blocked the proliferation and invasion of osteosarcoma cells in vitro and restrained tumor growth and metastasis in mice. CONCLUSION: We investigated the potential involvement of LAPTM4B in osteosarcoma progression and confirmed LAPTM4B as a novel therapeutic target for osteosarcoma.

Co-self-assembly of cationic microparticles to deliver pEGFP-ZNF580 for promoting the transfection and migration of endothelial cells.

The gene transfection efficiency of polyethylenimine (PEI) varies with its molecular weight. Usually, high molecular weight of PEI means high gene transfection, as well as high cytotoxicity in gene delivery in vivo. In order to enhance the transfection efficiency and reduce the cytotoxicity of PEI-based gene carriers, a novel cationic gene carrier was developed by co-self-assembly of cationic copolymers. First, a star-shaped copolymer poly(3(S)-methyl-morpholine-2,5-dione-co-lactide) (P(MMD-co-LA)) was synthesized using D-sorbitol as an initiator, and the cationic copolymer (P(MMD-co-LA)-g-PEI) was obtained after grafting low-molecular weight PEI. Then, by co-self-assembly of this cationic copolymer and a diblock copolymer methoxy-poly(ethylene glycol) (mPEG)-b-P(MMD-co-LA), microparticles (MPs) were formed. The core of MPs consisted of a biodegradable block of P(MMD-co-LA), and the shell was formed by mPEG and PEI blocks. Finally, after condensation of pEGFP-ZNF580 by these MPs, the plasmids were protected from enzymatic hydrolysis effectively. The result indicated that pEGFP-ZNF580-loaded MP complexes were suitable for cellular uptake and gene transfection. When the mass ratio of mPEG-b-P(MMD-co-LA) to P(MMD-co-LA)-g-PEI reached 3/1, the cytotoxicity of the complexes was very low at low concentration (20 µg mL-1). Additionally, pEGFP-ZNF580 could be transported into endothelial cells (ECs) effectively via the complexes of MPs/pEGFP-ZNF580. Wound-healing assay showed that the transfected ECs recovered in 24 h. Cationic MPs designed in the present study could be used as an applicable gene carrier for the endothelialization of artificial blood vessels.

Electrospun Poly(lactide-co-glycolide-co-3(S)-methyl-morpholine-2,5-dione) Nanofibrous Scaffolds for Tissue Engineering.

Biomimetic scaffolds have been investigated in vascular tissue engineering for many years. Excellent biodegradable materials are desired as temporary scaffolds to support cell growth and disappear gradually with the progress of guided tissue regeneration. In the present paper, a series of biodegradable copolymers were synthesized and used to prepared micro/nanofibrous scaffolds for vascular tissue engineering. Poly(lactide-co-glycolide-co-3(S)-methyl-morpholine-2,5-dione) [P(LA-co-GA-co-MMD)] copolymers with different l-lactide (LA), glycolide (GA), and 3(S)-methyl-2,5-morpholinedione (MMD) contents were synthesized using stannous octoate as a catalyst. Moreover, the P(LA-co-GA-co-MMD) nanofibrous scaffolds were prepared by electrospinning technology. The morphology of scaffolds was analyzed by scanning electron microscopy (SEM), and the results showed that the fibers are smooth, regular, and randomly oriented with diameters of 700 ± 100 nm. The weight loss of scaffolds increased significantly with the increasing content of MMD, indicating good biodegradable property of the scaffolds. In addition, the cytocompatibility of electrospun nanofibrous scaffolds was tested by human umbilical vein endothelial cells. It is demonstrated that the cells could attach and proliferate well on P(LA-co-GA-co-MMD) scaffolds and, consequently, form a cell monolayer fully covering on the scaffold surface. Furthermore, the P(LA-co-GA-co-MMD) scaffolds benefit to excellent cell infiltration after subcutaneous implantation. These results indicated that the P(LA-co-GA-co-MMD) nanofibrous scaffolds could be potential candidates for vascular tissue engineering.

Evaluation of Electrospun PCL-PIBMD Meshes Modified with Plasmid Complexes in Vitro and in Vivo.

Functional artificial vascular meshes from biodegradable polymers have been widely explored for certain tissue engineered meshes. Still, the foreign body reaction and limitation in endothelialization are challenges for such devices. Here, degradable meshes from phase-segregated multiblock copolymers consisting of poly(ε-caprolactone) (PCL) and polydepsipeptide segments are successfully prepared by electrospinning and electrospraying techniques. The pEGFP-ZNF580 plasmid microparticles (MPs-pZNF580) were loaded into the electrospun meshes to enhance endothelialization. These functional meshes were evaluated in vitro and in vivo. The adhesion and proliferation of endothelial cells on the meshes were enhanced in loaded mesh groups. Moreover, the hemocompatibility and the tissue response of the meshes were further tested. The complete tests showed that the vascular meshes modified with MPs-pZNF580 possessed satisfactory performance with an average fiber diameter of 550 ± 160 nm, tensile strength of 27 ± 3 MPa, Young's modulus of 1. 9 ± 0.2 MPa, water contact angle of 95° ± 2°, relative cell number of 122% ± 1% after 7 days of culture, and low blood platelet adhesion as well as weak inflammatory reactions compared to control groups.