Association between ambient temperatures and injuries: a time series analysis using emergency ambulance dispatches in Chongqing, China.

BACKGROUND: Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury. METHODS: In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated. RESULTS: The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI[1.127,1.300]). The risks of traffic accident injury (CRR: 1.346; 95%CI[1.167,1.552]), beating injury (CRR: 1.508; 95%CI[1.165,1.952]), fall-height injury (CRR: 1.871; 95%CI[1.196-2.926]) and injury of sharp penetration (CRR: 2.112; 95%CI[1.388-3.213]) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI [1.063,1.400]) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI[1.009,1.024]) and over 60 years of age (RR: 1.019; 95%CI[1.011,1.025]) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI[1.071,1.162]) and 46-59 years (RR: 1.069; 95%CI[1.023,1.115]) had significant impact on injury risk. CONCLUSIONS: This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P<0.001. As the severity of DR increased, Df values decreased, P=0.031. No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics. CONCLUSION: In this study, an artificial intelligence retinal vessel segmentation system is used with 99% accuracy, thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology. DR patients have a tendency of vascular occlusion and dropout. The presence of DME does not compromise the integral retinal vascular pattern.

The causal effect of gut microbiota on hepatic encephalopathy: a mendelian randomization analysis.

BACKGROUND: There is growing evidence for a relationship between gut microbiota and hepatic encephalopathy (HE). However, the causal nature of the relationship between gut microbiota and HE has not been thoroughly investigated. METHOD: This study utilized the large-scale genome-wide association studies (GWAS) summary statistics to evaluate the causal association between gut microbiota and HE risk. Specifically, two-sample Mendelian randomization (MR) approach was used to identify the causal microbial taxa for HE. The inverse variance weighted (IVW) method was used as the primary MR analysis. Sensitive analyses were performed to validate the robustness of the results. RESULTS: The IVW method revealed that the genus Bifidobacterium (OR = 0.363, 95% CI: 0.139-0.943, P = 0.037), the family Bifidobacteriaceae (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039), and the order Bifidobacteriales (OR = 0.359, 95% CI: 0.133-0.950, P = 0.039) were negatively associated with HE. However, no causal relationship was observed among them after the Bonferroni correction test. Neither heterogeneity nor horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: Our MR study demonstrated a potential causal association between Bifidobacterium, Bifidobacteriaceae, and Bifidobacteriales and HE. This finding may provide new therapeutic targets for patients at risk of HE in the future.

A Spatio-temporal Bayesian model to estimate risk and influencing factors related to tuberculosis in Chongqing, China, 2014-2020.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease that is one of the leading causes of death worldwide. This study aimed to investigate the spatial and temporal distribution patterns and potential influencing factors of TB incidence risk, and to provide a scientific basis for the prevention and control of TB. METHODS: We collected reported cases of TB in 38 districts and counties in Chongqing from 2014 to 2020 and data on environment, population characteristics and economic factors during the same period. By constructing a Bayesian spatio-temporal model, we explored the spatio-temporal distribution pattern of TB incidence risk and potential influencing factors, identified key areas and key populations affected by TB, compared the spatio-temporal distribution characteristics of TB in populations with different characteristics, and explored the differences in the influence of various social and environmental factors. RESULTS: The high-risk areas for TB incidence in Chongqing from 2014 to 2020 were mainly concentrated in southeastern and northeastern regions of Chongqing, and the overall relative risk (RR) of TB showed a decreasing trend during the study period, while RR of TB in main urban area and southeast of Chongqing showed an increasing trend. The RR of TB was relatively high in the main urban area for the female population and the population aged 0-29 years, and the RR of TB for the population aged 30-44 years in the main urban area and the population aged 60 years or older in southeast of Chongqing had an increasing trend, respectively. For each 1 µg/m3 increase in SO2 and 1% increase in the number of low-income per 1000 non-agricultural households (LINA per 1000 persons), the RR of TB increased by 0.35% (95% CI: 0.08-0.61%) and 0.07% (95% CI: 0.05-0.10%), respectively. And LINA per 1000 persons had the greatest impact on the female population and the over 60 years old age group. Although each 1% increase in urbanization rate (UR) was associated with 0.15% (95% CI: 0.11-0.17%) reduction in the RR of TB in the whole population, the RR increased by 0.18% (95% CI: 0.16-0.21%) in the female population and 0.37% (95% CI: 0.34-0.45%) in the 0-29 age group. CONCLUSION: This study showed that high-risk areas for TB were concentrated in the southeastern and northeastern regions of Chongqing, and that the elderly population was a key population for TB incidence. There were spatial and temporal differences in the incidence of TB in populations with different characteristics, and various socio-environmental factors had different effects on different populations. Local governments should focus on areas and populations at high risk of TB and develop targeted prevention interventions based on the characteristics of different populations.

Overcoming chemoresistance to b-raf inhibitor in melanoma via targeted inhibition of phosphoenolpyruvate carboxykinase1 using 3-mercaptopropionic acid.

