Rosmarinic acid activates the Ras/Raf/MEK/ERK signaling pathway to regulate CD8+ T cells and autophagy to clear Chlamydia trachomatis in reproductive tract-infected mice.

Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.

The accuracy and safety of using the electrocardiogram positioning technique in localizing the peripherally inserted central catheter tip position: A systematic review and meta-analysis.

AIM: We performed a systematic review and meta-analysis to examine the accuracy and safety of using the electrocardiogram (ECG) positioning technique to localize the peripherally inserted central catheter (PICC) tip position to provide objective evidence for its clinical application. METHODS: We searched the literature for randomized controlled trials evaluating the diagnostic analysis of using electrocardiograms to localize PICC tip positions in the MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and PsycINFO databases. We used a risk ratio with accompanying 95% confidence interval (CI) to express estimates. Reviewer Manager (RevMan) 5.1.0 was used to complete all statistical analyses. RESULTS: This systematic review identified 9 studies (N = 3,194 patients). Overall, the results of the meta-analysis revealed that, for patients in whom the ECG positioning method was used compared with patients in whom the landmark positioning method was used, the RR for accurate catheter tip positioning was RR = 1.17, and the difference was statistically significant. The RR for the incidence of complications was RR = 0.28, and the difference was statistically significant. CONCLUSIONS: The application of ECGs in PICC tip positioning can improve the accuracy of catheter tip positioning and reduce the incidence of related complications.

Correlation Between Functional Components in Codonopsis pilosula Roots and Soil Factors / 中国实验方剂学杂志

ObjectiveTo explore the correlation between the content of 4 functional components in Codonopsis pilosula roots from different areas and soil factors， and thereby to lay a theoretical basis for soil ecological regulation and improvement of quality of C. pilosula roots. MethodThe content of lobetyolin， atractylenolide Ⅲ， alcohol extract， and polysaccharides， as well as soil fertility and 16 soil factors in 24 batches of samples from different producing areas were determined. Principal component analysis （PCA） and Pearson's correlation analysis were used to explore the key soil factors leading to the variation of chemical component content in C. pilosula roots. ResultThe content of lobetyolin and atractylenolide Ⅲ in samples from Longxi was the highest， and the content of polysaccharides peaked in samples from Huguan. The content of lobetyolin was in positive correlation with soil total nitrogen， total phosphorus， total potassium， alkali-hydrolyzable nitrogen， and available potassium （P<0.01）， as well as soil organic matter， pH， available manganese， and available zinc （P<0.05）. There was a positive correlation between pH and atractylenolide Ⅲ content （P<0.05）. Soil total potassium was in positive correlation with alcohol extract and polysaccharide content （P<0.01）. Soil available zinc was positively correlated with alcohol extract and the polysaccharide content （P<0.05）. Sample sites with higher PCA scores were Pingshun， Huguan， and Longxi， which were significantly positively correlated with the content of polysaccharides in C. pilosula roots in different habitats. ConclusionThe content of functional components in C. pilosula roots can be improved by raising soil organic matter content and applying specific fertilizers.

Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology / 中华血液学杂志

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

Beginning in late 2020, the emergence and spread of multiple variant SARS-CoV-2 strains harboring mutations which may enable immune escape necessitates the rapid evaluation of second generation COVID-19 vaccines, with the goal of inducing optimized immune responses that are broadly protective. Here we demonstrate in a mouse immunogenicity study that two doses of a modified B.1.351 spike (S)-Trimer vaccine (B.1.351 S-Trimer) candidate can induce strong humoral immune responses that can broadly neutralize both the original SARS-CoV-2 strain (Wuhan-Hu-1) and Variants of Concern (VOCs), including the UK variant (B.1.1.7), South African variant (B.1.351) and Brazil variant (P.1). Furthermore, while immunization with two doses (prime-boost) of Prototype S-Trimer vaccine (based on the original SARS-CoV-2 strain) induced lower levels of cross-reactive neutralization against the B.1.351 variant, a third dose (booster) administered with either Prototype S-Trimer or B.1.351 S-Trimer was able to increase neutralizing antibody titers against B.1.351 to levels comparable to neutralizing antibody titers against the original strain elicited by two doses of Prototype S-Trimer.

