RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer.

Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.

Spatiotemporal dynamics and determinants of medical service efficiency in China.

BACKGROUND: Medical service efficiency is an important indicator for measuring the equity of medical services. Therefore, this study primarily focuses on investigating the spatiotemporal domain to explore both spatial and temporal characteristics, as well as influencing factors that affect medical service efficiency across diverse provinces in China. METHODS: The super Epsilon-based Measure (EBM) unexpected model has previously been utilized to quantify energy eco-efficiency, carbon emission efficiency, and green development efficiency. However, limited studies have applied this method to assess the efficiency of healthcare services. Therefore, this study investigates the application of the super-EBM-unexpected model in evaluating medical service efficiency, and further integrates spatial econometric models to explore the influencing factors of medical service efficiency and aims to identify potential avenues for improvement. RESULTS: The average efficiency of medical services in the 31 provinces of China ranges from 0.6 to 0.7, indicating predominantly low efficiency values. However, economically developed coastal areas exhibit relatively high efficiency levels above 1. Conversely, regions with relatively lower levels of economic development demonstrate lower efficiency rates at approximately 0.3. Evidently, substantial regional disparities exist. For the influencing factors, the enhancement of residents' living standards can effectively foster the medical service efficiency, while residential living standards of nearby areas can also exert an impact in this region. The influence of educational attainment on medical service efficiency exhibits a significant inhibitory effect. CONCLUSIONS: The majority of China's 31 provinces exhibit suboptimal medical service efficiency, with notable regional disparities. Future policy initiatives should be tailored to address the unique challenges faced by regions with lower levels of economic development, prioritizing enhancements in both the efficacy and quality of their healthcare systems.

Risk Management for Whole-Process Safe Disposal of Medical Waste: Progress and Challenges.

Over the past decade, the global outbreaks of SARS, influenza A (H1N1), COVID-19, and other major infectious diseases have exposed the insufficient capacity for emergency disposal of medical waste in numerous countries and regions. Particularly during epidemics of major infectious diseases, medical waste exhibits new characteristics such as accelerated growth rate, heightened risk level, and more stringent disposal requirements. Consequently, there is an urgent need for advanced theoretical approaches that can perceive, predict, evaluate, and control risks associated with safe disposal throughout the entire process in a timely, accurate, efficient, and comprehensive manner. This article provides a systematic review of relevant research on collection, storage, transportation, and disposal of medical waste throughout its entirety to illustrate the current state of safe disposal practices. Building upon this foundation and leveraging emerging information technologies like Internet of Things (IoT), cloud computing, big data analytics, and artificial intelligence (AI), we deeply contemplate future research directions with an aim to minimize risks across all stages of medical waste disposal while offering valuable references and decision support to further advance safe disposal practices.

Associations of IL-12, IL12R polymorphisms and serum IL-12 levels with high-risk human papillomavirus susceptibility in rural women from Luohe, Henan, China.

BACKGROUND: Interleukin 12 (IL-12) and interleukin 12 receptor (IL12R), key inflammatory cytokines in the immune system, participate in bridging the innate immunity and adaptive immunity. No previous work has reported the role of IL-12 and IL12R in high-risk human papillomavirus (hrHPV) susceptibility. The purpose of this study was to investigate the association of IL-12, IL12R polymorphisms, and serum IL-12 levels with hrHPV susceptibility in rural women from Luohe, Henan, China. METHODS: Two hundred sixty cases with hrHPV infection and 260 healthy controls were selected. Enzyme-linked immunosorbent assays were used to detect the serum IL-12 levels, and the polymorphisms of IL12B rs3212227, IL12RB1 rs393548, and IL12RB1 rs436857 were determined using DNA sequencing. RESULTS: The serum IL-12 levels were significantly lower in cases with hrHPV infection compared with those in healthy controls (P < .01).There was no significant difference in IL12 rs3212227, IL12RB1rs436857, and IL12RB1rs393548 genotype and allele frequencies between cases and controls (P > .05). Furthermore, with respect to the IL12 rs3212227 polymorphism with serum IL-12 levels, although serum IL-12 levels were lower in cases than in controls, we did not find any differences between serum IL-12 levels and genotypes in cases(P > .05). CONCLUSIONS: Our data demonstrates that low serum IL-12 levels may be associated with hrHPV susceptibility but are not associated with IL-12 gene polymorphisms; furthermore, IL-12 and IL12R gene polymorphisms may not contribute susceptibility to hrHPV in rural women from Luohe, Henan, China.

