Menaquinone-4 exerts a protective effect against carbon tetrachloride-induced acute liver injury in mice by alleviating ferroptosis / 临床肝胆病杂志

ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.

HPV16 E6 regulates miR-23a expression and promotes invasion and migration of cervical cancer cells / 实用医学杂志

Objective To investigate the effects of high-risk human papillomavirus 16 E6 protein(HPV16 E6 protein)on invasion and migration of cervical cancer SiHa cells via regulating the expression of expression miR-23a.Methods Tissue samples from 100 patients with cervical cancer HPV-negative,100 HPV-positive patients,and 100 paracancerous normal tissues were collected;cervical cancer SiHa cells were divided into blank group,E6 overexpression group,negative transfection group,and E6 + miR-23a mimics group.The expression of miR-23a and HPV16 E6 mRNA were detected by qRT-PCR;MTT assay was used to detect the cell proliferation inhibition rate;flow cytometry to detect the apoptosis;Transwell chamber assay to detect cell invasion,and scratch test to detect the ability of cell migration.The expression of HPV16 E6,apoptosis related proteins(Caspase-3,Bax,Bcl-2),and migration related proteins(MMP-2,MMP-9)was detected by WB.Results The expression level of miR-23a was decreased in cervical cancer tissues,and that was lower in HPV positive cervical cancer tissues.Overexpression of E6 decreased the expression level of miR-23a,cell proliferation inhibition rate,apoptosis rate,Caspase-3 and Bax protein expression,and increased the expression of Bcl-2 protein,scratch healing rate,inva-sion cell number,MMP-2,MMP-9 protein expression(P<0.05);miR-23a mimics reversed the effects of E6 overexpression on the above indicators.Conclusion HPV16 E6 promotes the invasion and migration of cervical cancer cells,which may be related to the regulation of miR-23a expression.

Abibliometric analysis of the current state of research on project management practices in hospital management / 现代医院

Objective To explore the research dynamics and hotspots of project management in the field of hospital man-agement,and analyze the contents that still need to be improved,so as to provide references for the subsequent research,and provide hospital managers with practical experience in hospital management.Methods Based on the PubMed database,we used the citexs data analysis platform to analyze the literature and big data from January 2012 to December 2022 on the application of project management in the field of hospital management.Results The effective literature was retrieved from 4236 articles,and the analysis found thatthe annualnumberofpublicationsinthisfield hasbeenincreasing,2021 sawthe highestannualnumberof 573 articles,and the fastest growth rate was 20.36% in 2017.The country with the most publications is the United States(1 546 articles,36.5% ),the research institution with the most publications is Monash University,Australia,the journal with the most publications is BMJ Open(124 articles),and the key words with the highest frequency of occurrence in the retrieved literature are quality improvement,primary care improvement,covid-19,telemedicine.Conclusion The research in this field has been rapidly developed and is in a fast rising phase.In almost every organization and industry,the share of project management or"projectization"is increasing,and project management has become an important part of hospital management research and prac-tice.In the context of building a modern hospital management system,the application of project management to hospital manage-ment is an effective means of improving the level of fine hospital management.

A bibliometric analysis of exploring the optimization path and theoretical basis of the management sys-tem of traditional Chinese medicine nursing technology in medical institutions / 现代医院

Objective To sort out and summarize the research hotspots and trends of Chinese medicine nursing technolo-gy at the present stage.Methods We searched the research literature on TCM nursing technology included in China Knowledge,Wanfang,and Wipu build-up to November 30,2023,and used CiteSpace 6.1.R6 software to perform co-occurrence analysis of research institutions and keyword clustering,timeline,and emergence analysis.Results A total of 5 771 documents were in-cluded,with a general upward trend in the number of publications,peaking at 692 publications in 2021.5 206 documents from 673 journals were included in the research literature,of which 19 journals had ≥50 publications(35.47％).2 087 research or-ganizations were involved,of which 27 had ≥20 publications(13.24％).Involving 9 484 authors,there were a total of 8 au-thors ≥5 in the cluster,indicating the existence of stable teamwork in the cluster.The keyword co-occurrence analysis yielded the research hotspots of TCM nursing technology as TCM nursing,training,nursing management,clinical efficacy,complica-tions,and quality of life.Conclusion Based on the econometrics and visualization analysis of the literature on TCM nursing technology,we explored the research hotspots and trends in this field,and provided two theoretical paths for medical institution managers to construct and optimize the management system of TCM nursing technology:to standardize the TCM nursing technology in hospitals and establish a clinical access management system;and based on the multidimensional management method,to inno-vate the training system of TCM nursing technology.

