Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To observe the effect of auricular pressure beans(APN)combined with Compound Tung-Leaf Burn Oil(CTBO)on perioperative anxiety and pain in patients undergoing circumcision.Methods:This study included 100 patients undergo-ing circumcision with the disposable circumcision anastomosis stapler in our hospital from August 2023 to November 2023,of whom 50 received routine circumcision nursing care(the control group)and other 50 APN combined with compound CTBO in addition(the ob-servation group).We compared between the two groups the anxiety scores before any intervention,30 minutes before and 24 hours and 10 days after operation,the pain scores 24 hours postoperatively and at the first change of wound dressing,the frequency of 3-day post-operative sleep awakenings,the incidence of complications,and the satisfaction of the patients.Results:Totally,94 patients com-pleted the study,46 in the observation and 48 in the control group.The anxiety scores exhibited no statistically significant difference between the two groups of patients before any intervention(P>0.05),but were markedly lower in the observation than in the control group at 30 minutes before and 24 hours and 10 days after surgery(P<0.05),and so were the pain scores24 hours after surgery and at the first change of wound dressing(P<0.05),and the frequency of 3-day postoperative sleep awakenings(P<0.05).The satis-faction rate of the patients was remarkably higher(P<0.05)while the incidence of complications significantly lower in the observation group than in the control(P<0.05).Conclusion:Auricular pressure beans combined with Compound Tung-Leaf Burn Oil can ef-fectively alleviate perioperative anxiety,reduce postoperative pain and improve satisfaction of the patients undergoing circumcision.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.

Clostridium difficile infection(CDI)is a major cause of hospital-acquired gastrointestinal infections in children.Current treatment for pediatric CDI primarily involves antibiotics;however,some children experience recurrence after antibiotic treatment,and those with initial recurrence remain at risk for further recurrences following subsequent antibiotic therapy.In such cases,careful consideration of treatment options is necessary.Fecal microbiota transplantation has been shown to be effective for recurrent CDI and has a high safety profile.This article reviews the latest research on the pathogenesis,risk factors,diagnosis,and treatment of pediatric CDI domestically and internationally,with a particular focus on fecal microbiota transplantation therapy.

Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.

OBJECTIVES: To investigate the clinical application of endoscopic esophageal dilation in the treatment of corrosive esophageal strictures in children. METHODS: A retrospective analysis was performed on the clinical data of 15 children with corrosive esophageal strictures who underwent endoscopic esophageal dilation in Children's Hospital, Zhejiang University School of Medicine. The clinical features, treatment modality of endoscopic esophageal dilation, number of dilations, complications, and prognosis were reviewed. RESULTS: A total of 96 esophageal dilations were performed in the 15 children with corrosive esophageal strictures, with a median of 6 dilations per child. Among them, 9 children (60%) underwent 6 or more dilations. The children with a stricture length of >3 cm had a significantly higher number of dilations than those with a stricture length of ≤3 cm (P<0.05). The children with strictures in a single segment had a significantly better treatment outcome than those with strictures in multiple segments (P=0.005). No complication was observed during all sessions of dilation. The overall effective rate (including significant improvement and improvement) of endoscopic esophageal dilation treatment was 87%, with 2 cases of failure. CONCLUSIONS Endoscopic esophageal dilation is an effective and relatively safe treatment method for corrosive esophageal strictures in children, and children with strictures in a single segment tend to have a better treatment outcome than those with strictures in multiple segments.
Child ; Humans ; Esophageal Stenosis/therapy* ; Constriction, Pathologic/complications* ; Dilatation/methods* ; Caustics ; Retrospective Studies ; Treatment Outcome

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

The main sources of natural drugs include various biological species such as plants, animals, and microorganisms. The accurate identification of these species is the bedrock of natural drug development. We propose a novel method of species identification in this paper: analysis of whole-genome (AGE), a molecular diagnostic method used to identify species by finding species-specific sequences from the whole genome and precisely recognizing the specific target sequences. We elaborate that the principle for species identification based on AGE is that the genome sequences of diverse species must differ and divide the implementation strategy of the method into two levels of research and application. Based on our analysis of its characteristics, the method would have the potential advantages of reliable principle, high specificity, and wide applicability. Moreover, three crucial concerns related to building method systems including genome acquisition, bioinformatics analysis, and database construction, are further discussed. In summary, we offer theoretical underpinnings and methodological guidance for the development of bioinformatics software and commercial kits, indicating AGE has great application potential in objects, subjects, and industries.

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg^-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.