1.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
2.Gelian Tiaotang Pills Ameliorate Renal Fibrosis in db/db Mice via NLRP3/Caspase-1/GSDMD Pathway
Lihui FAN ; Zhigang WANG ; Xia YANG ; Xiaolong MEI ; Kun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):136-145
ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)/cysteinyl aspartate-specific proteinase (Caspase)-1/gasdermin D (GSDMD) signaling pathway. MethodsForty db/db mice were randomly assigned into model, positive control (0.001 3 g·kg·d-1 dapagliflozin suspension), and high-, medium-, and low-dose Gelian Tiaotang pills (3.12, 1.56, and 0.78 g·kg·d-1 suspension of Gelian Tiaotang pills, respectively) groups, with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water, while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose (FBG) and body mass were measured every 4 weeks. Kidneys were weighed after sampling, and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride (TG), total cholesterol (TC), serum creatinine (SCr), and blood urea nitrogen (BUN). The pathological changes, extracellular matrix deposition, and renal fibrosis degree were examined by hematoxylin-eosin, periodic acid-schiff (PAS), and Masson staining, respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin (IL)-1β and IL-18 in the renal tissue. Immunohistochemistry (IHC) was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, and GSDMD-N in the renal tissue. ResultsCompared with the normal group, the model group generally had poor general states and increases in the body mass, kidney weight, kidney index, and levels of FBG, TG, TC, SCr, and BUN (P<0.01). In addition, glomerular pyknosis, increased matrix, vacuolar degeneration of renal tubular epithelial cells, and interstitial infiltration of inflammatory cells were observed in the model group (P<0.01), together with rises in the levels of IL-1β and IL-18 in the renal tissue (P<0.01) and up-regulated protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.01). Compared with the model group, 12 weeks of drug interventions reduced the body mass, kidney weight, and kidney index and lowered the levels of FBG, TG, TC, SCr, and BUN in the serum and IL-1β and IL-18 in the renal tissue (P<0.05, P<0.01). Furthermore, drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3, Caspase-1, cleaved Caspase-1, GSDMD, GSDMD-N, fibronectin, and collagen Ⅰ in the renal tissue (P<0.05, P<0.01). The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway, thus delaying the process of renal fibrosis in diabetes.
3.Research progress in chemical constituents and pharmacological activities of Inonotus obliquus
Jiamin CUI ; Hairan FAN ; Haimin KUAI ; Xiaolong HU ; Hao WANG
Journal of China Pharmaceutical University 2025;56(4):515-523
As a medicinal and edible fungus, Inonotus obliquus has a long history of folk application in Russia, Japan, and Northeast China. It is rich in terpenoids, steroids, polysaccharides, phenols, alkaloids, etc, and exhibits pharmacological activities including anti-tumor, hypoglycemic, anti-inflammatory, antioxidant, and lipid-lowering effects. Among these, lanostane-type tetracyclic triterpenes represent its characteristic constituents. This review systematically summarizes the research progress on the chemical components isolated and identified from I. obliquus and their pharmacological activities in recent years. The structures of terpenoids, steroids, and phenolic compounds are compiled and illustrated, with a particular focus on the skeletal types and structural characteristics of lanostane-type tetracyclic triterpenes. This work aims to provide some reference for the further investigation and comprehensive development and utilization of I. obliquus.
