Objective:To explore the association between uric acid and new-onset chronic kidney disease (CKD) in middle-aged and elderly hypertensive patients.Methods:This was a retrospective cohort study. Middle-aged and elderly hypertensive patients who had attended at least two annual health examinations at Yongshun Community Health Service Center in Tongzhou District, Beijing, from June 2016 to December 2020 were enrolled. The time interval between the two physical examinations was three years. The first physical examination time served as the baseline, and the second as the end of follow-up. Based on the uric acid level at baseline, the participants were divided into the normal uric acid group and the hyperuricemia group. The relevant clinical data of the participants were collected. The endpoint of the study was new-onset CKD. A multivariate logistic regression model was used to analyze the association between uric acid and new-onset CKD in hypertensive patients.Results:A total of 2 472 middle-aged and elderly hypertensive patients with an average age of (62.43±7.02) years were included. Of these, 733(29.7%) were male. There were 710 patients with hyperuricemia (hyperuricemia group) and 1 762 patients with normal uric acid levels (normal uric acid group).After adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes mellitus, estimated glomerular filtration rate (eGFR), and uric acid-lowering treatment, multivariate logistic regression analysis showed that combined with hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001). The results of multivariate logistic analysis showed that elevated uric acid level was an independent risk factor for new-onset CKD in both male and female middle-aged and elderly hypertensive patients (both P<0.05), and there was no sex interaction ( P for interactio n>0.05). The results of multivariate logistic analysis showed that the combination of asymptomatic hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001), and there was no gender interaction ( P for interactio n>0.05). Conclusions:Hyperuricemia is an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients, and elevated uric acid levels increase the risk of new-onset CKD in both male and female patients. Moreover, asymptomatic hyperuricemia may increase the risk of new-onset CKD.

Objective:To explore the association between uric acid and new-onset chronic kidney disease (CKD) in middle-aged and elderly hypertensive patients.Methods:This was a retrospective cohort study. Middle-aged and elderly hypertensive patients who had attended at least two annual health examinations at Yongshun Community Health Service Center in Tongzhou District, Beijing, from June 2016 to December 2020 were enrolled. The time interval between the two physical examinations was three years. The first physical examination time served as the baseline, and the second as the end of follow-up. Based on the uric acid level at baseline, the participants were divided into the normal uric acid group and the hyperuricemia group. The relevant clinical data of the participants were collected. The endpoint of the study was new-onset CKD. A multivariate logistic regression model was used to analyze the association between uric acid and new-onset CKD in hypertensive patients.Results:A total of 2 472 middle-aged and elderly hypertensive patients with an average age of (62.43±7.02) years were included. Of these, 733(29.7%) were male. There were 710 patients with hyperuricemia (hyperuricemia group) and 1 762 patients with normal uric acid levels (normal uric acid group).After adjusting for age, sex, body mass index (BMI), systolic blood pressure, diabetes mellitus, estimated glomerular filtration rate (eGFR), and uric acid-lowering treatment, multivariate logistic regression analysis showed that combined with hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001). The results of multivariate logistic analysis showed that elevated uric acid level was an independent risk factor for new-onset CKD in both male and female middle-aged and elderly hypertensive patients (both P<0.05), and there was no sex interaction ( P for interactio n>0.05). The results of multivariate logistic analysis showed that the combination of asymptomatic hyperuricemia was an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients ( OR=3.00, 95% CI: 1.87-4.80, P<0.001), and there was no gender interaction ( P for interactio n>0.05). Conclusions:Hyperuricemia is an independent risk factor for new-onset CKD in middle-aged and elderly hypertensive patients, and elevated uric acid levels increase the risk of new-onset CKD in both male and female patients. Moreover, asymptomatic hyperuricemia may increase the risk of new-onset CKD.

