ObjectiveTo clarify the associations between plasma fibrinogen （Fbg） and volumetric bone mineral density （vBMD） as well as osteoporosis measured by quantitative computed tomography （QCT）， and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis. MethodsPatients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis. The study analyzed the correlation between plasma Fbg and osteoporosis in patients. The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）. ResultsTotally 441 subjects were included in the analysis， with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4% （28/441）. As the level of plasma fibrinogen increased， the incidence of osteoporosis significantly increased （P<0.000 1）while the average bone mineral density of L1 and L2 were significantly decreased （P<0.05）. Compared with the first quartile of plasma Fbg（1.99g/L -2.37g/L）， the risk of osteoporosis in the fourth quartile of plasma Fbg （3.67g/L-4.46g/L） increased by 8.85 times after adjusting for related confounding factors. ConclusionThis study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension. Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis， aiding in early diagnosis and therapeutic monitoring. This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.

Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

Objective To explore the cost-benefit of computerized tomography perfusion imaging(CTP)in guiding endovascular treatment of patients with large vessel occlusion associated with delayed time window.Methods A total of 365 patients with great vascular occlusive stroke associated with delayed time window(6-24 h),who were admitted to the Tangshan Municipal Workers' Hospital of China to receive endovascular treatment from January 2016 to February 2022,were enrolled in this study.Based on whether the patient received CTP imaging guidance or not,the treatment cost and benefit of different treatment strategies were analyzed.Modified Rankin scale(mRS)was used to evaluate the patient's postoperative 3-month and 12-month neurological functions.The decision tree-Markov model was used to make cost-benefit analysis.Probability sensitivity analysis(PSA)was used to assess the influence of parameter uncertainty.Results The operation cost of CTP-guided endovascular treatment of large vessel occlusion was 1 526.87 Chinese yuan.According to the calculation method of disease and sequelae burden,it could bring direct burden of 1 089.23 Chinese yuan,direct+indirect burden of 3 204.85 Chinese yuan and direct+indirect+intangible burden of 5 083.07 Chinese yuan.Each Chinese yuan could get 0.178 8,0.231 8 and 0.263 4 earnings,respectively.The therapeutic cost of CTP-guided endovascular treatment of great vascular occlusive stroke was 26 689.13 Chinese yuan,producing 2.065 quality-adjusted life-year(QALY)for each patient,while the therapeutic cost and QALY of non-CTP-guided endovascular treatment were 33 299.07 Chinese yuan and 1.776 QALY respectively.PAS-analyzed incremental cost-benefit ratio(ICER)and incremental net monetary benefit(iNMB)were 22 592.82 and 7 846.43 respectively.At the cost-benefit threshold of ￥50 000/QALY,the probability that CTP guidance could get cost-benefit was up to 90.0％.The tornado chart analysis of one-way sensitivity analysis revealed that the initial mRS distribution guided by CTP had the greatest influence on iNMB,followed by the cost input in the first three months after operation.Conclusion For patients with great vascular occlusive stroke associated with delayed time window,CTP-guided endovascular treatment has high cost-benefit and effect value.

