Wnt5a-mediated autophagy contributes to the epithelial-mesenchymal transition of human bronchial epithelial cells during asthma.

BACKGROUND: The epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBECs) is essential for airway remodeling during asthma. Wnt5a has been implicated in various lung diseases, while its role in the EMT of HBECs during asthma is yet to be determined. This study sought to define whether Wnt5a initiated EMT, leading to airway remodeling through the induction of autophagy in HBECs. METHODS: Microarray analysis was used to investigate the expression change of WNT5A in asthma patients. In parallel, EMT models were induced using 16HBE cells by exposing them to house dust mites (HDM) or interleukin-4 (IL-4), and then the expression of Wnt5a was observed. Using in vitro gain- and loss-of-function approaches via Wnt5a mimic peptide FOXY5 and Wnt5a inhibitor BOX5, the alterations in the expression of the epithelial marker E-cadherin and the mesenchymal marker protein were observed. Mechanistically, the Ca2+/CaMKII signaling pathway and autophagy were evaluated. An autophagy inhibitor 3-MA was used to examine Wnt5a in the regulation of autophagy during EMT. Furthermore, we used a CaMKII inhibitor KN-93 to determine whether Wnt5a induced autophagy overactivation and EMT via the Ca2+/CaMKII signaling pathway. RESULTS: Asthma patients exhibited a significant increase in the gene expression of WNT5A compared to the healthy control. Upon HDM and IL-4 treatments, we observed that Wnt5a gene and protein expression levels were significantly increased in 16HBE cells. Interestingly, Wnt5a mimic peptide FOXY5 significantly inhibited E-cadherin and upregulated α-SMA, Collagen I, and autophagy marker proteins (Beclin1 and LC3-II). Rhodamine-phalloidin staining showed that FOXY5 resulted in a rearrangement of the cytoskeleton and an increase in the quantity of stress fibers in 16HBE cells. Importantly, blocking Wnt5a with BOX5 significantly inhibited autophagy and EMT induced by IL-4 in 16HBE cells. Mechanistically, autophagy inhibitor 3-MA and CaMKII inhibitor KN-93 reduced the EMT of 16HBE cells caused by FOXY5, as well as the increase in stress fibers, cell adhesion, and autophagy. CONCLUSION: This study illustrates a new link in the Wnt5a-Ca2+/CaMKII-autophagy axis to triggering airway remodeling. Our findings may provide novel strategies for the treatment of EMT-related diseases.

mtDNA-cGAS-STING axis-dependent NLRP3 inflammasome activation contributes to postoperative cognitive dysfunction induced by sevoflurane in mice.

The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane. However, the molecular mechanism by which sevoflurane activates the NLRP3 inflammasome in microglia remains unclear. The cGAS-STING pathway is an evolutionarily conserved inflammatory defense mechanism. The role of the cGAS-STING pathway in sevoflurane-induced NLRP3 inflammasome-dependent neuroinflammation and the underlying mechanisms require further investigation. We found that prolonged anesthesia with sevoflurane induced cognitive dysfunction and triggered the neuroinflammation characterized by the activation of NLRP3 inflammasome in vivo. Interestingly, the cGAS-STING pathway was activated in the hippocampus of mice receiving sevoflurane. While the blockade of cGAS with RU.521 attenuated cognitive dysfunction and NLRP3 inflammasome activation in mice. In vitro, we found that sevoflurane treatment significantly activated the cGAS-STING pathway in microglia, while RU.521 pre-treatment robustly inhibited sevoflurane-induced NLRP3 inflammasome activation. Mechanistically, sevoflurane-induced mitochondrial fission in microglia and released mitochondrial DNA (mtDNA) into the cytoplasm, which could be abolished with Mdivi-1. Blocking the mtDNA release via the mPTP-VDAC channel inhibitor attenuated sevoflurane-induced mtDNA cytosolic escape and reduced cGAS-STING pathway activation in microglia, finally inhibiting the NLRP3 inflammasome activation. Therefore, regulating neuroinflammation by targeting the cGAS-STING pathway may provide a novel therapeutic target for POCD.

Epoxyeicosatrienoic acids alleviate alveolar epithelial cell senescence by inhibiting mitophagy through NOX4/Nrf2 pathway.

