The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

The PCR-amplified severe fever with thrombocytopenia syndrome virus(SFTSV)Gn-DⅢ-Ⅲ gene was inserted into the pET-30a(+)prokaryotic expression vector to generate the re-combinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ.The plasmid was transformed into E.coli BL21(DE3)for Gn-DⅢ-m protein expression and the expression conditions were optimized.The Gn-DⅢ-Ⅲ protein purified with Ni-NTA column affinity chromatography was applied as the captured antigen to establish an indirect ELISA method for the detection of SFTSV antibody.The results demonstrated that the recombinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ was successfully constructed as identified by PCR and sequencing.The recombinant protein SFTSV Gn-D m-Ⅲ was soluble ex-pression in E.coli under the optimal induction conditions of 0.4 mmol/L IPTG at 25 ℃ for 4 h,and the protein purity was 91.77％after purification by Ni-NTA column.The optimal reaction con-ditions for the indirect ELISA of SFTSV antibody were as follows:coating antigen concentration(5 μg/mL),primary antibody(incubation at 37 ℃ for 1.5 h),and secondary antibody(diluted 1:10 000 and incubated at 37 ℃ for 1 h).The established method had no cross-reactivity with Rift Valley fever virus(RVFV),Ebola virus(EBOV),and tick-borne encephalitis virus(TBEV)posi-tive sera.The method had a high sensitivity,with P/N＞2.1 for SFTSV-positive sera diluted to 81920.Coefficients of variation for intra-and inter-batch reactions were less than 10％.Detection of four SFTSV-infected human clinical serum samples showed the serum samples from patients in re-mission were tested as positive(P/N＞2.1),while serum samples from patients with multiple or-gan failure were detected as negative(P/N＜2.1).The results indicated that the SFTSV Gn-D Ⅲ-Ⅲ protein was successfully expressed and purified,and it was used as the coating protein to estab-lish an indirect ELISA assay for SFTSV antibody,which possesses good specificity,sensitivity and reproducibility.This method might be applied to detect human SFTSV clinical serum samples.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

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 analyze the trend of dementia mortality rate among individuals aged 60 to 94 years in China from 1982 to 2021.Methods:Utilizing data from the Global Burden of Disease Study 2021, the Joinpoint regression model was employed to analyze the trend in the dementia mortality rate among Chinese older adults from 1982 to 2021. The age-period-cohort analysis method was used to decompose the age effect, period effect and cohort effect of dementia mortality data in Chinese elderly people.Results:From 1982 to 2021, the crude mortality rate of dementia in elderly women aged 60-94 in China (133.67/100 000-214.02/100 000) was higher than that in men (70.92/100 000-119.70/100 000), and the age-standardized mortality rate of dementia in women (230.74/100 000-246.87/100 000) was also higher than that in men (132.88/100 000-140.19/100 000). The age-standardized mortality rate of dementia in both genders showed an N-shaped fluctuation trend. The average annual percent change (AAPC) of dementia mortality rate in elderly males aged 60-94 was 0.07% (95% CI: 0.01%-0.13%), and the AAPC of dementia mortality rate in elderly females was -0.01% (95% CI:-0.08%-0.07%). Age effect analysis showed that from the age of 60, the risk of dementia death in males and females increased with age, especially among elderly people aged 75-94 who experienced a rapid increase in dementia mortality rate. The period effect analysis showed that the overall risk of dementia death in elderly men and women aged 60-94 was decreasing, but it had increased from 2017 to 2021. The cohort effect analysis showed that the risk of dementia death was lower in later birth cohorts. Conclusion:From 1982 to 2021, the dementia mortality rate among Chinese older adults aged 60 to 94 years exhibited fluctuations. Particularly, there has been a notable rebound in recent years. Special attention should be directed towards female seniors and those aged 75 to 94 years.

