Aim To explore the effects of Huannao Yicong decoction(HYD)on the learning and memory ability and brain iron metabolism in APP/PS1 mice and the correlation of HAMP knockout mice and APP/PS1 double transgenic model mice.Methods The ex-periment was divided into five groups,namely,HAMP-/-group(6-month HAMP gene knockout mice),APP/PS1 group(6-month APP/PS1-double-transgenic mice),HAMP-/-+HYD,APP/PS1+HYD,and negative control group(6-month C57BL/6J mice),with six mice in each group.The dose was ad-ministered(13.68 g·kg-1 weight),and the other groups received distilled water for gavage once a day for two months.After the administration of the drug,the mice in each group were tested for learning and memory in the Morris water maze;Biochemical detec-tion was performed to detect iron ion content in each mouse brain;Western blot and RT-qPCR were carried out to analyze hippocampal transferrin(TF),transfer-rin receptor1(TFR1),membrane iron transporter1(FPN1)divalent metal ion transporter 1(DMT1)and β-amyloid protein(Aβ)protein and mRNA expression levels in each group.Results Compared with the normal group,both HAMP-/-mice and APP/PS1 mice had reduced the learning and memory capacity,in-creased iron content in brain tissue,Aβ protein ex-pression increased in hippocampus of HAMP-/-group and APP/PS1 group mice(P＜0.01),the protein and mRNA expression of TF,TFR1 and DMT1 increased in hippocampal tissues of HAMP-/-and APP/PS1 groups(P＜0.01),and the FPN1 protein and mRNA expres-sion decreased(P＜0.01).Compared with the HAMP-and APP/PS1 groups,respectively,HAMP-/-+HYD group and APP/PS1+HYD group had improved learning and memory ability,decreased iron content,decreased Aβ protein expression(P＜0.01),decreased TF,TFR1,DMT1 protein and mR-NA expression(P＜0.01),and increased expression of FPN1 protein and mRNA(P＜0.01).Conclusions There is some association between HAMP-/-mice and APP/PS1 mice,HYD can improve the learning and memory ability of HAMP-/-and APP/PS1 mice and reduce the Aβ deposition.The mechanism may be related to the regulation of TF,TFR1,DMT1,FPN1 expression and improving brain iron overload.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Child ; Humans ; Mpox (monkeypox)/prevention & control* ; Disease Outbreaks

Background Intraseasonal variation in acute health effects of extreme heat remains insufficiently investigated. Emergency ambulance calls (EACs) may offer timely insights into the population's health during such extreme heat events. Objective To analyze intraseasonal variation in the association between extreme heat and hourly EACs during summer in Dezhou City, Shandong Province, China. Methods We collected data on all-cause hourly EACs in Dezhou City from 2021 to 2022 and assigned hourly temperature and humidity data (with a spatial resolution of 0.0625° × 0.0625°) to call addresses. Summer in this study was defined as from June to September each year, with June to July considered as early summer and August to September as late summer. Extreme heat was defined as the 99th percentile of the temperature range during the summer. We employed a time-stratified case-crossover design using conditional logistic regression integrating distributed-lag nonlinear models to compare the association between extreme heat and the risk of hourly EACs in both early and late summer periods. Results A total of 80389 EACs were recorded in Dezhou City during the study period. The analysis revealed a U-shaped association between hourly ambient temperature and EACs during summer, with the most significant effect observed at lag 0-30 h. Using the optimal temperature of 20.0°C as a reference, the cumulative odds ratio (OR) (lag 0-120 h) for extreme heat was 1.55 (95%CI: 1.40, 1.71) throughout summer. The cumulative effect of extreme heat was higher in late summer (OR=2.38, 95%CI: 1.91, 2.97) than in early summer (OR=1.37, 95%CI: 1.22, 1.54) (P<0.0001). Additionally, individuals aged 60 years and above had a higher risk throughout summer (OR=1.98, 95%CI: 1.70, 2.30) compared to those under 60 years (OR=1.23, 95%CI: 1.06, 1.42) (P<0.0001). Conclusion Intraseasonal variation is observed in the strength of association between extreme heat and hourly EACs during summer in Dezhou City. The higher risk observed in late summer than in early summer indicates that repeated exposures to heat may escalate health risks, and older adults are more vulnerable.

ObjectiveTo evaluate the measles surveillance system （MSS） in Jiading District， Shanghai from 2020 to 2022， and to provide evidence for the elimination of measles. MethodsDescriptive methods were used to analyze the MSS data and confirmed measles cases from 2020 to 2022 and to evaluate MSS performance indicators. ResultsA total of 120 suspected cases were reported through the MSS from 2020 to 2022， of which 12 were classified as measles， 9 as rubella， and 99 as non-measles /rubella. The incidence of reported non-measles /rubella was 1.44 per 100 000 population in 2020， 2.01 per 100 000 population in 2021， and 1.99 per 100 000 population in 2022. The rates of complete investigation within 48 hours， blood samples and etiology collection， timely delivery， and timely reporting were all 100%. Among the 12 confirmed measles cases from 2020 to 2022， seven routine immunization subjects completed the required doses of measles vaccines， while two out five adult cases had a history of measles vaccine-related immunization. The confirmed cases comprised six with fever accompanied by rash， five with rash alone， and one with fever alone. ConclusionThe MSS results in Jiading District， Shanghai are overall satisfactory. However， there is a need to improve sensitivity， especially in detecting and reporting cases with atypical symptoms. It is imperative to maintain high vaccination coverage for age-appropriate children， promote supplementary immunization activities， and elevate the overall immunity of the entire population.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To explore the effect of Shugan Lipi decoction on inflammation and intestinal flora,Toll like receptor 4(TLR4),T cell immunoglobulin domain and mucin domain-3(Tim-3)in non-alcoholic steatohepatitis(NASH)rats.Methods The NASH model was established by feeding methionine and choline deficient diet for 4 weeks.SD rats were randomly divided into blank group(intragastric administration with 0.9％NaCl),model group(NASH model,intragastric administration with 0.9％NaCl),and experimental group(NASH model,intragastric administration with 6.18g·kg-1 Shugan Lipi decoction).Illumina sequencing by synthesis method was used to detect the 16S rRNA sequence of rat Intestinal microbiota.Western blot method was used to detect the expression levels of Tim-3 and TLR4 proteins.Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-10 levels in each group of rats.Results After 4 weeks of medication,the relative abundance of Bacteroidetes in the blank,model and experimental groups were(47.96±10.52)％,(42.90±15.01)％and(57.15±10.99)％;the relative abundance of Firmicutes were(49.27±9.99)％,(53.06±11.47)％and(39.99±11.88)％;the relative expression levels of Tim-3 protein were 1.03±0.07,0.24±0.06 and 1.57±0.11;the relative expression levels of TLR4 protein were 1.04±0.11,3.23±0.33 and 0.94±0.27;the levels of TNF-α were(403.03±25.25),(576.87±60.29)and(385.16±37.67)pg·mL-1;the levels of IL-6 were(125.35±14.07),(189.75±34.30)and(113.71±18.35)pg·mL-1;the levels of IL-10 were(123.20±15.96),(66.71±11.94)and(119.54±10.57)pg·mL-1,respectively.The above indexes in the experimental group showed statistically significant differences compared with the model group(P＜0.01,P＜0.05).Conclusion Shugan Lipi decoction may regulate inflammatory cytokines by affecting intestinal flora and TLR4,Tim-3 protein expression,affect liver inflammatory response,and improve NASH.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.