Objective: To investigate the regional differences in the incidence of urothelial carcinoma among kidney transplant recipients between northern and southern China，so as to provide reference for early diagnosis of this disease. Methods: A comprehensive search was conducted across multiple databases，including CNKI，Wanfang，CBM，and PubMed，using the keywords “kidney transplantation” and “tumor” to collect clinical data from qualified kidney transplant centers.The latest and most complete literature data published by 17 transplant centers in northern China and 14 in southern China were included.Statistical analyses were performed to compare the incidence of post-transplant urothelial carcinoma and non-urothelial malignancies. Results: A total of 37 475 kidney transplant recipients were included，among whom 837 (2.23%) developed post-transplant malignancies，including urothelial carcinoma (366/837，43.73%)，non-urothelial carcinoma (444/837，53.05%)，and malignancies with unspecified pathology (27/837，3.23%).The incidence of malignancies was significantly higher in northern China than in southern China [(2.82±1.39)% vs. (1.67±0.83)%，P=0.011]，with a particularly pronounced difference in the incidence of urothelial carcinoma [(1.68±1.12)% vs. (0.32±0.32)%，P<0.001].No significant difference was observed in the incidence of non-urothelial carcinoma between the two regions [(1.11±0.56)% vs. (1.35±0.65)%，P=0.279].Additionally，female transplant recipients exhibited a higher incidence of malignancies than males in both regions (southern China：2.38% vs. 1.80%; northern China：8.93% vs. 2.52%). Conclusion: The incidence of urothelial carcinoma following kidney transplantation is significantly higher in northern China than in southern China，underscoring the importance of implementing regular tumor screening for kidney transplant recipients，particularly for female patients in northern China，to facilitate early diagnosis and timely intervention.

Objective To investigate the effects and mechanism of modified Ditan Decoction in regulating miR-149 on liver injury in rats with chronic intermittent hypoxia.Methods Totally 18 male SD rats were randomly divided into control group,model group,and modified Ditan Decoction,with 6 rats in each group.The model group and the modified Ditan Decoction group were modeled in a low oxygen chamber.During the modeling period,the modified Ditan Decoction group was given gavage of the modified Ditan Decoction for 12 consecutive weeks.HE staining was used to observe the pathological changes of liver tissue;the ultrastructural changes of liver tissue were observed by transmission electron microscopy,TUNEL staining was used to observe hepatocyte apoptosis,the contents of ALT,AST,SOD and MDA in liver tissue were detected,the mRNA and protein expression of miR-149,ATF6,GRP78 and CHOP in liver tissue were detected by RT-qPCR and Western blot.The correlation between the mRNA transcription levels of miR-149 and ATF6 was analyzed.Results Compared with the control group,a small amount of inflammatory cell infiltration in liver tissue of the model group,with irregular arrangement of liver cells,varying degrees of edema,expansion of endoplasmic reticulum,ribosome shedding,mitochondrial membrane rupture,and apoptosis rate of liver cells increased(P<0.05),the contents of ALT,AST and MDA significantly increased(P<0.05),while the content of SOD significantly decreased(P<0.05),the expression of miR-149 mRNA in liver tissue decreased(P<0.05),while the mRNA and protein expression of ATF6,GRP78 and CHOP increased(P<0.05).Compared with the model group,no obvious edema or inflammatory cell infiltration was observed in liver tissue of rats in the modified Ditan Decoction group,the liver cells were arranged in a regular manner,with slightly expanded endoplasmic reticulum and more uniform distribution of ribosomes,the mitochondrial membrane was relatively intact,and the apoptosis rate of liver cells decreased(P<0.05),the contents of ALT,AST and MDA decreased(P<0.05),while the content of SOD increased(P<0.05),the expression of miR-149 mRNA in liver tissue significantly increased(P<0.05),while the mRNA and protein expression of ATF6,GRP78 and CHOP significantly decreased(P<0.05).The level of miR-149 mRNA was significantly negatively correlated with that of ATF6 mRNA(r=-0.766).Conclusion Modified Ditan Decoction may inhibit liver oxidative stress response in chronic intermittent hypoxia rats and improve liver injury by regulating the miR-149/ATF6 pathway.

Objective:To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function.Methods:Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains.Results:Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens ( P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment ( r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory ( r=0.45, P=0.047) and information processing speed impairment ( r=0.50, P=0.026). Conclusions:Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*

Objective:To assess the effect of ambient temperature on mortalities of ischemic stroke and hemorrhagic stroke in Beijing, China.Methods:The stroke mortality surveillance data and meteorological data in Beijing from January 1, 2014 to December 31, 2019 were collected. Distributed lag nonlinear models were used to estimate the cumulative effects of ambient temperature on stroke mortality, including ischemic stroke and hemorrhagic stroke after adjusting for temporal trend, day of week, air pollution, and relative humidity. Stratified analysis was conducted to evaluate whether sex and age modify the effect.Results:From 2014 to 2019, a total of 99 222 stroke deaths occurred in Beijing, including 69 327 ischemic stroke deaths, 24 954 hemorrhagic stroke deaths, and 4 941 unspecific stroke deaths. Using distributed lag nonlinear models, it was found the effect of temperature on stroke mortality was nonlinear and lagged. The ischemic stroke mortality risk analysis shows that with the minimum ambient temperature (MMT) for mortality (10.0 ℃) as reference, the effect of extreme low temperature (-6.2 ℃) was lagged and the relative risk ( RR) was highest at lag 0-21 days ( RR=1.26, 95% CI:1.04-1.51). The effect of extreme high temperature occurred with a lag of 0-3 days, and the cumulative RR value was 2.13 (95% CI: 1.72-2.62) at lag 0-14 days. The hemorrhagic stroke mortality risk analysis shows that with the MMT for mortality (28.0 ℃) as reference, the RR of extreme low temperature on stroke mortality was highest at lag 0-21 days ( RR=2.14, 95% CI: 1.23-3.70), and the effect of extreme high ambient temperature was short and only has statistical significance in the cumulative effect with a lag of 0-3 days ( RR=1.14, 95% CI: 1.01-1.28). Stratified analysis revealed that the effects of extreme and moderate low ambient temperature on hemorrhagic stroke death were higher in women compared to men, and the difference is statistically significant. Extreme high ambient temperature might increase the risk of ischemic stroke deaths in populations of different genders and age groups. Conclusions:The effect of low ambient temperature on ischemic stroke mortality was lagged, and the effect on hemorrhagic stroke was persistent. The effect of high ambient temperature on ischemic stroke mortality was persistent, but more transient on hemorrhagic stroke mortality. Sex and age might modify the effect of ambient temperature on stroke mortality.