Mechanism of bis（2-ethylhexyl） phthalate in inducing cholestasis and liver injury in mice / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of bis（2-ethylhexyl） phthalate （DEHP） in inducing cholestasis and liver injury in mice. MethodsIn the in vivo experiment， adult female ICR mice were randomly divided into control group （corn oil） and DEHP group （200 mg/kg/d）， and a model of cholestasis was established by intragastric administration for 4 weeks. After blood and liver tissue samples were collected from all mice， a biochemical analyzer was used to measure the level of total bile acid （TBA） in serum and the liver， and a microplate reader was used to measure alkaline phosphatase （ALP） and gamma-glutamyl transpeptidase （GGT）； HE staining was used to observe the pathological changes of the liver； RT-PCR was used to measure the mRNA expression levels of the inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in the liver； liquid chromatography/triple quadrupole mass spectrometry was used to measure the bile acid profile in the liver of mice. In the in vitro experiment， AML-12 mouse hepatocytes were cultured and treated with DEHP （250 µmol/L）， DCA （125 µmol/L）， and CDCA （125 µmol/L） for 24 hours， and RT-PCR was used to measure the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the LSD-t test was used for further comparison between two groups. ResultsThe in vivo experiment showed that compared with the control group， the DEHP group had significant increases in the serum levels of TBA， ALP， and GGT and the level of TBA in the liver （the t values are respectively -4.396， -5.109， -8.504， -3.792 and -7.974， all P<0.05，）. Compared with the control group， the DEHP group had significant increases in cholic acid， chenodeoxycholic acid， taurocholic acid， deoxycholic acid， and ursodeoxycholic acid （the t values are respectively -2.802， -3.177， -2.633， -2.874 and -2.311， all P<0.05）. HE staining of the liver showed that the mice in the DEHP group had enlargement of the portal area， bile duct deformation， inflammatory cell infiltration around the bile duct， and significant increases in the mRNA expression levels of the inflammatory factors IL-1β， IL-6， and TNF-α in the liver （the t values are respectively -2.539， -2.823 and -4.636， all P<0.05）. The in vitro experiment showed that the actual difference in hepatocyte viability after 0-1 000 µmol/L DEHP treatment does not exceed 15%， but there were significant increases in the mRNA expression levels of the inflammatory cytokines IL-1β， IL-6， and TNF-α after treatment with DEHP at different concentrations of 125 µmol/L， 250 µmol/L， and 500 µmol/L （all P<0.05）. Compared with DEHP stimulation alone， the combined stimulation of CDCA and DEHP upregulates the cytokine in hepatocyte IL-1β mRNA levels （P<0.01）； the combined stimulation of DCA and DEHP can significantly increase the cytokine in hepatocyte IL-1β and IL-6 mRNA levels （all P<0.01）. ConclusionDEHP exposure can cause cholestasis and induce liver inflammation in mice， possibly by promoting the production of toxic bile acids and the secretion of inflammatory factors.

Mechanistic study of tripterygium glycosides in the treatment of ulcerative colitis through the Nur77-Traf2-P62 signaling pathway / 中国现代医生