Objective: This study examined the function of EP0 to provide a direction for its in-depth analysis. Methods: In this study, the EP0-deleted PRV mutant was obtained, and Tandem Mass Tagbased proteomic analysis was used to screen the differentially expressed proteins (DEPs) quantitatively in EP0-deleted PRV- or wild-type PRV-infected porcine kidney 15 cells. Results: This study identified 7,391 DEPs, including 120 and 21 up-regulated and downregulated DEPs, respectively. Western blot analysis confirmed the changes in the expression of the selected proteins, such as speckled protein 100. Comprehensive analysis revealed 141 DEPs involved in various biological processes and molecular functions, such as transcription regulator activity, biological regulation, and localization. Conclusions and Relevance: These results holistically outlined the functions of EP0 during a PRV infection and might provide a direction for more detailed function studies of EP0 and the stimulation of lytic PRV infections.

Objective To analyze the blood concentration monitoring results of 7 new antiepileptic drugs levetiracetam(LEV),oxcarbazepine(OXC),lamotrigine(LTG),topiramate(TPM),lacosamide(LCM),zonisamide(ZNS)and perampanel(PER)and provide a basis for clinical rational drug use.Methods Aretrospective analysis was conducted on the blood concentration monitoring results of 7 new antiepileptic drugs in a grade-A tertiary hospital in Beijing from November 2021 to March 2023,with a total of 6 537 valid concentration data collected.The patients were grouped according to age,gender and concomitant medication,and the blood drug concentration levels and compliance rates among the groups were analyzed and compared.Results The male to female patient ratio was 1.35∶1.There were statistically significant differences in the blood concentration distribution of OXC,LEV,LCM and TPM between genders(P<0.05).The blood concentration of LEV showed statistically significant differences between the pediatric group and the elderly group,as well as between the young adult group and the elderly group(P<0.05).The blood concentrations of OXC,ZNS and TPM showed statistically significant differences between the pediatric group and the young and middle-aged group,between the young and middle-aged group and the elderly group,and between the pediatric group and the young and middle-aged group,respectively(P<0.05).The highest and lowest overall compliance rates of blood concentration were observed for OXC and LCM,respectively.The compliance rates of OXC and TPM in the pediatric group were significantly higher than those in the young-middle-aged group,with statistically significant differences(P<0.05),while the compliance rate of LEV in the elderly group was significantly higher than that in the pediatric group and the young-middle-aged group,with a statistically significant difference(P<0.05).There were a total of 2 133 cases with combined drug use.LEV,OXC and LTG are frequently used and have good efficacy and weak interactions when added to treatment.Conclusion New antiepileptic drugs show a promising prospect in treatment,and therapeutic drug monitoring can further improve the effectiveness of individualized clinical treatment.

Objective To explore the effect of robot-assisted therapy combined with motor imagery therapy on upper limb motor function of patients with stroke.Methods A total of 75 patients with incipient stroke(course of disease＜3 months),who met the inclusion and exclusion criteria and were admitted to our center from Match 2019 to October 2022,were randomly divided into three groups(n=25)by random number table method.Besides conventional rehabilitation of upper limbs,group A received motor imagery therapy,group B received robot-assisted therapy and group C received robot-assisted therapy combined with motor imagery therapy for 8 weeks.The function of upper limbs and activities of daily living were evaluated by motion range of Armeo? Spring upper limb rehabilitation robot,simple Fugl-Meyer assessment-upper extremities(FMA-UE),and modified Barthel index(MBI)before treatment,after 4 weeks of treatment and 8 weeks of treatment.Results All the scores were significantly increased in the three groups after 4 weeks and 8 weeks of treatment(P＜0.001).All the scores of group B and C were higher than those of group A after 4 weeks and 8 weeks of treatment(P＜0.05).All the scores of group C were higher than those of group B after 8 weeks of treatment(P＜0.05).Conclusion Robot-assisted therapy combined with motor imagery therapy can further improve the upper limb motor function and activities of daily living for stroke patients.

