Establishment of risk stratification model for developing cirrhosis in patients with HBeAg-negative chronic hepatitis B virus infection / 中华检验医学杂志

Objective:To explore the independent predictive factors of cirrhosis in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection, and establish a nomogram model based on clinical laboratory data and analyze the predictive value of this model.Methods:The laboratory data of 596 patients with HBeAg-negative chronic HBV infection and 677 patients with hepatitis B cirrhosis, who were hospitalized in the First Hospital of China Medical University from 2011 to 2021, were retrospectively analyzed. Patients were randomly divided into training group ( n=892) and validation group ( n=381) at the ratio of 7∶3. The independent predictive factors of cirrhosis were analyzed by univariate logistic regression, multiple collinearity test and multivariate logistic regression. The nomogram model was established and the prediction value of this model was evaluated. Results:According to multivariate logistic regression analysis, hepatitis B core antibody ( OR=1.492, 95% CI 1.316-1.706), glutamine transpeptidase ( OR=1.015, 95% CI 1.010-1.022), platelet ( OR=0.986, 95% CI 0.982-0.988) and albumin ( OR=0.853, 95% CI 0.824-0.882) were independent predictors of cirrhosis ( P<0.05), and the nomogram was established based on the four indicators. Receiver operating characteristic curves showed that area under the curve of the nomogram was 0.933 (95% CI 0.916-0.950), and that of the validation group was 0.931 (95% CI 0.905-0.956). The calibration curves indicated the nomogram model was highly consistent with the actual outcome. Decision curves and clinical impact curves confirmed that the model had high net benefit and good clinical application performance. Conclusions:Hepatitis B core antibody, glutamine transpeptidase, platelet and albumin are independent predictors of cirrhosis among patients with HBeAg-negative chronic HBV infection. The newly developed nomogram model based on these factors could be used to predict cirrhosis risk in these patients.

Zanthoxylum bungeanum Aqueous Extract Treated Rheumatoid Arthritis by Inhibiting Synovial Cell Proliferation and Inducing Cell Apoptosis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of the water extract of Zanthoxylum bungeanum aqueous extract（ZBAE）on rheumatoid arthritis. MethodThe sixty SD rats were divided into normal group， model group ［complete Freund's adjuvant （CFA）， 10 mg·kg-1］， methotrexate（MTX） group （0.25 mg·kg-1）， low -， medium -， and high-dose ZBAE groups （90， 180， 360 mg·kg-1）. The rats in MTX group were given intraperitoneal injection for two weeks， three times a week， and the rats in ZBAE group were administrated for 14 days. The swelling of the ankle joint and body weight were observed， and arthritis scores were also performed. Computed tomography （CT）， hematoxylin-eosin （HE） staining and safranine-O and fast green staining were used to observe the effect of ZBAE on synovial hyperplasia and bone protection. Cell counting kit-8（CCK-8）method was used to detect the proliferation of the RA-FLSs cells treated with ZBAE. According to the results of CCK-8 experiment， the optimal concentration and time of administration were determined， blank group， low -， medium -， and high-dose ZBAE groups （0.08，0.10，0.12 g·L-1） were set up. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry，the migration ability of RA-FLSs cells was examined by scratch test. Western blot was used to detect the effect of ZBAE on phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， cyclin-dependent kinase 2 （CDK2）， Cyclin A and phosphorylated PI3K， Akt （p-PI3K，p-Akt） protein expression in RA-FLSs cells. ResultCompared with the normal group，joint swelling index and arthritis score were increased in the model group （P<0.05），the bone of the ankle was seriously damaged， and there was obvious synovial hyperplasia. Compared with the model group， the ZBAE group could significantly reduce the joint swelling index （P<0.05）， inhibit synovial hyperplasia and cartilage destruction. In vitro study showed that compared with the blank group， ZBAE could inhibit the migration of RA-FLSs （P<0.05）， promoted cell apoptosis （P<0.05）， and acted on RA-FLSs cells in S phase to inhibit cell proliferation. Moreover， the result of Western blot showed that compared with the blank group， the expression of p-PI3K， p-Akt， CDK2 and Cyclin A proteins were significantly decreased in the high dose group of ZBAE （P<0.05）. ConclusionThese results suggest that ZBAE has a therapeutic effect on rheumatoid arthritis by inhibiting synovial hyperplasia， promoting synovial apoptosis and inhibiting its migration.