Alveolar epithelial cell (AEC) senescence is considered to be a universal pathological feature of many chronic pulmonary diseases. Our previous study found that epoxyeicosatrienoic acids (EETs), produced from arachidonic acid (ARA) through the cytochrome P450 cyclooxygenase (CYP) pathway, have significant negative regulatory effects on cellular senescence in AECs. However, the exact mechanisms by which EETs alleviate the senescence of AECs still need to be further explored. In the present study, we observed that bleomycin (BLM) induced enhanced mitophagy accompanied by increased mitochondrial ROS (mito-ROS) content in the murine alveolar epithelial cell line MLE12. While EETs reduced BLM-induced mitophagy and mito-ROS content in MLE12 cells, and the mechanism was related to the regulation of NOX4/Nrf2-mediated redox imbalance. Furthermore, we found that inhibition of EETs degradation could significantly inhibit mitophagy and regulate NOX4/Nrf2 balance to exert anti-oxidant effects in D-galactose-induced premature aging mice. Collectively, these findings may provide new ideas for treating age-related pulmonary diseases by targeting EETs to improve mitochondrial dysfunction and reduce oxidative stress.

TREM-1 triggers necroptosis of macrophages through mTOR-dependent mitochondrial fission during acute lung injury.

BACKGROUND: Necroptosis of macrophages is a necessary element in reinforcing intrapulmonary inflammation during acute lung injury (ALI). However, the molecular mechanism that sparks macrophage necroptosis is still unclear. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor expressed broadly on monocytes/macrophages. The influence of TREM-1 on the destiny of macrophages in ALI requires further investigation. METHODS: TREM-1 decoy receptor LR12 was used to evaluate whether the TREM-1 activation induced necroptosis of macrophages in lipopolysaccharide (LPS)-induced ALI in mice. Then we used an agonist anti-TREM-1 Ab (Mab1187) to activate TREM-1 in vitro. Macrophages were treated with GSK872 (a RIPK3 inhibitor), Mdivi-1 (a DRP1 inhibitor), or Rapamycin (an mTOR inhibitor) to investigate whether TREM-1 could induce necroptosis in macrophages, and the mechanism of this process. RESULTS: We first observed that the blockade of TREM-1 attenuated alveolar macrophage (AlvMs) necroptosis in mice with LPS-induced ALI. In vitro, TREM-1 activation induced necroptosis of macrophages. mTOR has been previously linked to macrophage polarization and migration. We discovered that mTOR had a previously unrecognized function in modulating TREM-1-mediated mitochondrial fission, mitophagy, and necroptosis. Moreover, TREM-1 activation promoted DRP1Ser616 phosphorylation through mTOR signaling, which in turn caused surplus mitochondrial fission-mediated necroptosis of macrophages, consequently exacerbating ALI. CONCLUSION: In this study, we reported that TREM-1 acted as a necroptotic stimulus of AlvMs, fueling inflammation and aggravating ALI. We also provided compelling evidence suggesting that mTOR-dependent mitochondrial fission is the underpinning of TREM-1-triggered necroptosis and inflammation. Therefore, regulation of necroptosis by targeting TREM-1 may provide a new therapeutic target for ALI in the future.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature / 生物医学与环境科学（英文）

OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology / 中国中药杂志

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Changes in retinal nerve fiber layer and macular retinal thickness and predictive value of outcome in children with abnormal refractive amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes in retinal nerve fiber layer(RNFL)and macular retinal thickness(MRT)in children with refractive abnormalities and amblyopia, and their predictive value of outcome.METHODS: A total of 168 children with myopic refractive abnormalities and monocular amblyopia admitted to our hospital from January 2020 to October 2022 were selected as the observation group, with 118 cases of mild to moderate amblyopia and 50 cases of severe amblyopia, and 168 children with normal vision were included as the control group in a 1:1 ratio during the same period. The changes of RNFL and MRT in two groups of children were statistically counted, and the correlation between the severity of refractive abnormalities and RNFL and MRT in children with amblyopia was analyzed. Additionally, the observation group was divided into effective subgroup and ineffective subgroup based on the therapeutic effect. The general information, as well as RNFL and MRT of the effective subgroup and the ineffective subgroups before and after treatment were compared. Logistic was used to analyze the factors influencing efficacy, and ROC curves was plotted to analyze the predictive value of RNFL and MRT alone or in combination for efficacy.RESULTS: RNFL and MRT of cases of severe amblyopia were higher than those of the mild to moderate amblyopia and the control groups(all P<0.05); the severity of amblyopia in children with refractive abnormalities is positively correlated with RNFL and MRT(rs=0.745 and0.724, both P<0.001); among patients of mild to moderate and severe, there were statistically significant differences between the effective and ineffective subgroups in terms of initial treatment age, fixation form, treatment compliance, as well as RNFL, MRT, and their differences before and 1mo postoperatively(all P<0.05). Logistic analysis showed that initial treatment age, fixation nature, treatment compliance, RNFL and MRT before and 1mo postoperatively were all factors influencing the therapeutic effect of amblyopia with refractive abnormalities in children(all P<0.05); after 1mo of treatment, the combined prediction of RNFL and MRT was significantly better than that of single prediction in children with mild to severe amblyopia.CONCLUSION:There are differences in RNFL and MRT in children with abnormal refractive amblyopia, and they are closely related to the different degrees and curative effects of children. The combination of RNFL and MRT after 1mo of treatment has certain value in predicting children with different degrees of abnormal refractive amblyopia.