@#Objective To investigated the effect of tripterygium glycosides(TG)on dextran sodium sulfate(DSS)-induced colonic mucosal damage in ulcerative colitis(UC)mice and its regulatory mechanism.Methods Forty C57BL/6J mice were randomly divided into a normal group,a model group,and a tretinoin low,medium,and high dose group(administered at concentrations of 9.00mg/kg,27.03mg/kg,and 81.09mg/kg,respectively).The mice in the normal group were free to drink distilled water,and the rest of the mice drank 5％DSS to induce UC modeling.After modeling,mice in the model group were given 0.4ml of saline by gavage daily,and the rest of the mice in the treatment group were given the corresponding dose of TG for gavage intervention.The mass and disease activity index of the mice in each group were compared,and the pathological and histological damage of the colon was observed.Tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)levels were measured using the corresponding kits.Western blot Detection of Nur77,tumor necrosis factor receptor-associated factor 2(Traf2),nucleoporin 62(P62),autophagy protein-microtubule associated protein1 light chain 3(LC3)molecular expression.Results Compared with the blank group,the body weight,colon length,SOD,Nur77,Traf2,and LC3Ⅱ/LC3Ⅰ levels of mice in the model group were significantly decreased(P<0.05),and the DAI level,colon pathology score,TNF-α,MDA level,and P62 of the mice were significantly increased(P<0.05).Compared with mice in the UC model group,mice in the low,medium and high dose groups of tretinoin polyphenols showed significant increases in body weight,colon length,SOD,Nur77,Traf2,LC3Ⅱ/LC3Ⅰlevels(P<0.05),and mice with DAI scores,TNF-α,MDA levels in the colon,and P62 levels were significantly decreased(P<0.05).Mice in the medium and high dose groups of tretinoin polyphenols pathological scores were significantly reduced(P<0.05).Conclusion TG is able to treat ulcerative colitis through Nur77-Traf2-P62 signaling pathway.

Association between endoplasmic reticulum stress and ferroptosis in liver diseases / 临床肝胆病杂志

Research on the pathogenesis of liver diseases has attracted great attention. Endoplasmic reticulum stress (ERS) is a self-protective mechanism of cells, but sustained and severe ERS can induce apoptosis, autophagy, and ferroptosis, among which ferroptosis has been a research hotspot in recent years. Ferroptosis is mainly characterized by the accumulation of iron-dependent lipid peroxides and plays a key role in the development and progression of liver diseases, but there are currently few studies on the involvement of ERS in ferroptosis in liver diseases. This article summarizes the research advances in ERS-related signaling pathways, the mechanism of ferroptosis, and the involvement of ERS in liver diseases, so as to provide more ideas for research on the treatment of liver diseases.

A single-center research of peroral endoscopic myotomy for primary achalasia in patients over 60 years old / 中华消化内镜杂志

Objective:To explore the therapeutic effect of peroral endoscopic myotomy (POEM) for primary achalasia (AC) in patients aged over 60 years.Methods:Data of 146 patients aged ≥60 years (the elderly group) and 146 patients aged 18-59 years (the adult group) who received POEM from November 2010 to September 2019 at the Digestive Endoscopy Center of PLA General Hospital were retrospectively analyzed. Baseline data, surgery data, surgery-related complications and surgery-related efficacy were compared.Results:There was no significant difference in gender, Ling classification, HRM classification or previous treatment between the two groups ( P>0.05). All 292 patients successfully underwent POEM surgery. The clinical success (Eckardt score ≤3) rates in the elderly group and the adult group were 96.33% (105/109) and 96.77% (90/93), respectively with no significant difference between the two groups ( χ2=0.030， P>0.05). There was no significant difference in the length of myotomy between the two groups (7.09±2.49 cm VS 7.12±2.24 cm， t=0.472， P>0.05). Complications occurred in 26 cases (17.81%) in the elderly group and 21 cases (14.38%) in the adult group with no significant difference between the two groups ( χ2=0.634， P>0.05). There was no significant difference in the postoperative hospital stay (12.61±9.69 days VS 11.00±4.43 days, t=1.825, P>0.05) or the incidence of gastroesophageal reflux [43.33% (13/30) VS 51.52% (17/33), χ2=0.422, P>0.05] between the elderly group and the adult group. Conclusion:The efficacy of POEM for AC patients over 60 years old is equivalent to that of adult patients, and the incidence of complications is similar. POEM is safe and effective for AC patients over 60 years old.

