Objective:To investigate the effect of metformin(MET)on endoplasmic reticulum stress-induced apoptosis and its role and molecular mechanisms in preeclamptic(PE)rats.Methods:Thirty SD rats were ran-domly assigned into control,PE and MET groups,10 in each group.From days 14 to 18 of gestation,rats in the PE and MET groups were subcutaneously injected with L-nitro-arginine methyl ester(L-NAME)at a dose of 200 mg/(kg·d),while the control group was administered subcutaneous injections containing a 0.9％solution of sodium chloride at the same dose.Additionally,the MET group was administered MET by gavage at a dose of 200 mg/(kg·d)from days 13 to 18 of gestation.On days0,6,12,15,17,and 19 of pregnancy,blood pressure of rats was measured.On days 12 and 19 of pregnancy,24-hour urinary protein content was assessed.On day 20 of pregnan-cy,rats were anesthetized and underwent cesarean section to measure pup weight,crown-rump length,placental weight,and diameter.We used reverse transcription quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry(IHC)to detected mRNA and protein expression of apoptosis-related genes in rat placental tissue,and enzyme-linked immunosorbent assay(ELISA)to assess the expression of apopto-sis-related genes in rat serum.Results:Compared with the control group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuria level on day 19 of gestation were significantly higher,and body mass and top rump length of littermates were lower in the PE group,and the differences were statistically significant(P＜0.05);Compared with the PE group,systolic blood pressure on days 15,17 and 19 of gestation and 24h proteinuri-a level on day 19 of gestation were significantly decreased,and body mass and top rump length of littermates were increased in the MET group,and the differences were all statistically significant(P＜0.05).Pairwise com-parisons of placental weight,placental diameter,and the number of pups born among the three groups showed no statistically significant differences(P＞0.05).Compared to the control group,the PE group exhibited significantly increased expression of B-cell lymphoma-2(Bcl-2)associated X protein(Bax),bcl-2 antagonist/killer 1(Bak),and apoptosis-inducing factor(AIF)mRNA and protein in placental tissues,decreased expression of Bcl-2 mRNA and protein,as well as elevated levels of Bax,Bak,and AIF in serum,while Bcl-2 expression levels were de-creased.These differences were statistically significant(P＜0.05).Compared to the PE group,the MET group exhibited decreased expression of Bax,Bak,and AIF mRNA and protein in placental tissue,along with increased expression of Bcl-2 mRNA and protein.Serum levels of Bax,Bak,and AIF were decreased,while Bcl-2 expression levels were increased.All differences were statistically significant(P＜0.05).Conclusions:L-NAME significantly induced elevated levels of apoptosis in rat placental tissues,whereas MET was able to effectively inhibit L-NAME-induced apoptosis induced by endoplasmic reticulum stress,which has the potential to be a new therapeu-tic intervention point for PE.

OBJECTIVE Aimd to investigate the prevalence of olfactory dysfunction among healthy elderly individuals in China using a large sample size and to explore its correlations with demographic and other factors.METHODS A total of 5 258 participants who aged 60 and above underwent the T&T olfactometer test and completed questionnaires.The prevalence of olfactory dysfunction was reported,and logistic regression analyses were performed to assess the associations between olfactory dysfunction and other factors.RESULTS The overall prevalence of olfactory dysfunction in the study was 26.5%.Independent risk factors for olfactory dysfunction included advanced age,rural residence(OR=1.88,95%CI:1.60-2.22,P<0.01),current smoking(OR=1.45,95%CI:1.15-1.83,P<0.01),and self-reported olfactory dysfunction(OR=10.12,95%CI:8.44-12.14,P<0.01).In contrast,female gender(OR=0.70,95%CI:0.58-0.85,P<0.01)and high educational attainment were independently associated with a lower prevalence of olfactory dysfunction.CONCLUSION The prevalence of olfactory dysfunction among individuals aged 60 and above increased with age.Male gender,rural residence,low educational attainment,current smoking,and self-reported decline in olfactory function were independently associated with olfactory dysfunction.

Objective:To evaluate gait characteristics in early-stage Parkinson′s disease (PD) patients using an artificial intelligence-based quantitative motor function assessment system (Readygo) and validate whether PD patients with clinically normal gait actually exhibit objective gait impairments, and to explore the features and progression patterns of gait dysfunction in early PD.Methods:This cross-sectional, single-center study enrolled early-stage PD patients (Hoehn-Yahr stage≤2.5) from outpatient or inpatient departments of Beijing Hospital between October 2023 and October 2024, along with accompanying caregivers as healthy controls (HCs). Demographic data (sex, age, education level) were collected, and cognitive, psychological, and sleep-related scales assessments were administered. Based on the gait score (Item 3.10) from the Movement Disorder Society-Unified Parkinson′s Disease Rating Scale-Ⅲ (MDS-UPDRS-Ⅲ), PD patients were stratified into 3 subgroups: PD-normal gait (score=0), PD-mild gait impairment (score=1), and PD-moderate gait impairment (score=2). The Readygo system quantified gait parameters, including step width, stride length, step height, gait speed, stride velocity, swing velocity, and turn duration. Binary Logistic regression was uesd to identify biomarkers differentiating PD-normal gait group from HCs.Results:A total of 66 early-stage PD patients and 34 HCs were enrolled. Across the HCs, PD-normal gait, PD-mild gait impairment and PD-moderate gait impairment groups, there was a progressive decline in gait speed [1.07 (0.97, 1.15) m/s vs 0.97 (0.90, 1.06) m/s vs 0.90 (0.82, 1.00) m/s vs 0.77 (0.72, 0.86) m/s, H=29.949, P<0.001], bilateral stride velocity [left: 1.14 (1.07, 1.21) m/s vs 1.06 (0.94, 1.14) m/s vs 0.95 (0.88, 1.04) m/s vs 0.86 (0.76, 0.93) m/s, H=30.778, P<0.001; right: 1.12 (1.04, 1.22) m/s vs 1.04 (0.95, 1.13) m/s vs 0.96 (0.90, 1.04) m/s vs 0.89 (0.77, 0.90) m/s, H=29.561, P<0.001], and bilateral swing velocity [left: (2.56±0.28) m/s vs (2.38±0.32) m/s vs (2.19±0.33) m/s vs (1.96±0.32) m/s, F=14.132, P<0.001; right: 2.46 (2.35, 2.62) m/s vs 2.35 (2.13, 2.62) m/s vs 2.22 (2.05, 2.36) m/s vs 2.03 (1.71, 2.13) m/s, H=25.771, P<0.001], along with a progressive shortening of bilateral step length [left: 1.19 (1.14, 1.27) m vs 1.15 (1.04, 1.22) m vs 1.05 (0.93, 1.18) m vs 0.95 (0.80, 1.06) m, H=32.613, P<0.001; right: 1.20 (1.14, 1.30) m vs 1.13 (1.03, 1.22) m vs 1.07 (0.90, 1.17) m vs 0.97 (0.80, 1.03) m, H=30.528, P<0.001]. Conversely, turning time progressively lengthened [1.20 (1.09, 1.49) s vs 1.21 (1.10, 1.46) s vs 1.30 (1.19, 1.51) s vs 1.98 (1.53, 2.12) s, H=23.195, P<0.001]. Logistic regression identified that the right stride length was a discriminative factor between HCs and PD-normal gait group ( OR=0.023, 95% CI 0-0.291, P=0.012). Conclusions:As gait dysfunction worsens, PD patients demonstrate gradual reductions in speed-related parameters and stride length, with increasing turn duration.Early PD patients with clinically normal gait may already exhibit subtle impairments. Right stride length may serve as a potential biomarker to distinguish PD patients from HCs.

