Sorafenib and SIAIS361034, a novel PROTAC degrader of BCL-xL, display synergistic antitumor effects on hepatocellular carcinoma with minimal hepatotoxicity.

The overexpression of BCL-xL is closely associated with poor prognosis in hepatocellular carcinoma (HCC). While the strategy of combination of BCL-xL and MCL-1 for treating solid tumors has been reported, it presents significant hepatotoxicity. SIAIS361034, a novel proteolysis targeting chimera (PROTAC) agent, selectively induces the ubiquitination and subsequent proteasomal degradation of BCL-xL through the CRBN-E3 ubiquitin ligase. When combined with sorafenib, SIAIS361034 showed a potent synergistic effect in inhibiting hepatocellular carcinoma development both in vitro and in vivo. Since SIAIS361034 exhibits a high degree of selectivity for degrading BCL-xL in hepatocellular carcinoma, the hepatotoxicity typically associated with the combined inhibition of BCL-xL and MCL-1 is significantly reduced, thereby greatly enhancing safety. Mechanistically, BCL-xL and MCL-1 sequester the BH3-only protein BIM on mitochondria at baseline. Treatment with SIAIS361034 and sorafenib destabilizes BIM/BCL-xL and BIM/MCL1 association, resulting in the liberation of more BIM proteins to trigger apoptosis. Additionally, we discovered a novel compensatory regulation mechanism in hepatocellular carcinoma cells. BIM can rapidly respond to changes in the balance between BCL-xL and MCL-1 through their co-transcription factor MEF2C to maintain apoptosis resistance. In summary, the combination therapy of SIAIS361034 and sorafenib represents an effective and safe approach for inhibiting hepatocellular carcinoma progression. The novel balancing mechanism may also provide insights for combination and precision therapies in the treatment of hepatocellular carcinoma.

Two-year efficacy and safety of different anti-vascular endothelial growth factor regimens for neovascular age-related macular degeneration: a network meta-analysis of randomized controlled trials.

OBJECTIVES: To compare the 2-year efficacy and safety of various anti-vascular endothelial growth factor (VEGF) regimens for neovascular age-related macular degeneration (nAMD). METHODS: A comprehensive search was performed on multiple electronic databases up to April 2023 and updated in June 2024, to identify relevant randomized controlled trials (RCTs). Key outcomes included the proportion of patients achieving a vision gain of ≥15 letters and maintaining stable vision (loss of <15 letters) in best-corrected visual acuity (BCVA), changes in mean BCVA from baseline, serious ocular adverse events (SAEs), adverse events leading to treatment discontinuation and any cause of death at 2 years. RESULTS: Nineteen trials with 12,654 patients and 25 treatment regimens were analyzed in the study. All anti-VEGF regimens showed superior efficacy compared to sham therapy. Specifically, faricimab 6 mg (4+up to Q16W) and ranibizumab 0.5 mg (2-week T&E) displayed top-level effect in vision gain. Bevacizumab 1.25 mg (2-week T&E) and aflibercept 2 mg (2-week T&E) demonstrated the most stable vision outcomes. Bevacizumab 1.25 mg (2-week T&E) and ranibizumab 0.5 mg (2-week T&E) exhibited the most pronounced mean BCVA improvement. Compared to sham therapy, the risk of SAEs was significantly higher for brolucizumab 6 mg (3 + Q12W/ Q8W) (RR = 6.04, 95% CI: 1.30-28.02) and PDS 100 mg/ml (Q24W) (RR = 10.95, 95% CI: 2.14-56.02), but not for other anti-VEGF regimens. CONCLUSIONS: Ranibizumab 0.5 mg (2-week T&E) emerges as a potentially optimal regimen for nAMD over a 2-year period. Future studies need to consider the impact of baseline characteristics on treatment outcomes.

Management of drug supply chain information based on "artificial intelligence + vendor managed inventory" in China: perspective based on a case study.

