Objective:A two-sample bidirectional Mendelian randomization (MR) analysis was used to analyze the risk factors related to sunburn.Methods:Data were downloaded from the Gene-Wide Association Studies (GWAS) of the IEU Open GWAS project, and a two-sample bidirectional MR was conducted. In the forward MR analysis, the exposure factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment, while the outcome factor was sunburn. In the reverse MR analysis, the exposure factor was sunburn, while the outcome factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment. The data were analyzed using the "TwoSampleMR" package in R version 4.2.3. The result of the MR analysis were interpreted using the odds ratio ( OR) and the corresponding 95% confidence interval (95% CI), and a P-value <0.05 was considered statistically significant. In the analysis, we set a significance threshold of P-value<5×10 -8 (if sufficient instrumental variables cannot be obtained, the threshold will be adjusted to P-value<5×10 -6), eliminated linkage disequilibrium (with R2<0.001 and within a regional range of 10 000 kb), and screened single nucleotide polymorphisms (SNPs) that were significantly related to the research content, which would be set in the analysis as instrumental variables (IVs). For eligible IVs, a MR was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode method to explore the causal relationships between sunburn and various factors. The result obtained by the IVW method were taken as the main outcome indicator and summarized into a forest plot, while other method were used to supplement the IVW result. The heterogeneity of the IVs was evaluated by the Cochran Q-test. The direction of the causal effect and heterogeneity were evaluated through the scatter plot. The sensitivity of the result was analyzed by the leave-one-out test. The funnel plot was used to assess the potential bias. Results:9 851 867 SNPs related to skin color, 9 851 867 SNPs related to ease of skin tanning, 11 972 414 SNPs related to skin pigmentation, 9 851 867 SNPs related to facial aging, 16 121 213 SNPs related to atopic dermatitis, 24 191 078 SNPs related to contact dermatitis, 24 187 496 SNPs related to urticaria, 11 972 619 SNPs related to education attainment were obtained from the GWAS database. A total of 11 976 212 SNPs were obtained from the sunburn dataset. In the forward MR analysis, the IVW result showed a significant negative correlation between skin color and sunburn ( OR=0.68, 95% CI: 0.66-0.70, P<0.001); and a significant positive correlation between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment, and sunburn (ease of skin tanning: OR=1.30, 95% CI: 1.29-1.32, P<0.001; skin pigmentation: OR=1.76, 95% CI: 1.66-1.87, P<0.001; facial aging: OR=2.25, 95% CI: 1.67-3.04, P<0.001; atopic dermatitis: OR=1.02, 95% CI: 1.00-1.03, P=0.010; contact dermatitis: OR=1.01, 95% CI: 1.00-1.01, P=0.031; education attainment: OR=1.29, 95% CI: 1.22-1.36, P<0.001); while urticaria was not statistically significant ( P=0.056). The Cochran Q-test and scatter plot showed that there was a significant negative correlation between skin color and sunburn and a positive correlations between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment and sunburn. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the forward MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result. In the reverse MR analysis, the IVW result showed a significant negative correlation between sunburn and skin color ( OR=0.16, 95% CI: 0.12-0.21, P<0.001); and a significant positive correlation between sunburn and ease of skin tanning, skin pigmentation, facial aging (ease of skin tanning: OR=26.78, 95% CI: 20.52-34.93, P<0.001; skin pigmentation: OR=3.12, 95% CI: 2.57-3.78, P<0.001; facial aging: OR=1.30, 95% CI: 1.24-1.37, P<0.001); while atopic dermatitis ( P=0.477), contact dermatitis ( P=0.318), urticaria ( P=0.328) and education attainment ( P=0.627) as outcome factors were not statistically significant. The Cochran Q-test and scatter plot showed that there was a significant negative correlation between sunburn and skin color and a positive correlations between sunburn and ease of skin tanning, skin pigmentation, facial aging. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the reverse MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result . Conclusions:Skin color and sunburn are protective factors against each other; ease of skin tanning, skin pigmentation, and facial aging are bidirectional risk factors of sunburn; atopic dermatitis, contact dermatitis, and education attainment are risk factors of sunburn.