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Objective:To investigate the relevant situation of the emergency departments (ED) of general hospitals at all levels in Zhejiang Province participating in the prevention and control of Corona Virus Disease 2019 (COVID-19), and to provide a reference for further improving the capacity of emergency services.Methods:A multi-center cross-sectional investigation study was jointly initiated by the Zhejiang Provincial Emergency Medicine Quality Control Center, the Emergency Medicine Branch of Zhejiang Medical Association, and the Emergency Physicians Branch of Zhejiang Medical Doctors Association. Before investigation, experts were organized to develop a special questionnaire. Then the ED of general people's hospitals or Chinese Medicine hospitals at the county/district-level or above were included and their participations in the prevention and control of COVID-19 epidemic between March 9, 2020 and March 15, 2020 were investigated. The collected information included: basic information of the hospitals; participation of ED in fever clinics; the number of COVID-19 patients admitted to ED; the situation of ED support to the anti-epidemic front-line; and the epidemic prevention facilities of ED, and the early supply of medical protective equipments.Results:A total of 181 hospitals from 11 prefectures and cities across the province were finally included, including 52 (28.7%) Grade-A tertiary hospitals, 45 (24.9%) Grade-B tertiary hospitals, 64(35.4%) Grade-A secondary hospitals, and 20 (11.0%) Grade-B secondary or lower hospitals. Among them, 93 (51.4%) were COVID-19 designated hospitals, and 49 (27.1%) had the ability to detect COVID-19 nucleic acid; 177 (97.8%) set up independent fever clinics and 33 (18.6%) were managed by ED alone or mainly. The medical staffs of 65 (36.7%) fever clinics were all or mainly from ED. A total of 213 cases of COVID-19 were received/treated in 40.3% ED, accounting for 17.3% of the total number of cases in Zhejiang Province. A total of 3 848 doctors and nurses supported the front-line of epidemic prevention, of them, 253 supported Hubei Province (accounting for 12.5% ??of the total number). There were 68.5% and 76.8% ED having spare separate clinic and ordinary rescue single room to deal with the COVID-19. In addition, at the early days of anti-epidemic, more than 50% ED were in short supply or even had no medical protective equipment.Conclusions:The ED of Zhejiang Province plays an important role and has made a great contribution to the prevention and control of the COVID-19 epidemic. It is necessary to improve the conditions of ED to effectively respond to the prevention and control of daily infectious diseases.

Objective To investigate the clinical value of neutrophil to lymphocyte ratio (NLR) in evaluation of inflammation and prediction of cardiovascular events in maintenance hemodialysis (MHD) patients.Methods One hundred and eight stable MHD patients were recruited from Dialysis Center of Beijing Tongren Hospital from October 2015 to December 2015.The general information,complete blood count,hsCRP,biochemical test,iron metabolic indicators,pre-dialytic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.MHD patients were divided into the low NLR group and high NLR group according to the median of NLR (2.82).All patients were followed up for 18 months,cardiovascular events (CVE) were recorded during this period.Results In the high NLR group the dialysis vintage,white blood cell count,neutrophil count,NLR and hsCRP were significantly higher than those in the low NLR group [(88.0 ± 50.4) vs.(62.4 ± 40.6) months (t =2.48,P =0.02),(6.96 ± 1.82) × 109/L vs.(5.83 ± 1.33) × 109/L(t =3.14,P=0.00),(4.94 ± 1.38) × 109/L vs.(3.36 ±0.87) × 109/ L(t=6.08,P=0.00),(4.16±1.25) vs.(2.15 ±0.46) points(t=9.48,P=0.00),(7.85±4.92) vs.(3.13 ± 2.23) mg/L (t =4.97,P =0.00)].In the high NLR group lymphocyte count and transferrin saturation were significantly lower than those in the low NLR group[(1.25 ± 0.40) × 109/L vs.(1.58 ± 0.34) ×109/L,t=3.97,P=0.00;(25.7±10.2)％ vs.(32.6±17.2)％,t=2.17,P=0.03].There were no significant differences in age,sex,diabetes proportion,pre-dialytic SBP,pre-dialytic DBP,urea clearence index(Kt/V),hemoglobin,serum ferritin,serum calcium,serum phosphorus,intait parathyroid hormone,albumin,serum creatinine,carbon dioxide binding capacity and blood lipids between the two groups (P ＞ 0.05).Bivariate correlation analysis showed that NLR was positively correlated with dialysis vintage and hsCRP (r =0.311,P =0.01;r =0.574,P =0.00);white blood cell count and neutrophil count were positively correlated with hsCRP (r =0.327,P =0.00;r =0.488,P =0.00).During follow-up period 9 cases of CVE (16.7％) and 20 cases of CVE (37.0％) occurred in the low NLR group and high NLR group,respectively (x2 =5.70,P =0.03).Cox regression analysis showed that age,NLR and serum phosphorus level were risk factors of CVE in MHD patients (HR =1.075,P =0.00,HR =1.646,P =0.00;HR =1.912,P =0.02).Conclusion NLR can predict inflammation and is one of the risk factors for CVE in MHD patients.

Objective To explore the relationship of hydrogen sulfide (H2S) and the extracellular matrix of the diabetic nephropathic rats' glomerulars.Methods Twenty-one male rats(Sprague-Dawley) were randomly divided into Control group(n =7),DN group (n =7) and DN + H2 S group (n =7).Diabetes was induced in the rats except Control group rats by STZ (60mg/kg).The rats of the DN + H2S group were injected with NaHS every day,and rats of other groups were injected with NS.Eight weeks later,three groups were compared in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars.Results Compared with Control group,DN group rats were significantly increased in proteinuria of 24 hours and KW/BW (P ＜ 0.01).Kidney biopsy in DN groups rats were typical DN pathological manifestation.In treatment with NaHS,the DN rats in the DN + H2S group were decreased in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars (P ＜ 0.01),and was similar with the control group in the pathology of renal.Conclusion The H2 S control the multiplication of myofibroblast,and were decreased in the distribution of α-SMA in glomerulars.The H2S treatment may put off the progress of the extracellular matrix in the DN rats' glomerulars.

Objective To investigate the risk factors of hemorrhagic transformation(HT) in patients with acute cerebral infarction(ACI).Methods A total of 335 patients with ACI from June 2013 to September 2016 was enrolled in this study,including 47 patients in hemorrhagic transform group(HT group) and 288 patients in non-hemorrhagic transformation group(NHT group).The general clinical situation,laboratory indexes,imaging features and treatment measures of the two groups were collected and compared,and then the risk factors of HT in the patients with ACI were analyzed by Logistic regression analysis.Results Univariate analysisshowed that there were significant differences between the two groups in the history of diabetes mellitus,hìstory of atrial fibrillation,NHISS score,systolic blood pressure at admission,fasting blood glucose,glycosylated hemoglobin,low density lipoprotein cholesterol,fibrinogen,infarct location,large area infarction and thrombolytic therapy(P＜0.05).Logistic regression analysis showed that history of atrial fibrillation(OR =2.703,95 ％ CI 1.169-6.250),high fasting blood glucose(OR =2.098,95 ％ CI 1.532-2.875),large area infarction(OR=9.999,95％CI 4.648-21.510) and thrombolytic therapy(OR=6.557,95％CI 1.954-22.003) were independent risk factors for HT.Conclusion The history of atrial fibrillation,high fasting blood glucose,large area infarction and thrombolytic therapy are the risk factors for HT in patients with ACI.Corresponding nursing measures should be arranged to facilitate the disease treatment.

Objective To investigate the change of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the skin of diabetic rats, and to explore the potential role of MMP-9/TIMP-1. Methods Diabetic rats were induced with streptozotocin (STZ). Then all rats were maintained for 6 weeks. Routine pathological examination and immnnohistochemistry were made to reveal the histological and cytological appearances. RT-PCR and Western blotting were used to detect the expression of mRNA and protein of MMP-9 and TIMP-1 in the skin. Results Six weeks after STZ treatment, examination of HE-stained skin sections from normal and diabetic animals revealed that the epidermis and dermis layers were thinner in diabetic rats than those in control rats. The skin of diabetic rats showed features of atrophy such as disorganization of connective tissue fiber bundles and enlarged space between collagen fiber bundles. In contrast, thick bundles of connective tissue were observed in the dermis of normal rat skin. In normal skin, cells had a bipolar, spindle-shaped appearance in the thick collagen bundles, while in the skin of diabetic animals the interstitial cells had a rounded, shrunken and crenated appearance. The relative values of expression of MMP-9 in diabetic group were higher than those in normal group with significant difference, however, the relative values of expression of TIMP-I in diabetic group were lower than those in control group. Conclusion The changes in cutaneous histology and cytology appear earlier than skin wound. These "underlying disorders" may be associated with the imbalance of MMP-9/TIMP-1.