Melatonin inhibits arrhythmias induced by increased late sodium currents in ventricular myocytes / 药学学报

Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

Effects of raw and wine-processed Schisandra chinensis on neuro-endocrine-immune network in insomnia mice and its mechanism / 中国药房

OBJECTIVE To investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism. METHODS Fifty mice were randomly divided into blank group， model group， diazepam group， raw S. chinensis group and wine-processed S. chinensis group， with 10 mice in each group. Except for blank group， the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia； at the end of each day’s modeling， the corresponding doses of diazepam，raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded， and the total activity distance and upright times of the mice were detected； the EEG and EMG signals of mice were recorded， and the time ratio of sleep wake time （wake）， non-rapid eye movement （NREM） and rapid eye movement （REM） was analyzed； the contents of neurotransmitters [γ-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， dopamine （DA）， norepinephrine （NE）， cortisol （CORT）] in brain suprachiasmatic nucleus （SCN） were detected； and the expressions of tumor necrosis factor α （TNF-α） and interleukin 1β （IL-1β） were detected； the mRNA expressions of clock gene Bmal1， circadian clock gene Clock and cycle gene Per2 were all detected. RESULTS Compared with the blank group， the mental state of the model group mice was relatively depressed， the amount of food and water increased， the body mass decreased， the hair was rough and shiny， and the circadian rhythm was irregular； the total activity distance and upright times decreased significantly； the time ratio of wake increased significantly， while the time ratios of REM and NREM decreased significantly； the content of 5- HT in brain SCN decreased significantly， while the content of NE， DA and CORT increased significantly； the fluorescence intensity of IL-1β and TNF-α was significantly increased； the relative expression level of Bmal1 and Clock mRNA was significantly increased， while the relative expression level of Per2 mRNA was significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， the general state of mice in diazepam group， raw S. chinensis group and wine-processed S. chinensis group was improved obviously， and most of the above index levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Raw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice， the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.

Role of histone posttranslational modifications in the regulation of ovarian function / 生理学报

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.

Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS).@*METHODS@#A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups.@*RESULTS@#After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05).@*CONCLUSION@#Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Genomic epitopes of Xinjiang hemorrhagic fever virus and the evaluation of its laboratory testing value / 中华检验医学杂志

Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.

Polyarthritis, hyperuricemia and right shoulder pain: a report of one case with literature review / 中华风湿病学杂志

Objective:To improve the clinical differential diagnosis ability of rheumatoid arthritis (RA) complicated with gout and septic arthritis (SA).Methods:The clinical characteristics, diagnosis, and treatment of one RA patient with hyperuricemia and recurrent swelling and pain in right shoulder were reported and discussed.Results:A patient, with a history of RA for 10 years, hyperuricemia for 8 years, recurrent swelling and pain in right shoulder for 1 year. RA, gout, and SA were diagnosed before, and the response was poor after symptomatic treatment. In recent 1 month, the symptom was aggravated with the formation of fistula on the right shoulder. The laboratory tests for tuberculosis T cell interferon release test (IGRA) and tuberculin (PPD) test were negative, and the CD4 + cell count decreased. The comprehensive analysis of the imaging with right shoulder showed MSU deposition on right shoulder, with bone erosion, bone destruction, bone marrow edema, joint effusion, and multiple sites of connective tissue involvement (synovial bursa, tendon sheath, tendon, and muscle) GeneXpert MTB/RIF (GeneXpert), metagenomic next-generation sequencing (mNGS) of puncture fluid and joint fluid culture prompted Mycobacterium tuberculosis complex group. He was finally diagnosed with RA, gout, and osteoarticular tuberculosis (OAT). Symptoms were relieved after symptomatic treatment. Conclusion:RA patients with hyperuricemia have recurrent single arthritis. In addition to considering for gout, the presence of OAT should also be considered. The immune functional status of the patient and drug used may interfere with the interpretation of immune function tests. It is necessary to integrate the clinical characteristics of patients, a variety of imaging examinations, and etiological detection to confirm the diagnosis and avoid misdiagnosis.

