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With the development of digital technology， an increasing number of artificial intelligence （AI） technologies are being applied in the field of public health， significantly improving the efficiency of healthcare systems. However， such technological advancement also introduces a series of ethical risks. In this article， we conducted a systematic review by searching nine domestic and international databases and analyzing the ethical issues related to AI in public health， ultimately including 158 articles. Based on the analysis of the included literature， ethical risks were categorized into four aspects： data， algorithms， rights and responsibilities， and social impact. A total of 15 key issues were identified， among which privacy and confidentiality， informed consent， data security， and fairness， justice and inclusion emerged as the most prominent issues. The ethical challenges posed by AI in the field of public health cannot be ignored， and it is necessary to formulate ethical guidelines and practical recommendations for AI in this field， establish sound regulatory and review mechanisms， thereby ensuring the healthy development of AI research in public health.
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Objective:To explore the relationship between serum retinol binding protein(RBP)and metabolic-associated fatty liver disease(MAFLD)in elderly patients with type 2 diabetes mellitus(T2DM)and possible underlying metabolic mechanisms.Methods:A total of 3384 elderly T2DM patients hospitalized and with complete clinical records at the Department of Endocrinology and Metabolism, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between January 2003 and December 2012 were recruited in this retrospective study.Patients were divided into four groups according to the quartiles of serum RBP levels: the first quartile of serum RBP levels(<35 mg/L, 844 cases), the second quartile of serum RBP levels(35 mg/L≤ RBP ≤41 mg/L, 773 cases), the third quartile of serum RBP levels(42 mg/L≤ RBP ≤51 mg/L, 902 cases), and the fourth quartile of serum RBP levels(RBP>51 mg/L, 865 cases). Clinical data and laboratory test results were collected.Differences in the prevalence of MAFLD were compared between the four groups.The association between RBP and MAFLD was analyzed via binary logistic regression.Results:After adjusting for age and sex, the proportion of obesity( χ2=15.222, P<0.01), the percentage using lipid-lowering drugs( χ2=88.552, P<0.01), systolic blood pressure( F=12.002, P<0.01), diastolic blood pressure( F=6.872, P<0.01), waist circumference( F=9.563, P<0.01), waist-hip ratio( F=7.972, P<0.01), body mass index( F=9.057, P<0.01), serum creatinine( χ2=185.445, P<0.01), serum uric acid( χ2=314.691, P<0.01), 24-hour urinary albumin( χ2=91.012, P<0.01), alanine aminotransferase( χ2=17.049, P=0.003), γ-glutamyl transpeptidase( χ2=50.514, P<0.01), total cholesterol( F=45.669, P<0.01), triglycerides( χ2=361.269, P<0.01), low-density lipoprotein( F=8.772, P<0.01), fasting C-peptide( χ2=165.756, P<0.01), 2h postprandial C-peptide( χ2=120.690, P<0.01), and the homeostasis model assessment of insulin resistance(HOMA2-IR)( χ2=148.884, P<0.01)in elderly patients with T2DM all showed a clear upward trend.The prevalence of MAFLD also gradually increased across the quartiles of serum RBP levels[26.5%(224/844), 30.1%(233/773), 36.6%(330/902), and 41.8%(362/865)], respectively( χ2=52.526, P<0.01). Elderly T2DM patients with MAFLD had a significantly higher value of HOMA2-IR than those without MAFLD[2.0(1.31-2.8) vs.1.39(0.86-2.06), F=220.826, P<0.01]. After correcting for other confounding factors, binary logistic regression showed that serum RBP was strongly associated with the presence of MAFLD in elderly patients with T2DM( β=0.209, 95% CI: 1.079-1.408, OR=1.232, χ2=9.441, P<0.01). Conclusions:Elevated serum RBP levels are an independent risk factor for the development of MAFLD in elderly T2DM patients, possibly through increased insulin resistance induced by RBP.
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MiT family translocation renal cell carcinoma mainly includes Xp11.2/TFE3 gene fusion-related renal cell carcinoma (TFE3 RCC)and t(6; 11)/TFEB gene fusion-related renal cell carcinoma(TFEB RCC), which is rare and there is no standard treatment plan yet, and the prognosis is still controversial. For localized lesions, surgery is the first choice for treatment, and systemic treatment such as targeted drugs and immune checkpoint inhibitors can be combined when there is metastasis. The application of gene testing provides the basis for personalized treatment. TFE3 RCC is highly invasive and has a poor prognosis, while TFEB RCC usually has a biological behavior of inertia and a better prognosis.