Effects of physical activity on mental and behavioral health and functioning for college students: a systematic review using ICF / 中国康复理论与实践

ObjectiveTo construct the physical activity intervention effect category and framework for college students with mental and behavioral health and functioning problems based on International Classification of Functioning, Disability, and Health (ICF). MethodsThe typical mental and behavioral health and functioning condition of college students were systematically analyzed using ICF. Relevant literatures about the health and functioning outcomes of college students participating in physical activity were retrieved from the databases of PubMed, Web of Science, EBSCO, and CNKI, from the establishment to August 20th, 2022, and reviewed systematically. ResultsTen English literatures were included, involving ten randomized controlled trials with 848 participants aged 15 to 34 years from seven countries, mainly from the journals of rehabilitation science, sports rehabilitation, rehabilitation psychology and health psychology, and were mainly published after 2016. The typical mental and behavioral health and functioning problems of college students mainly focused on stress, anxiety, depression, sleep disorders, learning fatigue, mobile phone addiction, alcohol drinking disorder, sedentary behavior and physical inactivity. Physical activity interventions included Biodanza, Hatha Yoga, Tai Chi, basketball, Baduanjin, cycling, swimming, roller skating, baseball, skill training, stretching exercise, resistance training, and aerobic exercise, etc. The frequency of interventions was mainly a long-term (four to 14 weeks, one to three times per week) program of high-, moderate-, or low-intensity physical activity. The health outcomes included improving cognitive function, relieving stress, anxiety, depression and learning fatigue, reducing negative automatic thinking, enhancing mindfulness, reducing loneliness and deficiency, improving sleep quality, improving upper limb muscle endurance; promoting the development of exercise habits, increasing physical activity participation, improving activity performance and academic performance, reducing sedentary behavior, drinking behavior and problematic mobile phone use; increasing social interaction, improving health perception and psychosocial function, enriching and improving recreation and campus life, and improving the quality of interpersonal relationships, quality of life and well-being. ConclusionA conceptual framework of physical activity participation of college students with mental and behavioral health and functioning problems is constructed using ICF. The typical mental and behavioral health and functioning problems of college students are mainly classified as mental health and functioning problems, behavioral health and functioning problems. The intervention types of physical activity are divided into physical fitness category, skill category, sports category and combination category. Health outcomes can be reflected in three dimensions: physical and mental health, activity and behavioral health, and overall functioning and quality of life.

hiPSCs and organoids: prediction of arrhythmogenic risks for optimized traditional Chinese medicine / 中国中药杂志

Accurate assessment of the risks associated with traditional Chinese medicine(TCM), such as the potential to induce serious cardiovascular adverse reactions including cardiac arrhythmias, is crucial. This article introduced the pharmacological evaluation strategies for cardiac safety and the progress in cardiac organ research, with a focus on discussing the application prospects of human induced pluripotent stem cells(hiPSCs) and organoids in assessing the risks of TCM-induced cardiac arrhythmias. Compared with traditional animal models, hiPSCs and organoid models provide better reference and predictive capabilities, allowing for more accurate simulation of human cardiac responses. Researchers have successfully generated various cardiac tissue models that mimic the structure and function of the heart to evaluate the effects of TCM on the heart. The hiPSCs model, by reprogramming adult cells into pluripotent stem cells and differentiating them into cardiac cells, enables the generation of personalized cardiac tissue, which better reflects individual differences and drug responses. This provides guidance for the assessment of TCM cardiac toxicity risks. By combining organoid model with cardiac safety pharmacology strategies such as electrocardiogram monitoring and ion channel function assessment, the impact of TCM on the heart can be comprehensively evaluated. In addition, the application of the Comprehensive in Vitro Proarrhythmia Assay(CiPA) approach improves the accuracy of evaluation. Applying the CiPA approach to TCM research reveals potential risks and provides a scientific basis for the clinical application and industrial development of TCM. In conclusion, organoid model and cardiac safety pharmacology evaluation strategies provide important tools for assessing the cardiac toxicity risks of TCM. The combination of hiPSCs model, comprehensive assessment methods, and the CiPA strategy enables an accurate assessment of the risks of TCM-induced cardiac arrhythmias, thus providing a scientific basis for the safe use and international recognition of TCM in clinical practice. This contributes to ensuring the safety and efficacy of TCM and promoting its clinical application and global acceptance.

