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

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.

BACKGROUND:The repair of large-scale bone defects is still facing serious challenges.It is of great significance to develop personalized,low-cost,and osteogenic-inducing tissue engineering scaffolds for bone repair. OBJECTIVE:To explore the process of 3D printing bone tissue engineering scaffold containing pearl composite material by low-temperature condensation deposition method,and further test the physicochemical properties and in vitro biological functions of the composite scaffold. METHODS:Pearl powder was prepared by grinding and sieving.The pearl powder of different qualities was added into the poly-L-lactic acid ink,so that the mass ratio of pearl powder to poly-L-lactic acid was 0,0.1,0.2,0.3,and 0.5,respectively.The 3D-printed poly-L-lactic acid/pearl powder scaffolds were prepared using the low-temperature condensation deposition method.The microstructure,compressive properties,water contact angle,cytocompatibility,and in vitro bone differentiation ability of the printed poly-L-lactic acid/pearl powder composite scaffolds were detected. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the five groups of scaffolds all had micropores with a diameter of 2 μm or even smaller,irregular shapes and interconnectivity.(2)All the five groups had good compressive properties.The compressive strength of the pearl powder 0.5 group was higher than that of the other four groups(P<0.05).The water contact angle of the pearl powder 0.2 group and the pearl powder 0.5 group was smaller than that of the pearl powder 0 group(P<0.01,P<0.001).(3)Bone marrow mesenchymal stem cells were co-cultured with five groups of scaffolds for 1,3,and 5 days,respectively.The cell proliferation in pearl powder 0.1,0.2,0.3,and 0.5 groups cultured for 3 and 5 days was faster than that in pearl powder 0 group(P<0.05).After 1 day of culture,live-dead staining exhibited that the number of cells on the scaffold was small,but all of them were living cells.(4)Bone marrow mesenchymal stem cells were inoculated on the scaffold surface of the pearl powder 0 group and pearl powder 0.1 group respectively for osteogenic differentiation.The alkaline phosphatase activity induced for 4 and 6 days in the pearl powder 0.1 group was higher than that in the pearl powder 0 group(P<0.05).(5)The results showed that the poly-L-lactic acid/pearl powder composite scaffold had good compressive strength,hydrophilicity,cytocompatibility,and osteogenic properties.

OBJECTIVE To establish fingerprints and multi-components determination of Jieze lotion, and use chemometrics methods for quality evaluation. METHODS The HPLC-DAD fingerprints was established and 10 components were recognized by comparison with references. Meanwhile, their contents were determined. The data were evaluated by the methods of chemometrics such as similarity evaluation, cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis. RESULTS The similarity of 11 batches of Jieze lotion were all >0.95. The linearity was good(r≥0. 999 1) and the average recoveries were between 89.70% and 106.0% with the RSD of 1.52%−3.41%. Instrument precision, stability and reproducibility of the method were all great. The contents of the common ten components(gallic acid, protocatechuic acid, neochlorogenic acid, caftaricacid, 5-O-feruloylquinicacid, chlorogenic acid, phellodendrine chloride, magnoflorine, 4-O-feruloylquinic acid, berberinehydrochloride) were 40.103−55.841, 2.347−6.179, 8.336−23.810, 7.084−21.956, 33.098−53.833, 24.597−49.610, 21.587−31.188, 5.915−13.162, 115.381−189.702, 31.378−112.686 μg·mL−1, respectively. The results of chemometrics showed that the 11 batches of samples could be divided into 4 categories, and the strong characteristic peaks used to distinguish each batch of samples were berberine hydrochloride, 4-O-feruloylquinic acid, chlorogenic acid, neochlorogenic acid and 5-O-feruloylquinic acid. CONCLUSION The method is accurate and reliable, and it can be used for the quality control and comprehensive evaluation of Jieze lotion.

Objective To explore the effects of exposure to lipopolysaccharides in late pregnancy on age-related cognitive changes in offspring of mice,and to investigate whether there is a gender specific genetic effect.Methods Institute of cancer research(ICR)CD-1 mice during gestational days 15-17 were injected with lipopolysaccha-ride daily(LPS group,50 μg/kg),or equal volume of normal saline(CON group).At the age of 2 months after their delivery,LPS treated offspring mice(F1-LPS,male and female)were randomly selected and hybridized with age-matched wild-type CD-1 mice.F1-LPS males and females with different littermates,and F1-CON males and fe-males were hybridized to obtain F2 generations of different lineages.Similarly,F2-LPS mice were mated with wild-type mice to conceive the F3 generation.At the age of 3 and 18 months old,F1,F2,and F3 mice(n=8 in each group)were randomly selected to complete the Morris maze experiment in order to test their cognitive abilities.Re-sults Compared with 3-month-old CON mice,18-month-old CON mice showed poorer learning and memory abili-ties,especially in females.For Fl generation,the learning and memory abilities of the 3-month-old and 18-month-old F1-LPS mice were inferior to those of the same aged CON mice.For F2 generation,the 3-month-old F2-LPS-parental mice had poorer learning and memory compared to the same aged CON mice,while the F2-LPS-paternal mice only had poorer memory compared to the same aged CON group.The learning and memory abilities of 18-month-old F2-LPS paternal and F2-LPS-parental mice were inferior to those of the same aged CON mice.The learn-ing and memory abilities of F2-LPS maternal male mice were inferior to those of CON male mice,and the memory abilities of F2-LPS maternal mice were stronger than those of F2-LPS-parental mice.With regards to the F3 genera-tion,the memory of the 3-month-old F3-LPS-parental mice was poorer than that of the same aged CON mice.The learning and memory abilities of F3-LPS paternal and F3-LPS-parental mice at 18 months old were inferior to those of CON mice of the same age.The 18-month-old F3-LPS maternal and paternal male mice had better memory than F3-LPS-parental male mice.Conclusion Exposure to lipopolysaccharides in late pregnancy can accelerate age-re-lated cognitive decline in offspring mice,and it has a cross generational genetic effect and gender differences,mainly in paternal inheritance.