Efficacy of traditional Chinese medicine combined with anti-vascular endothelial growth factor in the treatment of wet age-related macular degeneration: A systematic review and network Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical efficacy of traditional Chinese medicine(TCM)combined with intravitreal injection of anti-vascular endothelial growth factor(VEGF)or anti-VEGF medicines alone in the treatment of wet age-related macular degeneration(wAMD).METHODS:A total of eight databases were searched for relevant literatures in English and Chinese, including Chinese National Knowledge Infrastructure(CNKI), Wanfang, CQVIP, SinoMed, PubMed, Web of Science, Cochrane Library, Embase. Taking patients with wAMD as research objects, the Chinese and English clinical randomized controlled trials(RCTs)published from the databases' inception to April 20, 2022, which compared TCM combined with anti-VEGF drugs with anti-VEGF drugs alone were selected. The outcome indicators were best corrected visual acuity(BCVA)and central macular thickness(CMT). Traditional Meta and network Meta analysis were used to examine the data.RESULTS:There were 39 eligible studies among the 617 retrieved articles, involving 28 oral administration of Chinese herbal medicines and 2 757 participants. For BCVA improvement, results of TCM combination therapy were more favorable than anti-VEGF alone(MD=0.07, 95%CI: 0.05～0.09). Sheng Puhuang Decoction(SPD)ranked highest in 1 and 2mo after treatment, and Xuefu Zhuyu Capsule(XZC)ranked highest in 3mo after treatment. In terms of reducing CMT, TCM combination therapy were better(MD=-25.32 μm, 95%CI: -30.06～-20.57). Danggui Mingmu Decoction(DMD)ranked the highest in 1mo after treatment. Bushen Huoxue Decoction(BHD)ranked the highest in 2mo. Erchen Erhuang Decoction(EED)ranked the highest in 3mo.CONCLUSIONS: Compared with anti-VEGF treatment alone, TCM combination therapy led to improved BCVA and reduced CMT. However, most of the included literature is small-sample, single-center, single-blind RCTs with an overall low quality.

Bioinformatics and Computer Simulation Approaches to the Discovery and Analysis of Bioactive Peptides.

The traditional process of separating and purifying bioactive peptides is laborious and time-consuming. Using a traditional process to identify is difficult, and there is a lack of fast and accurate activity evaluation methods. How to extract bioactive peptides quickly and efficiently is still the focus of bioactive peptides research. In order to improve the present situation of the research, bioinformatics techniques and peptidome methods are widely used in this field. At the same time, bioactive peptides have their own specific pharmacokinetic characteristics, so computer simulation methods have incomparable advantages in studying the pharmacokinetics and pharmacokineticpharmacodynamic correlation models of bioactive peptides. The purpose of this review is to summarize the combined applications of bioinformatics and computer simulation methods in the study of bioactive peptides, concentrating on the role of bioinformatics in simulating the selection of enzymatic hydrolysis and precursor proteins, activity prediction, molecular docking, physicochemical properties, and molecular dynamics. Our review shows that new bioactive peptide molecular sequences with high activity can be obtained by computer-aided design. The significance of the pharmacokinetic-pharmacodynamic correlation model in the study of bioactive peptides is emphasized. Finally, some problems and future development potential of bioactive peptides binding new technologies are being prospected.

