Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance, making them an invaluable asset in the era of antibiotic resistance. Numerous depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models. Additionally, some formulation approaches have been developed for improved stability and activity of depolymerases. However, depolymerase formulation is limited to liquid dosage form and remains in its infancy, posing a significant hurdle to their clinical translation, compounded by challenges in their applicability and manufacturing. Future development must address these obstacles for clinical utility. Here, after unravelling the history, diversity, and therapeutic use of depolymerases, we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases. Finally, the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

Urinary tract infection is the most common infectious complication after kidney transplantation.To further reduce the incidence of urinary tract infection after kidney transplantation,improve the diagnosis and treatment level of urinary tract infection after kidney transplantation in China,prevent the development of bacterial drug resistance and ensure the safety and effectiveness of drug use,Branch of Organ Transplantation of Chinese Medical Association organized experts in the fields of kidney transplantation and infectious diseases to consider clinical status of urinary tract infection after kidney transplantation in China,refer to"Diagnosis and Treatment of Urological and Andrological Diseases in China(2022 edition)"and"Urinary Tract Infection in Solid Organ Transplant Recipients in American Society of Transplantation Practical Guidelines for Infectious Diseases(2019 edition)",and formulate"Guidelines for Clinical Diagnosis and Treatment of Urinary Tract Infection in Kidney Transplant Recipients in China"from the perspectives of clinical classification and definition,epidemiology and etiology,diagnosis and treatment of urinary tract infection after kidney transplantation,respectively.

Background::Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM.Methods::Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People’s Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. Results::The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage.Conclusion::The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

There are few reports in China on the laparoscopic Burch procedure in the treatment of female stress urinary incontinence. Twenty-two female stress urinary incontinence patients admitted to our hospital were treated with laparoscopic Burch procedure, with an overall effective rate of 100%. The score of the International Continence Advisory Committee Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF) at one month after treatment was lower compared to that before the procedure. There were no complications during two months of follow-up.

Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.

Objective:To construct the core indicators for entrustable professional activities in specialists in obstetrics and gynecology.Methods:A study group was formed by the specialists in obstetrics and gynecology and the experts in medical education. The core indicators for entrustable professional activities were constructed for the specialists in obstetrics and gynecology based on literature review and clinical practice, and then the Delphi method was used to conduct two rounds of expert letter consultation for screening and optimization from March 2021 to January 2023 to further identify the core indications.Results:The expert positive coefficient was 100% for the two rounds of consultation, with an expert authority coefficient of 0.82, and the Kendall's coefficient of concordance was 0.221 and 0.213, respectively (both P<0.01). Ten core indicators and their content descriptions were constructed for entrustable professional activities in obstetrics and gynecology specialists, and the experts had a degree of recognition of more than 80% for the importance of these ten entrustable professional activities, with a coefficient of variation of <0.25. This study determined the expected entrustable level of each indicator for specialists at the completion of the course, which ranged from grade 3 to 5; the highest level of 4.48 was observed for the diagnosis and treatment of outpatients, which was between the levels of mastery and expert; the lowest level of 3.52 was observed for laparoscopic hysterectomy, which was between the levels of competency and mastery. Conclusion:This study preliminarily constructs the core indicators for entrustable professional activities in specialists in obstetrics and gynecology, which provides a new exploration for the standardized training of specialists.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.

Objective:To retrospectively analyze the BKV infection of recipients after kidney transplantation(RT)and provide references for diagnosing and treating BK virus infection post-RT.Methods:From January 1, 2018 to December 31, 2020, clinical and follow-up data were reviewed for 561 RT recipients(cadaveric and living donor kidney)at First Hospital of Jilin University. DNA loading of BK virus in blood and urine was determined by quantitative polymerase chain reaction(qPCR)and kidney allograft biopsy performed. Based upon the results, they are divided into four groups of A (372 cases), high-level BK viruria(group B, 128 cases), BK viremia(group C, 52 cases)and BK virus nephropathy(BKVN)(group D, 9 cases). The variables related to BK virus infection were screened by univariate analysis. Meaningful variables( P<0.1)are incorporated into the multi-factor ordered Logistic regression model for examining the independent risk factors of postoperative BK virus infection. Results:The incidence of high-level BKV viruria is 33.69%(189/561)at 18 months post-RT. The average detection time is(4.2±3.8)months, the incidence of BK viremia 10.87%(61/561)and the average detection time(5.2±3.6)months post-RT. The incidence of BKVN is 1.78%(9/561)and the average detection time(7.0±4.0)months post-RT. Univariate analysis showed that gender, age, immunotherapeutic regimen, history of acute rejection and type of donor are correlated with BKV infection. Multivariate Logistic regression analysis indicated that male recipient( P=0.013), immune maintenance regimen( P<0.001)and history of acute rejection( P=0.002)were independent risk factors for developing postoperative BKV infection. Conclusions:There is a high incidence of BKV infection within 12 months post-RT. Male recipient, history of acute rejection and immune maintenance regimen are independent risk factors for BKV infection post-RT.