4.LINC00626 promotes the malignant process of colorectal cancer metastasis through the JAK1/STAT3/KHSRP axis
Yanyan YU ; Xia KANG ; Linlin FAN ; Haifeng ZHANG ; Xiaolong WANG ; Haitao WEI ; Li LI
The Journal of Practical Medicine 2024;40(12):1643-1650
Objective To examine the regulation of malignant progression of colorectal cancer by LINC00626 via the JAK1/STAT3/KHSRP signaling axis and its molecular mechanism.Methods 96 individuals diagnosed with colorectal cancer at our hospital during June 11,2021 and June 11,2023 were chosen as research subjects,and their cancerous tissue and nearby normal tissue were collected.Cultivate colorectal cancer cell lines(SW620,HCT116,HT29,DLD-1,LOVO,Caco-2)and normal colorectal cells(NCM460)in vitro,and detect the expression of LINC00626 and KHSRP in colorectal cancer tissue and cell lines using qRT-PCR.Screening out cell lines infected with lentivirus,SW620 and HCT116 cell lines were transfected with knockdown lentivirus and its control,while HT29 and DLD-1 cell lines were transfected with overexpressing lentivirus and its control,respectively.Select stable transfected cell lines for cell function experiments to detect proliferation,migration,and invasion abilities.Detection of the effect of LINC00626 on the growth and migration of colorectal cancer tumors in live mouse experiments.The expression level of KHSRP protein in stable labeled cells was determined using a western blot analysis.Rescue experimental research on the regulatory relationship between LINC00626 and KHSRP.Results qRT-PCR showed low expression of LINC00626 and high expression of KHSRP in colorectal cancer tissues and cell lines.Cell function experiments showed that compared with the sh-NC group,the sh-LINC00626 group promoted cell proliferation,migration,and invasion in SW620 and HCT116 cells,while the overexpression group showed the opposite.Cell rescue experiments showed that,LINC00626+KHSRP significantly reversed the promotion effects of knocking down LINC00626 on cell proliferation,migration,and invasion.In the nude mouse experiment,com-pared with the sh-NC group,the sh-LINC00626 group showed a significant increase in tumor volume and weight,cell proliferation rate,and the number of lung metastases from colorectal cancer in the nude mice;Overexpression results in the opposite.The signal pathway experiment revealed that relative to the sh-NC group,the expression levels of JAK1 and STAT3 mRNA in the sh-LINC00626 group were significantly increased,whereas the results in the overexpression group were the opposite.Conclusion LINC00626 suppression the malignant progression of colorec-tal cancer metastasis through the JAK1/STAT3/KHSRP signaling axis.
5.Analysis of risk factors for long-term overactive bladder after radical prostatectomy
Ye YAN ; Xiaolong LI ; Haizhui XIA ; Xuehua ZHU ; Yuting ZHANG ; Fan ZHANG ; Ke LIU ; Cheng LIU ; Lu-Lin MA
Journal of Peking University(Health Sciences) 2024;56(4):589-593
Objective:To analyze the incidence and progression of overactive bladder(OAB)symp-toms following radical prostatectomy for prostate cancer patients and to identify related risk factors.Methods:A retrospective study was conducted on 263 local stage prostate cancer patients who underwent radical prostatectomy at Peking University Third Hospital from January 2013 to May 2017.Clinical base-line information,comprehensive imaging features,perioperative parameters,preoperative urinary control status,pathological diagnosis,and the incidence of OAB within one year postoperatively were collected and analyzed.In the imaging features,two parameters were defined:Bladder wall thickness(BWT)and bladder mucosal smoothness(BMS),which were used to predict the occurrence of OAB.Patients were evaluated based on their clinical baseline characteristics,including age,body mass index(BMI),co-morbidities,and prostate-specific antigen(PSA)levels.The imaging characteristics were assessed using preoperative MRI,focusing on BWT and BMS.Perioperative parameters included operative time,blood loss,and length of hospital stay.The OAB symptoms were assessed using the overactive bladder symptom score(OABSS)and the international prostate symptom score(IPSS).These scores were correlated with the postoperative incidence of OAB.Results:Among the 263 patients who underwent radical prostatecto-my,52(19.8%)exhibited OAB within one year postoperatively.Of the 40 patients with preoperative OAB symptoms,17(42.5%)showed remission postoperatively,while 23(57.5%)had persistent symptoms.Additionally,29 patients developed new-onset OAB,accounting for 55.77%of all postopera-tive OAB cases.Univariate analysis indicated that BWT,BMS,OABSS,and IPSS score were all associ-ated with the occurrence of postoperative OAB.Further multivariate analysis identified BMS as an inde-pendent risk factor for long-term OAB(P<0.001).Conclusion:Long-term postoperative overactive bladder is a common complication following radical prostatectomy.The findings suggest that preoperative MRI measurements of bladder wall thickness and bladder mucosal smoothness during bladder filling phase can predict the risk of OAB occurrence postoperatively.Identifying these risk factors preoperatively can help in counseling patients about potential complications and in developing strategies to mitigate the risk of developing OAB after surgery.Early detection and management of these parameters might improve the quality of life for patients undergoing radical prostatectomy.
6.Research Progress on Pathogenesis of Diabetic Kidney Disease Based on Ferroptosis and Intervention of Traditional Chinese Medicine
Lihui FAN ; Zhigang WANG ; Xia YANG ; Kun ZHANG ; Xiaolong MEI
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):917-927
Diabetic kidney disease(DKD)is the leading cause of end-stage renal disease worldwide and one of the major microvascular complications of diabetes.The pathogenesis of DKD is multifactorial,and its pathological process involves multiple pathways.Ferroptosis is a regulatory cell death characterized by iron dependent lipid peroxidation.Recently,an increasing number of studies have shown that ferroptosis is a key driving factor for the occurrence and development of DKD and has been identified to play a crucial role in the occurrence,development,and treatment of various kidney diseases.Traditional Chinese medicine has unique advantages in preventing and delaying the progression of DKD due to the characteristics of multi-component,multi-target,and multi-pathway.This article focuses on summarizing the impact of key regulatory factors and signaling pathways of ferroptosis on the pathological process of DKD,as well as the research progress of traditional Chinese medicine in regulating ferroptosis key factors and pathways for preventing and treating DKD.The aim of this study is to provide new ideas for the clinical treatment of DKD and the development of new traditional Chinese medicine drugs.