Integrating Westward Migration Spirit into the cultivation of medical professionalism / 中华内分泌外科杂志

"Westward Migration Spirit" is the precious spiritual wealth of Chinese Communist Party and the Chinese nation. The course teaching team takes the undergraduate students of clinical medicine as the teaching object, tries to integrate the "Westward Migration Spirit" into the cultivation of medical students’ medical professionalism, so as to endow new connotation of medical professionalism and promote the improvement of medical students’ professionalism. Through literature review, expert consultation and questionnaire survey, the paper sorted out the context of "Westward Migration Spirit" of Chongqing Medical University, and typical examples with the spirit of medical science and humanity were selected and integrated into the teaching. A questionnaire was designed to investigate the evaluation of 425 clinical medicine undergraduates and 5 teachers on the medical professionalism course integrated with "Westward Migration Spirit" . The results show that the students and teachers have good feedback to the medical professionalism courses integrated with the "Westward Migration Spirit" , and the course has a significant positive effect on the cultivation of medical students’ medical professionalism.

Correlation between dietary approaches to stop hypertension pattern and central obesity affected by PM2.5 exposure / 环境与职业医学

Background There is a lack of evidence on whether exposure to PM2.5 and its constituents would affect the relationship between the dietary approaches to stop hypertension (DASH) and central obesity. Objective To investigate the effect of exposure to PM2.5 and its constituents on the correlation between the DASH dietary pattern and the prevalence of central obesity. Methods The data were obtained from the baseline survey of the "Xinjiang Multi-Ethnic Natural Population Cohort Construction and Health Follow-Up Study" in Urumqi. A DASH score was calculated according to intake frequency of 8 food groups, and summed from intake frequency of recommended food groups scored from 1 to 5 from low to high, and intake frequency of restricted food groups scored from 1 to 5 from high to low. A higher DASH score indicates better compliance with the DASH dietary pattern. We estimated exposure using satellite-derived PM2.5 and a chemical transport model (GEOS-Chem) for its constituents, including organic carbon (OC), black carbon (BC), sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), and soil dust. Central obesity was defined by waist circumference: ≥90 cm for men or ≥85 cm for women according to Criteria of weight for adults (WS/T 428—2013). A logistic regression model was used to analyze the effects of the DASH dietary pattern as well as PM2.5 and its constituents on central obesity, and a stratified analysis was used to explore the effects of PM2.5 and its constituents on the association between the DASH dietary pattern and central obesity. Results The study included 9 565 urban residents, aged (62.30±9.42) years, with a central obesity prevalence rate of 60.75%. After adjusting for selected confounders, the DASH score Q5 group had a 17.5% lower risk of central obesity than the Q1 group (OR=0.825, 95%CI: 0.720-0.947). PM2.5 and its constituents OC, BC, SO42−, NH4+, and soil dust were positively associated with the prevalence of central obesity, but no association was observed between constituent NO3− exposure and central obesity. The stratified analysis revealed that the prevalence of central obesity was reduced in the DASH score Q5 group in participants exposed to low concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust, while the protective effect of the DASH pattern on central obesity disappeared in subjects exposed to high concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust. Conclusion Exposure to PM2.5 and its constituents NO3−, NH4+, and soil dust could attenuate the protective effect of the DASH pattern on central obesity.

Exploring the effects of artesunate and fuzheng huayu decoction on mitochondria in the treatment of schistosomiasis liver fibrosis / 中华肝脏病杂志

Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.

