ObjectiveTo observe the effect of Qishao capsules on renal injury in db/db mice with diabetic kidney disease （DKD），and explore its mechanism of protecting the kidney by inhibiting podocyte apoptosis. Methodsdb/m mice （7 mice） were used as the normal group，and db/db mice （35 mice） were randomly divided into a model group，a dapagliflozin group （0.001 g·kg^-1·d^-1），and low-，medium-，and high-dose groups of Qishao capsules （0.341 3，0.682 5，and 1.365 g·kg^-1·d^-1，respectively）. Drug intervention lasted for 8 consecutive weeks. After sampling，the serum renal function indicators ［creatinine（SCr），and urea nitrogen（BUN）］，fasting blood glucose （FBG），24 h urinary protein quantification （24 h-UTP）， and other indicators of the mice were measured. The pathological tissue morphology of the kidney was observed by periodic acid-silver methenamine （PASM） and Masson's trichrome （Masson） staining. Immunohistochemical detection of cysteine-dependent aspartate-specific protease （Caspase）-3 and B-cell lymphoma 2 （Bcl-2） was performed. Western blot was used to detect the protein expression of Caspase-8，Caspase-7，Caspase-3， and other molecules. Terminal deoxynucleotidyl transferase dUTP nick End labeling （TUNEL） staining was used to observe apoptosis in renal tissue. Immunofluorescence staining of Wilms tumor suppressor gene-1 （WT-1） was used to observe podocyte injury. Real-time polymerase chain reaction （Real-time PCR） was employed to detect Caspase-8 and Caspase-3 mRNA expression in the kidneys of experimental mice. Data analysis was conducted using statistical software GraphPad Prism 10. ResultsCompared with the normal group，the model group showed significantly increased 24 h-UTP，SCr，BUN，and FBG （P<0.01）. Additionally， PASM staining of renal tissue showed increased glycogen deposition，glomerular hypertrophy，and thickening of the basement membrane. Masson staining showed collagen fiber proliferation in renal tissue. Transmission electron microscopy showed thickening of the renal tissue basement membrane and fusion or loss of foot processes in the model group. The immunohistochemical results showed that Caspase-3 in the kidneys of the mice in the model group significantly increased （P<0.01），while the Bcl-2 protein expression level decreased significantly （P<0.01）. The number of TUNEL positive cells in renal tissue significantly increased （P<0.01）. The positive expression of WT-1 in podocytes was significantly reduced （P<0.01）. Western blot analysis showed significant upregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.01）. The mRNA expression levels of Caspase-8 and Caspase-3 in the kidneys increased significantly （P<0.01）. Compared with the model group，the Qishao capsules groups can significantly reduce the levels of 24 h-UTP，SCr，BUN，and FBG （P<0.01）. The pathological damage of renal tissue and podocyte injury were improved to some extent. Immunohistochemistry in the kidney showed a significant decrease in Caspase-3 （P<0.01） and a significant increase in Bcl-2 protein expression level （P<0.01）. Additionally， there were a significant decrease in the number of TUNEL positive cells in renal tissue （P<0.01），a significant increase in WT-1 positive expression in podocytes （P<0.01），marked downregulation of Caspase-8，Caspase-7，and Caspase-3 protein expression in renal tissue （P<0.05，P<0.01），and a significant decrease in Caspase-8 and Caspase-3 mRNA expression levels （P<0.01）. ConclusionQishao capsules can inhibit podocyte apoptosis by regulating the expression of Caspase-8，Caspase-7， and Caspase-3，thereby improving the diabetic renal injury in db/db mice.

In order to help the standardized residency training of nuclear medicine residents, the standardized residency training base of nuclear medicine residents in Peking University People's Hospital, combined with forty-five nuclear medicine departments of teaching hospital, established the WeChat official account of "Standardized Residency Training of Nuclear Medicine" and submitted one teaching case per week. The appearance of the WeChat official account of "Standardized Residency Training of Nuclear Medicine" has made up for the shortcomings of insufficient teaching cases in a single training base, strengthened the training of residents' imaging diagnostic thinking, and promoted mutual learning among the bases. By writing teaching cases, instructors and residents have opened up ideas, increased knowledge, improved self-learning ability, and cultivated imaging diagnostic thinking. With the flexible and practical features of the WeChat official account, the consciousness and sustainability of residents' learning have been enhanced.

Background Current evidence on whether occupational sulfur dioxide (SO₂) exposure affects the risk of hypertension is still limited, and the research results of the effect of environmental SO₂ exposure on risk of hypertension remain inconsistent. Objective To analyze the association between self-reported occupational exposure to SO₂ and the risk of hypertension, and the potential dose-response relationship between the years of exposure to SO₂ and the risk of hypertension. Methods Based on the Jinchang cohort, a nested case-control study design was adopted. A total of 841 newly diagnosed hypertension patients were followed up as the case group, and the control group was selected with 1∶1 individual matching based on non-occupational factors and occupational factors, respectively. The former matching conditions included age ±2 years old, same gender, working age ±2 years, and home address in the same sub-district. The latter was limited to working in the same workshop on the basis of the former conditions. Finally, the former included 717 controls and the latter included 488 controls. A unified questionnaire was used to collect general demographic characteristics, lifestyle habits, history of diabetes, family history of hypertension, and information on occupational exposure to SO₂ (self-reported history of occupational exposure to SO₂ and years of exposure to SO₂). Conditional logistic regression model was used to analyze the association between occupational exposure to SO₂ and hypertension, and the dose-response relationship between the years of SO₂ exposure and the risk of hypertension. Results In the nested case-control study matching with the non-occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO₂ was 2.39 (95%CI: 1.68-3.39); while when matching with the occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO₂ was 1.48 (95%CI: 1.04-2.12). The results of the dose-response relationship showed that as the SO₂ exposure years increased from 1-9 years, 10-19 years, 20-29 years, and 30 years and above, in the nested case-control study matching with non-occupational factors, the ORs of hypertension were 1.85 (95%CI: 0.68-5.08), 1.46 (95%CI: 0.58-3.67), 1.64 (95%CI: 1.00-2.67), and 4.95 (95%CI: 2.63-9.31), respectively; in the nested case-control study matching with occupational factors, the ORs of hypertension were 0.98 (95%CI: 0.40-2.41), 1.84 (95%CI: 0.72-4.70), 1.37 (95%CI: 0.82-2.29), and 2.44 (95%CI: 1.37-4.35), respectively. The two dose-response relationships were positive by χ² trend test (P_trend<0.05). Conclusion Self-reported occupational exposure to SO₂ is associated with the risk of hypertension in the study population, and the hypertension risk increases with the increase of SO₂ exposure years.

Objective: The relationship between outdoor temperature and blood pressure (BP) has been inconclusive. We analyzed data from a prospective cohort study in northwestern China to investigate the effect of outdoor temperature on BP and effect modification by season. Methods: A total of 32,710 individuals who participated in both the baseline survey and the first follow-up in 2011-2015 were included in the study. A linear mixed-effect model and generalized additive mixed model (GAMM) were applied to estimate the association between outdoor temperature and BP after adjusting for confounding variables. Results: The mean differences in systolic blood pressure (SBP) and diastolic blood pressure (DBP) between summer and winter were 3.5 mmHg and 2.75 mmHg, respectively. After adjusting for individual characteristics, meteorological factors and air pollutants, a significant increase in SBP and DBP was observed for lag 06 day and lag 04 day, a 0.28 mmHg (95% Conclusions This study demonstrated a significant negative association between outdoor temperature and BP in a high-altitude environment of northwest China. Moreover, BP showed a significant seasonal variation. The association between BP and temperature differed by season and individuals' demographic characteristics (age, gender, BMI), unhealthy behaviors (smoking and alcohol consumption), and chronic disease status (CVDs, hypertension, and diabetes).
Adult ; Blood Pressure/physiology* ; China/epidemiology* ; Environmental Exposure/statistics & numerical data* ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Seasons ; Temperature

Objective:To further understand the etiological distribution of fever of unknown origin (FUO) in patients underwent 18F-fluorodeoxyglucose (FDG) PET/CT imaging, and to explore the significance of 18F-FDG PET/CT in the diagnosis of different types of diseases in FUO patients. Methods:From January 2013 to August 2019, the clinical and PET/CT image data of 466 FUO patients (194 males, 272 females, age: 3-91(52.7±20.9) years) in Peking University People′s Hospital were retrospectively analyzed. The etiological distribution of FUO patients was analyzed according to the final clinical diagnosis. PET/CT imaging manifestations were analyzed for different types of diseases in FUO patients. The role of 18F-FDG PET/CT in differential diagnosis for FUO was evaluated through clinical questionnaire. Data were analyzed by using χ2 test. Results:The common disease types in FUO patients were rheumatic and immune disease (48.7%, 227/466), infection (28.5%, 133/466) and malignant tumor (11.2%, 52/466). For PET/CT imaging, 95.5% (445/466) of the patients were positive, of which 313 (70.3%, 313/445) were found to have focal lesions, and the other 132 (29.7%, 132/445) showed only nonspecific abnormal uptake. Lesions in different types of diseases were varied in the location, morphological changes as well as FDG uptake. The results of the questionnaire showed that PET/CT imaging could benefit 95.9% (447/466) of the patients in the FUO diagnosis and treatment. PET/CT reached direct etiological diagnosis of malignant tumors more frequently than other types of diseases ( χ2 values: 14.408-25.466, all P<0.001). PET/CT helped or directly reached the etiological diagnosis of rheumatologic diseases more frequently than infection and unknown cause group( χ2 values: 7.922, 9.647, both P<0.05). Conclusion:18F-FDG PET/CT imaging has high clinical value in the diagnosis of FUO etiology and can provide multilevel diagnostic information.

OBJECTIVE： To observe the effects of nicorandil on vascular endothelial function and angina pectoris recurrence in patients with unstable angina pectoris after percutaneous coronary intervention （PCI）. METHODS： Totally 195 patients with unstable angina pectoris were collected from Sichuan Provincial People’s Hospital during Jan. 2016-Mar. 2018， and then divided into control group （97 cases） and observation group （98 cases） according to random number table. Both groups received PCI， and then given basic treatment as Enoxaparin sodium injection， Isosorbide mononitrate sustained-release tablets， Aspirin enteric-coated tablets， Clopidogrel sulfate tablets and Atorvastatin calcium tablets after PCI. Observation group additional received Nicorandil tablet 5 mg， tid， on the basis of control group. Both groups were treated for 6 months. The levels of vascular endothelial function related indexes （FMD， ET-1， NO）， myocardial injury markers （cTnⅠ， CK-MB） and inflammatory factors （hs-CRP） were observed before and after PCI. The recurrent angina pectoris， the occurrence of MACE and ADR were recorded. RESULTS： 6 patients of control group and 4 patients of observation group withdrew from the study. One day before operation， there was no significant difference in the levels of vascular endothelial function， myocardial injury markers or inflammatory factors between 2 groups （P＞0.05）. One day after operation， the levels of FMD and NO in both groups decreased significantly， while the levels of ET-1， cTnⅠ and CK-MB increased significantly （P＜0.05）. The levels of FMD and NO were increased significantly in the 1st and 6th months after surgery， and the observation group was significantly higher than the control group； the levels of ET-1， cTnⅠ， CK-MB and hs-CRP were decreased significantly， and the observation group was significantly lower than the control group （P＜0.05）. The incidence and times of recurrent angina pectoris， duration， the proportion of grade Ⅲ angina pectoris and total incidence of MACE in observation group were significantly lower， less or shorter than control group （P＜0.05）. There was no statistical significance in total incidence of ADR between 2 groups （P＞0.05）. CONCLUSIONS： Additional use of nicorandil can improve vascular endothelial function， relieve the myocardial injury and inflammatory response， reduce the occurrence of recurrent angina pectoris and MACE after PCI and doesn’t influence the safety of routine treatment.

Objective: To investigate whether CD137-CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs) -derived exosomes through autophagy mediated Rab7 pathway. Methods: Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP-GFP-LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs-derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results: (1) The expressions of Rab7, LC3Ⅱ and p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3±0.9) vs. (10.3±1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7±4.0) and (10.7±1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs-derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs-derived exosomes was significantly higher in the CD137-activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137-activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱ protein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137-CD137L signaling may affect the secretion of mouse VSMCs-derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective To investigate whether CD137?CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs)?derived exosomes through autophagy mediated Rab7 pathway. Methods Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP?GFP?LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs?derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results (1) The expressions of Rab7, LC3Ⅱand p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3 ± 0.9) vs. (10.3 ± 1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7 ± 4.0) and (10.7 ± 1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs?derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs?derived exosomes was significantly higher in the CD137?activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137?activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱprotein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137?CD137L signaling may affect the secretion of mouse VSMCs?derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective: To understand the incidence of stroke in the population of Jinchang Cohort and the relationship between metabolic diseases and stroke, and provide scientific evidence for the prevention and treatment of stroke in the population. Methods: The epidemiological investigation data and physical examination data of the 33 042 follow-up participants in Jinchang Cohort were collected for a prospective cohort study. Restricted cubic splines functions was used to analyze the dose-response relationship between metabolic indexes and the risk of stroke incidence. Results: 1) The incidence rate of stroke in Jinchang Cohort was 1.59%, and the standardized incidence rate was 3.99%. 2) Hypertension (male HR=2.20, female HR=4.45) and dyslipidemia (male HR=1.49, female HR=1.79) were the risk factors of stroke incidence in the population and diabetes had influence on the incidence of stroke only in the males (HR=1.79), while obesity had influence only in the females (HR=1.64). The more kinds of metabolic diseases, the higher risk of stroke incidence was. 3) Systolic blood pressure had a non-linear dose-response correlation with the risk of stroke incidence, while diastolic blood pressure had a positive linear correlation with the risk of stroke incidence. Conclusions The incidence of stroke in Jinchang Cohort population was high compared with both domestic level and oversea level. The patients with metabolic diseases were the population at high-risk for stroke, and more attention should be paid to them in the prevention and treatment of stroke. Diastolic blood pressure might be more closely related to stroke.