The epidemiology and clinical features of post-exposure prophylaxis for rabies: A retrospective study of 9772 cases.

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P<0.0001). There was a greater possibility for elderly people to be bitten by dogs (P<0.0001). Dogs preferred to bite or scratch lower limbs (P<0.0001), while cats upper limbs (P<0.0001). Upper limbs were more possibly attacked by animals at home (P<0.0001). There were significant correlations among exposure grade, wound treatment and number of wounds. Conclusions: Lower extremity protection is needed for the elderly and when encountering dogs, and more attention needs to be paid to the upper extremities when encountering cats and household pets, as well as pets that are cute but need to be protected from bites or scratches.

The added value of apparent diffusion coefficient and microcalcifications to the Kaiser score in the evaluation of BI-RADS 4 lesions.

PURPOSE: To explore the added value of combining microcalcifications or apparent diffusion coefficient (ADC) with the Kaiser score (KS) for diagnosing BI-RADS 4 lesions. METHODS: This retrospective study included 194 consecutive patients with 201 histologically verified BI-RADS 4 lesions. Two radiologists assigned the KS value to each lesion. Adding microcalcifications, ADC, or both these criteria to the KS yielded KS1, KS2, and KS3, respectively. The potential of all four scores to avoid unnecessary biopsies was assessed using the sensitivity and specificity. Diagnostic performance was evaluated by the area under the curve (AUC) and compared between KS and KS1. RESULTS: The sensitivity of KS, KS1, KS2, and KS3 ranged from 77.1% to 100.0%.KS1 yielded significantly higher sensitivity than other methods (P < 0.05), except for KS3 (P > 0.05), most of all, when assessing NME lesions. For mass lesions, the sensitivity of these four scores was comparable (p > 0.05). The specificity of KS, KS1, KS2, and KS3 ranged from 56.0% to 69.4%, with no statistically significant differences(P > 0.05), except between KS1 and KS2 (p < 0.05).The AUC of KS1 (0.877) was significantly higher than that of KS (0.837; P = 0.0005), particularly for assessing NME (0.847 vs 0.713; P < 0.0001). CONCLUSION: KS can stratify BI-RADS 4 lesions to avoid unnecessary biopsies. Adding microcalcifications, but not adding ADC, as an adjunct to KS improves diagnostic performance, particularly for NME lesions. ADC provides no additional diagnostic benefit to KS. Thus, only combining microcalcifications with KS is most conducive to clinical practice.

Development and validation of a clinical predictive model for 1-year prognosis in coronary heart disease patients combine with acute heart failure.

Background: The risk factors for acute heart failure (AHF) vary, reducing the accuracy and convenience of AHF prediction. The most common causes of AHF are coronary heart disease (CHD). A short-term clinical predictive model is needed to predict the outcome of AHF, which can help guide early therapeutic intervention. This study aimed to develop a clinical predictive model for 1-year prognosis in CHD patients combined with AHF. Materials and methods: A retrospective analysis was performed on data of 692 patients CHD combined with AHF admitted between January 2020 and December 2020 at a single center. After systemic treatment, patients were discharged and followed up for 1-year for major adverse cardiovascular events (MACE). The clinical characteristics of all patients were collected. Patients were randomly divided into the training (n = 484) and validation cohort (n = 208). Step-wise regression using the Akaike information criterion was performed to select predictors associated with 1-year MACE prognosis. A clinical predictive model was constructed based on the selected predictors. The predictive performance and discriminative ability of the predictive model were determined using the area under the curve, calibration curve, and clinical usefulness. Results: On step-wise regression analysis of the training cohort, predictors for MACE of CHD patients combined with AHF were diabetes, NYHA ≥ 3, HF history, Hcy, Lp-PLA2, and NT-proBNP, which were incorporated into the predictive model. The AUC of the predictive model was 0.847 [95% confidence interval (CI): 0.811-0.882] in the training cohort and 0.839 (95% CI: 0.780-0.893) in the validation cohort. The calibration curve indicated good agreement between prediction by nomogram and actual observation. Decision curve analysis showed that the nomogram was clinically useful. Conclusion: The proposed clinical prediction model we have established is effective, which can accurately predict the occurrence of early MACE in CHD patients combined with AHF.