Objective:A two-sample bidirectional Mendelian randomization (MR) analysis was used to analyze the risk factors related to sunburn.Methods:Data were downloaded from the Gene-Wide Association Studies (GWAS) of the IEU Open GWAS project, and a two-sample bidirectional MR was conducted. In the forward MR analysis, the exposure factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment, while the outcome factor was sunburn. In the reverse MR analysis, the exposure factor was sunburn, while the outcome factors were skin color, ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, urticaria, and education attainment. The data were analyzed using the "TwoSampleMR" package in R version 4.2.3. The result of the MR analysis were interpreted using the odds ratio ( OR) and the corresponding 95% confidence interval (95% CI), and a P-value <0.05 was considered statistically significant. In the analysis, we set a significance threshold of P-value<5×10 -8 (if sufficient instrumental variables cannot be obtained, the threshold will be adjusted to P-value<5×10 -6), eliminated linkage disequilibrium (with R2<0.001 and within a regional range of 10 000 kb), and screened single nucleotide polymorphisms (SNPs) that were significantly related to the research content, which would be set in the analysis as instrumental variables (IVs). For eligible IVs, a MR was conducted using the MR Egger, Weighted median, Inverse variance weighted (IVW), Simple mode, and Weighted mode method to explore the causal relationships between sunburn and various factors. The result obtained by the IVW method were taken as the main outcome indicator and summarized into a forest plot, while other method were used to supplement the IVW result. The heterogeneity of the IVs was evaluated by the Cochran Q-test. The direction of the causal effect and heterogeneity were evaluated through the scatter plot. The sensitivity of the result was analyzed by the leave-one-out test. The funnel plot was used to assess the potential bias. Results:9 851 867 SNPs related to skin color, 9 851 867 SNPs related to ease of skin tanning, 11 972 414 SNPs related to skin pigmentation, 9 851 867 SNPs related to facial aging, 16 121 213 SNPs related to atopic dermatitis, 24 191 078 SNPs related to contact dermatitis, 24 187 496 SNPs related to urticaria, 11 972 619 SNPs related to education attainment were obtained from the GWAS database. A total of 11 976 212 SNPs were obtained from the sunburn dataset. In the forward MR analysis, the IVW result showed a significant negative correlation between skin color and sunburn ( OR=0.68, 95% CI: 0.66-0.70, P<0.001); and a significant positive correlation between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment, and sunburn (ease of skin tanning: OR=1.30, 95% CI: 1.29-1.32, P<0.001; skin pigmentation: OR=1.76, 95% CI: 1.66-1.87, P<0.001; facial aging: OR=2.25, 95% CI: 1.67-3.04, P<0.001; atopic dermatitis: OR=1.02, 95% CI: 1.00-1.03, P=0.010; contact dermatitis: OR=1.01, 95% CI: 1.00-1.01, P=0.031; education attainment: OR=1.29, 95% CI: 1.22-1.36, P<0.001); while urticaria was not statistically significant ( P=0.056). The Cochran Q-test and scatter plot showed that there was a significant negative correlation between skin color and sunburn and a positive correlations between the ease of skin tanning, skin pigmentation, facial aging, atopic dermatitis, contact dermatitis, education attainment and sunburn. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the forward MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result. In the reverse MR analysis, the IVW result showed a significant negative correlation between sunburn and skin color ( OR=0.16, 95% CI: 0.12-0.21, P<0.001); and a significant positive correlation between sunburn and ease of skin tanning, skin pigmentation, facial aging (ease of skin tanning: OR=26.78, 95% CI: 20.52-34.93, P<0.001; skin pigmentation: OR=3.12, 95% CI: 2.57-3.78, P<0.001; facial aging: OR=1.30, 95% CI: 1.24-1.37, P<0.001); while atopic dermatitis ( P=0.477), contact dermatitis ( P=0.318), urticaria ( P=0.328) and education attainment ( P=0.627) as outcome factors were not statistically significant. The Cochran Q-test and scatter plot showed that there was a significant negative correlation between sunburn and skin color and a positive correlations between sunburn and ease of skin tanning, skin pigmentation, facial aging. There was some heterogeneity among the IVs in research. The result of the leave-one-out test showed that no SNPs had a distinct impact on the causal effect, and the result of the reverse MR analysis were relatively stable. The result of the funnel plot showed that the included SNPs were symmetrically distributed, and there was no potential bias in the result . Conclusions:Skin color and sunburn are protective factors against each other; ease of skin tanning, skin pigmentation, and facial aging are bidirectional risk factors of sunburn; atopic dermatitis, contact dermatitis, and education attainment are risk factors of sunburn.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

Influenza imposes a significant disease burden on society and individuals annually, and influenza vaccination is considered a significant public health measure to prevent influenza and reduce influenza-related severe disease and death. The low influenza vaccination rate in China is partly due to certain factors affecting the willingness and behavior of individuals to receive them. Scientific research and targeted interventions on these factors can effectively improve the vaccination situation. Commonly used individual-level theoretical models for influenza vaccination behavior include the health belief model, protection motivation theory, and theory of planned behavior. This study reviews theoretical models commonly employed in researching influenza vaccination willingness and behavior. An overview of these practical applications and challenges models is presented to provide references for relevant research and intervention programs in China.