The resistance of melanoma to BRAF inhibitors remains a tough clinical challenge. In order to explore the underlying mechanism of drug resistance in melanoma, we established the resistant cell line to vemurafenib, and assessed the changes of drug-resistant cells on proliferation, apoptosis, oxidative stress and tumor stemness. Our results suggest that phosphoenolpyruvate carboxykinase1 (PCK1) is activated and inhibits the oxidative stress caused by vemurafenib in drug-resistant cells. Long term treatment of vemurafenib increases the expression of PCK1 which reduces the production of reactive oxygen species (ROS) by activating PI3K/Akt pathway. After the inhibition of PCK1 by 3-mercaptopropionic acid (3-MPA), the therapeutic sensitivity of vemurafenib is restored. In conclusion, this study disclosed that drug-resistant cells appeared to regulate their own proliferation, oxidative stress and tumor dryness by activating Akt/PCK1/ROS pathway, and shed new insights into acquiring drug resistance in melanoma.

Combining robot-assisted surgical system and 3D visualization system for teaching minimally invasive vitreoretinal surgery.

AIM: To investigate the feasibility of teaching minimally invasive vitreoretinal surgery with a robot-assisted surgical system and a three-dimensional (3D) visualization system. METHODS: Enucleated porcine eyes were established as an animal model for removing foreign bodies. Forty medical students were recruited to remove foreign bodies to compare the traditional microscope and the 3D system. One junior resident performed the surgical task with manual and robot-assisted operations on 20 porcine eyes for each group. One senior surgeon evaluated the retinal invasion by a graded injury degree. The learning curve for minimally invasive vitreoretinal surgery was described. RESULTS: Compared with the robot-assisted group, the injury degree was higher in the manual group. For the first ten surgeries, the manual and robot-assisted groups had injuries of 2.60±1.35 (4 to 0) and 1.80±1.62 (4 to 0), respectively. For the last ten surgeries, the injury degrees were 1.90±1.20 (3 to 0) and 0.80±0.42 (1 to 0). Considering the manual and robot-assisted groups together, 95%, 75% and 60% of the students considered surgical manipulation with the 3D visualization system to be more comfortable, easier and clearer, respectively. CONCLUSION: The robot-assisted surgical system and 3D visualization system may have value in teaching minimally invasive vitreoretinal surgery.

Macular density alterations in myopic choroidal neovascularization and the effect of anti-VEGF on it.

AIM: To analyse macular microvascular alterations in myopic choroidal neovascularization (mCNV) and the efficiency of anti-vascular endothelial growth factor (anti-VEGF) therapy for mCNV by optical coherence tomography angiography (OCTA). METHODS: A total of 123 patients were included in this retrospective study, divided into mCNV group, high myopia (HM) group, and normal group at the Affiliated Eye Hospital of Wenzhou Medical University from January 2017 to January 2019. Superficial vessel density, deep capillary density, foveal avascular zone (FAZ) area, A-circularity index (AI) and vessel density around the 300 µm width of the FAZ region density (FD) and the area of choroidal neovascularization (CNV) lesion (only for mCNV group) were measured on 3×3 mm2 OCTA images. FAZ area was corrected for axial length. Central macular thickness (CMT) was measured on OCT in mCNV group. Compared the parameters on OCTA of 3 groups and pre-anti-VEGF and post-anti-VEGF at 1, 2, 3, and 6mo follow-up in mCNV group. RESULTS: There were significant differences among 3 groups in superficial vessel density, deep capillary density and FD (P<0.05). FAZ area in HM group was smaller than normal group (P<0.05), but there was no significant difference between mCNV group and the other two group. AI increased in mCNV group (P<0.05). The mean CMT, area and flow area of CNV lesion decreased after treatment (P<0.05), while vessel density and FAZ didn't change. The mean CMT, area and flow area of CNV lesion statistically decreased after anti-VEGF treatment in mCNV group (P<0.05), while superficial vessel density, deep capillary density and FAZ area, AI and FD didn't change. The mean reduction ratio of lesions was 50.32% (7.07% to 100%). Lesion regression 100% was observed in 2 cases (4.88%). There was a negative correlation between the CNV lesion area and reduction ratio (r=-0.380, P=0.042) and the flow lesion area and reduction ratio (r=-0.402, P=0.030). CONCLUSION: Macular vessel density decreases, FAZ turns smaller and more irregular in mCNV eyes. Anti-VEGF therapy is efficient for mCNV without affecting vessel density and FAZ, but it is unable to completely eliminate CNV lesions in most cases. The bigger mCNV lesions have lower reduction ratio.

Prognostic genes of melanoma identified by weighted gene co-expression network analysis and drug repositioning using a network-based method.

Melanoma is one of the most malignant types of skin cancer. However, the efficacy and utility of available drug therapies for melanoma are limited. The objective of the present study was to identify potential genes associated with melanoma progression and to explore approved therapeutic drugs that target these genes. Weighted gene co-expression network analysis was used to construct a gene co-expression network, explore the associations between genes and clinical characteristics and identify potential biomarkers. Gene expression profiles of the GSE65904 dataset were obtained from the Gene Expression Omnibus database. RNA-sequencing data and clinical information associated with melanoma obtained from The Cancer Genome Atlas were used for biomarker validation. A total of 15 modules were identified through average linkage hierarchical clustering. In the two significant modules, three network hub genes associated with melanoma prognosis were identified: C-X-C motif chemokine receptor 4 (CXCR4), interleukin 7 receptor (IL7R) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG). The receiver operating characteristic curve indicated that the mRNA levels of these genes exhibited excellent prognostic efficiency for primary and metastatic tumor tissues. In addition, the proximity between candidate genes associated with melanoma progression and drug targets obtained from DrugBank was calculated in the protein interaction network, and the top 15 drugs that may be suitable for treating melanoma were identified. In summary, co-expression network analysis led to the selection of CXCR4, IL7R and PIK3CG for further basic and clinical research on melanoma. Utilizing a network-based method, 15 drugs that exhibited potential for the treatment of melanoma were identified.

Downregulation of RNF128 activates Wnt/ß-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma.

BACKGROUND: Ring finger proteins (RNFs) were involved in carcinogenesis. Here, we aimed to explore the detailed mechanism of RNF128 in the progression of melanoma. METHODS: We reanalyzed several gene expression profiles from the Gene Expression Omnibus (GEO) database and obtained the overlapped differential expressed RNF genes. Among them, RNF128 was selected to further explore its expression, the biological significance, and the underlying molecular mechanism, as well as the clinical relevance in melanoma patients. RESULTS: RNF128 was found to be significantly downregulated in the selected datasets, which was further verified in our melanoma tissues. Moreover, RNF128 downregulation was shown to correlate with the malignant phenotype of melanoma, and further functional assays demonstrated that low levels of RNF128 promoted melanoma progression via inducing cell epithelial-mesenchymal transition (EMT) and the acquisition of stemness. Mechanistically, RNF128 interference activated the Wnt pathway via simultaneously ubiquitinating CD44/cortactin (CTTN), resulting in CD44 and c-Myc transcription, thus revealed that RNF128 participated in a positive feedback of the Wnt pathway-CD44 loop. Clinically, we found that patients expressing low RNF128 and high CD44/CTTN levels had a poor prognosis. CONCLUSION: Downregulated RNF128 activates Wnt signaling to induce cellular EMT and stemness by ubiquitinating and degrading CD44/CTTN, and RNF128 is a reliable diagnostic and prognostic biomarker, and a deeper understanding of RNF128 may contribute to the treatment of melanoma.

TRIM44 activates the AKT/mTOR signal pathway to induce melanoma progression by stabilizing TLR4.

BACKGROUND: There is growing evidence that tripartite motif-containing protein 44 (TRIM44) plays crucial role in tumor development. However, the underlying mechanism of this deubiquitinating enzyme remains unclear. METHODS: Large clinical samples were used to detect TRIM44 expression and its associations with clinicopathological features and prognosis. Gain- and loss-of-function experiments in cell lines and mouse xenograft models were performed to elucidate the function and underlying mechanisms of TRIM44 induced tumor progression. Co-immunoprecipitation (Co-IP) assays and mass spectrometric analyses were applied to verify the interacting proteins of TRIM44. RESULTS: We found that TRIM44 was commonly amplified in melanoma tissues compared with paratumoral tissues. TRIM44 expression also positively correlated with more aggressive clinicopathological features, such as Breslow depth (p = 0.025), distant metastasis (p = 0.012), and TNM stage (p = 0.002). Importantly, we found that TRIM44 was an independent indicator of prognosis for melanoma patients. Functionally, overexpression of TRIM44 facilitated cell invasion, migration, apoptosis resistance and proliferation in vitro, and promoted lung metastasis and tumorigenic ability in vivo. Importantly, high level of TRIM44 induced melanoma cell epithelial-mesenchymal transition (EMT), which is one of the most important mechanisms for the promotion of tumor metastasis. Mechanistically, high levels of TRIM44 increased the levels of p-AKT (T308) and p-mTOR (S2448), and a specific AKT inhibitor inhibited TRIM44-induced tumor progression. Co-IP assays and mass spectrometric analyses indicated that TRIM44 overexpression induces cell EMT through activating AKT/mTOR pathway via directly binding and stabilizing TOLL-like receptor 4 (TLR4), and TLR4 interference impeded TRIM44 induced tumor progression. Moreover, we demonstrated that TRIM44 is the target of miR-26b-5p, which is significantly downregulated in melanoma tissues and may be responsible for the overexpression of TRIM44. CONCLUSIONS: TRIM44, regulated by miR-26b-5p, promotes melanoma progression by stabilizing TLR4, which then activates the AKT/mTOR pathway. TRIM44 shows promise as a prognostic predictor and a therapeutic target for melanoma patients.