Background::Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods::PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results::Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR= 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group. Conclusions::Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number::INPLASY202160099

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To explore the influencing factors of the long-term quality of life(QOL).Methods:According to the standard of diagnosis of primary lung cancer, a total of 74 patients with primary lung cancer were included in the study, who were first diagnosed by pathology and /or cytology and /or clinic from 1 January 2010 to 30 June 2016 in Tangshan Third Hospital, Heibei Province, and whose data were analyzed retrospectively.The Chinese version of FACT-L (4.0) QOL questionnaire was used to evaluate the QOL in 74 patients with primary lung cancer who survived more than three years.Multivariate regression statistical method was used to analyze the main influencing factors.Results:All patients with long-term survival lung cancer were treated by operation, their average QOL score was ( 126.62±13.29). Age, type of medical insurance and clinical stage had significant influence on QOL ( P<0.05). There was no significant difference in the total QOL scores between<50-year-old group(138.18±13.92) and ≥50-<60-year-old group(138.18±13.92, 137.04±12.82)(all P>0.05), but they were higher than that in ≥60-year-old group (115.28 ±13.11) (all P<0.05). The QOL of residents′ medical insurance patients (117.92 ±13.13) was lower than that of employees′ medical insurance patients (142.69±13.07) ( t=10.849, P=0.002). The QOL scores of stage Ⅰ and Ⅱ (140.34 ±12.88, 133.31±12.07) had no significant difference, but which were higher than that of stage III (96.84 ±13.46) ( P<0.05). Conclusion:Patients with long-term survival lung cancer after surgery could maintain a better QOL by early detection, timely surgery and constantly improving the medical security system to reduce the financial burden of patients.

Objective To evaluate the performance of the Sendai Guidelines,Fukuoka Guidelines and Pancreatic Cystic Lesions Management Guidelines (Chinese guidelines) in predicting malignant mucinous pancreatic cystic neoplasms (PCN).Methods A retrospective analysis of 196 patients,who received surgery and were pathologically identified as PCN or intraductal papillary mucinous neoplasms (IPMN),underwent surgical resection in Ruijin Hospital affiliated with Shanghai Jiao Tong University from January 2003 to April 2017 was performed.The differences on clinical and pathological parameters between malignant mucinous and benign mucinous PCN were compared.The accuracy,sensitivity,specificity,positive predictive value (PPV)and negative predictive value (NPV) of the indications for surgery in the Sendai,Fukuoka and Chinese Guidelines in predicting malignant mucinous PCN were calculated.Results Of 196 patients,39 patients (19.9％) were confirmed as malignant tumors and 157 patients (80.1％) were confirmed as benign tumors by pathology.There were significant differences on age,symptoms (abdominal pain,jaundice or pancreatitis),tumor solid composition,pancreatic duct diameter,tumor site,tumor diameter ＞3 cm,and serum CA199 level between malignant and benign patients (all P ＜0.05).But there were no significant differences on gender distribution,tumor diameter,mural nodules and the proportion of mucinous cystic neoplasm (MCN)and intra-ductal papillary mucinous neoplasm (IPMN).165 patients (84.2％) met the Sendai Guidelines,153 patients (78.1％) met the Chinese guideline,and only 61 patients (31.1％) met the Fukuoka Guidelines.All 39 patients with malignant tumors met the indications in Sendai Guidelines and Chinese guidelines,and only 35 patients had the indication for surgery in the Fukuoka Guidelines.The accuracy,sensitivity,specificity,PPV and NPV of the Fukuoka Guidelines for predicting the malignancy were 84.7％,89.7％,83.4％,57.4％ and 97.0％,compared to 35.7％,100％,19.8％,23.6％ and 100％ for the Sendai and 41.8％,100％,27.4％,25.5％ and 100％ for the Chinese guidelines,respectively.Conclusions The performance of the Chinese guideline is slightly better than the Sendai Guidelines,while both of them can lead to a larger number of patients undergoing unnecessary surgical resection.Though the rate of missed diagnosis could reach 10.3％,the Fukuoka Guidelines gets the highest accuracy.

Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear. In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis. Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2 macrophages infiltration. In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.