Artificial intelligence (AI) has important significance and great promise in the pathological diagnosis,imaging diagnosis,prognosis prediction,and molecular subtyping of prostate cancer (PCa). This review focuses on the progress of AI for the diagnosis and molecular classification of PCa,and briefly introduces the application of AI in the pathological diagnosis of needle biopsy and Gleason grading,pathological diagnosis and grading after prostatectomy,and prognosis prediction of PCa patients based on pathological sections. For the pathological diagnosis of needle biopsy and Gleason grading,AI has already comparable to general pathologists;for the pathological diagnosis and grading after prostatectomy,AI can accurately grade and classify tumors;and for the prognosis prediction of PCa patients,AI can directly extract relevant prognostic information from pathological tissue sections for prognosis prediction. In addition,AI can also predict gene mutations in PCa patients and suggest the probability of gene mutation by analyzing the pathological sections.

AIM:To investigate the therapeutic effect of enteric-coated sustained-release new dosage form of tadalafil on mice with renal fibrosis caused by unilateral ureteral obstruction(UUO).METHODS:Eight-week-old male C57BL/6J mice were divided into four groups randomly:sham group,UUO group,UUO+new dosage form of tadalafil(1 mg/kg)group and UUO+original patented drug of tadalafil(5 mg/kg)group.Surgery was performed to create a mouse UUO model,and therapeutic drugs were administered intragastrically for 7 d after modeling.A fully automated biochemi-cal analyzer was used to detect serum creatinine(SCr)levels of each group.Through renal histopathological staining(HE staining,Masson trichrome staining,and immunohistochemistry staining)and Western blot,we assessed the therapeutic effect of enteric-coated sustained-release new dosage forms of tadalafil on kidney fibrosis in mice,as well as its effect on the expression and distribution of fibronectin(FN)and α-smooth muscle actin(α-SMA).RESULTS:Compared with sham group,the SCr levels were significantly increased in mice with renal fibrosis,and renal tubules were dilated and in-filtrated with inflammation.Moreover,the expressions of FN and α-SMA were increased significantly(P<0.05).New dosage form and the original patented drug tadalafil both significantly reduced SCr levels in mice with renal fibrosis,im-proved the renal tissue structure on the affected side,reduced collagen fiber deposition,and inhibited FN and α-SMA ex-pression(P<0.05).CONCLUSION:Enteric-coated sustained-release new dosage form of tadalafil reduces the deposit of extracellular matrix in kidney interstitial tissue and attenuates fibrosis and renal function damage caused by ureteral ob-struction.New dosage form of tadalafil has significant advantages over the original patented drug because the low dose and high effectiveness.

Objective:Glioblastoma(GBM)and brain metastases(BMs)are the two most common malignant brain tumors in adults.Magnetic resonance imaging(MRI)is a commonly used method for screening and evaluating the prognosis of brain tumors,but the specificity and sensitivity of conventional MRI sequences in differential diagnosis of GBM and BMs are limited.In recent years,deep neural network has shown great potential in the realization of diagnostic classification and the establishment of clinical decision support system.This study aims to apply the radiomics features extracted by deep learning techniques to explore the feasibility of accurate preoperative classification for newly diagnosed GBM and solitary brain metastases(SBMs),and to further explore the impact of multimodality data fusion on classification tasks. Methods:Standard protocol cranial MRI sequence data from 135 newly diagnosed GBM patients and 73 patients with SBMs confirmed by histopathologic or clinical diagnosis were retrospectively analyzed.First,structural T1-weight,T1C-weight,and T2-weight were selected as 3 inputs to the entire model,regions of interest(ROIs)were manually delineated on the registered three modal MR images,and multimodality radiomics features were obtained,dimensions were reduced using a random forest(RF)-based feature selection method,and the importance of each feature was further analyzed.Secondly,we used the method of contrast disentangled to find the shared features and complementary features between different modal features.Finally,the response of each sample to GBM and SBMs was predicted by fusing 2 features from different modalities. Results:The radiomics features using machine learning and the multi-modal fusion method had a good discriminatory ability for GBM and SBMs.Furthermore,compared with single-modal data,the multimodal fusion models using machine learning algorithms such as support vector machine(SVM),Logistic regression,RF,adaptive boosting(AdaBoost),and gradient boosting decision tree(GBDT)achieved significant improvements,with area under the curve(AUC)values of 0.974,0.978,0.943,0.938,and 0.947,respectively;our comparative disentangled multi-modal MR fusion method performs well,and the results of AUC,accuracy(ACC),sensitivity(SEN)and specificity(SPE)in the test set were 0.985,0.984,0.900,and 0.990,respectively.Compared with other multi-modal fusion methods,AUC,ACC,and SEN in this study all achieved the best performance.In the ablation experiment to verify the effects of each module component in this study,AUC,ACC,and SEN increased by 1.6%,10.9%and 15.0%,respectively after 3 loss functions were used simultaneously. Conclusion:A deep learning-based contrast disentangled multi-modal MR radiomics feature fusion technique helps to improve GBM and SBMs classification accuracy.

Objective: To investigate the neural connections between Shenmen (HT7)-heart and the brain by observing the tracing viruses co-labeled brain nuclear groups after injection of the pseudorabies viruses (PRV), the reverse transsynaptic virus tracer carrying different fluorescent protein genes, into the myocardium and Shenmen (HT7) point, respectively.Methods: Pseudorabies virus 531 (PRV531) carrying the green fluorescent protein gene and pseudorabies virus 724 (PRV724) carrying the red fluorescent protein gene were injected into the left ventricular wall and Shenmen (HT7) point area of the left forelimb of six C57BL/6 mice, respectively. After 120 h, whole brain tissue was extracted under 4％ paraformaldehyde perfusion to prepare brain sections. Neuronal co-labeling with the tracing viruses was observed under fluorescence microscopy. Results: Co-labeled signals from the mouse ventricular wall and Shenmen (HT7) point region were found at all levels of the mouse central nervous areas, such as the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. The number of co-labeled neurons was higher in the primary motor area, the hypothalamic paraventricular nucleus, the subceruleus nucleus, and the paramedian reticular nucleus. Conclusion: There is a neural connection between Shenmen (HT7), the heart, and the brain, which may be most closely related to the autonomic nervous system.

Objective:To analyze the epidemiological characteristics of indigenous 2019-nCoV infection in population under 18 years old in 31 provinces of China, and provide evidence for the prevention and control of COVID-19.Method:Demographic and epidemiologic information of children and adolescents with 2019-nCoV infection reported in China between April 29, 2020 and May 31, 2022 were collected from China's Disease Prevention and Control Information System. We analyzed the epidemiological characteristics of the 2019-nCoV infection in children and adolescents and compared the epidemiological characteristics of the cases at different epidemic stages.Result:A total of 63 916 indigenous 2019-nCoV infection cases in children and adolescents were reported in China from April 29, 2020 to May 31, 2022, in which 14 777 (23.12%) were confirmed cases and 49 139 (76.88%) were asymptomatic cases. An obvious incidence peak (40 864 cases) was observed in April, 2022, and two sub-peaks were observed in January, 2020 and January, 2021, respectively. The 2019-nCoV infection cases occurred in 187 cities above prefecture level in 30 provinces, the cases reported in Shanghai (41 562 cases), Changchun (5 753 cases) and Jilin (3 888 cases) accounted for 80.11% of the total cases (51 203/63 916). The proportion of the cases in males was 54.34%. The age of the cases, M ( Q1, Q3) was 10 (5, 14) years, and 57.73% of the cases were 6 - 15 years old. The cases in students accounted for the highest proportion (56.14%). The interval between illness onset and diagnosis of confirmed cases, M ( Q1, Q3) was 1 (0, 2) days. Among the 2019-nCoV infection cases in children and adolescents, 76.88% were asymptomatic, 21.78% were mild ones, 1.32% were moderately severe ones, 0.02% were severe ones, and there were no critical cases and deaths. Compared with other age groups, the proportion of severe or critical cases was higher in children aged <1 year (0.12%). The proportion of asymptomatic infections was highest in Omicron variant epidemic (78.43%). Conclusion:The 2019-nCoV infection cases in children and adolescents aged <18 years in 31 provinces in China were mainly primary and secondary school students aged 6-15 years. Most cases were asymptomatic and mild ones with low clinical severity. It is still necessary to strengthen the surveillance for 2019-nCoV infection in children and adolescents to improve the prevention and control of COVID-19 in school age children.