Objective: To evaluate the effect of bioactive peptides combined with probiotics on serum uric acid (SUA) in patients with hyperuricemia (HUA), so as to provide the evidence for prevention and treatment of HUA. Methods: The patients with HUA aged 18 to 65 years were selected and randomly divided into an intervention group and a control group. The patients in the intervention group received bioactive peptides combined with probiotics for 28 days at a dose of 3 g/d, while the patients in the control group received an equal dose of placebos. Demographic information, body mass index (BMI), blood pressure and blood lipid were collected through questionnaire surveys, physical examination and laboratory tests. SUA levels were detected before and after 14 days and 28 days of interventions. The differences of SUA levels between the two groups were compared using generalized estimation equation. Results: Totally 108 patients with HUA were recruited, including 54 patients in the intervention group and 53 patients in the control group (1 dropout). Before interventions, there were no statistically significant differences in gender, age, course of HUA, exercise duration, frequency of alcohol consumption, frequency of meat broth consumption, BMI, prevalence of hypertension and prevalence of dyslipidemia between the two groups (all P>0.05). After 14 days of interventions, the SUA levels of the patients in the intervention group decreased by 3.00 μmol/L, while those in the control group increased by 7.00 μmol/L. After 28 days of interventions, the SUA levels of the patients in the intervention group and the control group decreased by 26.00 μmol/L and 16.00 μmol/L, respectively. However, there was no statistically significant interaction between the intervention time and group (both P>0.05). Subgroup analysis showed that after 28 days of interventions, the decrease in SUA levels in the patients aged 55 years and older and without hypertension in the intervention group was greater than those in the control group (both P<0.05). Conclusions Bioactive peptides combined with probiotics showed no significant difference in reducing SUA levels in patients with HUA compared to the control group. The effect was more significant for patients aged 55 years and older and without hypertension.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective:To standardize the quantitation of 18F-Florbetapir PET SUV ratio (SUVR) to the Centiloid (CL) scale, and analyze the positive rate of β-amyloid (Aβ) in Chinese Preclinical Alzheimer′s Disease (AD) Study (C-PAS). Methods:11C-Pittsburgh compound B(PIB) and 18F-Florbetapir images from public databases " Standard PIB" and " Florbetapir Calibration" were preprocessed by statistical parametric mapping (SPM) 12, and the transformative formulas from SUVR to CL were derived. Then a total of 942 subjects (357 males, 585 females; age (66.4±8.1) years) from C-PAS who received 18F-Florbetapir PET at the Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University from October 2018 to August 2023 were retrospectively included. CL values were calculated and the Aβ positive rates (CL value≤12, Aβ negative; 12< CL value<30, Aβ subtle pathology; CL value≥30, Aβ positive) of AD, mild cognitive impairment (MCI) and cognitive unimpaired (CU) groups were explored. Data were analyzed by using Kruskal-Wallis rank sum test, Dunn′s test (Bonferroni correction ) and χ2 test. Results:The formula for the 18F-Florbetapir SUVR converted to CL was CL=179.64×SUVR_Florbetapir-186.95. In the C-PAS cohort, the SUVR, CL value, Aβ positive rate (including subtle pathology) of patients with clinically diagnosed AD were 1.29±0.22, 43.97±39.23, 71.80%(140/195), which were 1.04(1.02, 1.14), 1.16(-4.04, 17.14), 28.50%(61/214) for patients with MCI, and 1.04(1.01, 1.08), 0.54(-5.29, 7.69), 15.38%(82/533) for CU subjects, respectively. SUVR, CL value and the ratio of negative, subtle and positive Aβ pathology of the above three groups exhibited statistical differences ( H=148.30, H=148.30, χ2=262.12, all P<0.001). Besides, mixed MCI group exhibited higher CL values ((2.45(-1.54, 46.32) vs -1.58(-6.33, 7.20); H=8.21, P=0.016; z=2.81, P=0.015) and Aβ positive rate (including subtle pathology) (41.18%(14/34) vs 14.64%(6/41); χ2 values: 12.71 and 10.63, both P<0.01), compared to non-amnestic MCI group. The CL values and Aβ positive rates were also increased with age in CU group. Conclusion:This study validates the feasibility of the CL formula with 18F-Florbetapir images and reveals Aβ deposition in C-PAS cohort, which can lay the foundation for multi-center Aβ PET studies in China.

Objective:To compare the localization accuracy of interictal 18F-FDG and 18F-flumazenil (FMZ) PET/CT imaging for focal cortical dysplasia (FCD). Methods:A retrospective analysis was conducted on 22 patients (12 males, 10 females; age 8-36 years) with pathologically confirmed FCD who underwent surgical resection at Huashan Hospital, Fudan University from July 2021 to June 2023. All patients underwent 18F-FDG and 18F-FMZ PET/CT scans before surgery. Surgical pathological diagnosis was used as the gold standard. Visual scoring was used to analyze the images. The accuracy of the two imaging methods in the localization of FCD was compared, and subgroup analysis (FCD Ⅱa, FCD Ⅱb) of different pathological type was further performed. Paired- t test, χ2 test or Fisher′s exact test was used to analyze the data. Results:The visual score of 18F-FMZ PET/CT was higher than that of 18F-FDG (3.00±0.82 vs 2.27±0.92; t=4.17, P=0.020). The accuracy of interictal 18F-FMZ PET/CT was 77.27%(17/22), which was higher than that of 18F-FDG PET/CT (36.36%, 8/22; χ2=7.50, P=0.006). Subgroup analysis showed that within the cohort of patients diagnosed with FCD Ⅱa ( n=18), 18F-FMZ PET/CT outperformed 18F-FDG in terms of accuracy for localization (15/18 vs 6/18; P=0.006). Conclusion:Compared to 18F-FDG, 18F-FMZ PET/CT demonstrates clearer and more accurate identification of lesion borders, and exhibits higher precision, which provides valuable guidance for preoperative localization.

Objective:To observe the role of Huaiqihuang Granules (HQ) in the long-term management of bronchial asthma in young children, and the effective effect on concomitant rhinitis.Methods:A prospective real-world multicenter study was conducted in children aged 2-5 years with asthma diagnosed in the outpatient department (from April 2016 to March 2019)who received either inhaled corticosteroid (ICS)/leukotriene receptor antagonist (LTRA)(control group); inhaled ICS/LTRA plus HQ(combination group), or HQ alone(HQ group). All patients were followed up at week 4, 8, 12 after treatment. The number of days with asthma symptoms, the frequency of severe asthma attacks, the level of asthma control, and the days with rhinitis symptoms in the last 4 weeks were recorded. Differences before and after treatment, and those among groups after treatment were compared using Kruskal- Wallis H test or Wilcoxon rank-sum test. Results:A total of 2 234 eligible patients were recruited, and 2 147 cases completed followed-up visits, including 477, 1 374 and 296 cases in the control group, combination group, and HQ group, respectively. After the treatment, all 3 groups showed significant declines in the days with asthma symptoms, frequency of severe asthma attack and the days with rhinitis symptoms (all P<0.01), and the rate of well-controlled asthma increased significantly ( P<0.01). It lasted until the end of follow-up. Among groups, patients in the combination group showed significantly less days of asthma symptoms than those of the other 2 group at week 8 and 12[0(0, 0.9) d vs.0(0, 0.3) d, P<0.05; 0(0, 0.1) d vs. 0(0, 1.0) d, P<0.01]. Patients in the combination group and HQ group showed a significantly lower rate of severe asthma attacks than that of the control group at week 12 [0(0, 1), 0(0, 1), 0(0, 2), all P<0.05]. The well-controlled rate of asthma in the combination group was significantly higher than that of the control group and HQ group at week 8 and 12 (89.6% vs. 85.9% vs.82.1%, H=15.28; 90.9% vs. 84.1% vs. 81.8%, χ2=29.32, all P<0.01). Conclusions:HQ can significantly alleviate symptoms of asthma and rhinitis, severe attack of asthma, and increase the control rate of asthma when used as an additional treatment or used alone.

Objective:To explore the β-amyloid (Aβ) deposition pattern of subjects with the preclinical Alzheimer′s disease (AD), community-derived amnestic mild cognitive impairment (aMCI) and normal cognition (NC) from communities of Shanghai.Methods:According to the inclusion and exclusion criteria, 273 subjects (104 males, 169 females; age (64.2±7.6) years) were recruited from Shanghai community and memory clinics from December 2018 to July 2020. All subjects underwent MRI, 18F-AV45 PET imaging and neuropsychological scale tests and were grouped into AD, aMCI and NC groups based on clinical diagnosis. Differences in demographic information, the neuropsychological scale tests′ scores and positive rate of Aβ deposition among each group were analyzed by one-way analysis of variance or χ2 test. Aβ deposition patterns of AD and MCI groups were analyzed at voxel level, and the differences of Aβ deposition among different groups were compared. Results:Among 273 patients, the positive rates of Aβ deposition in AD, aMCI and NC groups were 84.4%(38/45), 36.4%(20/55) and 23.1%(40/173), respectively ( χ2=58.37, P<0.001). Among AD, aMCI, NC and NC (Aβ-) groups ( n=132), the education years of AD group was the lowest ((9.7±4.6) years; F=8.86, P<0.001). In addition, there were significant differences in the scores of several neuropsychological scale tests among AD, aMCI, NC groups and NC (Aβ-) group ( F values: 27.68-235.50, all P<0.001). Compared with subjects in NC(Aβ-) group, the Aβ depositions in the aMCI and AD groups were widely distributed in the whole cerebral cortex; and AD group had higher Aβ deposition in bilateral frontal, parietal, temporal, occipital lobe, cingulate gyrus and precuneus than aMCI group. Conclusions:The positive rate of Aβ deposition in the preclinical AD population from the Shanghai community is obtained. There are significant different Aβ deposition patterns in subjects at different stages of AD.

Objective:To explore the association of the impaired cognition and the deposition of β-amyloid (Aβ) in normal cognitive (NC) and mild cognitive impairment (MCI).Methods:From December 2018 to January 2021, 305 subjects (113 males, 192 females; age (64.0±7.7) years) who completed neuropsychological tests and MRI in Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University and 18F-florbetapir (AV45) PET imaging in Huashan Hospital, Fudan University were retrospectively analyzed. The subjects were divided into MCI group and NC group based on neuropsychological tests, and each group was further divided into Aβ-positive and Aβ-negative based on PET imaging results. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Results:There were 118 subjects in MCI group and 187 subjects in NC group. The Aβ-positive rate in MCI group (37.3%, 44/118) was higher than that in NC group (26.2%, 49/187; χ2=4.19, P=0.041). The assessment performances of MCI group in general cognitive function, memory function, language function and executive function were inferior to those of NC group ( t values: from -10.63 to -6.31, z values: from -11.01 to -6.03, all P<0.001). The Auditory Verbal Learning Test-Long Delay Recall (AVLT-LDR) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in MCI group (1.00(0.00, 3.00) and 3.00(1.00, 4.00); z=-2.49, P=0.013). The Montreal Cognitive Assessment Basic (MoCA-B) score of Aβ-positive subjects was lower than that of Aβ-negative subjects in NC group (25.29±2.67 and 26.36±2.42; t=-2.61, P=0.010). Conclusion:Compared to Aβ-negative subjects, MCI patients with Aβ-positive perform worse on memory tests, and NC subjects with Aβ-positive perform worse on general cognitive function.

【Objective】 To analyze the dynamics of specific SARS-CoV-2 IgG antibodies in blood donors in Fuzhou area after receiving booster doses of inactivated COVID-19 vaccine and breakthrough infections, and to provide evidence for the timing of the collection of specific immune plasma or convalescent plasma and the subsequent vaccine doses. 【Methods】 A total of 109 volunteers who received the first booster dose of inactivated COVID-19 vaccine and 102 volunteers who experienced breakthrough infections were recruited at Fujian Blood Center from October to November 2021. Blood samples were collected at eight time points: 14 (11, 20) days before the booster dose (Time0), 14 (10, 23) days after the booster dose (Time1), 53 (45.5, 61) days after the booster dose (Time2), 88 (78, 101.5) days after the booster dose (Time3), 124 (112.5, 138.5) days after the booster dose (Time4), 158 (146, 174) days after the booster dose (Time5), 194 (179.5, 214) days after the booster dose (Time6) and within one month after the breakthrough infection (Time7). Serum SARS-CoV-2 IgG antibodies were detected using a chemiluminescence immunoassay. The dynamics of antibody levels were analyzed and the effects of age, gender, weight, BMI, blood type and smoking on antibody levels were also analyzed. 【Results】 The positive rate of SARS-CoV-2 IgG antibodies was 53.2% (58/109) at Time0, 100% (109/109) at Time1, and 95.4% (104/109) at Time6. The antibody levels were significantly higher at Time1 and Time6 than at Time0 (P<0.001). The highest level was observed at Time1, followed by a gradual decrease until Time2-Time6, which were 89.9% (9.74/10.84), 77.7% (8.42/10.84), 68.3% (7.4/10.84), 59.4% (6.44/10.84), and 53.9% (5.84/10.84) of the peak value at Time1 (P<0.001). There were no significant differences in IgG antibody levels among different gender, weight, BMI, age, blood type and smoker or non-smoker at the same time points (P values all >0.05). The IgG antibody level at Time7 was 2.07 times than that at Time1 (P<0.001). There were no significant differences in IgG antibody levels between asymptomatic groups and symptomatic groups and also between fever-free groups and fever groups (P values all >0.05). The IgG antibody level in breakthrough infection group was significantly higher than that in non-breakthrough infection group (P<0.001). 【Conclusion】 Booster doses of inactivated COVID-19 vaccine and breakthrough infections can stimulate stronger immune responses in the body. It is recommended to collect specific immune plasma or convalescent plasma within one month after breakthrough infections or booster doses of COVID-19 vaccine for special purposes. The timing of subsequent vaccine doses should be based on the dynamics of antibody levels. It is necessary to continuously monitor antibody levels to provide evidence for subsequent vaccine doses.

Abstract: Objective To investigate the clinical features and risk factors for severe tsutsugamushi disease, so as to provide reference for diagnosis and differentiation of severe tsutsugamushi disease as soon as possible. Methods The clinical data of 178 cases of inpatients with tsutsugamushi disease admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from January 2016 to September 2021 were collected and analyzed according to their gender, age, underlying diseases, clinical characteristics at admission, laboratory examination results within 24 hours of admission and epidemiological history. The patients were divided into the severe group and the non-severe group according to the diagnostic criteria. The data of clinical characteristics, laboratory examination and prognosis of the two groups were compared. Multivariate logistic regression analysis was performed on the variables with statistical significance and the receiver operating characteristic curve (ROC) was drawn. Results A total of 178 patients were included in this study, with 37 in the severe group and 141 in the non-severe group. Compared with the non-severe group, the age of the severe group was older, the underlying diseases were more, the incidence of dyspnea and the levels of white blood cell, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, cystatin C, uric acid and serum creatinine were significantly increased, the levels of platelet and albumin were significantly decreased (all P<0.05). The dyspnea [odds ratio (OR value)=8.93, 95% confidence interval (CI): 1.200-66.424; P=0.032], total bilirubin (OR=1.091, 95%CI: 1.028-1.159; P=0.004) and serum creatinine (OR=1.052, 95%CI: 1.004-1.102; P=0.033) were independent risk factors for severe tsutsugamushi disease. The area under ROC curve of total bilirubin and serum creatinine were 0.777 and 0.764, respectively (both P<0.01), indicating high predictive value for severe tsutsugamushi disease. The optimal cut-off value for total bilirubin was 23.01 µmol/L, with a sensitivity of 54.10% and a specificity of 90.60%; the optimal cut-off value for creatinine was 126.45 µmol/L, with a sensitivity of 43.20% and a specificity of 100.00%. The case fatality rate of severe tsutsugamushi disease was 2.70%. Conclusions The patients with severe tsutsugamushi disease are older, and have more underlying diseases. Dyspnea, increased total bilirubin and elevated serum creatinine are independent risk factors for severe tsutsugamushi disease, which can help in the early identification of severe tsutsugamushi disease early.