Sacubitril/valsartan attenuates left ventricular remodeling and improve cardiac function by upregulating apelin/APJ pathway in rats with heart failure / 中华心血管病杂志

Objective: To investigate the effect and mechanism of sacubitril/valsartan on left ventricular remodeling and cardiac function in rats with heart failure. Methods: A total of 46 SPF-grade male Wistar rats weighed 300-350 g were acclimatized to the laboratory for 7 days. Rats were then divided into 4 groups: the heart failure group (n=12, intraperitoneal injection of adriamycin hydrochloride 2.5 mg/kg once a week for 6 consecutive weeks, establishing a model of heart failure); heart failure+sacubitril/valsartan group (treatment group, n=12, intragastric administration with sacubitril/valsartan 1 week before the first injection of adriamycin, at a dose of 60 mg·kg-1·d-1 for 7 weeks); heart failure+sacubitril/valsartan+APJ antagonist F13A group (F13A group, n=12, adriamycin and sacubitril/valsartan, intraperitoneal injection of 100 μg·kg-1·d-1 APJ antagonist F13A for 7 weeks) and control group (n=10, intraperitoneal injection of equal volume of normal saline). One week after the last injection of adriamycin or saline, transthoracic echocardiography was performed to detect the cardiac structure and function, and then the rats were executed, blood and left ventricular specimens were obtained for further analysis. Hematoxylin-eosin staining and Masson trichrome staining were performed to analyze the left ventricular pathological change and myocardial fibrosis. TUNEL staining was performed to detect cardiomyocyte apoptosis. mRNA expression of left ventricular myocardial apelin and APJ was detected by RT-qRCR. ELISA was performed to detect plasma apelin-12 concentration. The protein expression of left ventricular myocardial apelin and APJ was detected by Western blot. Results: Seven rats survived in the heart failure group, 10 in the treatment group, and 8 in the F13A group. Echocardiography showed that the left ventricular end-diastolic diameter (LVEDD) and the left ventricular end-systolic diameter (LVESD) were higher (both P<0.05), while the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the heart failure group than in the control group (both P<0.05). Compared with the heart failure group, rats in the treatment group were featured with lower LVEDD and LVESD (both P<0.05), higher LVEF and LVFS (both P<0.05), these beneficial effects were reversed in rats assigned to F13A group (all P<0.05 vs. treatment group). The results of HE staining showed that the cardiomyocytes of rats in the control group were arranged neatly and densely structured, the cardiomyocytes in the heart failure group were arranged in disorder, distorted and the gap between cells was increased, the cardiomyocytes in the treatment group were slightly neat and dense, and cardiomyocytes in the F13A group were featured similarly as the heart failure group. Masson staining showed that there were small amount of collagen fibers in the left ventricular myocardial interstitium of the control group, while left ventricular myocardial fibrosis was significantly increased, and collagen volume fraction (CVF) was significantly higher in the heart failure group than that of the control group (P<0.05). Compared with the heart failure group, the left ventricular myocardial fibrosis and the CVF were reduced in the treatment group (both P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). TUNEL staining showed that the apoptosis index (AI) of cardiomyocytes in rats was higher in the heart failure group compared with the control group (P<0.05), which was reduced in the treatment group (P<0.05 vs. heart failure group), this effect again was reversed in the F13A group (P<0.05 vs. treatment group). The results of RT-qPCR and Western blot showed that the mRNA and protein levels of apelin and APJ in left ventricular myocardial tissue of rats were downregulated in heart failure group (all P<0.05) compared with the control group. Compared with the heart failure group, the mRNA and protein levels of apelin and APJ were upregulated in the treatment group (all P<0.05), these effects were reversed in the F13A group (all P<0.05 vs. treatment group). ELISA test showed that the plasma apelin concentration of rats was lower in the heart failure group compared with the control group (P<0.05); compared with the heart failure group, the plasma apelin concentration of rats was higher in the treatment group (P<0.05), this effect was reversed in the F13A group (P<0.05 vs. treatment group). Conclusion: Sacubitril/valsartan can partially reverse left ventricular remodeling and improve cardiac function in rats with heart failure through modulating Apelin/APJ pathways.