Analysis of high-risk behaviors related to HIV infection in men who have sex with men recruited by different methods / 中华皮肤科杂志

Objective:To analyze high-risk behaviors related to HIV infection in men who have sex with men (MSM) recruited by different methods in Zhenjiang city, and to provide a reference for precise prevention and control of acquired immunodeficiency syndrome (AIDS) .Methods:From April to June in 2020, MSM in Zhenjiang city were recruited as research subjects through the center for disease control and prevention (CDC) voluntary counseling and testing (VCT) clinic and community-based organizations (CBOs) . Information such as demographic characteristics, drug abuse, HIV testing history and high-risk sexual behavior were collected through a unified questionnaire survey. Chi-square test or Fisher′s exact test was used to analyze differences in relevant characteristics of MSM recruited by different methods.Results:A total of 641 MSM were recruited by the two methods, including 442 (68.95%) recruited from CBOs and 199 (31.05%) from CDC; the proportion of MSM aged under 20 years was significantly higher in the CBO group (6.56%) than in the CDC group (1.01%, χ2 = 9.20, P = 0.002) ; the proportions of MSM receiving health education information on potential hazards of drug use from professional health institutions and new network media were significantly higher in the CDC group (7.54% [15/199], 16.58% [33/199], respectively) than in the CBO group (3.39% [15/442], χ2 = 5.28, P = 0.022; 9.50% [42/442], χ2 = 6.66, P = 0.010) . In terms of characteristics of sexual behavior, the CBO group showed significantly increased proportions of individuals having group sex (25.21%, 30 cases) and those having unprotected sexual intercourse with women (47.51%, 210 cases) compared with the CDC group (7.50% [6 cases], χ2 = 10.13, P = 0.001; 27.64% [55 cases], χ2 = 22.35, P < 0.001, respectively) , but significantly decreased proportions of heterosexuals (2.04%, 9 cases) , individuals unknowing about the HIV status of sexual partners (22.40%, 99 cases) and those having unprotected anal sex with men (39.82%, 176 cases) compared with the CDC group (6.53% [13 cases], χ2 = 8.37, P = 0.004; 39.70% [79 cases], χ2 = 20.48, P < 0.001; 57.29% [114 cases], χ2 = 16.90, P < 0.001, respectively) . Compared with the CDC group, the CBO group showed significantly decreased proportions of individuals ever having an HIV test (74.43% [329 cases] vs. 80.90% [161 cases], χ2 = 3.19, P = 0.074) and those getting the latest HIV test from CDC (23.10% [76 cases] vs. 57.14% [92 cases], χ2 = 99.41, P < 0.001) , as well as decreased prevalence of HIV infection (5.20% [23 cases] vs. 13.07% [26 cases], χ2 = 21.85, P < 0.001) . Conclusions:The MSM recruited from CBO and CDC are complementary in terms of demographics and behaviors, and can represent the general MSM population. Specific prevention and control measures for AIDS should be taken according to different characteristics of the MSM population.

A nomogram for predicting lymph node metastasis in early gastric cancer / 中华胃肠外科杂志

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

Can health technology assessments assist the global campaign against poverty? / 《全球健康杂志（英文）》

Although a key tenant of the Sustainable Development Goals is to achieve universal health coverage,the global drug gap persists—over a third of the global population lack access to essential medicines.Without access to affordable drugs,people have worse health outcomes,higher medical expenses,and productivity loss,pushing them into poverty.Health technology assessments (HTAs) offer an opportunity to decrease the global drug gap and increase access to essential medicines by overcoming barriers to medicine access.These barriers include drug procurement,drug affordability for payers and patients,a patient's ability to obtain essential medicines,and health system capacity.Using HTAs can therefore close the global drug gap by increasing access to affordable essential medicines.In turn,people have better health outcomes,spend less money on medical care,and can have better productivity.Ultimately,use of HTAs can lift the population out of poverty and force fewer people into poverty by creating better health outcomes at affordable prices.

