Parkinson's disease is a neurodegenerative disease associated with abnormal copper metabolism in the brain,which leads to misfolding and aggregation of α-synuclein-copper complexes,which is an important pathological sign of Parkinson's disease.Copper metabolism,i.e.,cellular metabolic processes involving copper ions,is closely related to the pathogenesis of α-synuclein aggregation,dopamine metabolism,mitochondrial dysfunction,oxidative stress,and ferroptosis in Parkinson's disease.In this review,we summarize the molecular metabolic mechanism of copper toxicity by studying the pathological role of copper metabolism in Parkinson's disease,to support our further understanding of the mechanism of action and drug development.

Objective:To explore the predictive value of low-dose biphasic (inspiratory and expiratory) CT air trapping sign and semi-quantitative score in predicting abnormal blood gas parameters and progression to severe disease in COVID-19 patients.Methods:Patients with non-severe COVID-19 who were diagnosed by nucleic acid testing and hospitalized in designated hospitals in Wuxi City from January 23 to February 29, 2020 were prospectively and consecutively recruited. All patients received low-dose biphasic CT examination on admission and repeated CT examination at regular intervals during the course. On the inspiratory phase admission of the bipolar CT, the scope of the lesion was evaluated by semi-quantitative score, and the air trapping sign on bipolar CT was assessed. The differences of semi-quantitative score, the presence of the air trapping sign and other clinical factors were compared between the patients with abnormal and the normal blood gas index, as well as between the cases progressed to severe disease and cases without disease progression using the independent sample t-test or χ 2 test. The area under the curve (AUC) of receiver operating characteristic (ROC) and the comprehensive discriminant improvement index (IDI) were used to evaluate the predictive effectiveness of the semi-quantitative scores, air trapping sign, and combination of two factors in differentiating cases with abnormal and normal blood gas indexes, as well as in differentiating cases with and without disease progression to severe COVID-19 cases. Results:In total 51 non-severe COVID-19 cases were included, with 16 cases showed air trapping sign during the first biphasic CT examination on admission. During the course of the disease, there were 13 patients with abnormal blood gas index, and 9 cases displaying air trapping sign (9/13). All 7 cases with progression to severe cases showed air trapping sign (7/7). Patients with advanced age, air trapping sign and higher semi-quantitative score were found more likely to have abnormal blood gas index ( t=3.10, χ 2=9.38, t=3.34, P<0.05); patients with advanced age, underlying diseases, air trapping sign and higher semi-quantitative score were more likely to develop into severe disease ( t=2.68, χ 2=6.65, χ 2=4.25, t=4.33, P<0.05). The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing abnormal blood gas index from normal blood gas index was 0.803, 0.754 and 0.794 respectively. The AUC of semi-quantitative score, air trapping sign and combination of two factors in distinguishing cases with progression to severe cases from non-progression was 0.881, 0.898 and 0.932, respectively. Air trapping sign combined with semi-quantitative score significantly improved the prediction effectiveness of disease progression, compared with semi-quantitative score or air trapping sign (IDI=0.271, 0.117). Conclusion:Air trapping sign and semi-quantitative score might be used as effective indicators to predict the progression of COVID-19 cases, and the combination of these two factors might be more helpful to predict the disease progression.

Acute kidney injury (AKI), characterized by acute renal dysfunction, is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease (CKD). Regardless of the initial insults, the progression of CKD after AKI involves multiple types of cells, including renal resident cells and immune cells such as macrophages. Recently, the involvements of macrophages in AKI-to-CKD transition have garnered significant attention. Furthermore, substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis. In this review, we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization, and transdifferentiation in the development of AKI-to-CKD transition. In addition, the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.
Acute Kidney Injury/drug therapy* ; Disease Progression ; Humans ; Kidney ; Macrophages ; Renal Insufficiency, Chronic

Background Diabetes mellitus is a major public health issue at present. Previous studies have shown that ambient air pollution is a risk factor for diabetes. Objective This study aims to explore the acute effects of ambient air pollution on diabetes related death in Shanghai Jing’an District. Methods Daily air pollution data, meteorological data, and diabetes related mortality data in 2013−2019 in Shanghai Jing’an District were collected. A generalized additive model (GAM) was established to conduct time-series analysis on the short-term effect of ambient air pollution on diabetes related mortality, and gender- and age-stratified analysis on susceptibility of various groups to ambient air pollution exposures. Results For every 10 μg·m⁻³ increase of the concentrations of PM_2.5, PM₁₀, SO₂, and NO₂, the diabetes related mortality increased by 2.47% (95%CI: 1.56%−3.38%), 2.02% (95%CI: 1.29%−2.75%), 5.75% (95%CI: 2.99%−8.58%), and 3.93% (95%CI: 2.49%−5.39%) at lag05 respectively (P<0.05). In the stratified analysis, exposures to increased concentrations of PM_2.5, PM₁₀, SO₂, and NO₂ raised the mortality risks from diabetes in male, female, and ≥65 years oldgroups (P<0.05). However, the differences in mortality risks from diabetes due to air pollution within gender and age groups were statistically insignificant. Conclusion In Shanghai Jing'an District, the elevated levels of ambient air pollutants, including PM_2.5, PM₁₀, SO₂, and NO₂, are significantly associated with the increase of diabetes related mortality, and there are lag effects and cumulative effects. The ≥65 years olds are more susceptible to the impact of air pollution on diabetes related deaths.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective To analyze the clinical features and risk factors of cirrhotic patients complicated with infections. Methods The clinical and laboratory characteristics of cirrhotic patients complicated with infections hospitalized from April 2014 to June 2017 were retrospectively analyzed. Relevant risk factors for infection and mortality were explored. Results The overall incidence of infections was 17.6％ in 1670 hospitalized cirrhotic patients. Among the recruited 208 patients in this study, alcoholic, viral hepatitis B or C and autoimmune liver diseases accounted for 29.8％ (62/208), 26.0％ (54/208), and 22.1％ (46/208), respectively. The most common infection site was respiratory tract (70.2％ ), followed by urinary tract, intestinal and intra-abdomen. Forty-six pathogens were isolated from 32 patients, including 22 (47.8％ ) Gram negative bacteria, 16 (34.8％ ) Gram positive bacteria and 2(4.3％ ) mycobacterium tuberculosis, 5 (10.9％) fungi and 1 (2.2％) mycoplasma. The mortality in patients with nosocomial infections (16.7％,7/42) was higher than that in patients with community-acquired infections (6.0％,10/166, P=0.025). All 17 deaths occurred in decompensated cirrhosis. Multivariate analysis demonstrated that hepatic encephalopathy and prothrombin time were independent risk factors of mortality. Conclusions Patients with decompensated cirrhosis are more susceptible to infections. Hepatic encephalopathy and prothrombin time are independent risk factors for death.

Objective This study aimed to examine temporal trends in all cancer-eliminated life expectancy and potential years of life lost (PYLL) in Kunshan city, Jiangsu province, between 1981 and 2015. Methods Data were collected from the vital records of Kunshan city. Cancer-eliminated life expectancy and PYLL were calculated by sex,and the Chinese population from the year 2000 was used to calculate age-standardized PYLL. Estimated annual percentage changes (APC) and 95% confidence intervals (CI) were used to examine temporal trends in increased cancer-eliminated life expectancy. Results Between 1981 and 2015,there was a significant decrease in age-standardized PYLL among males (APC=-2.31%, 95% CI:-2.51% to-2.11%) and females (APC=-1.91%, 95% CI:-2.26% to-1.56%). However, an increase was found in cancer-eliminated life expectancy in males and females, from 3.23 to 4.72 years in males(APC=2.42%,95% CI:1.64% to 3.20%)and from 1.10 to 2.94 years in females(APC=3.91%, 95% CI: 1.78% to 6.04%). Conclusion An overall decrease in age-standardized PYLL was observed when all cancers were considered,and an increase in cancer-eliminated life expectancy was found, suggesting that premature deaths due to cancers were reduced gradually. However, the negative effects of cancer on the health of the whole population have not been fully alleviated.

Objective: To investigate the clinicopathologic and molecular features of the rare cribriform morular variant of papillary thyroid carcinoma (CMV-PTC). Methods: The clinicopathologic data of 10 patients with CMV-PTC were retrospectively reviewed. Immunohistochemical (IHC) staining was done using LSAB method. DNA sequencing for APC were applied using Sanger method. BRAF V600E mutation was examined using ARMS method. The cytological, morphological, IHC and molecular features were analyzed. Results: All patients were female at an average age of 27 years old. The tumors were mostly located in the right lobe of thyroid. Fine needle aspiration cytology was performed in three patients; two were diagnosed as suspicious for PTC and one as PTC. Nine tumors presented as solitary nodule and two as multiple nodules in both lobes. Infiltration was demonstrated in three cases. The average size was 2.6 cm. The neoplastic cells were arranged in papillary, cribriform, solid and glandular patterns, with rare or without colloid inside the lumen. The number of morula varied, ranging from zero to many. The neoplastic cells were variably enlarged, showing round, oval or spindle shape. Nuclear irregularity was identified as irregular membrane, nuclear grooves or pseudoinclusion, but no typical ground glass feature. Peculiar nuclear clearing could be observed in the morular cells. IHC staining showed the neoplastic cells were negative for thyroglobulin and p63, but positive for TTF1, cytokeratin 19 and estrogen receptor. Diffuse staining with cytokeratin was seen in the neoplastic cells and the morula. Specific cytoplasmic and nuclear staining of β-catenin was seen in the neoplastic cells but not the morula. Ki-67 proliferation index was 1%-30%. No recurrence or metastasis was observed. One patient was demonstrated to harbor both somatic and germline mutations of the APC gene, who was found to have adenomatous polyposis and her mother died of colonic carcinoma. No BRAF V600E mutation was detected. Conclusions CMV-PTC is rare and shows atypical cytological and clinicopathological features, and it is easily misdiagnosed.TG, TTF1, ER and β-catenin are specific IHC markers for CMV-PTC. The morula is negative for cytokeratin 19, in contrast to squamous metaplasia. Although CMV-PTC has indolent clinical behavior, a definite diagnosis is necessary to rule out the possibility of APC gene mutation and related extra-thyroidal neoplasm, such as FAP and Gardner syndrome.

Objective To explore the temporal trend of cancer death rates in different age and the influencing factors in Kunshan,Jiangsu province,1981 to 2015.Methods Data were derived from cancer rcgistry and vital registration system.The Chinese age structure in 2000 was used to calculate age-standardized death rates (ASR),and annual percentage changes (APC) and 95％ confidence interval (Cl) were used to estimate the temporal trend of cancer death rates.Difference decomposition method was applied to analyze the contribution of demographic and non-demographic factors for the change of cancer mortality.Results Between 1981 and 2015,the age standardized all cancers death rate decreased from 162.49 to 93.74 per 100,000 (APC=-l.6％,95％ CI:-1.8％--1.5％).However,the ASR for those aged 70 years or above was stable over time (APC=0.2％,95％ CI:-0.2％-0.5％),whereas aged 30-69 years was decreased from 240.01 in 1981 to 93.28 in 2015 (APC=-2.8％,95％ CI:-3.0％--2.6％).In addition,the proportion of leading cancers were changed obviously.The proportion of lung cancer increased from 1981 to 2015,while gastric cancer,liver cancer,esophageal cancer and colorectal cancer decreased.Compared with the crude cancer mortality in 1993,the effect of the demographic and non-demographic factors to the increased death rate in 2015 were 308.93％ and-208.93％,respectively.Conclusion The ASR death rate of all cancers was decreasing,and the rate in those aged 30 to 69 years decreased significantly,whereas stable in those aged 70 years or above.The effect of demographic characteristics on cancer mortality was significantly greater than that of non-demographic characteristics.

Objective To analyze the overactive bladder symptom score (OABSS) in evaluating bladder dysfunction in the different stages among type 2 diabetes mellitus patients,and to explore the value of bladder hyperactivity symptom score in screening early diabetic bladder dysfunction.Methods A total of 1 157 patients with type 2 diabetes mellitus,aged 40-88 yearswith mean age of 60.2 years,were enrolled from October 2013 to October 2016.The survey included the patients' characteristics,past history,current history,OABSS and quality of life (QOL) index scores.T test,single factor analysis of variance and multiple regression analysis are used to analyze the results.Results As many as 1 157 were qualified for final statistical analysis.OABSS is 1.94 ± 1.23 in group with diabetes duration ＜ 10 years,3.24 ± 1.45in group with diabetes duration 10-20 years,and 4.00 ± 1.72 in group with diabetes duration ＞ 20 years.The differences of OABSS in the different duration of diabetes was statistically significant.As diabetic duration increased,OABSS value increased (F =48.419,P ＜ 0.001).The difference of OABSS in the different HbA1c level,age and concurrent peripheral neuropathy was statistically significant.There was no significant difference of OABSS in the different BMI and distinct therapies.There was no significant difference of OABSS in diabetes with hypertension and without hypertension,with cardiopathy and without cardiopathy,with cerebrovascular disease (CVD) and without CVD,with hyperhpemia and without hyperlipemia.The significant factors were used to make multivariate analysis.The results showed that the duration of diabetes,HbA1 c level,age,peripheral neuropathy were still statistically significant.Standardized partial regression coefficient of diabetic duration was 0.366.OABSS was positively correlated with QOL score (r =0.434,P ＜ 0.001).Conclusions The related symptoms in OABSS with diabetic bladder dysfunction is correlated with the duration of diabetes,HbA1c level,age,concurrent peripheral neuropathy among type 2 diabetes.The duration of diabetes was the most significant factor.OABSS is likely to be one of the tools to assess the early symptoms of diabetic bladder dysfunction.