Predictive Value of Non-high-Density Lipoprotein Cholesterol and Neutrophil-Lymphocyte Ratio for Coronary Artery Vulnerable Plaques in Type 2 Diabetes Mellitus.

Background: Patients with diabetes have an increased risk of developing vulnerable plaques (VPs), in which dyslipidemia and chronic inflammation play important roles. Non-high-density lipoprotein cholesterol (non-HDL-C) and neutrophil-lymphocyte ratio (NLR) have emerged as potential markers of both coronary artery VPs and cardiovascular prognosis. This study aimed to investigate the predictive value of non-HDL-C and NLR for coronary artery VPs in patients with type 2 diabetes mellitus (T2DM). Methods: We retrospectively enrolled 204 patients with T2DM who underwent coronary computed tomography angiography between January 2018 and June 2020. Clinical data including age, sex, hypertension, smoking, total cholesterol, low-density lipoprotein cholesterol, HDL-C, triglyceride, non-HDL-C, glycated hemoglobin, neutrophil count, lymphocyte count, NLR, and platelet count were analyzed. Multivariate logistic regression was used to estimate the association between non-HDL-C, NLR, and coronary artery VPs. Receiver operating curve analysis was performed to evaluate the value of non-HDL-C, NLR, and their combination in predicting coronary artery VPs. Results: In our study, 67 patients (32.84%) were diagnosed with VPs, 75 (36.77%) with non-VP, and 62 (30.39%) with no plaque. Non-HDL-C and NLR were independent risk factors for coronary artery VPs in patients with T2DM. The areas under the ROC curve of non-HDL-C, NLR, and their combination were 0.748 [95% confidence interval (CI): 0.676-0.818], 0.729 (95% CI: 0.650-0.800), and 0.825 (95% CI: 0.757-0.887), respectively. Conclusion: Either non-HDL-C or NLR could be used as a predictor of coronary artery VPs in patients with T2DM, but the predictive efficiency and sensitivity of their combination would be better.

Prognostic Evaluation of Patients with Rectal Neuroendocrine Neoplasms and Hepatic Metastases: A SEER Database Analysis.

Background: This study is aimed at investigating the clinical characteristics and prognosis-affecting factors of patients with rectal neuroendocrine neoplasms (r-NENs) and hepatic metastases and offering a scientific-theoretical basis for selective use of an optimized treatment method for r-NENs. Methods: This study was retrospectively evaluated based on the analysis of the data from Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Results: A total of 4,723 r-NEN patients were enrolled in this study, including 168 patients with hepatic metastases (3.56%). Kaplan-Meier analysis revealed that the overall survival (OS) of patients with hepatic metastases receiving primary tumor excision was obviously greater than that of patients without receiving primary tumor excision (OS: nonsurgical patients vs. patients undergoing local resection: P < 0.0001 and nonsurgical patients vs. patients undergoing radical resection: P < 0.0001); the patients with hepatic metastases in the chemotherapy group had a significantly worse prognosis compared with those in the nonchemotherapy group (OS: P = 0.021). Multivariate cox regression analysis revealed that independent affecting factors of overall and tumor-related prognoses in patients with hepatic metastases included tumor grade (G3 and G4), surgical treatment, and chemotherapy. Conclusion: Among r-NEN patients with hepatic metastases, those undergoing radical excision of lower-grade tumors and chemotherapy will have a better prognosis.

TCF-3-mediated transcription of lncRNA HNF1A-AS1 targeting oncostatin M expression inhibits epithelial-mesenchymal transition via TGFß signaling in gastroenteropancreatic neuroendocrine neoplasms.

Long noncoding RNAs play key roles in several cancers, but their potential functions in gastroenteropancreatic neuroendocrine neoplasms remain to be investigated. We performed GeneChip assay to explore differentiated lncRNAs in gastric NENs and peri-cancerous tissues. The regulation of HNF1A-AS1 on biological behavior of GEP-NENs cells and in vivo xenograft model was confirmed by CCK8, colony formation assay, transwell, western blot and qRT-PCR. We next detected the potential transcription factors and the binding sites between them with bioinformatic analysis. qRT-PCR was performed to analyze the exact relationship between them. HNF1A-AS1 expression was decreased in gastric NENs tissues (p < 0.01). Over-expression of HNF1A-AS1 suppressed cellular proliferation, migration and invasion. Knockdown of transcription factor 3 inhibited the expression of HNF1A-AS1 and promoted cellular migration and invasion. Oncostatin M was identified as the downstream target of HNF1A-AS1. Inhibition of transforming growth factor-ß activity inhibited HNF1A-AS1/Oncostatin M-mediated epithelial-mesenchymal transition. Our data suggest that transcription factor 3/HNF1A-AS1/Oncostatin M axis inhibits the tumorigenesis and metastasis of gastroenteropancreatic neuroendocrine neoplasms via transforming growth factor-ß signaling.