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Background@#Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. @*Objective@#This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. @*Methods@#Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. @*Results@#Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. @*Conclusions@#GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.
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Objective To investigate the effects of oral probiotics on gut microbiota diversity,colony structure,and intergroup differences in mice with subcutaneous colon cancer tumors,based on 16S rRNA sequencing technology.Methods Twenty-four 6-week-old male BALB/c mice were divided randomly into normal control group(NC group,n = 8),model group(M group,n = 8),and probiotic + model group(PM group,n = 8)after adaptive feeding for 1 week.Mice in the PM group were given 200 μL probiotic mixed solution(Bifidobacterium longum and Lactobacillus delbrueckii subsp.bulgaricus mixed lyophilized powder,2×108 colony-forming units)by gavage three times/week for 7 weeks,while the M group and PM group received 200 μL normal saline.At 10 weeks old,0.2 mL CT26.WT cell suspension(1×107/mL)was inoculated subcutaneously into the left hind limbs of M group and PM group,while NC group were inoculated with 0.2 mL normal saline.The general state of mice was observed,the growth of subcutaneous tumor was monitored,and the changes of intestinal flora structure were detected by 16S rRNA sequencing.Results The subcutaneous tumors of the M group were prominent,and the subcutaneous tumor volume and weight of the PM group were significantly reduced(P<0.05).Compared with NC group,Alpha diversity index was lower in the M group,and a significant difference of Beta diversity inter groups(P<0.01).And supplementation of probiotics had a certain effect on gut microbiota diversity in the M group.Compared with M group,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Bacteroides were higher in the PM group,while the relative abundance of Firmicutes,Desulfobacterota,Lachnospiraceae_NK4A136_group,Alistipes were lower in the PM group.LEfSe analysis showed that Muribaculaceae and Bacteroides in the PM group were different species with high abundance(LDA values>4).Conclusions Oral probiotics may improve the gut microbiota by increasing the relative abundance of beneficial Muribaculaceae and Bacteroides in subcutaneous tumors in mice with colon cancer.
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Objective To investigate the association of uric acid excretion(UUAE)with obesity and abdominal obesity in newly diagnosed patients with type 2 diabetes mellitus(T2DM).Methods A total of 1175 newly diagnosed T2DM patients hospitalized in the Department of Endocrinology and Metabolism of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from January 2006 to December 2012.According to the quartile of UUAE,they were divided into Q1 group(UUAE＜2383 μmol/24 h,n=295),Q2 group(2383≤UUAE＜2953 μmol/24 h,n=292),Q3 group(2954≤UUAE＜3680 μmol/24 h,n=292)and Q4 group(UUAE＞3680 μmol/24 h,n=293).Clinical data and laboratory examination results were collected,and the prevalence of obesity and abdominal obesity was compared among the four groups.The associations of UUAE with obesity and abdominal obesity were analyzed.Results The prevalence of obesity was 47.9%,while the prevalence of abdominal obesity was 61.9%in the whole study population.After adjusting for age,the prevalence of abdominal obesity was higher in women than in men(P＜0.05).After adjusting for age and gender,the prevalence of obesity and MS was higher in Q4 group than in Q1,Q2,and Q3 groups(P＜0.05),and the prevalence of abdominal obesity was higher in Q4 group than in Q1 and Q2 groups(P＜0.05).Compared with Q1 group,the proportion of men,BMI,WC,DBP,FIns,2 hIns,HOMA-IR,TG,ALT,γ-GT,SUA,UAlb in Q4 group increased(P＜0.05),age,HbA1c,HDL-C decreased(P＜0.05).Logistic regression analysis showed that after adjusting for confounding factors,UUAE was a factor affecting obesity and abdominal obesity.Conclusion UUAE increases the risk of obesity,abdominal obesity and MS in newly diagnosed T2DM patients.UUAE may be used as a simple indicator to assess the risk of metabolic disorders such as obesity and MS in T2DM patients.
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Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.
