Can uric acid affect the immune microenvironment in bladder cancer? A single-center multi-omics study.

Metabolic abnormalities are one of the important factors in bladder cancer (BCa) progression and microenvironmental disturbance. As an important product of purine metabolism, uric acid's (UA) role in BCa metabolism and immunotherapy remains unclear. In this study, we conducted a retrospective analysis of a cohort comprising 39 BCa patients treated with PD-1 and 169 patients who underwent radical cystectomy at Shanghai Tenth People's Hospital. Kaplan-Meier curves and Cox regression analysis showed that the prognosis of patients with high UA is worse (p = 0.007), and high UA is an independent risk factor for cancer specific survival in patients with BCa (p = 0.025). We established a hyperuricemia mouse model with BCa subcutaneous xenografts in vivo. The results revealed that the subcutaneous tumors of hyperuricemia mice had a greater weight and volume in comparison with the control group. Through flow cytometric analysis, the proportion of CD8+ and CD4+ T cells in these subcutaneous tumors was seen to decline significantly. We also evaluated the relationship of UA and BCa by muti-omic analysis. UA related genes were significantly increased in the CD8+ T cell of non-responders to immunotherapy by single-cell sequencing. An 11-gene UA related signature was constructed and the risk score negatively correlated with various immune cells and immune checkpoints. Finally, a nomogram was established using a UA related signature to forecast the survival rate of patients with BCa. Collectively, this study demonstrated that UA was an independent prognostic biomarker for BCa and was associated with worse immunotherapy response.

Increased Levels of Pro-Inflammatory and Anti-Inflammatory Cellular Responses in Parkinson's Disease Patients: Search for a Disease Indicator.

BACKGROUND Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and it arises when most of the dopaminergic neurons of substantia nigra region die. Several mechanisms have been postulated as the causative event in PD pathology, and neuroinflammation is most crucial among them. MATERIAL AND METHODS We analyzed T-helper 17 (Th17) cells and myeloid-derived suppressor cells (MDSCs) from 80 PD patients to assess inflammatory processes and to find a cost-effective means to evaluate PD prognosis. RESULTS We found significantly increased numbers of Th17 cells and MDSCs count in peripheral circulation in PD patients compared with controls (p<0.001). A positive correlation was found between Th17 cells and MDSCs in PD patients (r=0.421, p<0.05). CONCLUSIONS Our results show the effector role of Th17 cells and MDSCs in PD pathology and shows their utility as effective biomarkers for PD diagnosis.

Transmission and control pressure analysis of the COVID-19 epidemic situation using multisource spatio-temporal big data.

Taking the Guangdong-Hong Kong-Macao Greater Bay Area as the research area, this paper used OD cluster analysis based on Baidu migration data from January 11 to January 25 (before the sealing-off of Wuhan) and concluded that there is a significant correlation 1the migration level from Wuhan to the GBA and the epidemic severity index. This paper also analyzed the migration levels and diffusivity of the outer and inner cities of the GBA. Lastly, four evaluation indexes were selected to research the possibility of work resumption and the rating of epidemic prevention and control through kernel density estimation. According to the study, the amount of migration depends on the geographical proximity, relationship and economic development of the source region, and the severity of the epidemic depends mainly on the migration volume and the severity of the epidemic in the source region. The epidemic risk is related not only to the severity of the epidemic in the source region but also to the degree of urban traffic development and the degree of urban openness. After the resumption of work, the pressure of epidemic prevention and control has been concentrated mainly in Shenzhen and Canton; the further away a region is from the core cities, the lower the pressure in that region. The mass migration of the population makes it difficult to control the epidemic effectively. The study of the relationship between migration volume, epidemic severity and epidemic risk is helpful to further analyze transmission types and predict the trends of the epidemic.

Early predicting indicators of conversion from mild to moderate in overseas-imported COVID-19 cases.

BACKGROUND: Due to the ongoing pandemic of coronavirus disease 2019 (COVID-19) in foreign countries and regions, many overseas people arrive in China by air. Currently, most of the new cases of COVID-19 were imported from overseas. Here, we evaluated the predictive effect of the level of blood albumin (ALB) and serum prealbumin (PA) level in overseas-imported cases on the conversion of mild COVID-19 to moderate and its value in guiding nutritional support for these travelers. METHODS: We retrospectively analyzed serum levels of ALB and PA of 193 patients with imported COVID-19 admitted to the Shanghai Public Health Clinical Center at the time of admission on April 8, 2020. RESULTS: Since the first overseas-imported case was admitted to Shanghai on March 5, 2020, 195 overseas-imported cases have been treated in the Shanghai Public Health Clinical Center. The disease was mild or moderate. A total of 193 patients (111 males and 82 females) entered our analysis and the disease was moderate in 108 patients and mild in 85 patients. Patients were aged 6 to 66 years (mean: 28 years). There was a strong negative correlation between the proportion of moderate type and ALB (P=0.0073); thus, patients with a lower level of ALB were more likely to be diagnosed with moderate type. The correlation coefficient was close to 0 in the scatter plot, indicating that there was no linear correlation between PA and the diagnosis of moderate type (P>0.05). There was a strong negative correlation between age and ALB level (P<0.001), while length of hospital stay did not show a linear correlation with ALB or PB levels (both P>0.05). Therefore, older patients had lower levels of ALB and were more likely to develop moderate COVID-19. CONCLUSIONS: The serum ALB level can be an early predictive indicator for the conversion of mild COVID-19 to moderate in cases imported overseas and may guide nutritional support.