A preliminary study on the logical data and knowledge map of the ancient book Nv Ke Xin Fa based on knowledge element indexing / 国际中医中药杂志

Objective:Using the information technology of knowledge element theory to analyze the content of the ancient Chinese medicine book Nv Ke Xin Fa, and to explore the original thinking and implicit knowledge of the author of the book Nv Ke Xin Fa. Methods:Based on the theory and technology of knowledge element, the indexing data was read as logical data by using MS SQL Server database and then the knowledge graph of traditional Chinese medicine was constructed by using neo4j database.Results:There are 345 knowledge bodies and 1 478 knowledge elements in the Nv Ke Xin Fa, mainly including prescription name (280), composition (275) and usage (224); There are 711 semantic types, mainly including prescriptions (232), etiology and pathogenesis (221), syndrome manifestations (125) and treatment (88); 187 semantic associations, mainly syndrome differentiation and treatment (172); Knowledge of semantic association.There are 34 body types, with leucorrhea (16), amenorrhea (13), blood Avalanche (13) and asthenia (13). Conclusions:Zheng Qinyu paid attention to distinguishing the texture of leucorrhea in the treatment of leucorrhea, put forward the pathogenesis and treatment principles and methods of leucorrhea in the stages of "before childbirth" and "after childbirth", and made it clear that the application scope of Buzhong Yiqi Decoction involves menstruation, leucorrhea, pregnancy and the whole cycle of childbirth.Mrs Zheng Qinyu pays great attention to the protection on the spleen and stomach of the middle coke and regulation of Qi that could rise and fall, which could provide a reference for modern clinical diagnosis and treatment of leukorrhagia diseases.

Quality Evaluation of Aurantii Fructus Based on Fingerprint Qualitative Analysis， Multi-component Quantitative Analysis and Chemometrics / 中国实验方剂学杂志

ObjectiveTo establish an integrated method of fingerprint qualitative， multi-component quantitative analysis and chemometrics， and to evaluate the quality attributes and differences of Aurantii Fructus from different production areas and origins. MethodAnalysis was performed on COSMOSIL 5C18-MS-Ⅱ column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile-0.2% phosphoric acid solution for gradient elution （0-4 min， 19%A； 4-5 min， 19%-21%A； 5-18 min， 21%A； 18-19 min， 21%-28%A； 19-27 min， 28%A； 27-28 min， 28%-40%A； 28-36 min， 40%A； 36-37 min， 40%-50%A； 37-42 min， 50%-60%A； 42-46 min， 60%-95%A； 46-55 min， 95%-100%A）， the flow rate was 1 mL·min-1， the column temperature was 30 ℃， the detection wavelength was set at 320 nm， and the injection volume was 10 μL. High performance liquid chromatography （HPLC） fingerprints of Aurantii Fructus from different production areas and origins were established. Then， the quality of 26 batches of samples was evaluated by cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA）. A method for the determination of 12 components was developed and verified， and a thermal map-based CA of Aurantii Fructus from different production areas and origins was carried out based on the content difference of samples. ResultThe fingerprint and determination methods were well verified. The similarity of HPLC fingerprint of 12 batches of Aurantii Fructus was 0.85-0.996， 20 common peaks were calibrated and 14 of them were assigned. The resolution and linear relationship of 12 components in quantitative analysis were good. The recovery rates were 99.2%-101.0% with RSD≤2.0%. The results of CA， PCA and OPLS-DA indicated that the differentiation of Aurantii Fructus in different production areas was great， and there were differences among different cultivars. ConclusionThe qualitative analysis of fingerprint and quantitative analysis of multiple indexes based on the same chromatographic analysis conditions are convenient， accurate and reliable， and combined with chemometrics， the identification and quality analysis of Aurantii Fructus from different production areas and origins can be realized， which can provide reference for quality control and evaluation of Aurantii Fructus.

Identification and expression analysis of WRKY gene family in eukaryotic algae / 生物工程学报

WRKY is a superfamily of plant-specific transcription factors, playing a critical regulatory role in multiple biological processes such as plant growth and development, metabolism, and responses to biotic and abiotic stresses. Although WRKY genes have been characterized in a variety of higher plants, little is known about them in eukaryotic algae, which are close to higher plants in evolution. To fully characterize algal WRKY family members, we carried out multiple sequence alignment, phylogenetic analysis, and conserved domain prediction to identify the WRKY genes in the genomes of 30 algal species. A total of 24 WRKY members were identified in Chlorophyta, whereas no WRKY member was detected in Rhodophyta, Glaucophyta, or Bacillariophyta. The 24 WRKY members were classified into Ⅰ, Ⅱa, Ⅱb and R groups, with a conserved heptapeptide domain WRKYGQ(E/A/H/N)K and a zinc finger motif C-X4-5-C-X22-23-H-X-H. Haematococcus pluvialis, a high producer of natural astaxanthin, contained two WRKY members (HaeWRKY-1 and HaeWRKY-2). Furthermore, the coding sequences of HaeWRKY-1 and HaeWRKY-2 genes were cloned and then inserted into prokaryotic expression vector. The recombinant vectors were induced to express in Escherichia coli BL21(DE3) cells and the fusion proteins were purified by Ni-NTA affinity chromatography. HaeWRKY-1 had significantly higher expression level than HaeWRKY-2 in H. pluvialis cultured under normal conditions. High light stress significantly up-regulated the expression of HaeWRKY-1 while down-regulated that of HaeWRKY-2. The promoters of HaeWRKY genes contained multiple cis-elements responsive to light, ethylene, ABA, and stresses. Particularly, the promoter of HaeWRKY-2 contained no W-box specific for WRKY binding. However, the W-box was detected in the promoters of HaeWRKY-1 and the key enzyme genes HaeBKT (β-carotene ketolase) and HaePSY (phytoene synthase) responsible for astaxanthin biosynthesis. Considering these findings and the research progress in the related fields, we hypothesized that the low expression of HaeWRKY-2 under high light stress may lead to the up-regulation of HaeWRKY-1 expression. HaeWRKY-1 may then up-regulate the expression of the key genes (HaeBKT, HaePSY, etc.) for astaxanthin biosynthesis, consequently promoting astaxanthin enrichment in algal cells. The findings provide new insights into further analysis of the regulatory mechanism of astaxanthin biosynthesis and high light stress response of H. pluvialis.

Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Impact of the medical burden under chronic disease management for the elderly based on the "combination of medical care and pension" model: a preliminary study / 中华医学教育探索杂志

Objective:To study whether the "combination of medical care and pension" service model can effectively control the development of chronic disease in the elderly and reduce the direct economic burden caused by the disease.Methods:A total of 180 elderly participants who received the "combination of medical care and pension" service model for chronic disease management in Chongqing, China were investigated and analyzed statistically. Epidata 2.0 was used for data entry, SPSS 20.0 was used for data analysis, and paired sample t test was used for comparison between groups. Results:After 12 months of chronic disease management, hospitalization events and expenses of the elderly were reduced, among which the number of hospitalization was reduced by 0.24 timed on average, the length of hospitalization was reduced by 10.41 days on average, and the hospitalization expenses were reduced by 11 144 yuan on average. The direct economic burden due to chronic diseases was reduced by approximately 8 844.5 yuan, accounting for 33.8% of the average cost of hospitalization for the elderly without the application of the model.Conclusion:The chronic disease of the elderly is well controlled by chronic disease management through the "combination of medical care and pension" service model.

Analysis of the social and clinical factors affecting the age of children when receiving surgery for hypospadias: a retrospective study of 1611 cases in a single center / 亚洲男科学杂志(英文版)

We aimed to explore the associations between the age at which children undergo surgery for hypospadias and a range of social and clinical factors in a single center. Our aim was to promote the early surgical treatment of children with hypospadias. For a 6-year period, social and clinical data were collected from all children undergoing surgery to repair hypospadias in Children's Hospital of Chongqing Medical University (Chongqing, China), located in southwest of China. We analyzed the correlations between age at surgery and a range of social and clinical factors. A total of 1611 eligible cases were recruited, with a mean age of 54.3 months and a median age of 42 months: 234 cases (14.5%) were classified into a "timely operation" group, 419 (26.0%) cases into a "subtimely operation" group, and 958 (59.5%) cases into a "delayed operation" group. According to multivariate regression analyses, the higher the regional economic level, the closer the urethral opening to the perineum, and the higher the educational level of the guardians was, the younger the children were when they underwent the initial surgery for hypospadias; this was also the case for families without other children. Our subgroup analysis showed that the primary educational level of the guardians was a risk factor for subtimely surgery in their children (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.08-2.15, P < 0.05). A lower regional economic level (OR = 1.87, 95% CI: 1.26-2.78, P < 0.01), a lower educational level of the guardians (OR = 3.84, 95% CI: 2.31-6.41, P < 0.01), and an anterior-segment urethral opening (OR