Network pharmacology approaches for research of Traditional Chinese Medicines / 中国天然药物

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines (TCMs) for the treatment of diseases. TCMs, in "multi-component, multi-target, multi-pathway" paradigm, show satisfactory clinical results in complex diseases. New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases. Network pharmacology (NP) provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases. The development and application of NP has promoted the safety, efficacy, and mechanism investigations of TCMs, which then reinforces the credibility and popularity of TCMs. The current organ-centricity of medicine and the "one disease-one target-one drug" dogma obstruct the understanding of complex diseases and the development of effective drugs. Therefore, more attentions should be paid to shift from "phenotype and symptom" to "endotype and cause" in understanding and redefining current diseases. In the past two decades, with the advent of advanced and intelligent technologies (such as metabolomics, proteomics, transcriptomics, single-cell omics, and artificial intelligence), NP has been improved and deeply implemented, and presented its great value and potential as the next drug-discovery paradigm. NP is developed to cure causal mechanisms instead of treating symptoms. This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research, mechanism elucidation, target prediction, safety evaluation, drug repurposing, and drug design.

Study on Analytical Method of Leachable Substances of Allogeneic Products / 中国医疗器械杂志

Products made from allogeneic tissue are largely used in clinical treatment due to its wide source compared with autologous tissue, causing less secondary trauma of patients and the good biocompatibility. Various organic solvents and other substances introduced in the production process of allogeneic products will leach down into the human through clinical treatment, thus bringing varying degrees of harm to patients. Therefore, it is very necessary to detect and control the leachables in such products. Based on the classification and summary of leachable substances existing in the allogeneic products, the preparation of extract and the establishment of the detection techniques for known and unknown leachable are briefly introduced in this study, in order to provide research method for the study of leachable substances of allogeneic products.

Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease / 神经科学通报·英文版

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.

Review of Leachable Substances in Hemodialyzer / 中国医疗器械杂志

With the rapid development of my country's hemodialysis industry, the application of hemodialysis machines has become more and more extensive, but at the same time, the quality control technology of hemodialysis machines is not perfect. Especially for a wide range of leachable substances in dialyzers, there are few studies and detection methods. This study first briefly describes the development of hemodialyzers, and then expounds the common types of leachables, extraction methods, and chromatography and mass spectrometry conditions. It is summarized that the research plan of leachable substances is to determine the type first, then formulate the extraction plan, and then establish the detection method. Finally, we look forward to the research prospects of hemodialyzer leachables, and point out that with the deepening and extensive development of research, it can further promote the healthy development of the hemodialyzer industry.

CDK4/6 signaling pathway and its targeted therapeutic agents in cancer therapy: a review / 生物工程学报

The development and progression of most cancers have been well recognized as the result of highly activated cell cycle. Cyclin dependent kinase 4/6 plays important roles not only in mitosis, but also in multiple biological processes that contribute to cancer development, such as aging, apoptosis and histone modification. Three FDA approved CDK4/6 inhibitors, Palbociclib, Ribociclib and Abemaciclib, have been used as targeted cancer therapeutic agents to benefit patients with endocrine therapy-resistant breast cancer and other types of cancer, prolonging their survival. However, the clinical application of these inhibitors also leads to acquired drug resistance and other problems. This paper reviews the regulatory roles of CDK4/6, the application of CDK4/6 inhibitors in cancer and the challenge of drug resistance.