Polymorphism of IFN-γ +874T/A associated with production of IFN-γ affects human papillomavirus susceptibility in rural women from Luohe, Henan, China.

PURPOSE: In this paper, the association between polymorphisms of IFN-γ +874T/A (rs2430561), IFN-γR1 -56 T/C (rs2234711), IFN-γR1 +95 C/T (rs7749390), and IFN-γR1 -611A/G (rs 1327474) and human papillomavirus (HPV) susceptibility was investigated in rural women from Luohe, Henan, China. PATIENTS AND METHODS: A total of 520 rural women were enrolled from Luohe, including 260 with HPV infection and mild dysplasia or less and 260 without HPV infection. Single-nucleotide polymorphisms (SNPs) of IFN-γ +874T/A, IFN-γR1 -56 T/C, IFN-γR1 +95 C/T and IFN-γR1 -611A/G were genotyped using TaqMan Pre-Designed SNP Genotyping Assays. Serum IFN-γ levels were measured using Human IFN-γ Quantikine ELISA Kit. Multivariate logistic regression analysis was performed to identify the SNPs associated with HPV susceptibility. Serum IFN-γ levels were compared between different genotypes. RESULTS: The polymorphism of IFN-γ +874T/A was associated with HPV susceptibility and +874A carriers had an increased risk. Moreover, the odds ratio was higher in +874 AA carriers than in +874 AT carriers (1.672 vs 2.874). Serum IFN-γ levels were highest in IFN-γ +874 TT carriers, intermediate in AT carriers, and lowest in AA carriers (2.86±1.14 vs 1.57±0.79 vs 0.41±0.22 pg/mL, all P<0.05). CONCLUSION: The polymorphism of IFN-γ +874T/A was associated with HPV susceptibility in rural women from Luohe, Henan, China, and +874A carriers had an increased risk. The possible mechanism was that +874A carriers had a low production of IFN-γ.

The application of poly (glycerol-sebacate) as biodegradable drug carrier.

Poly (glycerol-sebacate) (PGS) is an elastomeric biodegradable polymer which possesses the ideal properties of drug carriers. In the present study, we prepared a series of PGS implants (5-FU-PGSs) loaded with different weight percent of 5-fluorouracil (2, 5, 7.5 and 10%). We studied the infrared spectrum properties, in vitro degradation and drug release, in vivo degradation and tissue biocompatibility of 5-FU-PGSs, in order to provide detailed information for the application of PGS as biodegradable drug carrier in cancer therapy. Macroscopically, all 5-FU-PGS wafers in phosphate buffer solution (PBS) kept their geometries during the degradation period of 30 days. The in vitro degradation rates of 5-FU-PGSs were accelerated when higher concentration of 5-FU was doped. Scanning electron microscopy observation showed that the surfaces of 5-FU-PGSs with higher concentration of 5-FU had irregular pits. The cumulative drug release profiles of 5-FU-PGSs exhibited a biphasic release with an initial burst release in the first day. After 7 days, almost 100% cumulative release of 5-FU was found for all 5-FU-PGSs.The degradation rate of 5-FU-PGSs in vivo was much quicker than that in vitro. Hematoxylin and eosin staining showed that no remarkable inflammations were observed in the tissue surrounding 5-FU-PGS implants, suggesting 5-FU-PGSs had good biocompatibility and no tissue toxicity. In vitro anti-tumor activity assay suggested that 5-FU-PGSs exhibited anti-tumor activity through sustained-release drug mode. These results demonstrate that PGS is a candidate of biodegradable drug carriers.