A novel resveratrol-curcumin hybrid, a19, attenuates high fat diet-induced nonalcoholic fatty liver disease.

Both inflammation and fibrosis are essential in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Taking inflammatory cytokines and signaling pathways as vital mediators, the inhibition of inflammation response may be an effective approach for treating NAFLD. a19, a resveratrol-curcumin hybrid, has been confirmed to exhibit a good anti-inflammatory activity by preventing LPS-induced inflammatory response in macrophages. The study aims to evaluate the protective effect of a19 on high fat diet (HFD)-induced NAFLD. In the present study, compound a19 significantly inhibited the HFD-induced lipid accumulation, liver injury, liver inflammation and fibrosis in mouse model. In vitro, a19 obviously suppressed the expression of PA-induced inflammatory cytokines and fibrosis markers mRNA. Meanwhile, the anti-inflammatory effect of a19 was found to be associated with the inhibition of ERK signal pathway. These results indicated that a19 can be potentially used as a protective agent for NAFLD.

Curcumin analog L48H37 induces apoptosis through ROS-mediated endoplasmic reticulum stress and STAT3 pathways in human lung cancer cells.

Lung cancer is the leading cause of cancer-related deaths. Curcumin is a well-known natural product with anticancer ability, however, its poor bioavailability and pharmacokinetic profiles have limited its application in anticancer therapy. Previously, we reported that L48H37, a novel analog of curcumin with higher bioavailability, ameliorated LPS-induced inflammation, but the anticancer effect of L48H37 is still unknown. In the present study, we have investigated the effects of L48H37 in human lung cancer cells. Our results show that L48H37 decreases lung cancer cell growth and colony formation. These alterations were mediated through induction of G2/M cell cycle arrest and apoptosis in lung cancer cells. After L48H37 treatment, ER stress-related proteins were increased, and the expression of p-STAT3 was decreased in a dose-dependent manner. L48H37 also induced the accumulation of ROS in lung cancer cells, and pretreatment with NAC could fully reverse L48H37-induced reactive oxygen species (ROS) increase. Blocking ROS was able to reverse L48H37-induced endoplasmic reticulum (ER) stress, cell cycle arrest, and apoptosis. Finally, we show that L48H37 inhibits the growth of lung cancer xenografts without exhibiting toxicity. Treatment of mice bearing human lung cancer xenografts with L48H37 was also associated with indices of ER stress activation. In summary, our results provide evidence for a novel anti-tumor candidate for the treatment of lung cancer.

Development of resveratrol-curcumin hybrids as potential therapeutic agents for inflammatory lung diseases.

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. Resveratrol and curcumin are proven to have potent anti-inflammatory efficacy, but their clinical application is limited by their metabolic instability. Here, a series of resveratrol and the Mono-carbonyl analogs of curcumin (MCAs) hybrids were designed and synthesized by efficient aldol construction strategy, and then screened for anti-inflammatory activities in vitro and in vivo. The results showed that the majority of analogs effectively inhibited the LPS-induced production of IL-6 and TNF-α. Five analogs, a9, a18, a19, a20 and a24 exhibited excellent anti-inflammatory activity in a dose-dependent manner along with low toxicity in vitro. Structure activity relationship study revealed that the electron-withdrawing groups at meta-position and methoxyl group (OCH3) at the para position of the phenyl ring were important for anti-inflammatory activities. The most promising compound a18 decreased LPS induced TNF-α, IL-6, IL-12, and IL-33 mRNA expression. Additionally, a18 significantly protected against LPS-induced acute lung injury in the in vivo mouse model. The research of resveratrol and MCAs hybrids could bring insight into the treatment of inflammatory diseases and compound a18 may serve as a lead compound for the development of anti-ALI agents.

Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.

Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents.