BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective: To investigate the current status and influencing factors of overweight and obesity among adults in Jiaxing City, Zhejiang Province, so as to provide a basis for developing targeted weight management measures. Methods: In 2024, a multistage stratified random cluster sampling method was employed to recruit permanent residents aged ≥18 years from Jiaxing City for questionnaire surveys. Data on basic information, lifestyle behaviors, and history of chronic diseases were collected. Height and body weight were measured, and overweight and obesity were determined based on body mass index (BMI). The influencing factors of overweight and obesity among adults were analyzed by a multivariable logistic regression model. Results: Totally 10 509 questionnaires were allocated, and 9 802 valid questionnaires were recovered, with an effective recovery rate of 93.27%. Among the respondents, 4 808 (49.05%) were males and 4 994 (50.95%) were females, with a mean age of (51.27±17.26) years. A total of 4 884 overweight and obesity individuals were identified, with a detection rate of 49.83%. Multivariable logistic regression analysis showed that gender (male, OR=1.719, 95%CI: 1.578-1.873), age (≥60 years, OR=0.802, 95%CI: 0.652-0.986), educational level (bachelor and above, OR=0.640, 95%CI: 0.518-0.791), marital status (being married/cohabiting, OR=1.224, 95%CI: 1.009-1.486), adequate nut intake (OR=0.910, 95%CI: 0.832-0.995), hypertension (OR=2.462, 95%CI: 2.219-2.732), and dyslipidemia (OR=1.629, 95%CI: 1.444-1.837) were statistically associated with overweight and obesity among adults. Conclusion The detected rate of overweight and obesity among adults in Jiaxing City was relatively high, and was mainly associated with gender, age, education level, marital status, nut intake, hypertension, and dyslipidemia.

Objective: To investigate the trend in mortality of injury in Jiaxing City, Zhejiang Province, from 2010 to 2022, so as to provide the evidence for developing injury prevention and intervention strategies. Methods: Data on injury mortality in Jiaxing City from 2010 to 2022 were obtained from the Jiaxing Chronic Disease Monitoring Information Management System. Crude mortality was calculated, and standardized mortality was computed using data of the Sixth National Population Census in 2010. Descriptive analysis of injury mortality and cause of injury death was conducted by gender and age. The average annual percent change (AAPC) was used to analyze the trend in mortality of injury from 2010 to 2022. Results: From 2010 to 2022, the crude injury mortality in Jiaxing City was 79.24/100 000, and the standardized mortality was 47.08/105. The crude injury mortality was higher in males than in females (80.51/100 000 vs. 78.01/100 000, P<0.05). The standardized injury mortality for the total population, males, and females showed significant declining trends (AAPC=-2.011%, -2.373% and -1.542%, all P<0.05). The crude injury mortality increased with age (P<0.05), peaking in the age group of ≥85 years (1 806.46/100 000). Decreasing trends were observed in the age groups of 0-<15 years, 15-<45 years, and 45-<65 years (AAPC=-7.794%, -4.698% and -4.521%, all P<0.05), while no significant trend was found in the age group of ≥65 years. The top five causes of injury death were falls (29.96/100 000), motor vehicle traffic accidents (17.81/100 000), drowning (6.50/100 000), suicide (5.40/100 000), and poisoning (0.69/100 000). Drowning was the leading cause of injury death in the age group of 0-<15 years, while falls were the primary cause in the age group of ≥65 years. Motor vehicle traffic accidents were the top cause of injury death in age groups of 15-<45 years and 45-<65 years. From 2010 to 2022, the standardized mortality of falls showed an upward trend (AAPC=1.094%, P<0.05), while the standardized mortality of motor vehicle traffic accidents, drowning, and suicide demonstrated downward trends (AAPC=-7.576%, -2.745% and -2.786%, all P<0.05). Conclusions The standardized injury mortality in Jiaxing City showed an overall downward trend from 2010 to 2022. Falls were the leading cause of injury death, and particular attention should be paid to the prevention and control of falls among the elderly aged ≥65 years.

Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.

Objective To investigate the correlation between red blood cell distribution width(RDW),systemic immune-inflammation index(SII)and major depressive disorder(MDD).Methods The clinical data of 176 MDD patients hospitalized in the clinical psychology department of our hospital from 2020 to 2022 and 209 non-MDD comparators who were routinely examined in Hebei General Hospital were retrospectively analyzed.Blood analysis was conducted to obtain values of RDW,SII,and red blood cell distribution width/platelet ratio(RPR).The data was used to plot the receiver operator characteristic(ROC)curve to determine the optimal threshold and the area under the curve(AUC)for RDW to discriminate between patients and controls.Result Patients in the MDD group had significantly higher RDW[median and quartiles:13.20(12.70,13.98)vs.12.80(12.40,13.35)],and SII levels[median and quartiles 510.87(350.95,878.12)vs.405.33(313.74,539.92)]compared with those in non-MDD group(P<0.05).There was no significant difference in RPR between the two groups(P>0.05).Multifactorial logistic regression analysis showed that RDW was positively correlated with MDD after adjusting for confounders(OR=3.086,95% CI:1.926-4.944).ROC curve showed that the optimal threshold for RDW to differentiate the risk of developing MDD was 12.85,with an AUC of 0.647(95% CI:0.592-0.702;P<0.001).Conclusion Present study shows that high RDW is a risk factor for the occurrence of MDD and an important parameter for the risk of developing depression.

Background Air quality health index (AQHI) has been widely used to quantify the health effects of multiple pollutants observed in population-based epidemiological studies, and can better reflect the widespread linear non-threshold between air pollution and health effects. Objective To explore an AQHI for pediatric respiratory diseases (AQHI_r) in Shanghai and evaluate its feasibility. Methods The daily numbers of hospital outpatient visits for pediatric respiratory diseases from 2015 to 2019 were obtained from five general hospitals in Xuhui, Baoshan, Hongkou, Jinshan, and Chongming Districts of Shanghai. Monitoring data on air pollutants (PM_2.5, PM₁₀, SO₂, NO₂, and O₃), air quality index (AQI), and meteorological variables (temperature, relative humidity, air pressure, and wind speed) were collected from five air quality monitoring sites nearest to selected hospitals. Time-series analysis using generalized additive model (GAM) was conducted to estimate the associations between respiratory-related pediatric outpatient visits and the concentrations of air pollutants. The sum of excess risk (ER) of hospital outpatient visits was used to construct AQHI_r. To assess the predictive power of AQHI_r, the associations of AQHI_r and AQI with the number of pediatric respiratory outpatient visits in three hospitals in Xuhui, Hongkou, and Chongming districts were compared. Results Air pollutants had various effects on respiratory diseases outpatient visits. PM_2.5, NO₂, and O₃ had most significant impacts on lag0 day and the associated ERs of hospital outpatient visits for each 10 μg·m⁻³ increase in pollutant concentration were 1.27% (95%CI: 0.88%-1.66%), 0.75% (95%CI: 0.40%-1.11%), and 0.36% (95%CI: 0.10%-0.62%), respectively. PM₁₀ and SO₂ had most significant impacts on lag3 day and the associated ERs of hospital outpatient visits for each 10 μg·m⁻³ increase in pollutant concentration were 0.81% (95%CI: 0.51%-1.12%) and 5.64% (95%CI: 3.37%-7.96%), respectively. There were significant effects of combinations of two pollutants among PM_2.5, PM₁₀, NO₂, SO₂, and O₃ except for PM₁₀+NO₂, SO₂+PM_2.5, and SO₂+NO₂ (P<0.05). According to the results of single-pollutant and two-pollutant models, PM_2.5, NO₂, SO₂, and O₃ were selected to construct AQHI_r. The comparison showed that for every interquartile range increase in AQHI_r, the ER for pediatric outpatient visits was higher than that for the value corresponding to AQI. Conclusion Air pollutants in Shanghai have an impact on the number of pediatric respiratory outpatient visits. The AQHI_r based on and outpatient visits for pediatric respiratory diseases can be a sensitive index to predict the effects of air pollution on children's respiratory health.

Background Non-occupational carbon monoxide (CO) poisoning is a public health problem that seriously affect people’s health and lives. Objective To describe the prevalence of non-occupational CO poisoning during 2007—2018 in Shanghai, analyze its epidemiological characteristics and potential influencing factors, and explore effective prevention and control measures. Methods Daily reported non-occupational CO poisoning cases and meteorological factors from 2007 to 2018 were collected in Shanghai, epidemiological characteristics were analyzed by descriptive epidemiology methods, and a distributed lag nonlinear model was used to assess the association between temperature and non-occupational CO poisoning. Results A total of 2264 non-occupational CO poisoning events and 3866 cases from 2007 to 2018 were reported in Shanghai, including 59 death cases. More than half of the poisoning cases were female (56.3%), and young adults accounted for more cases than any other age group (54.8%). The poisoning events mainly occurred in winter (from December to next February); however, cases reported in summer increased in recent years. The peak period of the events was from 20:00 to 24:00. Households (85.2%) and restaurants (8.0%) were the common places of non-occupational CO poisoning events, and the main cause was improper use of gas water heater (36.9%). A nonlinear curve was found between daily average temperature of current day and the occurrence of non-occupational CO poisoning. Temperature was negatively associated with the risk of non-occupational CO poisoning when the temperature was lower than 9.6 ℃, while a positive association was found during 9.7-26.0 ℃. Conclusion Winter is a high season for non-occupational CO poisoning in Shanghai, rising cases reported in summer is also worthy of attention. Supervision should be strengthened to ban sales of unqualified gas water heaters, and health education on CO poisoning prevention and control should be conducted through multiple channels, in order to reduce the incidence of CO poisoning.

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Objective:To analyze the clinical features, diagnosis and treatment plan, clinical outcomes of pregnancy with cervical cancer.Methods:The clinical data of 10 pregnant women with cervical cancer from January 2008 to October 2018 in Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University, the First Hospital of Dalian Medical University, Dalian Central Hospital, Dalian Women and Children′s Medical Center and Wafangdian Central Hospital of Liaoning Province were retrospectively analyzed.Results:The incidence of pregnancy with cervical cancer was 0.004% (10/238 128). Among the 10 cases of pregnancy with cervical cancer, the gestational weeks ≤ 20 weeks at the time of diagnosis was in 6 cases, and they all chose to terminate the pregnancy; the gestational weeks 20 +1 to 30 weeks at the time of diagnosis was in 1 case, and the patient chose to terminate the pregnancy; the gestational weeks >30 weeks at the time of diagnosis was in 2 cases, and they all chose to continue the pregnancy; 1 case was diagnosed after delivery. There were 3 newborns, including 1 premature infants, and they all survived. Conclusions:It is helpful to the diagnose of the disease to strengthen cervical cancer screening before pregnancy and improve the examination of patients with abnormal symptoms during pregnancy. The treatment plan should be individualized according to the pregnancy status, stage of the disease, and wishes of the patient and family.

Objective To establish the high-throughput screening fluorescence polarization assay for HSP90 inhibitor.Methods E.coli strain BL21 ( DE3) competent cells were transformed with pET24α( +)-HSP90αplasmid.The cell lysate supernatant was induced to product the soluble protein and purified with Ni-NTA agarose.Western blot analysis was used to identify whether the purified protein is HSP90α.The fluorescence polarization assay for screening HSP90 inhibitors was established and optimized using varying concentrations of recombinant HSP90 protein and molecular probe VER00051001.Meanwhile, the binding activity of GA and NVP-AUY922 for HSP90αwas measured by fluorescence polarization assay.Results HSP90αwas induced expression and purified successfully.The fluorescence polarization assay was performed using 80 nM probe VER00051001 and 2.01μg/mL HSP90α, with the Z factor of 0.83.GA and NVP-AUY922 competed with the probes VER00051001 for binding sites of HSP90, with IC50 of 55 nM and 13 nM, respectively.Conclusion A reliable model was established using fluorescence polarization assay for screening HSP90 inhibitors.