Objectives: To employ a drug supply chain information system to optimize drug management practices, reducing costs and improving efficiency in financial and asset management. Methods: A digital artificial intelligence + vendor managed inventory (AI+VMI)-based system for drug supply chain information management in hospitals has been established. The system enables digitalization and intelligentization of purchasing plans, reconciliations, and consumption settlements while generating purchase, sales, inventory reports as well as various query reports. The indicators for evaluating the effectiveness before and after project implementation encompass drug loss reporting, inventory discrepancies, inter-hospital medication retrieval frequency, drug expenditure, and cloud pharmacy service utilization. Results: The successful implementation of this system has reduced the hospital inventory rate to approximately 20% and decreased the average annual inventory error rate from 0.425‰ to 0.025‰, significantly boosting drug supply chain efficiency by 42.4%. It has also minimized errors in drug application, allocation, and distribution while increasing adverse reaction reports. Drug management across multiple hospital districts has been standardized, leading to improved access to medicines and enhanced patient satisfaction. Conclusion: The AI+VMI system improves drug supply chain management by ensuring security, reducing costs, enhancing efficiency and safety of drug management, and elevating the professional competence and service level of pharmaceutical personnel.

Prioritization of drug targets for thyroid cancer: a multi-omics Mendelian randomization study.

OBJECTIVES: Recurrence or tumor metastasis and drug resistance remain the major challenge in the treatment of thyroid cancer. It is needed to identify novel drug targets for thyroid cancer. METHODS: Summary data-based Mendelian randomization (SMR) and colocalization analysis were performed to evaluate the associations between gene methylation, expression, protein levels with thyroid cancer. We additionally performed protein-protein interaction (PPI) network, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses to further explore the potential roles of identified genes in thyroid cancer. RESULTS: SDCCAG8 and VCAM1 genes were associated with risk of thyroid cancer with tier 1 evidence, while TCN2 gene was with tier 3 evidence. SDCCAG8 gene was associated with risk of papillary thyroid cancer with tier 1 evidence. At the level of circulating proteins, genetically predicted higher levels of SDCCAG8 (OR = 0.46, 95% CI 0.34-0.64) and VCAM1 (OR = 0.21, 95% CI 0.10-0.45) were inversely associated with thyroid cancer risk; higher level of TCN2 was associated with an increased risk of thyroid cancer (OR = 1.30, 95% CI 1.15-1.47); and the higher level of SDCCAG8 (OR = 0.40, 95% CI 0.28-0.58) was associated with a decreased risk of papillary thyroid cancer. The bioinformatics analysis showed that SDCCAG8, VCAM1 and TCN2 might play roles in immune-related pathways. CONCLUSION: SDCCAG8, VCAM1 and TCN2 genes were associated with thyroid cancer risk with evidence at multi-omics levels. There were potential roles of SDCCAG8, VCAM1 and TCN2 in immune-related pathways. Our findings might improve the understanding of the pathogenesis of thyroid cancer and discovery of novel potential drug targets for this disease.

Association and mechanism of montelukast on depression: A combination of clinical and network pharmacology study.

BACKGROUND: Post-marketing surveillance found montelukast use was associated with an increased risk of depression. However, results of observational studies are inconsistent. OBJECTIVE: This study aimed to assess whether montelukast exposure is associated with depression and elucidate the possible molecular mechanism. METHOD: We conducted a cross-sectional study of 9508 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Multivariable regression was used to evaluate the association between montelukast exposure and depression. Network pharmacology was conducted to identify the mechanisms of montelukast on depression. RESULTS: Montelukast exposure had a higher prevalence of depression (37.4 %). In a multivariable logistic regression model adjusted for sociodemographic, behavioural, and health characteristics, montelukast exposure was associated with depression (odds ratio [OR]: 1.61; confidence interval [CI]: 1.18-2.19). Network pharmacology was identified 69 key targets of montelukast on depression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in endocrine resistance, chemical carcinogenesis-receptor activation, estrogen signaling pathway, etc. LIMITATIONS: Cross-sectional data. CONCLUSIONS: The study implies a potential positive association between long-term montelukast exposure and depression through multi-faceted mechanisms. It is suggested that attention be given to the possibility of depression in patients undergoing prolonged montelukast therapy.

Leukotriene-modifying agents may increase the risk of depression: A cross-sectional study.

INTRODUCTION: Post-market monitoring has shown a potential link between the use of leukotriene-modifying agents (LTRAs) and an increased risk of neuropsychiatric events, such as depression. However, observational studies have produced inconsistent findings, offering no definitive conclusions. OBJECTIVE: To assess the potential correlation between LTRAs exposure and depression in US adults. METHOD: This cross-sectional study, based on population data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle. The Patient Health Questionnaire-9 was used to assess depression. Multivariable regression was used to evaluate the association between LTRAs exposure and depression. Sensitivity and subgroup analyses were conducted, with the calculation of the E-value. Network pharmacology was employed to investigate the influence of LTRAs on mechanisms of depression. RESULTS: Among the 9414 participants, 595 (6.3 %) were classified as having depression. LTRAs exposure was associated with a higher prevalence of depression (16.9 % vs. 6.0 %). The multivariable logistic regression results showed that LTRAs use increased the risk of depression (OR = 1.70; 95 % CI, 1.05-2.75). An association between LTRAs exposure and depression was found in sensitivity analyses conducted regardless of multivariable linear regression with the PHQ-9 score as a continuous variable (ß = 0.97; 95 % CI, 0.44-1.50) or multivariable logistic regression with the PHQ-9 cut-off of 5 (OR = 1.52; 95 % CI, 1.08-2.14). The association between LTRAs and depression was stable in the different subgroups. CONCLUSION: LTRAs exposure is positively associated with depression in US adults. Therefore, the risk for depression in patients receiving long-term LTRAs treatment should be considered.

Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure: Exposure to severe AKI and baseline and post-AKD kidney function. Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Fungal Endophthalmitis: Clinical Characteristics, Pathogens, and Factors Affecting Visual Outcome.

AIMS: The aims of this study are to investigate the etiology, microbiological spectrum, and risk factors associated with visual outcomes of fungal endophthalmitis (FE) in a tertiary eye specialty hospital in Shanghai, China. METHODS: This was a retrospective, single-center case series. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. Logistic regression was used to analyze the factors related to visual outcomes. RESULTS: This study involved 102 eyes of 92 patients with FE, including 63 males (66.3%). The mean age was 44.4 ± 19.8 years. The most common etiology of FE was trauma (56.5%). The predominant fungal species isolated were Aspergillus spp. (31/93, 33.3%). Pars plana vitrectomy (PPV) and intravitreal antifungal agents was performed initially in 86 (84.3%) and 83 (81.4%) eyes, respectively. Only 35 (34.3%) eyes achieved final best corrected visual acuity (BCVA) of 20/400 or better. Ten (9.8%) eyes had a final BCVA of light perception or worse, and five (4.9%) had to be enucleated. The factors determining better visual outcomes included initial visual acuity better than finger-counting (FC) (odds ratio (OR) 5.811, p = 0.036), the absence of corneal infiltrate (OR 10.131, p = 0.002), and Candida species infection (OR 6.325, p = 0.011). CONCLUSIONS: Early diagnosis of FE and a timely vitrectomy, combined with an intravitreal injection of an antifungal drug, can mitigate the devastating results of intraocular fungal infection. Not being infected by Aspergillus spp., an initial BCVA that was no worse than FC, and the absence of corneal involvement were related to better visual prognosis.

Etiology, Microbiological Isolates, and Antibiotic Susceptibilities in Inpatients with Refractory Auricular Perichondritis: A 10-Year Retrospective Study.

Purpose: This study aimed to elucidate the etiologies, microbiological profiles, antibiotic susceptibilities of bacteria and outcomes of patients with auricular perichondritis. Patients and Methods: This was a single-center retrospective study. Inpatients diagnosed with auricular perichondritis at a university teaching hospital in eastern China between January 2013 and December 2022 were included in this study. Results: A total of 127 patients were enrolled, with an average age of 50.6 ± 16.9 years. In addition to cases in which the etiology remained undetermined in 37% of the patients, postoperative infection emerged as the predominant cause (37.8%), followed by trauma (18.1%). Among the 61 cultured isolates, 21.3% were gram-positive bacteria, 55.7% were gram-negative bacteria, and 23.0% were fungal isolates. The most frequent isolate was Pseudomonas aeruginosa (30/61, 49.2%). Notably, the incidence of fungal infections was markedly higher among postoperative patients than among post-traumatic patients (41.7% vs 7.1%, p = 0.03). The proportions of gram-negative bacteria (60.0% vs 50.0%) and fungal isolates (28.6% vs 15.4%) exhibited an increasing trend during the period of 2018-2022, as compared to the previous period of 2013-2017. The bacterial isolates exhibited high susceptibility to vancomycin (100%), amikacin (100%), cefepime (94.6%), and ceftazidime (90.9%). In contrast, overall susceptibility to fluoroquinolones was relatively low (65.2-67.4%), demonstrating a declining trend in the susceptibility of Pseudomonas aeruginosa. Notably, 78.7% of the patients received an initial treatment regimen covering Pseudomonas aeruginosa. Within 30 days of discharge, 8.5% (6/71) experienced an infection recurrence. Conclusion: Auricular perichondritis predominantly originates from iatrogenic (postoperative) infections. Antibiotic therapy covering Pseudomonas aeruginosa is a sensible and appropriate empirical treatment in the majority of patients with auricular perichondritis. However, increased resistance to fluoroquinolones has become a notable concern, suggesting the need to seek new, more aggressive strategies.

Adverse events associated with brolucizumab: a disproportionality analysis of the FDA adverse event reporting system (FAERS).

BACKGROUND: The safety information of brolucizumab primarily comes from clinical trials experience. This study aimed to explore the ocular and systemic adverse events (AEs) associated with brolucizumab among real-world patients through data mining the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports submitted to the FAERS database between October 2019 and March 2023 were extracted. The reporting odds ratio was used to evaluate AE signals associated with brolucizumab. RESULTS: There were 4,380,839 AE reports extracted from the FAERS database, and 3,313 of which were with brolucizumab as primary suspected. A total of 150 ocular AE signals were identified. Ninety-nine were known ocular AEs listed in brolucizumab' label, primarily including vision-related AEs, intraocular infections, and retinal disorders. Fifty-one were unexpected ocular AE signals, including keratic precipitates, retinal perivascular sheathing, dry eye, glaucoma, etc. Meanwhile, several serious systemic AE signals, including arterial thromboembolic events and rhinorrhea, were also identified. CONCLUSIONS: Several unexpected ocular and systemic AE signals associated with brolucizumab were identified through data mining of the FAERS database.

Efficacy and Safety of Immune Checkpoint Inhibitors Combined With Chemotherapy as First-line Treatment for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Different clinical trials for recurrent or metastatic nasopharyngeal carcinoma have studied different combinations of immuno-oncology in first-line treatment, but the optimal choice has not been determined. OBJECTIVE: To systematically examine and compare the efficacy and safety of different immune checkpoint inhibitors (ICIs) combined with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. METHODS: Several electronic databases were systematically searched up to February 2023. Articles meeting the inclusion criteria were included. RESULTS: Three RCTs were eligible in the study. Compared with placebo plus gemcitabine-cisplatin (GP), toripalimab plus GP (HR = 0.59, 95% CI: 0.37-0.95) was significantly associated with a better OS. Tislelizumab plus GP generated best progression-free survival (PFS) benefit (HR = 0.50, 95% CI: 0.37-0.67), greatest improvement in 1-year PFS rate (RR = 3.00, 95% CI: 1.84-5.22), and objective response rate (ORR) (RR = 1.26, 95% CI: 1.04-1.53) over the placebo plus GP. Furthermore, tislelizumab plus GP appeared to be safer than toripalimab plus GP and camrelizumab plus GP in terms of adverse events (AEs)-grade ≥3, treatment-related AEs (TRAEs)-grade ≥3, serious AEs (SAEs), treatment-related SAEs (TRSAEs), and AEs leading to discontinuation of treatment. CONCLUSION AND RELEVANCE: In recurrent or metastatic nasopharyngeal carcinoma, programmed death 1 (PD-1) inhibitors plus GP as first-line treatment have better survival outcomes than placebo plus GP with comparable toxicity. Toripalimab plus GP shows the best OS benefit over placebo plus GP, while tislelizumab plus GP generates the best PFS, 1-year PFS rate, ORR, and safety. Tislelizumab plus GP could be the best choice among the ICIs combined with chemotherapy regimens as first-line treatment in recurrent or metastatic nasopharyngeal carcinoma.

The sensitivity of mTORC1 signaling activation renders tissue regenerative capacity.

A better understanding of how and why the regenerative capacity differs among species will not only provide insights into the regeneration process but also hold value for the development of regenerative medicine and the improvement of healing procedures. In a recent Nature article, Zhulyn et al. identify a critical role played by the activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling in enhancing tissue regenerative capacity in animals.

Management and Prognosis of Acute Post-Cataract Surgery Endophthalmitis: A 10-Year Retrospective Analysis in Eastern China.

Acute post-cataract surgery endophthalmitis (APSE) is a serious vision-threatening complication of cataract surgery. Analysis of the management and prognosis in cases of APSE may provide better guidance for future treatment. Fifty-six patients (56 eyes) diagnosed with APSE between 2013 and 2022 were retrospectively reviewed. The incidence of APSE rate was 0.020% (95% CI: 0.011-0.029%). Intraocular cultures were positive in 18 (32.1%) cases, with 21 organisms isolated. Coagulase-negative staphylococci was the predominant isolate (12/21; 57.1%). The time from surgery to the onset of endophthalmitis was 7 days (interquartile range: 3-16) in patients with good best-corrected visual acuity (BCVA) (≥20/70) and 3 days (interquartile range: 1-8) in those with poor BCVA (<20/70). Multivariate linear regression analysis revealed that initial BCVA (logMAR) (p < 0.001), time from onset to initial intravitreal antibiotics (IVAs) (p < 0.001), and positive culture of highly virulent pathogens (p = 0.018) displayed significantly positive associations with the final BCVA (logMAR). Adjunctive use of intravitreal corticosteroids and systemic antibiotics were unrelated to a favorable final BCVA. In conclusion, the severity of the visual condition at baseline, as well as delayed treatment, are risk factors for poor visual outcomes in APSE.

Renal Impact of Culprit-Only versus Multi-Vessel Revascularization for Cardiogenic Shock Complicating Acute Myocardial Infarction: Systematic Review and Meta-Analysis.

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries. Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled. Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87). Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI.

The Worsening Renal Perfusion Index Predicts the Prognoses of Heart Failure Patients Treated with Sacubitril/Valsartan.

INTRODUCTION: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V. METHODS: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox's models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates. RESULTS: In the Cox's model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF. CONCLUSIONS: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRPSV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF.

The emerging roles of Hedgehog signaling in tumor immune microenvironment.

The Hedgehog (Hh) signaling pathway is pervasively involved in human malignancies, making it an effective target for cancer treatment for decades. In addition to its direct role in regulating cancer cell attributes, recent work indicates that it has an immunoregulatory effect on tumor microenvironments. An integrated understanding of these actions of Hh signaling pathway in tumor cells and tumor microenvironments will pave the way for novel tumor treatments and further advances in anti-tumor immunotherapy. In this review, we discuss the most recent research about Hh signaling pathway transduction, with a particular emphasis on its role in modulating tumor immune/stroma cell phenotype and function, such as macrophage polarity, T cell response, and fibroblast activation, as well as their mutual interactions between tumor cells and nonneoplastic cells. We also summarize the recent advances in the development of Hh pathway inhibitors and nanoparticle formulation for Hh pathway modulation. We suggest that targeting Hh signaling effects on both tumor cells and tumor immune microenvironments could be more synergistic for cancer treatment.

Efficacy and safety of loteprednol etabonate versus fluorometholone in the treatment of patients after corneal refractive surgery: a meta-analysis.

PURPOSE: To perform a systematic evaluation of the efficacy and safety of loteprednol etabonate (LE) 0.5% versus fluorometholone (FML) 0.1% for treating patients after corneal refractive surgery with the aim of providing an evidence-based rationale for clinical drug selection. METHODS: Electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, WanFang, and CNKI) were searched (from inception to December 2021) for comparative clinical studies that evaluated LE versus FML treatment for post-corneal refractive surgery patients. Meta-analysis was performed using the RevMan 5.3 software. The pooled risk ratio (RR) and weighted mean difference (WMD) with corresponding 95% confidence interval (CI) were calculated. RESULTS: Nine studies with a total sample size of 2677 eyes were included in this analysis. FML 0.1% and LE 0.5% produced a similar incidence of corneal haze within 6 months after surgery (P = 0.13 at 1 month, P = 0.66 at 3 months, and P = 0.12 at 6 months). There was no statistically significant difference between the two groups in terms of the mean logMAR postoperative uncorrected distance visual acuity (WMD: - 0.00; 95% CI: - 0.01 to 0.00; P = 0.29) and spherical equivalent (WMD: 0.01; 95% CI: - 0.01 to 0.03; P = 0.35). LE 0.5% appears to have a higher tendency to reduce the incidence of ocular hypertension compared FML 0.1%, but there was no statistical significance (RR: 0.63; 95% CI: 0.27 to 1.50; P = 0.30). CONCLUSION: This meta-analysis demonstrated that LE 0.5% and FML 0.1% had comparable efficacy in preventing corneal haze and corticosteroid-induced ocular hypertension, with no difference in visual acuity in patients after corneal refractive surgery.