Enriched rehabilitation improves dual-task gait disorder after a transient ischemic attack / 中华物理医学与康复杂志

Objective:To observe the effect of enriched rehabilitation on dual-task gait disorder after a transient ischemic attack (TIA) and explore its mechanism.Methods:Sixty TIA patients were randomly divided into a control group and an observation group, each of 30. Another 30 healthy counterparts were selected to form a healthy control group. All of the TIA patients were given routine medication to lower blood pressure and improve brain function, while the observation group was additionally provided with enriched rehabilitation training for 12 weeks. Before and after the intervention, the gait and cognitive functioning of all of the subjects were quantified and their event-related potentials (P300s) and serum brain-derived neurotrophic factor (BDNF) levels were also measured.Results:Before the treatment there were significant differences between the TIA groups and healthy controls in all of the measurements, but there were no significant differences between the control and observation groups. After the treatment, no significant improvement was observed in any of the control group′s results, but there was significant improvement in the observation group′s gait parameters, cognitive functioning, average serum BDNF concentration and in the average latency and amplitude of its P300 signals.Conclusions:Enriched rehabilitation can improve the gait of TIA patients, perhaps through increasing their serum BDNF concentration and improving their cognition.

Application of programmed nursing in cardiopulmonary bypass cardiac surgery / 中国实用护理杂志

Objective:Study the application of programmed nursing in the cooperation of cardiopulmonary bypass surgery.Methods:From January 2018 to December 2018, 111 consecutive patients undergoing elective cardiopulmonary bypass cardiac surgery in Dalian Municipal Central Hospital were selected as the research objects. According to the random number table method, they were divided into two groups. 54 cases in the control group and 57 cases in the study group.The control group adopted the routine intraoperative care model, and the observation group was adopted the nursing of cardiac surgery under programmed cardiopulmonary bypass. The mechanical ventilation time, operation time, hospitalization time, incidence of adverse events of intraoperative nursing and complications were compared between the two groups.Results:The operation time, mechanical ventilation time and hospitalization time in the study group were (152.89 ± 18.10) min, (8.30 ± 2.27) h and (11.75 ± 2.54) d respectively, which were less than those in the control group (182.04 ± 18.39) min, (11.72 ± 2.93) h and (14.26 ± 2.97) d, and the difference was statistically significant ( t=8.41, 6.91, 4.78, all P<0.05). There were 8 cases of intraoperative nursing adverse events in the control group and no intraoperative adverse events in the study group, the difference was statistically significant ( χ2=9.03, P<0.01). All patients had no two or more complications at the same time. There were 3 cases (5.26%) of postoperative complications in the study group, lower than 14 cases (25.92%) in the control group, the difference was statistically significant ( χ2=9.03, P<0.05). Conclusions:In cardiopulmonary bypass surgery, programmed nursing can effectively reduce the operation time and hospitalization time, reduce the incidence of adverse events and postoperative complications, improve the efficiency of the operation.

Research on the current situation and development direction of male nurses in Dalian / 中国实用护理杂志

Objective:To understand the current situation of male nurses in Dalian area and explore its future development direction.Methods:From August to September in 2020, 189 male nurses who had been engaged in clinical nursing for more than one year in 29 hospitals in Dalian were selected by convenient sampling method, and they were investigated by questionnaire. SPSS 25.0 software was used for statistical analysis. The counting data were described by rate or constituent ratio. Logistic regression analysis was used to analyze the important factors influencing male nurses′ willingness to change profession.Results:A total of 189 male nurses were investigated, 137 of them were under 30 years old, accounting for 72.5%. They had high education background and low professional title, mainly concentrated in ICU, operation room and emergency department of public owned 3A or 3B hospitals, with a monthly income of 3 000 to 8 000 yuan. 33 nurses(17.5%) chose nursing profession because they couldn′t change careers by profession adjustment. 135 nurses (71.4%) considered that work pressure was high. 70 nurses (37.0%) had the idea of changing careers. The main influencing factors included:nursing career was not in accordance with individual interest, dislike of female boss, low income. The prominent problem in nursing career was "inconvenience in gender""the confusion of self-positioning".Conclusions:The hospital should improve the income of male nurses, reduce the work pressure, establish magnetic hospital, establish career planning for them, and expand the team of male nurses. Male nurses should take the initiative to improve their professional ability and professional title, so as to provide necessary conditions for the realization of nursing managers, educators, researchers and other professional goals.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study / 生物医学与环境科学（英文）

Objective@#The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.@*Methods@#A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.@*Results@#Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.@*Conclusions@#Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

Mechanism of Fluspirilene suppressing HCC through decreasing Akt expression / 中国药理学通报

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.