Objective:To analyze the effect of carbapenem antibiotics on the blood concentration of valproate(VPA)in elderly patients with epilepsy, while also exploring the potential drug interactions between carbapenem antibiotics and VPA, as well as possible solutions.Methods:This retrospective study included patients aged 80 years and older who were treated with a combination of VPA and carbapenem antibiotics in the Department of Geriatrics at Beijing Hospital from January 2017 to December 2022, as well as older hospitalized patients with epilepsy.Data collected encompassed patients' demographic information, details related to epilepsy, information on infection medications, changes in VPA blood concentration, clinical management, and clinical outcomes.Results:A total of 12 patients were included in the study.The average age of the participants was 92±7.0 years.The baseline dosage of VPA was 1 000 mg(range: 650 to 1 250 mg), and the baseline VPA serum concentration was 56.59 mg/L(range: 38.00 to 61.73 mg/L)during treatment with carbapenem antibiotics.Nine patients experienced seizure recurrence during the combination therapy, representing 75% of the total cohort.The VPA dosage was increased in 10 patients, with a mean increase of 522 mg(range: 200 to 892 mg), and the duration of this dosage increase was 8 days(range: 7 to 9 days).All patients exhibited a decrease in VPA serum concentration, with the lowest concentration decreasing by an average of 71.9%±15.69%.The VPA serum concentration during carbapenem treatment was significantly lower than both the baseline and post-withdrawal concentrations, measuring 12.30 mg/L(range: 10.49 to 22.47 mg/L)compared to 56.59 mg/L(range: 38.00 to 61.73 mg/L)( Z=-3.059, P=0.002)and 43.74 mg/L(range: 41.48 to 73.14 mg/L)( Z=-2.803, P=0.005). Conclusions:Carbapenems can markedly decrease serum concentrations of VPA and heighten the incidence of seizures in elderly patients with epilepsy.Increasing the dose of VPA may not enhance its serum concentration; therefore, we recommend avoiding the concomitant use of VPA and carbapenems.

Objective:To evaluate the clinical features of dystonia in patients with different types of atypical Parkinson syndrome (APS).Methods:A total of 104 patients with APS admitted in the Department of Neurology, Beijing Hospital from January 2015 to June 2023 were enrolled in the study, including 57 cases of multiple system atrophy (MSA), 38 cases of progressive supranuclear palsy (PSP) and 9 cases of corticobasal degeneration (CBD). Among 104 cases there were 63 males (60.6%), the mean age of patients was (62.3±8.9) years (54 to 73 years). The sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopa therapy, numbers of Hoehn & Yahr scale≥3 after 3 years of disease, and MRI findings were documented in patients with different type APS.Results:The overall frequency of dystonia in this series was 45.2%(47/104), and 33.3% (19/57) for MSA group, 50.0% (19/38) for PSP group, 9/9 for CBD group. The types of dystonia were anterocollis, retrocollis, blepharospasm, oromandibular, foot/limb dystonia, Pisa syndrome and myoclonus. In all 47 cases presenting dydtonia, dystonia was not the first complaint and it did not respond to levodopa therapy.Conclusion:In this series of atypical Parkinson syndrome, dystonia is a common feature of the disease, while it is not the first symptom at disease onset, and usually does not respond to levodopa therapy.