Magnolol attenuates right ventricular hypertrophy and fibrosis in hypoxia-induced pulmonary arterial hypertensive rats through inhibition of the JAK2/STAT3 signaling pathway / 中国药理学与毒理学杂志

OBJECTIVE Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol is a com?pound isolated from Magnolia officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. METHODS ① Male SD rats (220 g) were randomly divided into 5 groups (n=10): the normoxia group, the hypoxia group, the hypoxia plus Magnolol (10 and 20 mg·kg-1·d-1) group, and the vehicle group. Rats in the normoxia group were kept in a normoxia environment for 4 weeks, while rats in the hypoxia group were kept in a hypoxic chamber (10％ O2). The rats in the hypoxia plus magnolol groups were administered with magnolol at 10 or 20 mg·kg-1 (ip) once a day for 4 weeks. At the end of 4 weeks, the heart function was assessed by Doppler echocardiography, and then the rats were anesthetized with sodium pentobarbital (30 mg·kg-1, ip). The RVSP was measured by the right heart catheterization method. The heart tissues were collected and dissected to calculate the index of RV remodeling (RV/LV+IVS, RV/tibial length, or RV/body weight). Part of the RV samples was fixed with 4％paraformaldehyde for morphological analysis, while other samples were frozen at-80℃for molecular studies (measurements of ANP, BNP,α-SMA, and col?lagen Ⅰ/Ⅲ mRNA expression as well as p-JAK2/JAK2 and p-STAT3/STAT3 protein levels). ② To evaluate the effect of magnolol on hypoxia-induced myocardial hypertrophy and fibrosis, H9c2 or cardiac fibroblasts were divided into 7 groups: the control group, cells were cultured under normal conditions; the hypoxia group, cells were cultured under hypoxic condition (3％ O2);the hypoxia plus magnolol 10 mg·kg-1 group, magnolol10μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus magnolol 30 mg·kg-1 group, magnolol 20μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus TG-101348 group, TG-101348 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;the hypoxia plus JSI-124 group, JSI-124 (a specific inhibitor of JAK2) 1μmol·L-1 was added to the culture medium before the hypoxia treatment;and the hypoxia plus vehicle group, an equal volume of vehicle (DMSO) was added to the culture medium before the hypoxia treatment. At the end of the experiments, the cells were collected for morphological and molecular analysis. RESULTS In vivo, male Sprang-Daley rats were exposed to 10％ O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of RV remodeling index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3;these changes were attenuated by treating rats with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3％ O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagenⅠ, collagenⅢandα-SMA). Administration of mag?nolol and TG-101348 or JSI-124 (JAK2 selective inhibitors) could prevent the process of myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. CONCLUSION Magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway.

Clinical features and prognosis of pediatric acute megakaryocytic leukemia / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features and prognosis of children with acute megakaryocytic leukemia (AMKL) and the clinical effect of acute myeloid leukemia 03 (AML03) regimen for the treatment of pediatric AMKL.@*METHODS@#The clinical data were collected from 47 children with AMKL who were diagnosed from May 2011 to December 2019. The treatment outcomes and prognostic factors were analyzed. The Kaplan-Meier method and the log-rank test were used for survival analysis.@*RESULTS@#Among the 47 children with AMKL, 22 with non-Down syndrome-AMKL were treated by the AML03 regimen, with a median follow-up time of 11.4 months. For the 22 non-Down syndrome-AMKL patients, the remission rate of bone marrow cytology was 85% and the negative rate of minimal residual disease (MRD) was 79% after induction Ⅱ, with a 2-year overall survival (OS) rate of (50±13)% and a 2-year event-free survival (EFS) rate of (40±12)%. The group with positive immunophenotypic marker CD56 had significantly lower 2-year EFS and OS rates than the group with negative CD56 (@*CONCLUSIONS@#Children with AMKL tend to have a low remission rate and a poor prognosis. Positive immunophenotypic marker CD56, bone marrow cytology during early treatment response, and MRD results are important factors influencing the prognosis. Allogeneic hematopoietic stem cell transplantation has no significant effect on the prognosis of AMKL.