Objective To investigate the value of transient elastography (TE) in the staging of hepatic fibrosis in patients with autoimmune liver disease (ALD). Methods PubMed, Embase, the Cochrane Library, CNKI, Wanfang Data, and VIP databases were searched for English and Chinese articles on TE in the staging of hepatic fibrosis in ALD published from January 2000 to January 2021. Two reviewers independently performed data extraction for the articles included, and QUADAS2 was used for quality assessment. The bivariate mixed effects model in Stata 15.0 software was used to perform the Meta-analysis. Results A total of 11 articles were included, with 1041 patients in total. In the diagnosis of significant hepatic fibrosis (F≥2), TE had a pooled sensitivity of 0.81 (95% CI : 0.75-0.86), a specificity of 0.87(95% CI 0.79-0.92), and an area under the receiver operating characteristic curve (AUC) of 0.91(95% CI 0.88-0.93); in the diagnosis of advanced hepatic fibrosis (F≥3), TE had a pooled sensitivity of 0.81(95% CI 0.74-0.87), a sensitivity of 0.90(95% CI 0.85-0.93), and an AUC of 0.92(95% CI 0.90-0.94); in the diagnosis of early-stage liver cirrhosis (F4), TE had a pooled sensitivity of 0.87(95% CI 0.74-0.93), a specificity of 0.93(95% CI 0.87-0.97), and an AUC of 0.96(95% CI 0.94-0.97). Conclusion TE has a good diagnostic value in evaluating significant liver fibrosis, advanced liver fibrosis, and early-stage liver cirrhosis in patients with ALD, especially with a relatively high diagnostic accuracy for early-stage liver cirrhosis.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

Objective:To study the prevalence and correlations of HIV infection among cross-border couples in the Dehong prefecture.Methods:A cross-sectional mass screening study with questionnaire interview and HIV testing was conducted among 17 594 registered cross-border couples from May 2017 through June 2018.Results:Among 32 400 participants, the overall prevalence of HIV infection was 2.27% (736/32 400), 2.44% (375/15 372) for Chinese citizens, and 2.12% (361/17 028) for foreign spouses. Among all the 13 853 couples with both spouses receiving HIV testing, 13 415(96.84%) were seroconcordant-negative couples, 142(1.03%) were serocondordant-positive couples, and 296(2.13%) were serodiscordant couples, including 167(1.20%) couples with positive husband and negative wife and 129(0.93%) couples with positive wife and negative husband. Multiple logistic regression analyses indicated that HIV infection was associated with drug use and risky sexual behaviors for male spouses. In contrast, HIV infection was associated with risky sexual behaviors for female spouses.Conclusion:The prevalence of HIV among cross-border couples in Dehong prefecture is high, underscoring the urgent need to scale up HIV testing, prevention, and behavioral intervention.

Objective:To analyze the longitudinal characteristics of CD4 +T lymphocytes (CD4) among the adult HIV/AIDS on antiretroviral therapy (ART) and the related factors. Methods:A retrospective cohort of adult HIV/AIDS starting ART in Dehong Dai and Jingpo Autonomous Prefecture (Dehong) in 2007-2016 was followed up to December 31, 2018. Group-based trajectory models were utilized to identify CD4 subgroups based on immune recovery (whether and when CD4 reached the average level of >500 cells/μl). The demographics and information at ART baseline were described, and the related factors were analyzed with polytomous logistic regression. The SAS 9.4 software was used for statistical analysis.Results:A total of 7 605 adults with HIV/AIDS were included, of which the median ( P 25, P 75) age at ART were 36 (30,43) years old, 61.0% were male, 42.5% were Han nationality, and 60.8% with the education of primary school or below. The follow-up duration M ( P 25, P 75) was 6.1 (4.1,8.1) years. HIV/AIDS in Dehong showed four CD4 trajectory subgroups from low to high: below the average level, primary recovery to a normal level, full recovery to a moderate level, and normal steady level, accounting for 34.4%, 39.8%, 20.6%, and 5.2%, respectively. When compared with corresponding control groups, age <35 years at ART, female, education of middle school or above, sexual transmission, no opportunistic infection, CD4 ≥200 cells/μl, baseline regimen with tenofovir (TDF) and time from HIV diagnosis to ART <1 year were the related factors facilitating the higher CD4 subgroups. Conclusions:The various CD4 immune recoveries of HIV/AIDS were changing patterns after ART. Starting ART with a high CD4 level was beneficial to CD4 recovery to normal level during the follow-up period. Early initiation of ART and exceptional attention to CD4 immune recovery should be encouraged after the ART.