Objective:To explore the gait and eye movement parameters in early Parkinson's disease(PD)with sleep disorders, and analyze their association with underlying pathophysiological mechanisms.Methods:This study was a cross-sectional single-center design that included 82 early PD patients with Hoehn-Yahr(H-Y)staging ≤2.5 who visited Beijing Hospital from October 2023 to May 2025.Patients were divided into two groups according to the PDSS-2 score(total score ≤15 for the no sleep disorder group and total score >15 for the sleep disorder group). Gait and eye movement parameters were collected respectively through the ReadyGo system and the EyeKnow eye movement system, and analyzed in combination with clinical scales.Multivariate logistic regression was employed to identify independent characteristic parameters associated with sleep disorders.Results:In terms of gait, the sleep disorder group had significantly lower step speed, left-right stride speed, and left-right swing speed(all P<0.05), and significantly higher variability of left-right stride time( P=0.017, 0.026). Regarding eye movements, the sleep disorder group had significantly more vertical smooth pursuit offsets[(56.24±2.87)times vs.(45.98±18.18)times, P=0.040], significantly higher maximum real-time variability of the right eye in response to light stimuli(90.75 vs.67.95%, P=0.006), and a longer latency to error responses in the counter-scanning task(337.06 vs.286.63 ms, P=0.005). To precisely control for confounding factors, key covariates such as mood and disease severity were included in the multivariate logistic regression model.After comprehensive adjustment, higher anxiety levels(Hamilton Anxiety Rating Scale, HAMA)( OR=1.32, P<0.001)and an increased number of vertical smooth pursuit offsets( OR=1.06, P=0.010)were independent factors associated with sleep disorders in early PD patients. Conclusions:In early PD patients, sleep disorders are closely associated with specific abnormalities in gait and eye movement parameters.In particular, vertical smooth pursuit offsets may serve as an objective biomarker independent of emotional status, reflecting the dysfunction of shared neural circuits.However, further mechanism studies are needed to verify whether they reflect the dysfunction of shared neural circuits.

Objective:To evaluate the efficacy and safety of rituximab (RTX) in the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN).Methods:This was a single-center, retrospective and single-arm study. The clinical data of AAGN patients who received RTX induction therapy at the First Affiliated Hospital of Zhejiang University School of Medicine from April 2016 to July 2021 and had a follow-up period of more than 6 months were collected. The follow-up was up to June 2022. The Birmingham Vasculitis Activity Score (BVAS) from 2003 was used to assess vasculitis activity. The treatment regimen for RTX was once every 1 to 2 weeks, with 375 mg/m 2 each time. For some patients, the dose was adjusted according to the immune status before medication. The clinical outcomes, renal remission, recurrence and safety was analyzed. Kaplan-Meier method was used to analyze the cumulative renal remission rate. Results:A total of 43 AAGN patients were included in the study, with age of (57.6±16.6) years, 19 males (44.2%) and 34 (79.1%) newly treated patients. There were 34 patients (79.1%) with positive myeloperoxidase-ANCA and 8 patients (18.6%) with positive proteinase 3-ANCA. The dosage of RTX used at the 12-month follow-up was 600 (500, 1 200) mg. At 6 months of follow-up, 32 patients (74.4%) achieved renal remission, and renal remission time was 5.0 (3.3, 5.8) months. Three patients (7.0%) progressed to end-stage renal disease, and two patients (4.7%) died. Compared with patients without renal remission, patients with renal remission had lower baseline serum creatinine ( Z=-2.853, P=0.004), serum uric acid ( t=-2.861, P=0.007), urine protein/urine creatinine ratio ( Z=-2.130, P=0.033) and proportion of methylprednisolone pulse therapy ( χ 2=5.002, P=0.025), and higher estimated glomerular filtration rate ( Z=-2.728, P=0.006). At 12 months of follow-up, 33 patients (76.7%) achieved renal remission, and the cumulative renal remission rate was 82.4%. Two patients (4.7%) had renal recurrence, 5 patients (11.6%) progressed to end-stage renal disease, and 3 patients (7.0%) died. Infection (4 patients, including 2 severe infections) was the main adverse event, all of which occurred within 6 months of RTX treatment. Conclusions:The clinical remission rate and safety of RTX in the treatment of AAGN are both relatively high.