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Objective:To explore the clinical characteristic and risk factors of subcutaneous tophus among hospitalized gout patients.Methods:The clinical data of 646 inpatients with gout from April 2014 to December 2019 in Tianjin Medical University Chu Hsien-I Memorial Hospital were retrospectively analyzed. The patients were divided into tophus group (172 cases) and non-tophus group (474 cases) according to the presence of subcutaneous tophus. The body height, body mass, waist circumference, hip circumference and blood pressure were measured. The total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), urea nitrogen, creatinine, uric acid and C-reactive protein (CRP) were detected; urine was collected for 24 h to detect uric acid. The body mass index (BMI), estimated glomerular filtration rate (eGFR) and uric acid excretion fraction (FUA) were counted. Binary Logistic regression analysis was used to analyze the independent risk factors of subcutaneous tophus among hospitalized gout patients.Results:The proportion of male, course of disease, number of joint involved in attack, rate of smoking history, rate of drinking history, smoking amount, alcohol consumption volume, length of time spent drinking, length of time spent smoking, LDL-C, urea nitrogen, serum creatinine and serum uric acid in tophus group were significantly higher than those in non-tophus group: 98.84% (170/172) vs. 94.09% (446/474), 10 (5, 16) years vs. 5 (2, 9) years, 6 (4, 8) joints vs. 3 (2, 5) joints, 66.86% (115/172) vs. 58.44% (277/474), 65.70% (113/172) vs. 57.38% (272/474), 11 (0, 20) cigarettes /d vs. 10 (0, 20) cigarettes/d, 100 (0, 250) ml/d vs. 50 (0, 162) ml/d, 10 (0, 26) years vs. 0 (0, 20) years, 20 (0, 30) years vs. 10 (0, 20) years, (3.44 ± 0.98) mmol/L vs. (3.25 ± 0.97) mmol/L, 5.81 (4.61, 7.46) mmol/L vs. 5.38 (4.39, 6.66) mmol/L, 89.4 (74.3, 107.5) μmol/L vs. 85.1 (72.5, 98.9) μmol/L and 514.4 (452.9, 595.2) μmol/L vs. 499.0 (404.8, 572.4), the onset age, red blood cell, hemoglobin and eGFR were significantly lower than those in non-tophus group: (37.78 ± 10.56) years old vs. (40.17 ± 13.06) years old, (4.72 ± 0.74) × 10 9/L vs. (4.88 ± 0.56) × 10 9/L, (141.15 ± 17.19) g/L vs. (146.00 ± 13.06) g/L and 87.7 (65.9, 108.4) ml/min vs. 93.3 (75.9, 113.1) ml/min, and there were statistical differences ( P<0.05 or <0.01); there were no statistical differences in family history of diabetes, family history of hypertension, family history of gout, BMI, waist-hip ratio, blood pressure, FUA, white blood cell, TC, TG, HDL-C and CRP between 2 groups ( P>0.05). The patients were grouped according to the course of disease, the incidences of tophus in patients with course of disease ≤5.0 years, 5.1 to 10.0 years and >10.0 years were 15.34% (50/326), 27.67% (44/159) and 48.45% (78/161), and there was statistical difference ( χ2 = 60.59, P<0.01); the patients were grouped according to the quartiles of serum uric acid, the incidences of tophus in patients with serum uric acid <424.05 μmol/L, 424.05 to 505.24 μmol/L, 505.25 to 576.17 μmol/L and ≥576.18 μmol/L were 14.91% (24/161), 32.72% (53/162), 29.01% (47/162) and 29.81% (48/161), and there was statistical difference ( χ2 = 15.70, P<0.01). Binary Logistic regression analysis result showed that the course of gout, smoking amount, number of joint involved in attack, serum uric acid and LDL-C were the independent risk factors of subcutaneous tophus among hospitalized gout patients ( OR = 1.069, 1.020, 1.317, 1.002 and 1.262; 95% CI 1.032 to 1.097, 1.006 to 1.032, 1.223 to 1.417, 1.000 to 1.003 and 1.033 to 1.541; P<0.01 or <0.05). Conclusions:The duration of disease, number of involved joint, serum uric acid level, unhealthy lifestyles and lipid metabolism disorders are the independent risk factors of subcutaneous tophus among hospitalized gout patients.
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Adenocarcinoma of the rete testis is a rare testicular malignant tumor with high invasiveness and poor prognosis. Due to the lack of specific tumor marker and characteristic features in imaging, early diagnosis of testicular reticulum adenocarcinoma is difficult, and a final diagnosis depends on the pathological and immunohistological examination. At present, there is no systematic treatment guidance, and radical orchiectomy is preferred. This article reported a 66-year-old patient with right adenocarcinoma of the rete testis who underwent right radical orchiectomy. He refused adjuvant radiotherapy or chemotherapy after surgery, and developed lung, liver, and retroperitoneal lymph node metastasis 8 months afterwards. He was followed up at 15 months, when he was died of multiple metastases.
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Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted with PD-L1 in order to stabilize it, while abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing