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 investigate the protective effect of artesunate(Art)against apoptosis and mitophagy induced by NaF in osteocytes MLO-Y4,and to explore the molecular mechanism.METHODS MLO-Y4 cells were treated with NaF(2 mmol·L-1)for 48 h to establish an in vitro model of osteocytes injuries,and the cells were divided into the cell control group,NaF(2 mmol·L-1)group and NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups.The cells were pretreated for 2 h and NaF was added for 48 h.The cell survival of MLO-Y4 cells was detected by MTT assay.The cell viability of MLO-Y4 cells was measured by Calcein-AM staining.The lactate dehydrogenase(LDH)content in the supernatant was examined by the LDH detection kit.The level of intracellular reactive oxygen species(ROS)was examined by DCFH-DA staining.The malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were detected by chemical colorimetry.Apoptosis was measured by Hoechst33342 staining and Annexin-V/PI staining.The level of mitochondrial membrane potential(MMP)was measured by JC-1 staining.The formation of autophagic vacuoles and morphological mitochondrial changes were observed via Lyso-tracker staining and Mito-Tracker staining.The ATP content was detected with the luciferase method.The expression of microtubule-associated protein light chain 3(LC-3)in mitochon-dria was examined by immunofluorescence staining.Protein expressions of LC-3,P62,E3 ubiquitin-ligase(Parkin)and PTEN-induced putative kinase 1(PINK1)were detected by Western blotting.RESULTS Compared with the cell control group,the cell survival rate and cell viability were significantly reduced in the NaF group(P<0.01),LDH content in the supernatant,the level of intracellular ROS,the MDA content,apoptosis rate and autophagic vesicle formation were remarkably increased(P<0.01),protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly upregulated along with the elevation of LC-3 in damaged mitochondria(P<0.01),while P62 levels,SOD activity,MMP and ATP contents were reduced in NaF cells(P<0.05,P<0.01).Compared with NaF group,the cell viability and survival rate of MLO-Y4 cells in NaF+Art 0.25,0.50 and 1.00 μmol·L-1 groups were significantly increased(P<0.01);the content of LDH in supernatants was decreased obviously(P<0.01);the levels of intracellular ROS and MDA content were markedly reduced(P<0.05,P<0.01);the apoptosis rate and autophagic vesicle formation were remarkably decreased(P<0.05,P<0.01);protein levels of Parkin and PINK1,and the conversion of LC-3Ⅱ from LC-3Ⅰ were markedly down-regulated along with the accumulation of LC-3 in damaged mitochondria(P<0.01);MMP and ATP content were also reduced(P<0.05,P<0.01);while SOD activityand P62 levelwere significantly increased(P<0.05,P<0.01).CONCLU-SION Art has a protective effect against oxidative damage induced by NaF in MLO-Y4 cells,which might be related to the inhibition of apoptosis and mitophagy.

ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Objective:To investigate the effect of instantaneous flow rate on the consistency of diagnostic accuracy of severe degenerative mitral regurgitation (DMR) using proximal isovelocity surface area (PISA).Methods:From June 2019 to June 2021, 75 patients with DMR who underwent echocardiography in Department of Echocardiography of Zhongshan Hospital, Fudan University were prospectively enrolled. The instantaneous flow rate of DMR during the systolic phase was calculated using M-mode PISA(PISA M-mode), and a time-integrated curve was plotted. Regurgitant volume (RVol) and effective regurgitant orifice area (EROA) were calculated by traditional PISA (PISA max), pair PISA (PISA pair), and PISA M-mode, respectively. RVol acquired from cardiac magnetic resonance (CMR) volumetric method in 22 patients of the enrolled patients. The correlation and consistency of RVol acquired between the three PISA methods and CMR were compared. Agreement of diagnostic accuracy of severe mitral regurgitation (sMR) acquired between the three PISA methods and multi-parameter algorithm by American Society of Echocardiography (ASE) was analyzed using Cohen′s Kappa analysis. Results:The curve of instantaneous flow rate of DMR showed unimodal pattern with the peak at mid-late systolic phase. The correlation of RVol acquired between PISA methods and CMR was moderate for PISA max and PISA pair ( r=0.77, 0.80, both P<0.001), whereas PISA M-mode presented strong correlation with CMR ( r=0.87, P<0.001). RVol acquired from PISA max was larger than that of CMR[(69.1±37.1) ml vs (49.0±29.0)ml, P=0.002]. Both PISA max and PISA pair were shown moderate agreement of diagnostic accuracy of sMR with ASE multi-parameters algorithm (RVol: κ=0.496, 0.525, both P<0.001; EROA: κ=0.570, 0.578, both P<0.001), while PISA M-mode presented strong agreement (RVol: κ=0.867 and EROA: κ=0.802, both P<0.001). Conclusions:Based on the unimodal pattern of instantaneous flow rate in patients with DMR, PISA max may significantly overestimate RVol, exposing a significant proportion of patients with DMR to unnecessary MR surgery. PISA M-mode presents better correlation and consistency with CMR on the quantification of RVol compared with PISA max and PISA pair, and may improve the diagnostic accuracy of quantification of sMR using PISA.