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.

Objective To explore the risk factors of hemorrhagic transformation and prognosis of acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From June 2017 to June 2019,211 patients with AIS undergoing intravenous thrombolysis were selected as the research object. Among them,34 patients with hemorrhagic tromsformation (HT) were recorded as HT group,and 177 patients without hemorrhagic transformation The patient was recorded as a non-HT group,with a bleeding conversion rate of 16.11%. The relationship between intensive blood pressure reduction and bleeding conversion and prognosis in patients with AIS intravenous thrombolysis was analyzed during intravenous thrombolysis. Results Univariate analysis revealed gender,age,time interval between onset to start of treatment (OTT),blood glucose at admission,baseline blood pressure,and baseline from the onset to start of treatment (reombinant tissue plasminogen activator,rt-PA) The National Institute of Health stroke scale (NIHSS) score,type 2 diabetes,atrial fibrillation,and venous thrombolysis have statistically significant differences (P<0.05 or P<0.01),which is a vein Risk factors related to HT after thrombolysis;binary logistic analysis showed that the baseline NIHSS score of 17.5 was divided into independent risk factors for the transformation of venous thrombolysis hemorrhage in AIS patients (OR=1.639,P=0.013). Atrial fibrillation (OR=9.129,P<0.01) is an independent risk factor for the prognosis of patients with intravenous thrombolysis. Conclusion The baseline NIHSS score of 17.5 is divided into independent risk factors for HT after intravenous thrombolysis in AIS patients,and intensive blood pressure reduction during intravenous thrombolysis is a related risk factor for HT;atrial fibrillation is an independent risk factor for the prognosis of patients with intravenous thrombolysis.

The causes of stroke in young people are diverse, most of which are cardiogenic. However, cerebral embolism caused by cardiac myxoma is rare. Intravenous thrombolysis is given in the time window, and the therapeutic effect depends on the nature of embolus. This case is a young female patient, with acute onset, excluding bleeding on the basis of the symptoms, signs and craniocerebral CT. After diagnosed as acute ischemic stroke, the patient was performed an immediate intravenous thrombolysis, though the curative effect was poor. Excluding contraindications six hours after onset, bridging mechanical thrombectomy was performed, postoperative embolus biopsy indicating myxoma. Atrial myxoma was removed in cardiac surgery two months later, and the pathology indicated atrial myxoma. The patient recovered well during the out-of-hospital follow-up, and no further embolization occurred. Therefore, it is suggested that bridging mechanical thrombectomy may be safe and effective for acute ischemic stroke caused by atrial myxoma when intravenous thrombolysis is ineffective, and myxoma resection should be performed immediately after the disease is stable.

Objective: To observe the variation trend of the peripheral blood lymphocyte-to-monocyte ratio (LMR) during radiotherapy in patients with esophageal cancer and analyze the relationship between LMR and the radiation-induced injury, aiming to provide parameters for accurate evaluation of radiotherapy responses and clinical efficacy. Methods: Clinical data of 248 eligible patients undergoing definitive radiotherapy in our department from January 2013 to December 2015, 248 were retrospectively analyzed. The routine peripheral blood examination was performed weekly before, during and at the end of radiotherapy. The absolute number of lymphocyte and monocyte was recorded to calculate the LMR. The standard classification of LMR value was conducted based on the median value of each parameter. All data including the lesion length, lesion location, clinical stage and LMR were analyzed using the Kaplan-Meier, cox and logistic regression methods, respectively. Results: LMR displayed an exponential decline during radiotherapy. Univariate analysis showed that the average LMR value was the influential factor of overall survival (P=0.011) and progression-free survival (P=0.017). The mean LMR value almost exerted significant effect upon local control rate (P=0.053). No significant correlation was observed between the mean LMR value and radioactive esophagitis and pneumonitis. Stratified analysis based on the results of multivariate analysis demonstrated that patients with higher average LMR value still had longer survival. Logistic regression model revealed that the length of esophageal lesion and irradiation pattern were the influential factors of the mean LMR value. Conclusions LMR value displays an exponential decline during radiotherapy. The greater amplitude prompts the worse prognosis. The wider the irradiation field and the greater decrease in LMR exert more obvious impact on the prognosis.

Objective To compare the dissolution curves of metronidazole tablets from 38 national manufactures and original drugs of Britain in four dissolution mediums,and provide the reference for the quality and clinical effect consistency evaluation of metronidazole tablets.Methods Paddle method was adopted at 50 r · min-1 in four dissolution mediums with the volume of 900 mL.The dissolution profiles were determined by ultraviolet spectrophotometry.The cumulative dissolution percentages were calculated and the dissolution curves were drawn.Similarity factor (f2)was used for comparing of the differences between dissolution curves.Results The dissolution profiles of 4 manufactures in pH 1.2 and 9 manufactures in pH 4.5 were similar (f2 ≥ 50)to that of original drugs,only 1 and 3 were similar to original drugs in water and pH 6.8,respectively.There are no companies whose dissolution curve were similar to that of original drugs in 4 dissolution mediums.Conclusion Great difference exists between domestic manufactures and pharmaceutical enterprises of origin in dissolution behaviors of metronidazole tablets.In order to ensure the consistency between the metronidazole tablets generics and original drugs of Britain in quality and clinical effect.It is advisable for the relevant companies to improve their product quality by improving the formulation and preparation.