Significance of tumor protein p53 mutation in cellular process and drug selection in brain lower grade (WHO grades II and III) glioma.

Aim: Tumor protein p53 (TP53) mutant is one of the most frequently mutated genes in glioma. Results: The Cancer Genome Atlas data has shown that TP53 mutation is present in 49% of lower grade (World Health Organization [WHO] grades II and III) glioma patients. Data from The Genomics of Drug Sensitivity in Cancer database showed that three drugs: (5Z)-7-oxozeaenol, dabrafenib and nutlin-3a (-), have shown more resistance in patients with TP53 mutation. We identified 1100 differentially expressed genes. Functional enrichment analysis showed that the differentially expressed genes are mainly concentrated in the transport of ionic and cancer-related pathways. The top ten hub genes were identified and an outcome analysis revealed the most critical genes related to prognosis. Conclusion: Our results identified the key genes and pathways that might provide the basic proof to improve individualized treatment in patients with glioma.

The epidemiologic and clinical features of suspected and confirmed cases of imported 2019 novel coronavirus pneumonia in north Shanghai, China.

BACKGROUND: A recent cluster of pneumonia cases in Wuhan (China) is known to be caused by a novel beta-coronavirus named the corona virus disease 2019 (COVID-19) and can be spread through human-to-human transmission. METHODS: Data of 21 patients with laboratory-confirmed COVID-19 and 84 patients with suspected COVID-19 were analyzed by RT-PCR. The epidemiologic and clinical features as well as clinical outcomes were compared between the confirmed and suspected cases. RESULTS: Altogether 105 patients had been enrolled in this study by February 15, 2020 in north Shanghai, including 21 confirmed cases and 84 suspected cases of COVID-19. The incubation period of these confirmed patients with imported COVID-19 was 17.6 days (IQR 5-34 days) and the median time from symptom onset to diagnosis was 145.64 h (IQR 21-441 h). More than 50% of the confirmed patients were older than 51 (range, 51-60) years. Fifty (59.5%) of the 84 probably patients were younger than 40 years, including 27 (32%) patients younger than 30 years. Most confirmed patients were men (61.9%, 13/21), and less than 50% of them had underlying diseases, including diabetes (9.5%, 2/21), hypertension (19%, 4/21), COPD (23.8%, 5/21), and CD (23.8%, 5/21). In addition, 10 (47.6%) of the 21 confirmed patients were ordinary employees, and 12 (57.2%) of them had recently been to Wuhan or had close contacts with people from Wuhan. Of the 84 suspected patients, 28 (33.3%) were retired employees; 69 (82.1%) had recently been to supermarkets and groceries or had a history of traveling abroad or to other cities of China. The common onset symptoms of the patients in both groups were fever and cough. The symptom of Sputum production was more pronounced in probably patients (40.5%, 34/84) than that in confirmed patients (9.5%, 2/21). More than 50% imported patients (53.3%, 56/105) had one and two affected lobes. Twenty-nine (27.6%) of the 105 imported patients had been discharged, no patient had died, and all the other patients are still in hospital. CONCLUSIONS: The overall incubation period in this cohort of imported confirmed COVID-19 patients was longer than that in Wuhan, mostly infecting older men. The disease onset of imported COVID-19 infection was occult, and the clinical symptoms were usually mild, mostly presenting as low fever, fatigue, light cough, and mild dyspnea.

Validation of the Pangao PG-800B26 upper arm blood pressure monitor in the general population according to the European Society of Hypertension and the British Hypertension Society protocols.

OBJECTIVE: This study aimed to evaluate the accuracy of the automated oscillometric upper arm blood pressure monitor Pangao PG-800B26 for home blood pressure monitoring according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010 and the British Hypertension Society (BHS) protocols. PARTICIPANTS AND METHODS: Systolic and diastolic blood pressures were measured sequentially in 33 and 85 adults, respectively, on the basis of the ESH-IP and BHS protocols using a mercury sphygmomanometer (two observers) and the device (one supervisor). The procedures and analysis methods of the protocols were followed precisely. RESULTS: The device fulfilled the criteria of the ESH-IP, with device-observer differences of 1.01±5.16 and -0.58±4.17 mmHg for systolic and diastolic blood pressure, respectively. Furthermore, the A/A grade of the BHS protocol was also achieved for overall grading and for the three pressure levels, with average differences of 0.85±6.35 and -0.15±5.65 mmHg for systolic and diastolic blood pressure, respectively, which also fulfilled the requirements of the Association for the Advancement of Medical Instrumentation. CONCLUSION: The Pangao PG-800B26 fulfilled the criteria of the ESH-IP 2010 and achieved the A/A grade of the BHS protocol, and hence can be recommended for home use in adults.