A case of primary amoebic meningoencephalitis (PAM) treated in the First Affiliated Hospital of Xinxiang Medical University in March 6, 2022 was reported.The proband was a 14-year-old boy, who was admitted to the hospital because of " fever, headache and vomiting for 2 days" . Metagenomic next-generation sequencing (mNGS) was consequently conducted to examine the pathogens in cerebrospinal fluid.Naegleria infection was detected, so the child was diagnosed with PAM.The disease developed rapidly, and the patient died 29 hours after admission.In the paper, a total of 13 studies were reviewed, and 15 children with PAM were reported.Of the reported cases, only 1 case survived, 14 cases died.PAM had a low incidence, a dangerous condition, and high mortality.Most cases were diagnosed by autopsy or pathogen diagnosis in cerebrospinal fluid.This case is confirmed by mNGS of pathogens, and it is rarely reported at home and abroad.

ObjectiveTo investigate the clinical effect of Shipiyin combined with diosmin in the treatment of lymphedema with spleen Yang deficiency syndrome（SYDS）after modified radical mastectomy and the specific effect on the function of the affected limb. MethodEighty-two patients with lymphedema with SYDS after modified radical mastectomy from outpatient and inpatient department of breast department and oncology department of the First Affiliated Hospital of Hunan University of Chinese Medicine were randomly divided into an observation group（41 cases） and a control group（41 cases）. The control group was given diosmin tablets（0.9 g per time， two times per day）on the basis of conventional treatment，and the observation group was given Shipiyin（one dose per day）on the basis of the control group. The course of treatment was 14 days. The clinical symptoms were observed and the limb circumference，traditional Chinese medicine（TCM） syndrome score，functional assessment of cancer therapy-breast cancer（FACT-B） score，disability of arm， shoulder and hand questionnaire（DASH） score，and joint range of motion were measured to analyze the TCM syndrome therapeutic effect and clinical efficacy. ResultAfter 14 days of treatment， the total effective rate of the observation group was 85.37% （35/41） and that of the control group was 63.41% （26/41） in the TCM symptoms， showing a statistically significant difference （Z=-2.212， P<0.05）. In terms of the clinical efficacy， the total effective rate in the observation group was 82.93% （34/41） and that in the control group was 75.61% （31/41）， indicating a statistically significant difference （Z=-2.061， P<0.05）. Compared with the situations before treatment， the scores of clinical symptoms such as the swelling of the upper limb， pain， sense of heaviness， stuffiness， fatigue， fullness， tightness， and skin keratosis and pruritus in the two groups were significantly lowered （P<0.01） after treatment. Compared with the control group， the observation group could better improve the swelling and fullness（P<0.01），as well as the feeling of pain，heaviness，stuffiness，fatigue，tightness，skin keratosis and pruritus （P<0.05）of the upper limbs of patients. The affected limb circumference， TCM syndrome score， and DASH score decreased significantly， while the FACT-B score and upper limb joint range of motion increased significantly in the two groups after treatment （P<0.01）. Compared with the control group， the observation group showed significantly reduced limb circumference at 10 cm proximal to the elbow striae， lowered TCM syndrome score， elevated FACT-B score（P<0.05）， decreased DASH score and improved range of motion of the upper limb joint （P<0.01） after treatment. ConclusionShipiyin combined with diosmin has better clinical efficacy in the treatment of lymphedema with SYDS after modified radical mastectomy than diosmin alone，which can better improve the clinical symptoms，signs，quality of life and limb functional activity of patients. This provides a new clinical program for the treatment of lymphedema after breast cancer surgery with integrated Chinese and western medicine.

Objective:To explore the characteristics, clinical manifestations and gene mutation types of Cornelia de Lange syndrome (CdLs), and to improve the understanding of the disease.Methods:Clinical data and gene test results of a pediatric case of CdLs diagnosed in the First Affiliated Hospital of Xinxiang Medical University in August 2019 were analyzed retrospectively.Results:A female patient with 2 years and 8 months old presented a special appearance with a low and flat nose, a wide eye distance, audition ears, a downward inclination of the mouth corner, a high arch of the jaw and a small jaw deformity, who had recurrent seizures, speech and mental retardation.The result of gene test showed the mutation of SMC1A gene c. 2923C > T, and thus the patient was diagnosed as type 2 CdLs. Conclusions:CdLs is a rare genetic metabolic disease with special facial features and physical signs.There is only one case of CdLs with gene mutation of SMC1A in China through literature review.The mutation of SMC1A gene c. 2923C>T in CdLs cases has not been reported at home and abroad, which expands the variation spectrum of the SMC1A gene.