Objective:To analyze the trend of dementia mortality rate among individuals aged 60 to 94 years in China from 1982 to 2021.Methods:Utilizing data from the Global Burden of Disease Study 2021, the Joinpoint regression model was employed to analyze the trend in the dementia mortality rate among Chinese older adults from 1982 to 2021. The age-period-cohort analysis method was used to decompose the age effect, period effect and cohort effect of dementia mortality data in Chinese elderly people.Results:From 1982 to 2021, the crude mortality rate of dementia in elderly women aged 60-94 in China (133.67/100 000-214.02/100 000) was higher than that in men (70.92/100 000-119.70/100 000), and the age-standardized mortality rate of dementia in women (230.74/100 000-246.87/100 000) was also higher than that in men (132.88/100 000-140.19/100 000). The age-standardized mortality rate of dementia in both genders showed an N-shaped fluctuation trend. The average annual percent change (AAPC) of dementia mortality rate in elderly males aged 60-94 was 0.07% (95% CI: 0.01%-0.13%), and the AAPC of dementia mortality rate in elderly females was -0.01% (95% CI:-0.08%-0.07%). Age effect analysis showed that from the age of 60, the risk of dementia death in males and females increased with age, especially among elderly people aged 75-94 who experienced a rapid increase in dementia mortality rate. The period effect analysis showed that the overall risk of dementia death in elderly men and women aged 60-94 was decreasing, but it had increased from 2017 to 2021. The cohort effect analysis showed that the risk of dementia death was lower in later birth cohorts. Conclusion:From 1982 to 2021, the dementia mortality rate among Chinese older adults aged 60 to 94 years exhibited fluctuations. Particularly, there has been a notable rebound in recent years. Special attention should be directed towards female seniors and those aged 75 to 94 years.

To address the key challenges in multivariate statistical modeling,a higher-order derivative approach combined with vector space angle multiplicative error correction was proposed for establishing an acid value prediction ordinary least squares(OLS)regression model based on attenuated total reflectance-Fourier transform infrared(ATR-FTIR)spectroscopy.By using acid values measured by potentiometric titration as reference,ATR-FTIR spectroscopy was utilized for direct calibration and prediction of acid values on 96 kinds of lubricating oil samples from a wind turbine.Firstly,the simulated hyperbolic(SH)method was employed to obtain accurate fourth derivative spectrum,resolving overlapping bands and enhancing spectral selectivity.Then,from the calibration set(48 samples),informative spectral regions were identified based on correlation coefficients.Next,the sample with the highest acid value was selected as the reference and1/(1+tan(θ/2))was used as the metric relation of the spectrum to suppress the multiplicity error caused by factors such as the change of effective optical path in ATR-FTIR spectroscopy.After pretreatment of the spectrum by the method of fourth-order derivative combined with angular quantity,the number of variables decreased from 1737 to 8,and the matrix condition number decreased from 1.85×1015 to 56.34,which effectively eliminated the collinearity issue for OLS regression.Direct OLS modeling on spectral preprocessed data achieved a determination coefficient of 0.981 for 47 validation samples,with a relative error range of-8.38%-8.22%,outperforming the commonly used partial least squares(PLS)method(Determination coefficient of 0.865,relative error of-27.82%-22.38%).It was proved that effective data preprocessing significantly improved the prediction accuracy of the model.Furthermore,when the number of calibration set was compressed to 25 and the number of validation set was expanded to 70,the model retained 8 variables with a condition number of 42.60,the determination coefficient of validation set was 0.972,and the relative error ranged from-10.80%to 12.31%.Comparing with the PLS method(Determination coefficient of 0.724,relative error of-34.26%-53.84%),the improvement was more obvious,which showed that the method could still have high prediction accuracy even with fewer modeling samples as well as robustness against multiplicative error interference.

Objective: To analyze the trends of the age of menarche among Chinese Han girls aged 9 to 18 years from 2010 to 2019. Methods: Data were extracted from the Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019. A total of 253 037 Han girls aged 9 to 18 years with complete data on menarche were selected in this study. They were asked one-on-one about their menstrual status, age and residence information. The median age of menarche was estimated by probability regression. U tests were used to compare the difference in median age at menarche in different years. Results: The median age at menarche (95%CI) among Chinese Han girls was 12.47 (12.09-12.83) years in 2010, 12.17 (11.95-12.38) years in 2014 and 12.05 (10.82-13.08) years in 2019, respectively. Compared with that in 2010, the median age at menarche in 2019 decreased by 0.42 years (U=-77.27, P<0.001). The annual average changes were-0.076 years from 2010 to 2014 (U=-57.19, P<0.001) and-0.023 years from 2014 to 2019 (U=-21.41, P<0.001), respectively. The average annual changes in urban areas in the periods of 2010 to 2014 and 2014 to 2019 were-0.071 years and 0.006 years, respectively, while those in rural areas were-0.082 years and-0.053 years, respectively. The average annual changes in the regions of north, northeast, east, south central, southwest and northwest were-0.064, -0.099, -0.091, -0.080, -0.096 and-0.041 years in the period of 2010 to 2014 and 0.001, -0.040, -0.002, -0.005, -0.043 and-0.081 years in the period of 2014 to 2019. Conclusion: The age of menarche among Chinese Han girls aged 9 to 18 years shows an advanced trend from 2010 to 2019, and the trends in urban and rural areas and different regions have different characteristics.