Predicting the Severity of Acute Pancreatitis With Red Cell Distribution Width at Early Admission Stage.

Red cell distribution width (RDW) has been proposed as an early prognosis marker with increased mortality in variety of pathophysiological conditions. We hypothesized that elevated RDW could be used in judging the severity of acute pancreatitis (AP). We retrospectively and prospectively studied 545 and 72 AP patients, who were admitted to the Shanghai Tenth People's Hospital of Tongji University, respectively. Compared with mild acute pancreatitis, significantly higher RDW was observed in patients with moderately severe acute pancreatitis and sever acute pancreatitis (14.03 ±â€Š1.74% vs. 13.23 ±â€Š1.23%, P < 0.000). RDW values were also found positively correlated with the patient's blood urea nitrogen (r = 0.120, P = 0.026), creatinine (r = 0.182, P = 0.000), age (r = 0.099, P = 0.028), and bedside index of severity in acute pancreatitis scoring system (r = 0.147, P = 0.001), and were negatively correlated with the serum albumin (r = -0.244, P = 0.000). The area under the receiver-operating characteristics was as follows-RDW: 0.677 (95% confidence interval [CI], 0.619-0.735, P < 0.000); combination of RDW and albumin: 0.693 (95% CI, 0.625-0.761, P < 0.000); and the optimal cutoff value for RDW to predict whether patients with AP should be in intensive care unit (ICU) was 13.55 with a sensitivity of 54.5% and a specificity of 73.6%. In the validation study, AP with RDW ≥ 13.55% had significantly higher ICU admission ratio than those with RDW < 13.55% (44.4% vs. 9.8%, P < 0.000). In conclusion, RDW is positively associated with AP severity, and is likely a useful predictive parameter of AP severity.

Knowledge deficiency of work-related radiation hazards associated with psychological distress among orthopedic surgeons: A cross-sectional study.

Knowledge and concern degree about work-related radiation hazards remained unknown among orthopedic surgeons. The aim of the cross-sectional study is to investigate whether the knowledge degree of work-related radiation is associated with psychological distress among orthopedic surgeons. This cross-sectional study sent electronic questionnaire via WeChat to orthopedic surgeons nationwide. Concern and knowing degree over radiation exposure was evaluated by a single self-reported question. Professional evaluation of concern degree was reflected by general psychological distress, which was assessed with the Kessler 10 scale (K10) and depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D). Only 43.23% (115/266) respondents knew well about radiation and a total of 78.20% (208/266) respondents considered radiation exposure as a great concern. Among those who reported concerns about radiation exposure, a total of 57.69% (120/208) respondents reported knowing little about radiation. Respondents who reported concerns over radiation exposure were significantly associated with higher scores on CES-D and K10 (P < .05). Among respondents who reported concerns over radiation exposure, those who have fewer knowledge about radiation, had higher CES-D and K10 scores than those who knew well about radiation (P < .05). Among respondents who reported no concerns over radiation exposure, those who knew little about radiation still had higher CES-D and K10 scores (P < .05). Fewer radiation knowledge tends to induce more radiation concerns associated with higher psychological distress in orthopedic surgeons. Radiation knowledge should be enhanced for surgeons who daily work with radiation-related fluoroscopy.

Effects of kallistatin on oxidative stress and inflammation on renal ischemia-reperfusion injury in mice.

BACKGROUND: Kallistatin (KS) is a serine proteinase. The result of KS on 'Renal Ischemia- Reperfusion Injury' (IRI) has not clearly been researched. In this study, investigative research has been conducted to draw results on the administration of human KS on kidney response conducted within a mouse model of IRI. MATERIALS AND METHODS: BALB/c mice were used and given 30 min ischemia that was injected into the kidney which was followed with 24 h reperfusion. The human KS gene contained within an adenoviral vector was injected intravenously 30 min before reperfusion and 12h after reperfusion. Analyses illustrated what impact KS had on renal IRI in realtion to tubular necrosis, apoptotic cell death, inflammatory cytokines, renal function, and inflammatory cell infiltration. RESULTS: KS gene transfer significantly had a positive impact on renal function (reduced blood urea-nitrogen: 73.5±13.6 vs. 195.4±14.6 mg/dL at day three, p < 0.05 and the serum creatinine levels: 0.23±0.02 vs. 0.71±0.14 mg/dL at day three, p < 0.05), reduced tubular necrosis and apoptosis of IRI kidneys. The permeation of cells that were inflamed and the manufacturing of pro-inflammatory cytokines (RANTES-is regulated through been activated with normal T-cell which are expressed and secreted, tumour necrosis interleukin-1ß factor-α, and interferon-γ) resulted in significantly suppressing KS in mice with IRI. The efficacy to scavenge superoxide in tubule cells was also demonstrated by high-performance liquid chromatography. CONCLUSION: Our study suggests a novel role of KS in renal protection after 'Renal Ischemia-Reperfusion Injury' blocking of oxidative stress and renal inflammation.