Protective effects of Lonicerae Japonicae Flos against acute alcoholic liver injury in rats based on network pharmacology / 中国中药杂志

This study aims to explore underlying mechanism of Lonicerae Japonicae Flos(LJF) in protecting rats against acute alcoholic liver injury(ALI) based on mitogen-activated protein kinase(MAPK) pathway. First, the targets of LJF in preventing ALI were predicted by network pharmacology and the component-target-pathway network was constructed, so that the key targets of LJF components acting on MAPK pathway were screened. Second, male SD rats were randomized into the control(KB) group, model(MX) group, positive(YX) group, and LJF high-(GJ), medium-(ZJ), and low-(DJ) dose groups. Each administration group was given(ig) corresponding drugs for 7 days and KB group and MX group received(ig) equal volume of distilled water every day. Except for KB group, rats were given Chinese spirit(56%, 3 days) for ALI modeling. The levels of aspartate transaminase(AST), alanine transaminase(ALT), interleukin-6(IL6) and tumor necrosis factor-α(TNF-α) in serum and malondialdehyde(MDA), glutathione(GSH), superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in liver tissue of rats in each group were detected. Furthermore, we employed quantitative real-time PCR(qRT-PCR) to probe the effects of LJF on the key targets of MAPK pathway in ALI rats. A total of 28 active components of LJF were screened from TCMSP database, and 317 intersected with ALI-related targets. According to Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, the 317 targets involved 226 pathways, which were mainly liver disease, inflammation, immunity, apoptosis and other related pathways. According to the MAPK pathway-target-active component network, the key active components of LJF, such as chlorogenic acid, hederagenol, and hyperoside, acted on 25 key targets of MAPK pathway. The results of in vivo experiments showed decreased levels of AST, ALT, and MDA in DJ, ZJ, and GJ groups(P<0.01 or P<0.05), reduced levels of IL6 in DJ and GJ groups(P<0.01 or P<0.05), and improved levels of SOD and GSH in ZJ and GJ groups(P<0.01 or P<0.05). The results of qRT-PCR demonstrated that the expression levels of mitogen-activated protein kinase kinase 4(MAPK2 K4) and mitogen-activated protein kinase 3(MAPK3) were decreased in DJ, ZJ, and GJ groups(P<0.01). The network pharmacology and experimental verification showed that the active components in LJF can reduce the inflammatory factor level and enhance the activities of SOD and GSH-Px by inhibiting the expression of key targets of MAPK pathway, thus alleviating and preventing liver damage caused by alcohol.

Use of transnasal ileus catheter in elderly patients with mechanical intestinal obstruction / 中华普通外科杂志

Objective:To evaluate the treatment efficiency using transnasal ileus catheter in elderly patients with mechanical small intestinal obstruction.Method:Ninety geriatric patients with mechanical small intestinal obstruction admitted to Xuanwu Hospital of Capital Medical University from Jan 2018 to Dec 2019 were divided into intestinal obstruction catheter group with transnasal ileus catheter insertion ( n=40) and nasogastric tube group ( n=50). Results:The transnasal ileus catheter retained for (91.0±33.5) h significantly shorter than that in nasogastric tube group ((149.3±82.3) h, t=3.323, P=0.002). Compared to nasogastric tube group, the exhaust time, defecation time, feeding time, time to gas-liquid level disappearance and time to contrast agent appearance in the colon in intestinal obstruction catheter group were significantly shorter [(55.9±40.9) h vs. (127.6±59.1) h, t=5.149; (69.8±42.3) h vs. (134.9±48.4) h, t=5.371; (104.3±35.1) h vs. (178.3±79.8) h, t=4.297; (106.2±36.6) h vs. (175.8±79.1) h, t=4.050 and (101.4±37.3) h vs.(172.4±72.9) h, t=4.407, all P<0.05]. In addition, the length of hospital stay was shorter and in hospital expenses were lower [(8.1±3.8) d vs. (11.6±6.7) d, t=2.248; (8 236±5 451)￥ vs. (15 320±9 582)￥, t=3.293, all P<0.05]. Conclusion:The use of transnasal ileus catheter was safe and effective to relieve the symptoms of mechanical small intestinal obstruction, hence improving the success rate of conservative treatment.