COVID-19 vaccine response and safety in patients with cancer: An overview of systematic reviews.

Background: To date, the COVID-19 pandemic does not appear to be overcome with new variants continuously emerging. The vaccination against COVID-19 has been the trend, but there are multiple systematic reviews on COVID-19 vaccines in patients with cancer, resulting in redundant and sub-optimal systematic reviews. There are still some doubts about efficacy and safety of the COVID-19 vaccine in cancer patients. Purpose: To identify, summarize and synthesize the available evidence of systematic reviews on response and COVID-19 vaccine safety in patients with cancer. Methods: Multiple databases were searched from their inception to May 1, 2022 to fetch the relevant articles. Study quality was assessed by AMSTAR2. The protocol of this study was registered on PROSPERO (CRD42022327931). Results: A total of 18 articles were finally included. The seroconversion rates after first dose were ranged from 37.30-54.20% in all cancers, 49.60-62.00% in solid cancers and 33.30-56.00% in hematological malignancies. The seroconversion rates after second dose were ranged from 65.30-87.70% in all cancers, 91.60-96.00% in solid cancers and 58.00-72.60% in hematological malignancies. Cancer types and types of therapy could influence vaccine response. COVID-19 vaccines were safe and well-tolerated. Conclusions: This study suggests COVID-19 vaccine response is significantly lower in cancer patients. Number of received doses, cancer types and treatment strategies could influence response of COVID-19 vaccine in cancer patients. COVID-19 vaccines are safe and well-tolerated. Considering the emergence of several new variants of SARS-CoV-2 with potential influence on ongoing vaccination programs, there is a need for booster doses to increase the effectiveness of COVID-19 vaccines. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022327931, identifier CRD42022327931.

Artificial intelligence-based internet hospital pharmacy services in China: Perspective based on a case study.

Background: Recently, internet hospitals have been emerging in China, saving patients time and money during the COVID-19 pandemic. In addition, pharmacy services that link doctors and patients are becoming essential in improving patient satisfaction. However, the existing internet hospital pharmacy service mode relies primarily on manual operations, making it cumbersome, inefficient, and high-risk. Objective: To establish an internet hospital pharmacy service mode based on artificial intelligence (AI) and provide new insights into pharmacy services in internet hospitals during the COVID-19 pandemic. Methods: An AI-based internet hospital pharmacy service mode was established. Initially, prescription rules were formulated and embedded into the internet hospital system to review the prescriptions using AI. Then, the "medicine pick-up code," which is a Quick Response (QR) code that represents a specific offline self-pick-up order, was created. Patients or volunteers could pick up medications at an offline hospital or drugstore by scanning the QR code through the window and wait for the dispensing machine or pharmacist to dispense the drugs. Moreover, the medication consultation function was also operational. Results: The established internet pharmacy service mode had four major functional segments: online drug catalog search, prescription preview by AI, drug dispensing and distribution, and AI-based medication consultation response. The qualified rate of AI preview was 83.65%. Among the 16.35% inappropriate prescriptions, 49% were accepted and modified by physicians proactively and 51.00% were passed after pharmacists intervened. The "offline self-pick-up" mode was preferred by 86% of the patients for collecting their medication in the internet hospital, which made the QR code to be fully applied. A total of 426 medication consultants were served, and 48.83% of them consulted outside working hours. The most frequently asked questions during consultations were about the internet hospital dispensing process, followed by disease diagnosis, and patient education. Therefore, an AI-based medication consultation was proposed to respond immediately when pharmacists were unavailable. Conclusion: The established AI-based internet hospital pharmacy service mode could provide references for pharmacy departments during the COVID-19 pandemic. The significance of this study lies in ensuring safe/rational use of medicines and raising pharmacists' working efficiency.