Objective:To evaluate the predictive performance of the individualized drug delivery decision-making system including Smart Dose, PharmVan and JPKD on predicting the Vancomycin plasma concentration and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with Vancomycin and received therapeutic drug monitoring (TDM) admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to July 2020 were retrospectively collected. Smart Dose and PharmVan were used to predict the plasma concentration of Vancomycin of the initial regimen. Smart Dose, PharmVan and JPKD were used to predict the plasma concentration of Vancomycin of the adjustment regimen for patients whose initial steady-state trough concentration were not qualified. The relative predictive error (PE) between the measured plasma concentration and predicted plasma concentration was calculated and box plotted. Mann-Whitney U test was used to evaluate the difference of the absolute value of PE (APE) predicted by each software for Vancomycin plasma concentration. The TDM results were divided into accurate prediction group (APE < 30%) and the inaccurate prediction group (APE≥30%) according to the APE value. Patients and disease characteristics including gender, age, body weight complication, Vancomycin medication and TDM results were collected from electronic medical records. Univariate analysis and multivariate Logistic regression analysis were used to screen the related factors that influence the predictive performance of Smart Dose, PharmVan and JPKD; and receiver operating characteristic curve (ROC curve) was drawn to evaluate its predictive value. Results:A total of 185 patients were enrolled, and 258 plasma concentration of Vancomycin were collected, including 185 concentrations of initial regimen and 73 concentration of adjustment regimen. There was no significant difference in the APE of the initial regimen of plasma concentration between Smart Dose and PharmVan. No significant difference in the APE of the adjustment regimen of plasma concentration was found among Smart Dose, PharmVan and JPKD. The accuracy of Smart Dose in predicting the plasma concentration of the adjustment regimen was better than that of the initial regimen [22.94% (10.50%, 36.24%) vs. 29.33% (13.07%, 47.99%), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of initial regimen showed that the proportion of patients with hypertension in the accurate prediction group was significantly higher than that in the inaccurate prediction group [43.3% (42/97) vs. 27.3% (24/88), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of adjustment regimen showed that the proportion of patients with valvular heart disease in the accurate prediction group was significantly lower than that in the inaccurate prediction group [23.4% (11/47) vs. 46.2% (12/26), P < 0.05]. The univariate analysis of factors affecting the performance of JPKD in predicting the concentration of adjustment regimen showed that the body weight of patients in the accurate prediction group was significantly higher than that in the inaccurate prediction group (kg: 62.8±14.9 vs. 54.8±12.8, P < 0.05). Multivariate Logistic regression analysis indicated that hypertension was a beneficial factor for Smart Dose to predict the initial plasma concentration of Vancomycin [odds ratio ( OR) = 0.526, 95% confidence interval (95% CI) was 0.281-0.983, P = 0.044], and low body weight was an independent risk factor for the inaccurate prediction of JPKD for adjustment regimen ( OR = 1.042, 95% CI was 1.001-1.085 , P = 0.043). ROC curve analysis indicated that the area underROC curve (AUC) of the body weight for evaluating the accuracy of JPKD in predicting Vancomycin plasma concentration was 0.663, and 95% CI was 0.529-0.796 ( P = 0.023). When the body weight was less than 55.95 kg, the risk of inaccurate prediction of JPKD in predicting Vancomycin plasma concentration was increased, and the predictive sensitivityand specificity were 75% and 60% respectively. Conclusions:There is no significant difference in the predictive performance of Smart Dose, PharmVan or JPKD on Vancomycin plasma concentration. Smart Dose had a better predictive performance for the Vancomycin plasma concentration of adjustment regimen than initial regimen. Smart Dose had a better predictive performance when the patient was concomitant with hypertension. JPKD had a poor predictive performance for low-body weight patients. The predictive performance of JPKD was decreased when the body weight was lower than 55.95 kg.

Objective:To investigate the sedentary behavior of the elderly in Taiyuan nursing homes and analyze its influencing factors, so as to provide theoretical basis for the construction of targeted intervention programs for sedentary behavior.Methods:A total of 215 elderly people in 6 nursing homes in Taiyuan from October 2019 to January 2020 were investigated by general data questionnaire and sedentary behavior questionnaire. Descriptive analysis, single factor analysis and multiple linear stepwise regression analysis were used to explore the influencing factors of sedentary behavior.Results:The sedentary time of the elderly in Taiyuan nursing homes was (8.85±2.81) h/d, and 83% (174/209) of the elderly had a sedentary time≥6 h/d. Gender, age, type of disease, type of residence, sedentary hobby and environmental safety in homes were the important factors influencing sedentary behavior of the elderly in nursing homes( P<0.05). Conclusions:The sedentary behavior of the elderly in nursing homes is not optimistic. Targeted intervention measures should be taken to improve the sedentary behavior of the elderly and promote the healthy aging of the elderly in nursing homes.