Target gene panel method versus whole-exome sequencing in detection of idiopathic hypogonadotropic hypogonadism in males / 中华男科学杂志

Objective@#To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method.@*METHODS@#We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method.@*RESULTS@#Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%.@*CONCLUSIONS@#For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.

Application of individualized setting of femoral opening point and valgus angle in artificial total knee arthroplasty for patients with external femoral arch / 中国骨伤

OBJECTIVE@#To investigate whether shifting the femoral opening point and setting a personalized femoral valgus angle can improve the lower limb force line of total knee arthroplasty (TKA) patients with external femoral arch.@*METHODS@#From March 2016 to October 2018, 50 patients (55 knees) with osteoarthritis with genu varus deformity combined with external femoral arch for TKA were selected. There were 10 males and 40 females. The age ranged from 63.1 to 80.5 years old, with an average of (67.8±5.8) years old. Forty-five cases were unilateral and 5 cases were bilateral. The osteoarthritis stages of 55 knees were Kellgren-Lawrence grade Ⅲ to Ⅳ; and the course of disease ranged from 2 to 10 years. PreoperativeSpecial Surgery (Hospital for Special Surgery) scores:pain was 15.20±3.52; function was 8.30±2.96;mobility was 10.15±2.85;muscle strength was 4.20±1.95;flexion deformity was 5.50±3.05;stability was 6.15±2.20; total score was 47.93±3.39. The external femoral arch angle ranged from 6.4° to 16.7°, with a mean of (10.63±2.29) °. The tibiofemoral angle ranged from 7.4° to 12.6°, with a mean of (12.04±3.59)°. The anatomical distal femoral angle ranged from 83.10° to 91.20°, with a mean of (84.55± 1.66)°. And the distance from the center of the knee joint to the lower limb line of force ranged from 2.01 to 6.00 cm, with a mean of (3.57±1.12) cm. During the replacement surgery, the femoral opening point and the valgus angle were individually set to obtain a good line of force of the lower limbs.@*RESULTS@#Before the operation, the distance of femoral opening point ranged from 0.24 to 0.74 cm, with a mean of (0.54±0.10) cm. The distance between the internal and external condyles of the femur ranged from 6.86 to 8.12 cm, with a mean of (7.27±0.27) cm. The preoperative valgus correction angle (VCA) ranged from 7.20° to 13.80°, with a mean of (9.38±1.38) °. The post-correction valgus correction angle' (VCA') ranged from 6.10° to 9.50°, with a mean of (7.36±0.82) °. All patients were followed up, and the duration ranged from 3 to 36 months, with an average of (13.5±5.8) months. All patients obtained good knee function after operation. Three months after operation, HSS scores included pain of 25.30±3.05, function of 18.25±2.05, mobility of 16.05±0.75, muscle strength of 6.20±2.10, flexion deformity of 8.80±1.85, stability of 8.20±1.75; and the total score ranged from 90.00 to 93.00, with an average of 91.82±0.98. The total score was higher than that before operation (@*CONCLUSION@#In TKA combined with external femoral arch, good lower limb force line and knee joint function can be obtained by externally shifting the femoral opening point and setting a personalized femoral valgus angle.

Expert consensus on rehabilitation strategies for traumatic spinal cord injury / 中华创伤杂志

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.