Clinical study of soluble thrombomodulin and urinary neutrophil gelatinase-associated lipocalin in early prediction of sepsis-induced acute kidney injury / 中华急诊医学杂志

Objective:To compare the early diagnostic value of the indicators of endothelial injury, renal injury, inflammation and coagulation in patients with sepsis-induced acute kidney injury (AKI).Methods:A retrospective study was performed on 119 patients with sepsis from February 2017 to March 2018. Lab tests were performed on patients at admission, which included:ing soluble thrombomodulin (sTM), tissue plasminogen activators and inhibitors (t-PAI-C), antithrombin III (AT-III), thrombin-antithrombin (TAT) complex, plasmin-alpha 2, plasmin inhibitor complex (PIC), fibrin degradation product (FDP), fibrinogen (FIB), D-Dimer, prothrombin time (PT), prothrombin time international normalized ratio (PT-INR), procalcitoni (PCT), white blood cell (WBC), neutrophil (Neu), and platelet count (PLT). The receiver-operating characteristic curve was used to analyze the predictive value of the above indicators, and logistic regression analysis was used to analyze the risk factors of sepsis-induced AKI. A prospective study was conducted from April 2018 to September 2018 and 46 patients were enrolled. The lab tests results retrieved including sTM, t-PAI-C, FDP, AT-III, TAT, PIC, FIB, D-Dimer, PT, PCT, serum cystatin C (Cys C), urine albumin (microalbumin) and albumin to creatinine ratio (ACR), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary N-acetyl-beta-glucosaminidase (uNAG), and urinary retinol-binding protein (uRBP). As same with the previous group, the receiver-operating characteristic curve was used to analyze the diagnostic value of the above indicators, and logistic regression Was used to analyze the risk factors of sepsis-induced AKI.Results:(1) In the retrospective study: sTM, D-Dimer, PCT, PT, and PT-INR were statistically different. sTM, D-Dimer, PCT, PT, and PT-INR had a good diagnostic value for septis-induced AKI, among which, sTM had a highest diagnostic value (AUC: 0.857; 95% CI: 0.790, 0.924), better sensitivity (64.4%) and specificity (91.8%). The high expression of sTM and history of chronic kidney disease were independent risk factors for septis-induced AKI.(2) In the prospective study: PCT, sTM , Cys C, and uNGAL were statistically different. PCT, sTM, Cys C, uNGAL showed good predictive features for septis-induced AKI. sTM had the highest sensitivity (>0.999) while uNGAL had the highest specificity (0.800). The high expression of sTM was an independent risk factor for septis-induced AKI. Conclusions:sTM and uNGAL represent endothelial injury and renal tubular injury respectively. sTM is an independent risk factor of sepsis-induced AKI.

Application of Logistic regression and decision tree analysis in prediction of acute myocardial infarction events / 浙江大学学报·医学版

OBJECTIVE: To evaluate the application of decision tree method and Logistic regression in the prediction of acute myocardial infarction (AMI) events. METHODS: The clinical data of 295 patients, who underwent coronary angiography due to angina or chest pain with unidentified causes in Zhejiang provincial People's Hospital during October 2018 and April 2019, were retrospectively analyzed. Fifty five patients were identified as AMI. Logistic regression and decision tree methods were performed to establish predictive models for the occurrence of AMI, respectively; and the models created by decision tree analysis were divided into Logistic regression-independent model (Tree 1) and Logistic regression-dependent model (Tree 2). The performance of Logistic regression and decision tree models were compared using the area under the receiver operating characteristic (ROC) curve. RESULTS Logistic regression analysis showed that history of coronary artery disease, multi-vessel coronary artery disease, statin use and apolipoprotein (ApoA1) level were independent influencing factors of AMI events (all P<0.05). Logistic regression-independent decision tree model (Tree 1) showed that multi-vessel coronary artery disease was the root node, and history of coronary artery disease, ApoA1 level (the cutoff value:1.314 g/L) and anti-platelet drug use were descendant nodes. In Logistic regression-dependent decision tree model (Tree 2), multi-vessel coronary artery disease was still the root node, but only followed by two descendant nodes including history of coronary artery disease and ApoA1 level. The area under the curve (AUC) of ROC of Logistic regression model was 0.826, and AUCs of decision tree models were 0.765 and 0.726, respectively. AUC of Logistic regression model was significantly higher than that of Tree 2 (95% CI=0.041-0.145, Z=3.534, P<0.001), but was not higher than that of Tree 1 (95% CI=-0.014-0.121, Z=-1.173, P>0.05). CONCLUSIONS The predictive value for AMI event was comparable between Logistic regression-independent decision tree model and Logistic regression model, implying the data mining methods are feasible and effective in AMI prevention and control.