7.Surgical strategy for lumbar degenerative diseases with segment instability between upper instrument vertebra and adjacent upper vertebra
Xi LI ; Lei LIU ; Zhe ZHANG ; Yuzhu XU ; Peiyang WANG ; Xiaolong LI ; Guozhen LIU ; Lele ZHANG ; Zhiyang XIE ; Yuao TAO ; Pan FAN ; Yuntao WANG
Chinese Journal of Orthopaedics 2024;44(10):658-668
Objective:To summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.
8.Correlation between the Detection of Multiple Cytokine Levels in Neonatal Umbilical Cord Plasma and Early-onset Neonatal Sepsis
Zhengjiang CHANG ; Qian WEI ; Xiaolong LIU ; Zhaoying FU ; Meini CHEN ; Jinwei HE ; Haiyan FAN
Journal of Modern Laboratory Medicine 2024;39(4):150-154
Objective To investigate correlation between the expression level of multiple cytokine levels in neonatal umbilical cord plasma and early-onset sepsis for screening out the cytokines with good diagnostic value for early-onset neonatal sepsis(EONS).Methods Full-term neonates and preterm neonates(Gestational age ≥ 32 weeks)of 310 cases between September 2021 and June 2023 were selected as study subjects.According to clinical signs,laboratory results and blood culture,these subjects were divided into 3 groups:control group without sepsis,EONS blood culture positive group and EONS blood culture negative group.Umbilical cord blood plasma of all subjects was collected within 72 hours after birth.The expression levels of cytokines IL-2,IL-4,IL-6,IL-9,IL-10,IL-21,IFN-γ and TNF-α were determined,and cytokines with high expression levels(high correlation)were screened out.Receiver operating characteristic(ROC)curve was used to analyze the specificity and sensitivity of the selected cytokines in the diagnosis of neonatal early-onset sepsis.Results Among the 8 cytokines mentioned above,the concentrations of IL-6,IL-9 and IL-21 in cord blood plasma of neonatal early-onset sepsis positive blood culture patients(392.6±258.7pg/ml,11.9±7.5pg/ml,29.1±16.8 pg/ml)and negative blood culture patients(353.8±244.5pg/ml,10.4±6.3pg/ml,27.7±19.2pg/ml)were higher than those of the control group(34.9±25.1pg/ml,5.9±4.5pg/ml,10.8±10.1 pg/ml),with significant differences(t=23.961,20.732;15.174,17.824;22.466,21.193,all P<0.01),and the increase of IL-6 concentration was the most obvious.ROC curve analysis(the cut-off values of IL-6,IL-9 and IL-21:123.0 pg/ml,3.60 pg/ml,6.00 pg/ml,respectively)showed that the areas under the ROC curve for IL-6,IL-9 and IL-21 alone detection were 0.876(95%CI:0.786~0.955),0.782(95%CI:0.667~0.875)and 0.825(95%CI:0.737~0.913),respectively.The area under the ROC curve for the combined detection of IL-6,IL-9 and IL-21 was 0.930(95%CI:0.875~0.997).The combined detection of IL-6,IL-9 and IL-21 improved the specificity and sensitivity of the test than IL-6,IL-9 and IL-21 alone detection,and the differences were statistically significant(Z=2.137,2.391,2.257,all P<0.05).There was no significant difference in cytokine expression between positive blood culture and negative blood culture neonates with early-onset sepsis(t=0.276~3.377,all P>0.05).Conclusion The cytokines expression of IL-6,IL-9 and IL-21 in neonatal umbilical cord plasma of neonatal early-onset sepsis were increased.Combined detection of IL-6,IL-9 and IL-21 has good diagnostic value for early-onset neonatal sepsis.