OBJECTIVE:To systematically evaluate the correlation between phase angle and sarcopenia and its diagnostic indexes.METHODS:The PubMed,EMbase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect studies on the correlation between phase angle and sarcopenia and its diagnostic indexes from database inception to May 8,2024. Two reviewers independently screened literature,extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using RevMan 5.3 and Stata 14.0 software. RESULTS:A total of 50 eligible articles were included. Meta-analysis results showed that compared with the non-sarcopenic population,the phase angle was significantly reduced in sarcopenic patients[standardized mean difference (SMD)=-0.99,95％ confidence interval (CI) (-1.09,-0.90),P<0.00001]. The results of subgroup analysis indicated that the difference of phase angle was more significant in patients with severe sarcopenia and Asian sarcopenia. Moreover,reduction in the phase angle was more obvious in patients with malignant tumors and respiratory diseases with sarcopenia. And skeletal muscle mass index (Pearson's r=0.565,P<0.00001),grip strength (Pearson's r=0.446,P<0.00001),and gait speed (Pearson's r=0.405,P<0.00001) all showed a moderate positive correlation with phase angle. However,appendicular skeletal muscle mass index showed a very weak positive correlation with phase angle (Pearson's r=0.139,P=0.02). CONCLUSION:Phase angle has a significant difference between sarcopenia and non-sarcopenia population,and it is correlated with the diagnostic indexes of sarcopenia to different extents. It suggests that phase angle has some clinical values in the objective diagnosis of sarcopenia. However,the results may be influenced by some factors such as sarcopenia severity and detection instruments of phase angle. Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

Objective To investigate the effect of blood glucose control parameters on the prognosis of severe pneumonia patients based on continuous glucose monitoring(CGM)system.Methods A retrospective analysis was conducted on 51 severe pneumonia patients monitored by CGM at the Fourth Affiliated Hospital of Soochow University from November 2021 to August 2023.Assessed parameters included baseline clinical characteristics,glycosylated hemoglobin(HbA1c),mean glucose,standard deviation(SD),coefficient of variability(CV),mean amplitude of glycemic excursions(MAGE),maximum glucose level,minimum glucose level,and time in range(TIR)of glucose within the target range(3.9-10.0 mmol/L)as a proportion and levels of inflammatory indicators before and after treatment.Based on the 28-day follow-up results,the patients were divided into the survival group(39 cases)and the death group(12 cases).The blood glucose parameters of the two groups were compared.Multivariate Logistic regression model was used to analyze the influence of blood glucose parameters and infection indexes on the prognosis of patients with severe pneumonia.The efficacy of blood glucose parameters in the diagnosis of 28-day mortality was further evaluated by receiver operator characteristic curve(ROC curve).Results The acute physiology and chronic health evaluationⅡ(APACHEⅡ),SD and CV of blood glucose in death group were higher than those in survival group[APACHEⅡscore:20.5(14.0)vs.15.0(7.0),SD(mmol/L):2.6±0.7 vs.2.1±0.5,CV:(27.7±5.8)%vs.(23.7±4.3)%].However,the TIR(3.9-10.0 mmol/L)proportion was statistically lower than that of survival group[59.0%(17.0%)vs.68.0%(35.0%)],the differences were all statistically significant(all P<0.05).After using CGM,the white blood cell count(WBC)and hypersensitive C-reactive protein(hs-CRP)were significantly decreased[WBC(×109/L):9.2(6.5)vs.11.1(9.2),hs-CRP(mg/L):39.4(59.0)vs.56.2(133.8),both P<0.05].Multivariate Logistic regression showed that TIR(3.9-10.0 mmol/L)proportion was an independent risk factor for 28-day mortality in patients with severe pneumonia[odds ratio(OR)=0.923,95%confidence interval(95%CI)was 0.852-0.999,P=0.046].The ROC curve showed that TIR proportion was valuable in predicting the clinical outcomes of patients with severe pneumonia.Area under the curve(AUC)=0.720,95%CI was 0.563-0.878,P=0.022;when the cut-off value was 63.5%,the sensitivity and the specificity were 59.0%and 83.3%respectively.Conclusion Increase of TIR(3.9-10.0 mmol/L)proportion in patients with severe pneumonia could improve clinical outcomes,especially when TIR proportion≥63.5%.