Progresses of echocardiography in evaluation on cardiomyopathy / 中国医学影像技术

Cardiomyopathy is a type of diseases with complex etiology and varied manifestations. Traditional echocardiography is the first-line examination method for screening and diagnosing cardiomyopathy, which has the advantages of non-invasion and convenience. In recent years, new techniques of echocardiography can provide more information for diagnosis of cardiomyopathy. The progresses of echocardiography in evaluation of cardiomyopathy were reviewed in this article.

Mitochondrial Autophagy and NLRP3 Inflammasome in Pulmonary Tissues from Severe Combined Immunodeficient Mice after Cardiac Arrest and Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

<p><b>Background</b>The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury.</p><p><b>Methods</b>A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1.</p><p><b>Results</b>(1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P = 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t = -1.36, P < 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t = -0.33, P < 0.01), whereas phos-ULK1 (Ser) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P < 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P < 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P = 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome.</p><p><b>Conclusions</b>There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.</p>

A clinical study of sepsis-related coagulation disorder / 中华急诊医学杂志

Objective To study in the correlation of the laboratory markers of coagulation,fibrinolysis and thrombosis in patients with sepsis and SOFA score,the procalcitonin (PCT) concentration and seven-day survival rate.Methods From February 2017 to March 2018,119 patients with sepsis admitted in ICU and another 119 patients with non-sepsis undergoing selective surgery were enrolled as control in this study.APTT (activated partial thromboplastin time),PT-INR (prothrombin time-international normalized ratio),FIB (fibrinogen),AT-Ⅲ (antithrombin Ⅲ),D-Dimer,FDP (fibrinogen degradation products),sTM (soluble thrombomodulin),TAT (thrombin antithrombin complex),PIC (plasmin-a2 plasminogen inhibitor complex) and t-PAI-C (tissue plasminogen activator and its inhibitor complex),were simultaneously monitored at admission.The correlation between the given laboratory markers mentioned and SOFA score,the PCT concentration and seven-day survival rate were analyzed with the Spearman correlation analysis.Results (① In the patients with sepsis,a positive correlation between SOFA score and sTM,t-PAI-C,TAT respectively was found,and a negative correlation between SOFA score and PLT (platelet count) was observed,and no correlation between SOFA score and PIC was noticed.(②) A positive correlation between PCT and sTM,t-PAI-C respectively was significant,a negative correlation between PCT and PLT was marked,and no correlation between PCT and AT-Ⅲ,TAT,PIC respectively was found.(③) A negative correlation between seven-day survival rate and sTM,t-PAI-C and TAT respectively was obvious,a positive correlation between seven-day survival rate and AT-Ⅲ,PLT respectively was occurred,and no correlation between seven-day survival rate and PIC was determined.Conclusions Soluble thrombomodulin (sTM),thrombin-antithrombin (TAT),antithrombin Ⅲ (AT-Ⅲ) and tissue plasminogen activator inhibitor complex (t-PAI-c) were good clinical monitoring indicators of coagulation disorder in patients with sepsis,which were the representative of the endothelial cell damage with highly activated coagulation,relatively insufficient anti-coagulation function and poor fibrin degradation ability.These were good adjuvants to PLT,INR and APTT for core diagnostic criteria of coagulation disorder in sepsis.

Neuroprotective effects of saffron on chronic focal cerebral ischemia through inhibiting glial scar formation in rats / 中国药理学与毒理学杂志