Establishment of an Iron-overloaded Mouse Model with Tuberculosis and Analysis of the Iron Metabolism Index / 中国医学科学院学报

Objective To establish a mouse model of exogenous iron overload combined with tuberculosis(TB). Methods C57BL/6N mice were divided into negative control, low-, medium-, and high-dose iron groups and received intraperitoneal injection of iron dextran at 0, 3.75, 7.50, and 15.00 mg/dose(3 times/week for 4 weeks), respectively.After 4 weeks, the organ morphology and body weight of the mice were evaluated.The content of serum iron, ferritin, transferrin, and transferrin receptor was determined by ELISA.Heart, liver, spleen, lung, kidney, and small intestine were analyzed for tissue iron content and iron deposition pathology.

A combined quality evaluation method that integrates chemical constituents, appearance traits and origins of raw Rehmanniae Radix pieces / 中国天然药物

The quality control of Chinese herbal medicine is a current challenge for the internationalization of traditional Chinese medicine. Traditional quality evaluation methods lack quantitative analysis, while modern quality evaluation methods ignore the origins and appearance traits. Therefore, an integrated quality evaluation method is urgent in need. Raw Rehmanniae Radix (RRR) is commonly used in Chinese herbal medicine. At present, much attention has been drwan towards its quality control, which however is limited by the existing quality evaluation methods. The present study was designed to establish a comprehensive and practical method for the quality evaluation and control of RRR pieces based on its chemical constituents, appearance traits and origins. Thirty-three batches of RRR pieces were collected from six provinces, while high-performance liquid chromatography (HPLC) was applied to determine the following five constituents, including catalpol, rehmannioside A, rehmannioside D, leonuride and verbascoside in RRR pieces. Their appearance traits were quantitatively observed. Furthermore, correlation analysis, principal components analysis (PCA), cluster analysis and t-test were performed to evaluate the qualities of RRR pieces. These batches of RRR pieces were divided into three categories: samples from Henan province, samples from Shandong and Shanxi provinces, and those from other provinces. Furthermore, the chemical constituents and appearance traits of RRR pieces were significantly different from diverse origins. The combined method of chemical contituents, appearance traits and origins can distinguish RRR pieces with different qualities, which provides basic reference for the quality control of Chinese herbal medicine.

Metabolic regulation in constructing microbial cell factories / 生物工程学报

The regulation of the expression of genes involved in metabolic pathways, termed as metabolic regulation, is vital to construct efficient microbial cell factories. With the continuous breakthroughs in synthetic biology, the mining and artificial design of high-quality regulatory elements have substantially improved our ability to modify and regulate cellular metabolic networks and its activities. The research on metabolic regulation has also evolved from the static regulation of single genes to the intelligent and precise dynamic regulation at the systems level. This review briefly summarizes the advances of metabolic regulation technologies in the past 30 years.

Fructose and metabolic diseases: too much to be good / 中华医学杂志(英文版)

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.

Psychological impact of coronavirus disease (2019) (COVID-19) epidemic on medical staff in different posts in China: A multicenter study.

OBJECTIVE: An outbreak of coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and poses a big challenge to medical staff and general public. The aim is to investigate psychological impact of COVID-19 epidemic on medical staff in different working posts in China, and to explore the correlation between psychological disorder and the exposure to COVID-19. METHODS: A multicenter WeChat-based online survey was conducted among medical staff in China between 26 February and 3 March 2020. Medical staff deployed to Hubei province from other provinces and medical staffs in different posts outside Hubei were selected to represent diverse exposure intensities to the threat of COVID-19. Anxiety, depression, sleep quality, stress and resilience were evaluated using scales including GAD-7, PHQ-9, PSQI, PSS-14, and CD-RISC-10. Latent class analysis was performed to identify potential staff requiring psychological support. RESULTS: A total of 274 respondents were included, who serving at 4 posts as follows, staff backing Hubei province, isolation wards outside Hubei, fever clinic and infectious disease department, and other departments outside Hubei. The total scores of anxiety, depression, sleep quality and stress were statistically different among groups, meanwhile an increasing tendency of anxiety, depression and sleep quality scores with increasing risk of exposure to COVID-19 was found (p < 0.05). Subsequent post-hoc analysis indicated that the staff backing Hubei had higher scores of anxiety, depression, sleep quality and perceived stress (adjusted p < 0.05). The combined prevalence of anxiety, depression and insomnia of staff backing Hubei reached as high as 38%. Four-class latent class analysis showed 3 categories of population (69.4%) may need psychological support. CONCLUSIONS: High prevalence of anxiety, depression and insomnia exist in medical staff related to COVID-19. The higher the probability and intensity of exposure to COVID-19 patients, the greater the risk that medical staff will suffer from mental disorders, suggesting continuous and proper psychiatric intervention are needed.