Objective: To analyze the long-term trend of the age of spermarche among Chinese Han boys aged 11 to 18 from 2010 to 2019 and its association with nutritional status. Methods: The data from Chinese National Surveys on Students' Constitution and Health in 2010, 2014 and 2019 were used. The age, residence and spermarche of the participants were collected by questionnaire, and their height and weight were measured. A total of 184 633 Han boys aged 11‒18 years with complete data on spermarche, height, and weight were included in this study. The probability regression method was used to calculate the median age (95%CI) at spermarche in different areas, and the trend of age at spermarche in different groups was compared. The multivariate logistic regression model was used to analyze the association between nutritional status and spermarche of Chinese Han boys aged 11‒18 years. Results: The median age of spermarche (95%CI) was 13.85 (13.45-14.22) years old among Chinese Han boys aged 11‒18 years in 2019, with 0.18 years earlier than that in 2010. The median age at spermarche in urban and rural boys was 13.89 and 13.81 years, respectively. Compared with that in 2010, the age at spermarche in urban and rural boys was 0.08 and 0.27 years earlier, respectively. After adjusting for age, province and urban/rural areas, compared with normal weight, spermarche was negatively associated with wasting and positively associated with overweight and obesity, with OR (95%CI) about 0.73 (0.67-0.80), 1.09 (1.02-1.17) and 1.09 (1.01-1.18), respectively. Conclusion: The age of spermarche generally shows an advanced trend among Chinese Han boys and is associated with nutritional status.

Objective: To analyze and predict the epidemic trend of overweight and obesity among children and adolescents aged 7-18 years in China from 1985 to 2019. Methods: Data were collected from the Chinese National Survey on Students Constitution and Health in 1985, 1995, 2000, 2005, 2010, 2014, and 2019 with the sample size of 409 945, 204 931, 209 209, 234 420, 215 317, 214 353, and 212 711, respectively. Overweight and obesity were evaluated according to the "classification standard of the weight index value of overweight and obesity screening for Chinese school-age children and adolescents" of the Working Group on Obesity in China (WGOC). The detection rate and average annual growth rate of overweight and obesity, and single obesity among children and adolescents aged 7-18 years were calculated, and ArcGis10.6 software was used to analyze the difference in the prevalence of overweight and obesity among children and adolescents in different regions in 2019. Polynomial regression function was used to fit the prevalence and average annual growth rate of overweight and obesity, and single obesity among children and adolescents from 1985 to 2019, and to predict the prevalence of overweight and obesity and single obesity among children and adolescents in China. Results: In 2019, the total prevalence of overweight and obesity among children and adolescents aged 7-18 years in China was 23.4%, and the prevalence of single obesity was 9.6%. The prevalence of overweight and obesity among urban children and adolescents was higher than that in rural areas (25.4% vs. 21.5%), and the prevalence in boys was higher than that in girls (28.4% vs. 18.4%) (both P values<0.001). In 2019, there was a large regional disparity in the prevalence of overweight and obesity in different provinces, with the lowest in Guangdong (12.2%) and the highest in Shandong (38.9%), and the high epidemic areas were mainly concentrated in North China and Northeast China. From 1985 to 2019, the prevalence of overweight and obesity among children and adolescents aged 7-18 years in China increased from 1.2% to 23.4%, with an increase of 18.1 times, while the prevalence of obesity alone increased from 0.1% to 9.6%, with an increase of 75.6 times. The prevalence of overweight and obesity in urban boys, urban girls, rural boys and rural girls increased from 1.3%, 1.5%, 0.5%, and 1.6% in 1985 to 31.2%, 19.4%, 25.6%, and 17.4% in 2019, with an increase of 22.3, 11.7, 54.2, and 10.1 times, respectively. According to the prediction model, the prevalence of overweight and obesity among children and adolescents aged 7-18 years in China will increase from 23.4% in 2019 to 32.7% in 2030, and the prevalence of obesity alone will increase from 9.6% in 2019 to 15.1% in 2030. The growth of rural children and adolescents is obvious. By 2025, the prevalence of overweight and obesity among rural children and adolescents in China will comprehensively exceed that of urban, and there will be an "urban-rural reversal" phenomenon. At the same time, the prevalence of children's obesity in China's low, medium and high epidemic areas will also continue to increase. By 2035, the prevalence of overweight and obesity among children and adolescents in medium epidemic areas will exceed that in high epidemic areas, and there will be a "provincial reversal" phenomenon. Conclusion: From 1985 to 2019, the overweight and obesity of children and adolescents in China will continue to grow rapidly with large regional differences.