Nucleosides-based identification model for Fritillariae Cirrhosae Bulbus / 中国中药杂志

A high performance liquid chromatography( HPLC) method was established for the fast,and precise determination of ten nucleosides in Fritillariae Cirrhosae Bulbus and its counterfeits. Then multivariate statistical analyses,such as clustering analysis,principal component analysis( PCA),and Fisher' s linear discriminant analysis( LDA),were conducted to establish a discriminant function model for an integrated analysis. The results indicated that data acquisition time of a single sample was shortened within 16 min by the HPLC method. In the range of 5-1 000 mg·kg~(-1),the mass concentrations of all nucleosides exhibited good linear relationships with the corresponding peak areas( R2> 0. 999). The spiked recoveries were in the range of 93. 83%-108. 9% with RSDs of0. 12%-1. 3%( n = 5). The limit of quantitation( LOQ) was 0. 98-4. 13 mg·kg~(-1). As revealed by the clustering analysis,Fritillariae Cirrhosae Bulbus and the counterfeits could be discriminated into two clusters based on the content of nucleosides. Fisher's LDA could achieve this discrimination,while PCA dimension reduction failed. The accuracy of the discriminant function model established on the screened characteristic indicators reached 97. 5%. The present study proposed a new identification method of Fritillariae Cirrhosae Bulbus with one-dimensional indicators,which is simple,accurate,and reliable. It can provide a scientific basis for further optimizing the identification techniques for Fritillariae Cirrhosae Bulbus and inspiration for quality control strategy development of Chinese medicinal materials.

[Study on anti-osteoporosis effect of Eucommiae Cortex based on GC-MS metabonomics].

Based on GC-MS metabolomics and biochemical index analysis, the mechanism of bone mass loss in osteoporosis and the evaluation of anti-osteoporosis in Eucommiae Cortex were studied. The OVX rats model was established by bilateral ovariectomized. The routine indexes such as BMC, BMD, BGP and TRAP5 b were determined. The GC-MS technique was used to analyze the metabolism profile of serum samples between the control group, model group and medicine group, and multiple statistical analysis methods including principal component analysis(PCA), partial least squares-linear discriminant analysis(PLS-LDA) and subwindow rearrangement analysis(SPA) were used to screen and identify biomarkers. Five metabolites were selected as potential biomarkers, glycine, lysine, tryptophan, docosahexaenoic acid and glucose. Except for the significant increase of tryptophan in serum of OVX rats, the other four metabolites were significantly decreased. Moreover, the five biomarkers of the medicine group had a trend of returning to rats in control group. The significantly altered metabolite levels indicated that Eucommiae Cortex may relieve the symptoms of osteoporosis by regulating amino acid metabolism and oxidative stress.

S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-levels of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important new platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.

Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19

The coronavirus disease 2019 (COVID-19) outbreak is an ongoing global health emergence, but the pathogenesis remains unclear. We revealed blood cell immune response profiles using 5 mRNA, TCR and BCR V(D)J transcriptome analysis with single-cell resolution. Data from 134,620 PBMCs and 83,387 TCR and 12,601 BCR clones was obtained, and 56 blood cell subtypes and 23 new cell marker genes were identified from 16 participants. The number of specific subtypes of immune cells changed significantly when compared patients with controls. Activation of the interferon-MAPK pathway is the major defense mechanism, but MAPK transcription signaling is inhibited in cured patients. TCR and BCR V(D)J recombination is highly diverse in generating different antibodies against SARS-CoV-2. Therefore, the interferon-MAPK pathway and TCR-and BCR-produced antibodies play important roles in the COVID-19 immune response. Immune deficiency or immune over-response may result in the condition of patients with COVID-19 becoming critical or severe.

Analysis of serum vitamin D levels and clinical characteristics in elderly patients with active pulmonary tuberculosis / 中华老年医学杂志

Objective:To investigate serum levels of 25-hydroxyvitamin D [25-(OH)D3], the vitamin D receptor(VDR), LL-37, cytokines such as interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in elderly and non-elderly patients with pulmonary tuberculosis, and to study the correlation between serum vitamin D levels and clinical characteristics.Methods:A total of 56 elderly patients and 56 non-elderly patients with active pulmonary tuberculosis admitted to Chengdu Public Health Clinical Center from January 2019 to March 2019 were enrolled.The levels of 25-(OH)D3, VDR, LL-37, IL-6 and TNF-α were detected by ELISA and compared between the two groups.Clinical data such as the number of T lymphocytes, lesions and cavities in bilateral lung fields and extra-pulmonary tuberculosis were collected.Results:There were significant differences in serum vitamin D levels [(28.94±12.88)nmol/L vs.(34.47±12.78)nmol/L, t=3.650, P=0.025], while levels of VDR, LL-37, IL-6 and TNF-α(all P>0.05)were similar between the elderly and non-elderly groups.Besides, patients in the elderly group were associated with significantly lower levels of CD4 + T lymphocytes [(295.71±153.83)×10 6/L vs.(421.25±206.00)×10 6/L]and CD8 + T lymphocyte count [159.5(101.0, 239.0)×10 6/L vs.261.5(187.0, 409.0)×10 6/L]than those in the nonelderly group(all P=0.000). Also, there were more severe pulmonary tuberculosis cases in the elderly group than the non-elderly group [(51/56, 91.1%) vs.(28/56, 50.0%), χ2=22.730, P=0.000]. The serum level of 25-(OH)D3 was positively correlated with CD4 + T cell count in elderly patients( r=0.190, P< 0.05). Conclusions:Elderly patients with pulmonary tuberculosis have a high proportion of severe tuberculosis and reduced serum levels of vitamin D, CD4 + T cell count and CD8 + T cell count, compared with non-elderly patients.Attention should be paid to vitamin D levels and their potential impact on disease progression in elderly patients with active tuberculosis.

A case of small cell neuroendocrine carcinoma of ovary / 中国综合临床

Objective:Small cell neuroendocrine carcinoma of the ovary is a kind of ovarian cancer with a very low incidence.Its clinical manifestations are not obvious.The diagnosis should be based on the pathology and neuroendocrine indicators, and its primary nature should be determined.The main treatment is operation combined with platinum based chemotherapy.The survival period is related to clinical stage and treatment plan.The patient was hospitalized for 2 days because of the aggravation of abdominal distention and pain for half a year.The diagnosis of adnexal mass was confirmed by pathology.After three cycles of neoadjuvant chemotherapy (etoposide+ cisplatin), the patients underwent abdominal " total hysterectomy+ greater omentum resection+ appendectomy+ right pelvic wall peritoneal biopsy+ mesenteric biopsy" . After the operation, the patients received three cycles of EP chemotherapy, and they have been followed up for 15 months.

A case of small cell neuroendocrine carcinoma of ovary / 中国综合临床

Objective@#Small cell neuroendocrine carcinoma of the ovary is a kind of ovarian cancer with a very low incidence.Its clinical manifestations are not obvious.The diagnosis should be based on the pathology and neuroendocrine indicators, and its primary nature should be determined.The main treatment is operation combined with platinum based chemotherapy.The survival period is related to clinical stage and treatment plan.The patient was hospitalized for 2 days because of the aggravation of abdominal distention and pain for half a year.The diagnosis of adnexal mass was confirmed by pathology.After three cycles of neoadjuvant chemotherapy (etoposide+ cisplatin), the patients underwent abdominal " total hysterectomy+ greater omentum resection+ appendectomy+ right pelvic wall peritoneal biopsy+ mesenteric biopsy" . After the operation, the patients received three cycles of EP chemotherapy, and they have been followed up for 15 months.

Comparative study on free and bound phenolic acids before and after drying of Salvia miltiorrhiza / 中国中药杂志

There were significant differences in phenolic acid content between fresh and dried Salvia miltiorrhiza before and after drying. That is to say, the content of phenolic acid in S. miltiorrhiza significantly increased with the increase of dehydration during the drying process.In order to investigate the differences and transformation of free and bound phenolic acids before and after the drying process of S.miltiorrhiza, we studied hydrolysis method, hydrolysates and hydrolysis regularity of phenolic acids in S.miltiorrhiza. UPLC method was used to determine four main hydrolysates of bound phenolic acids, namely danshensu, caffeic acid dimer(SMND-309), caffeic acid, przewalskinic acid A(prolithosperic acid), and three main free phenolic acids in S.miltiorrhiza, namely rosmarinic acid, lithospermic acid, salvianolic acid B. The results of the acid-base hydrolysis experiment of salvianolic acid showed that the alkaline hydrolysis effect was significantly better than acid hydrolysis. The optimal alkaline hydrolysis condition was hydrolysis at 70 ℃ for 4 h with 2 mol·L~(-1) NaOH solution containing 1% ascorbic acid(Vit C). The hydrolysates of free phenolic acids were the same with the hydrolysates of bound phenolic acids. Fresh S.miltiorrhiza contains a low level of free phenolic acids and a high level of bound phenolic acids, which were exactly opposite to dried S.miltiorrhiza. It was suggested that a large amount of bound phenolic acids was accumulated during the growth of S.miltiorrhiza. These bound phenolic acids were coupled with polysaccharides on the cytoderm through ester bonds to form insoluble phenolic acids, which was not easy to be detected by conventional methods. However, during drying and dehydration processes, the bound phenolic acids were converted to a large amount of free phenolic acids under the action of the relevant enzyme.

Study on anti-osteoporosis effect of Eucommiae Cortex based on GC-MS metabonomics / 中国中药杂志

Based on GC-MS metabolomics and biochemical index analysis, the mechanism of bone mass loss in osteoporosis and the evaluation of anti-osteoporosis in Eucommiae Cortex were studied. The OVX rats model was established by bilateral ovariectomized. The routine indexes such as BMC, BMD, BGP and TRAP5 b were determined. The GC-MS technique was used to analyze the metabolism profile of serum samples between the control group, model group and medicine group, and multiple statistical analysis methods including principal component analysis(PCA), partial least squares-linear discriminant analysis(PLS-LDA) and subwindow rearrangement analysis(SPA) were used to screen and identify biomarkers. Five metabolites were selected as potential biomarkers, glycine, lysine, tryptophan, docosahexaenoic acid and glucose. Except for the significant increase of tryptophan in serum of OVX rats, the other four metabolites were significantly decreased. Moreover, the five biomarkers of the medicine group had a trend of returning to rats in control group. The significantly altered metabolite levels indicated that Eucommiae Cortex may relieve the symptoms of osteoporosis by regulating amino acid metabolism and oxidative stress.

Subnational inequalities of early marriage and fertility among Chinese females from 1990 to 2010 / 北京大学学报(医学版)

OBJECTIVE@#To analyze the inequality of early marriage and adolescent fertility with respect to local economic development among Chinese females aged 15-19 years from 1990 to 2010.@*METHODS@#Aggregated data were extracted from the Chinese National Census from 1990 to 2010. We calculated the ever-married rate and fertility rate of female adolescents aged 15-19 years. Using gross domestic product (GDP) per capita as an indicator for socio-economic status of a province, we calculated the slope index of inequality (SII) and the concentration index (CI) to analyze the subnational inequalities of early marriage and adolescent fertility. Weighted linear regression models were also established to assess the associations between GDP per capita and the ever-married rate/fertility rate.@*RESULTS@#The ever-married rate for Chinese female adolescents aged 15-19 years decreased from 4.7% in 1990 to 1.2% in 2000, and rebounded to 2.1% in 2010. From 1990 to 2000, the fertility rate decreased from 22.0 per 1 000 to 6.0 per 1 000, and further decreased to 5.9 per 1 000 in 2010. In 1990, the socio-economic inequalities of the ever-married rate and fertility rate for female adolescents aged 15-19 years were not statistically significant (P for SII or CI>0.05). The values of SII revealed that, in 2000 and 2010, female adolescents with the lowest GDP per capita had an ever-married rate 2.4% (95%CI: 0.4-4.4) and 2.3% (95%CI: 0.3-4.2) higher than those with the highest GDP per capita, respectively. In the meantime, in 2000 and 2010, female adolescents with the lowest GDP per capita had a fertility rate 12.9 per 1 000 (95%CI: 5.4-20.5) and 9.3 per 1 000 (95%CI: 4.6-14.0) higher than those with the highest, respectively. In 2000 and 2010, the CIs for marriage were -0.32 (P=0.02) and -0.17 (P=0.03), respectively, and the CIs for childbirth were -0.37 (P<0.01) and -0.26 (P<0.01), respectively. In 2000, the ever-married rate and the fertility rate were estimated to increase by 1.4% (95%CI: 0.1-2.7) and 7.9 per 1 000 (95%CI: 2.9-12.8) with 100% increase in GDP per capita, respectively; in 2010, the numbers were 1.5% (95%CI: 0.1-2.9) and 6.7 per 1 000 (95%CI: 3.2-10.1), respectively.@*CONCLUSION@#Subnational socio-economic inequality of early marriage and adolescent fertility existed in 2000 and 2010. Female adolescents residing in less-developed areas were more likely to engage in early marriage and childbirth. Reducing income inequality and increasing education investment for poverty-stricken areas seem to be effective measures to reduce this inequality.

Trends of prevalence of excellent health status and physical fitness among Chinese Han students aged 13 to 18 years from 1985 to 2014 / 北京大学学报(医学版)

OBJECTIVE@#To analyze the trends of prevalence of excellent health status and physical fitness among Chinese Han students aged 13 to 18 years from 1985 to 2014.@*METHODS@#In the study, 738 523 students aged 13 to 18 years were extracted from the 1985 to 2014 Chinese National Survey on Students' Constitution and Health. Height, weight, vital capacity and indicators of physical fitness were measured for each student. According to National Standards for Students' Physical Health (2014 Revision), students meeting an overall score ≥ 90.0 were considered to be of excellent health status and physical fitness. We used the Chi-square test to compare the differences in prevalence of excellent health status and physical fitness among different subgroups and draw maps of regional distribution of prevalence by using ArcGIS.@*RESULTS@#From 1985 to 2014, the average height, weight, and BMI for Chinese Han students aged 13 to 18 years increased consistently, while the average vital capacity and indicators of physical fitness fluctuated largely. The overall prevalence of excellent health status and physical fitness increased from 2.7% in 1985 to 4.4% in 1995, dropped consistently to 1.1% in 2005, rebounded 0.6 percentage points in 2010, and increased to 2.2% in 2014. In each survey year, the prevalence for the boys was always higher than for the girls (P<0.001), the prevalence for middle school students aged 13 to 15 years was always higher than for high school students aged 16-18 years (P<0.001), and the prevalence for students in eastern region was higher than in western and central regions (P<0.001). In 1985 and 1995, the prevalence in certain provinces in eastern and central regions was <1%. In 2005, almost half provinces (14/30) had a prevalence <1%. In 2014, provinces in eastern coastal areas had relatively high prevalence of excellent health status and physical fitness in students aged 13 to 18 years, while provinces in central and western regions had relatively low prevalence.@*CONCLUSION@#A fluctuating trend of the prevalence of excellent health status and physical fitness has been observed among Chinese Han students aged 13 to 18 years during the past three decades. There is great difference between the current prevalence of excellent health status and physical fitness and the goal of Outline of the Healthy China 2030 Plan, thus, the effective interventions and strategies for promoting students' physical activity and physical fitness are urgently needed in China.

Analysis of epidemiological characteristics of report cases of rotavirus diarrhea in children under 5 years old in China, 2005-2018 / 中华预防医学杂志

To analyze the epidemiological characteristics of rotavirus in children under 5 years old in China (excluding China Hong Kong, Macau and Taiwan data, the same below) from 2005 to 2018. Data on other infectious diarrhea in the country from 2005 to 2018 were downloaded from the National Notifiable Disease Report System was to build a database for report cases of rotavirus diarrhea in children under 5 years of age, and descriptive epidemiological methods were used to analyze the data. In 2005-2018, a total of 820 588 cases of rotavirus infection in children under 5 years old were reported nationwide, with male 500 944 cases, and with an average annual incidence of 63.7/100 000. The reported incidence showed a fluctuating upward trend increased from 8.4/100 000 to 178.1/100 000. The number of reporting provinces increased from 17 to 30. The reported incidence showed a peak of season from November to following February. The reported cases of rotavirus diarrhea in children under 5 months of age was 13.1%(107 845 cases), and the high-incidence age ranged from 6 months to 2 years old, accounting for 70.3% (576 874 cases), with a peak of 11-13 months (163 947 cases). The top three provinces (cities) reporting the incidence rate were Zhejiang (535.2/100 000), Guangdong (334.3/100 000) and Beijing (317.3/100 000), the provinces with the low reported case rates were Shanxi (0.9/100 000), Heilongjiang (1.6/100 000) and Liaoning (2.5/100 000), but there was no case reported in Tibet; The report cases of south region (745 526 cases) were 9.9 times north region (74 935 cases).The cases of rotavirus infection and other diarrhea pathogens were detected simultaneously accounted for 1.8% (15 030 cases) and mainly were positive for rotavirus and adenovirus (90.1%, 13 544 cases). The rate of rotavirus infection in children has increased rapidly since the age of 6 months, and 84.4% of the reported cases were infants before the age of 2 years.

Neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio in early pregnant women with hypertensive disorders / 中华全科医师杂志

Objective To investigate the correlation of systemic inflammation parameters including neutrophil to lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR) with the pregnancy outcome of hypertension disorders of pregnancy.Methods Two hundred and twelve pregnant women in first-trimester with hypertensive disorders and 212 matched healthy subjects (control group) were enrolled in the study.The differences in white blood cell count (WBC),neutrophil (N),lymphocyte (L),monocyte (M),NLR and MLR were compared between groups.Results The WBC,N,M,NLR and MLR values were significantly higher in pregnant women with hypertensive disorders than those in healthy controls (9.1 × 109/L vs.8.5×10g/L,Z=4.89,P＜0.01;6.6× 109/L vs.5.9×109/L,Z=4.33,P＜0.01;0.5×109/L vs.0.4×109/L,Z=3.83,P=0.01;3.7 vs.3.3,Z=1.97,P=0.04;0.3 vs.0.2,Z=3.83,P=0.01).The pregnant women were divided into gestational hypertension group (n=48),mild and severe preeclampsia group (n=77),chronic hypertension with superimposed preeclampsia group (n=55) and chronic hypertension complicating pregnancy group (n=32).There were no significant differences in the WBC,N,L,M,NLR and MLR values among all groups (P＞0.05).Multivariate logistic regression analysis showed that NLR was a predictive factor of hypertensive disorders of pregnancy (OR=1.68,95％CI:1.07-2.62,P＜0.05).Conclusions NLR might be a useful systemic inflammation marker for the prediction of hypertensive disorders in women with early pregnancy.