OBJECTIVE To explore the neuro-protective effects of saffron (Crocus satius L.) on chronic focal cerebral ischemia in rats.METHODS SD rats were randomly divided into 6 groups:sham control group,MCAO group,edaravone group and saffron 30,100,300 mg·kg-1groups.Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).Saffron was administered orally by once daily from 2 h to 42 d after ischemia. At 42 d after cerebral ischemia, neurological deficit score, spontaneous activity test,elevated plus maze test,marble burying test and novel objective recognition test were used to evaluate the effects of saffron on the behevioural change. Infarct volume, survival neuron density, activated astrocyte number, and the thickness of glial scar were also detected. GFAP expression and inflammatory cytokine contents in ischemic peripheral region were detected by Western blot and ELISA,separately.RESULTS Saffron(100,300 mg·kg-1)improved the body weight decrease, neurological deficit and spontaneous activity. Saffron (30-300 mg·kg- 1) increased the traveled distance ratio and total time in open arm, decreased the buried marble number, which indicated that saffron could ameliorate anxiety- and depression-like behaviors. Saffron (100, 300 mg·kg-1)improved the learning and memory function,which manifested by increased discrimination ratio(DR)and discrim-ination index (DI) in T2test. The results of toluidine blue found saffron treatment (100, 300 mg·kg-1) decreased the infarct volume and increased the neuron density in cortex and hippocampal.The activated astrocyte number,the thickness of glial scar and GFAP expression in ischemic peripheral region decreased after saffron. Saffron (100, 300 mg·kg-1) decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in ischemic peripheral region.CONCLUSION Saffron exerted neuro-protective effects on chronic focal cerebral ischemia,which could be related with inhibiting the activation of astrocyte and glial scar,following with the decrease of inflammatory reaction.

Comparison of corneal biomechanical parameters between keratoconus and laser corneal refractive surgery / 眼科新进展

Objective To measure biomechanical parameters of the cornea after keratoconus and laser corneal refractive surgery by Scheimpflug noncontact tonometry (Corvis ST),and analyze the changes and differences in these parameters.Methods From April 2011 to November 2016,63 patients (96 eyes) with clinically diagnosed as keratoconus were selected as the keratoconus group,and 60 patients (120 eyes) underwent laser corneal refractive surgery between November 2016 to March 2017 were selected as postoperative cornea group,and totally 51 healthy person (102 eyes) who received physical examination during the same period were selected as healthy cornea group.Scheimpflug noncontact tonometry (Corvis ST) was performed to measure the length of appl 1,length of appl 2,velocity of appl 1,velocity of appl 2,maximum deformation amplitude,apex distance and radius of curvature in the three groups.Total comparison of biomechanical parameters was performed using ANOVA test among the three groups,while pairwise comparison was performed to analyze the difference of these parameters by SNK methods.Pearson or Spearman correlation analysis was applied to assess the differences in corneal morphological and biomechanical parameters.Results There was no significant difference in length of appl 1,length of appl 2 of the three groups (all P ＞ 0.05).And velocity of appl 1 in the keratoconus group was significantly higher than that of the healthy cornea group [(0.189 ± 0.230) m · s-1 vs.(0.151 ± 0.017)m · s-1] (P ＜ 0.05).As for velocity of appl 2,the keratoconus group was larger than the healthy cornea group,both which were larger than the postoperative cornea group,and the differences were significant (all P ＜ 0.05).And this was true of maximum deformation amplitude in the three groups,with the significant differences(all P ＜ 0.05).The apex distance in the keratoconus group was significantly longer than that in the healthy cornea group (P ＜ 0.05).The radius of curvature of the keratoconus group,postoperative cornea group and healthy cornea group were (5.696 ± 0.881) mm,(7.129 ± 0.681) mm and (7.012 ± 0.728) ram,respectively,which approached significant differences(all P ＜ 0.05).There was significant correlation between the anterior surface refractive power (Km) and apex distance and radius of curvature in the keratoconus group (r =-0.205,0.1 84;P =0.023,0.041),and maximum posterior surface elevation had a statistically significant correlation with velocity of appl 2,maximum deformation amplitude and radius of curvature (r =-0.579,-0.307,0.256,P =0.022,0.002,0.000).For the eyes in the postoperative cornea group,there were no significance correlation between the anterior surface refractive power (Km) and biomechanical properties (P ＞ 0.05),but significant correlation with length of appl 2 (r =-0.297,P =0.026).There were no significant correlation between maximum posterior surface elevation and biomechanical properties (P ＞ 0.05).Conclusion The corneal biomechanical parameters are decreased in eyes after keratoconus and laser corneal refractive surgery,and Corvis ST can become an auxiliary examination tool for earlier diagnosis of secondary keratoconus after corneal refractive surgery.