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.

Etomidate reversibly blocks 11-β-hydroxylated steroid dehydrogenase inhibits the synthesis of cortisol by adrenal cells.This product is a special injection.When evaluating the quality and efficacy of the generic and the reference preparations,it should be based on pharmaceutical and non-clinical consistency and adopt a step-by-step research strategy,firstly,bioequivalence(BE)was studied.In bioequivalence study,the research type,dosage and method,bioequivalence evaluation,safety monitoring and pharmacodynamics(PD)evaluation should be considered and designed reasonably.Based on the pharmacokinetics(PK)characteristics of etomidate medium-long chain fat emulsion injection and the bioequivalence study of its generic drug before its domestic market,the general design requirements and relevant considerations for the bioequivalence study of this product were systematically discussed.The purpose is to provide useful reference and guidance for domestic research and development of generic drugs.

Objective To investigate the prognosis of patients with hepatitis B virus(HBV)-related intrahepatic cholangiocarcinoma(ICC)whose HBV DNA was negative before surgical.Methods A retrospective analysis was conducted on the clinical data of 97 ICC patients who underwent surgery resection at the Fifth Medical Center of Chinese PLA General Hospital between October 2010 and January 2017.All patients were divided into HBV-related ICC(HBV-ICC)group(n=62)and non-HBV-related ICC(Con-ICC)group(n=35).HBV-ICC group included 34 patients with HBV core antigen positive(HBcAb+)and HBV surface antigen positive(HBsAg+),and 28 patients with HBcAb positive and HBsAg negative.Kaplan-Meier analysis was used to plot survival curves and compare the overall survival(OS)and postoperative recurrence-free survival(RFS)among patients in Con-ICC,ICC patients with HBsAg+/HBcAb+,and ICC patients with HBsAg-/HBcAb+.Univariate and multivariate Cox proportional hazard models were used to analyze independent influencing factor for OS,RFS and early postoperative recurrence among gender,age,pathogenic factor,liver cirrhosis,Child-Pugh grade,carbohydrate antigen 19-9(CA199),alpha-fetoprotein(AFP),glutamine transferase(GGT),alkaline phosphatase(ALP),total bilirubin(TBil),direct bilirubin(DBil),American Joint Committee on Cancer(AJCC)stage,tumor size,tumor number,tumor differentiation,microvascular invasion,lymph node metastasis,hepatectomy procedure,cholecystectomy,and follow-up treatment.Results Of the 97 patients,the median age was 56 years,and 79(81.4%)of them were male.The median follow-up time was 92.2 months.Eighty-eight(90.7%)patients presented with tumor recurrence and 73(75.3%)died.In multivariate analyses,HBV-ICC and CA199>37 kU/L were independent predictors of OS(HR=0.45,95%CI 0.26-0.77,P=0.003;HR=2.10,95%CI 1.24-3.57,P=0.006),RFS(HR=0.43,95%CI 0.27-0.68,P<0.001;HR=1.78,95%CI 1.12-2.81,P=0.014),and postoperative early recurrence(HR=0.42,95%CI 0.26-0.70,P=0.001;HR=2.02,95%CI 1.20-3.39,P=0.008).AJCC stage Ⅲ was an independent risk factor for postoperative RFS(HR=1.81,95%CI 1.04-3.14,P=0.037).Multiple tumor lesions was an independent risk factor for postoperative RFS and early recurrence(HR=1.73,95%CI 1.07-2.77,P=0.024;HR=1.90,95%CI 1.12-3.24,P=0.017).There was no statistically significant difference in OS,RFS,and early recurrence between HBV-ICC patients with HBsAg-/HBcAb+and Con-ICC patients(P<0.05),whereas HBsAg+/HBcAb+was a significant factor affecting postoperative OS(HR=0.32,95%CI 0.16-0.62,P=0.001),RFS(HR=0.32,95%CI 0.18-0.55,P<0.001),and early recurrence(HR=0.29,95%CI 0.15-0.54,P<0.001)in ICC patients.Conclusions The prognosis of HBV-ICC patients with preoperative HBV-DNA-is better than that of Con-ICC patients.The prognosis of HBV-ICC patients with HBcAb+/HBsAg-is worse than that of HBV-ICC patients with HBcAb+/HBsAg+,but similar to Con-ICC patients.Therefore,the postoperative stratified management of HBV-ICC patients should be emphasized.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Purpose: The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear. Methods: Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias. Results: A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57–52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01–2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12–1.99; p = 0.006).There was an interaction between the molecular subtype and the surgery interval for OS (pinteraction = 0.014) and RFS (pinteraction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups. Conclusion Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.

Background: and Purpose The accurate prediction of functional outcomes in patients with acute ischemic stroke (AIS) is crucial for informed clinical decision-making and optimal resource utilization. As such, this study aimed to construct an ensemble deep learning model that integrates multimodal imaging and clinical data to predict the 90-day functional outcomes after AIS. Methods: We used data from the Korean Stroke Neuroimaging Initiative database, a prospective multicenter stroke registry to construct an ensemble model integrated individual 3D convolutional neural networks for diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR), along with a deep neural network for clinical data, to predict 90-day functional independence after AIS using a modified Rankin Scale (mRS) of 3–6. To evaluate the performance of the ensemble model, we compared the area under the curve (AUC) of the proposed method with that of individual models trained on each modality to identify patients with AIS with an mRS score of 3–6. Results: Of the 2,606 patients with AIS, 993 (38.1%) achieved an mRS score of 3–6 at 90 days post-stroke. Our model achieved AUC values of 0.830 (standard cross-validation [CV]) and 0.779 (time-based CV), which significantly outperformed the other models relying on single modalities: b-value of 1,000 s/mm2 (P<0.001), apparent diffusion coefficient map (P<0.001), FLAIR (P<0.001), and clinical data (P=0.004). Conclusion The integration of multimodal imaging and clinical data resulted in superior prediction of the 90-day functional outcomes in AIS patients compared to the use of a single data modality.

BACKGROUND: To enhance articular cartilage healing, microfractures (Mfx) and bone marrow aspirate concentrate (BMAC) are commonly used, and some form of scaffold is often used together to increase its efficacy. Herein, we compared the efficacy of atelocollagen scaffold to that of collagen scaffold when used with Mfx or BMAC on osteochondral defect of animal. METHODS: This experiment was designed in two stages, and therapeutic effects of Mfx and BMAC were respectively evaluated when used with atelocollagen or collagen scaffold. Femoral condyle defects were artificially created in male New Zealand White rabbits, and in each stage, 12 rabbits were randomly allocated into three treatment groups: test group with additional atelocollagen scaffold, the positive control group with collagen scaffold, and the negative control group.Then, for 12 weeks, macroscopic and histological evaluations were performed. RESULTS: At 12 weeks, defects in the test group were fully regenerated with normal cartilage-like tissue, and were well integrated with the surrounding cartilage at both stages experiment, whereas defects in the control groups were not fully filled with regenerated tissue, and the tissue appeared as fibrous tissue. Histologically, the regenerated tissue in the test group showed a statistically significant improvement compared to the positive and negative control groups, achieving a similar structure as normal articular cartilage. CONCLUSION The results showed that implantation of the atelocollagen scaffold enhanced cartilage regeneration following osteochondral defects in rabbits. This suggests that the atelocollagen scaffold can be used with Mfx or BMAC for effective regeneration of osteochondral defects.