9.The application value of the quantitative parameters of collateral circulation in evaluating the clinical prognosis of patients with acute ischemic stroke
Xian FAN ; Tianle WANG ; Li ZHU ; Xiaolong LI ; Xiwu RUAN ; Han WANG
Journal of Practical Radiology 2024;40(10):1587-1591
Objective To investigate the application value of the quantitative parameters of collateral circulation based on computed tomography perfusion(CTP)in evaluating the clinical prognosis of patients with acute ischemic stroke(AIS).Methods A total of 126 patients with AIS caused by middle cerebral artery occlusion were enrolled,collateral circulation were reconstructed and scored via multiphase computed tomography angiography(mCTA)based on CTP.The hypoperfusion intensity ratio(HIR)and collateral vessel density(CVD)were calculated.All patients were divided into good prognosis group(72 cases)and poor prognosis group(54 cases)based on 90 d modified Rankin scale(mRS)scores.Differences in cardiovascular risk factors,National Institutes of Health Stroke Scale(NIHSS)scores,Albert stroke program early CT(ASPECT)scores,Tmax>10 s volume,Tmax>6 s volume,core infarct area volume,and final infarct volume between the two groups were compared.Binary logistic regression was employed to identify independent predictors of the clinical prognosis,and the DeLong test was used to compare the efficacy of different predictors in predicting clinical prognosis.Results The good prognosis group had significantly higher ASPECT scores,mCTA scores,and CVD,but significantly lower HIR,Tmax>10 s volume,and baseline NIHSS scores compared to the poor prognosis group(P<0.05).Binary logistic regression analysis showed that ASPECT scores[odds ratio(OR)=0.780],mCTA scores(OR=0.669),CVD(OR=0.595),and HIR(OR=28.968)were independent predictors of clinical prognosis(P<0.05).DeLong test found no significant difference in area under the curve(AUC)values between mCTA scores,CVD and HIR in predicting the clinical prognosis of AIS patients(P>0.05).Conclusion Quantitative parameters such as CVD and HIR related to collateral circulation have a strong diagnostic efficacy in predicting the 90 d clinical prognosis in patients with AIS.
10.Effect of traditional Chinese medicine and compounds for supplementing qi and activating blood circulation and inducing resuscitation on regulating stem cells to promote nerve repair of acute ischemic stroke
Chunmiao YING ; Xiaolong PAN ; Feixiang LIU ; Na CHEN ; Feiyan FAN ; Yunke ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(1):121-130
BACKGROUND:Endogenous neurogenesis and exogenous stem cell transplantation in the brain show great therapeutic potential for neurological diseases including ischemic stroke,repairing and replacing lost neurons,promoting synaptic remodeling,and inhibiting apoptosis.Traditional Chinese medicine and compound therapy for supplementing qi,activating blood circulation and inducing resuscitation for the treatment of neurological dysfunction after ischemia have certain advantages,targeting nerve repair through a variety of ways,including promoting endogenous neurogenesis and exogenous stem cell survival,proliferation,homing,and inducing neuronal differentiation. OBJECTIVE:To summarize the mechanism of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke,in order to provide a reference for the research and treatment of new drugs in ischemic stroke. METHODS:The articles from CNKI and PubMed databases about traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation in promotion of nerve repair in the acute phase of ischemic stroke from 2010 to 2022 were searched,with"supplementing qi and activating blood circulation;inducing resuscitation;traditional Chinese medicine(TCM);compounds;ischemic stroke;nerve repair;stem cells"as Chinese and English search terms.After excluding old and duplicate views,the retrieved literature was analyzed and collated,and a total of 124 articles were included for analysis. RESULTS AND CONCLUSION:(1)The definition of stem cells,ischemic stroke and the nerve repair pathway in the acute phase of ischemic stroke were sorted out.(2)The mechanism of action of traditional Chinese medicine and compound for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke was summarized,mainly including promoting stem cell proliferation,improving stem cell viability and survival rate,promoting nerve cell homing,inducing stem cell differentiation to neurons,inhibiting apoptosis of nerve cells,promoting axon regeneration,regulating angiogenesis and remodeling,improving the level of neurotrophic factors and repairing the integrity of the blood-brain barrier.(3)Through the existing research,the relevant factors and signaling pathways of traditional Chinese medicines and compounds for supplementing qi,activating blood circulation and inducing resuscitation to promote nerve repair in the acute phase of ischemic stroke were summarized,such as Nestin protein expression,DCX protein expression,brain-derived neurotrophic factor,vascular endothelial growth factor and Wnt/β-catenin signaling pathway,Notch signaling pathway,PI3k/Akt signaling pathway,BDNF/TrkB signaling pathway and ERK/MAPK signaling pathway.It provides a relevant reference for future research on ischemic stroke-specific drugs and new clinical treatment methods.

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