Comparison of the Quality of Generic and Original Preparations of Thioctic Acid Injection and Study on Its Acute Toxicity Test in Mice / 中国药房

OBJECTIVE： To compare the quality of original preparations of Thioctic acid injection and generic preparations from 2 domestic manufacturers， discuss the acute toxicity test of mice and to investigate the project of consistency evaluation methods. METHODS： According to the quality standard that stated in Chinese Pharmacopeia， physicochemical properties （characters， pH， osmotic pressure， etc.， contents and related substances of samples of Thioctic acid injection as well as LD50 in acute toxicity test （n＝10）， and mortality of mice after administration of injection solution （n＝30） were compared among 3 manufacturers. RESULTS： The physicochemical properties as and related substances of the original drug and 2 generic drugs were all in line with the quality standard； the contents of 3 samples ranged 95％-105％. The acute toxicity test results showed that the LD50 values of 2 generic drugs （LD50： 247.911 mg/kg， 95％ confidence interval： 222.209-277.999 mg/kg；LD50： 215.291 mg/kg， 95％ confidence interval： 196.637-235.053 mg/kg） were smaller than that of original drug （LD50： 266.534 mg/kg， 95％ confidence interval： 250.597-283.418 mg/kg）， but there was no statistical difference （P＞0.05）. The results of 3 repeated experiments showed that there was statistical significance in the number of animal death caused by the 2 generic drugs （26， 28） was more than that of the original drug （19） （all P＜0.05）， when injection solution was injected into mice in a single dose. After administration of the original drug， mice showed excitatory reactions such as movement and squeal， while 2 generic drugs showed inhibitory reactions. CONCLUSIONS： 2 generic drugs of Thioctic acid injection and the original drug all conform to the relevant regulations of Chinese Pharmacopoeia in terms of preparation quality standards， but the results of acute toxicity test are quite different， so it is difficult to prove the consistency between the 2 generic drugs and the original drug. Therefore， acute toxicity test is necessary for the consistency evaluation of injections.

The effect of adipose-derived stem cells on the lung colonization, TNF-α and IL-4 in rats with LPS-induced acute lung injury / 中华急诊医学杂志

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.

Adipose-derived stem cells：isolation, culture and differentiation into endothelial progenitor cells / 中国组织工程研究

BACKGROUND:Adipose-derived stem cels are regarded as the potential seed cels for tissue engineering. Colagenase digestion is used to isolate adipose-derived stem cels from fat pads currently. However, there are some problems, such as cumbersome operation and high cost. OBJECTIVE: To study the basic biological characteristics of adipose-derived stem cels by tissue explants culture and to explore the differentiation potential into osteoblasts, adipocytes and endothelial progenitor cels in vitro. METHODS:Adipose-derived stem cels were isolated by tissue explants technique from the bilateral groin fat pads of rats under aseptic conditions, and cultured in vitro. Cel counting kit-8 was used to detect the proliferative activity, and flow cytometry was employed to analyze the expression of cel surface markers. Passage 4 adipose-derived stem cels were cultured in osteogenic medium, adipogenic medium and endothelial progenitor cel medium for 2-3 weeks, and then the cels were identified. RESULTS AND CONCLUSION:Adipose-derived stem cels that were isolated by tissue explants culture were easily cultured, and after subculture, cels were mainly spindle-shaped and grew in clone-like manner with swirling arrangement. Cels that experienced repeated subcultures stil kept stronger proliferative ability and the cel growth curve was shaped as a parabola. Immunochemical staining analysis revealed that adipose-derived stem cels were positive for CD44, CD90 and CD29, but negative for CD31, CD45. After adipogenic/osteogenic induction, the cels were respectively positive for oil red O staining and alizarin red staining. Induced endothelial progenitor cels were identified with CD34 and the ability to uptake Dil-ac-LDL and FITC-UEA. These findings indicate using the using tissue explants culture, high-purity adipose-derived stem cels easy to proliferate can be harvested, highly express stem cels-related antigens, and have the ability to differentiate into osteoblasts, adipocytes and endothelial progenitor cels, which meet the needs of seed cels in tissue engineering research.

Study on Chemical Constituents from Petroleum Ether Fraction ofLiparis nervosa / 世界科学技术-中医药现代化

This article was aimed to study the chemical constituents of the petroleum ether fraction of Liparis nervosa.Chemicalcompoundswereisolatedandpurifiedthroughvariouschromatographytechniques.The accurate structures of chemical compounds were confirmed with spectral data and literatures. The results showed that7chemicalconstituentswereisolatedfromthepetroleumetherfractionofLiparis nervosa,whichwere moscatin (1), batatasin Ⅲ (2), bergapten (3), isoimpinellin (4), xanthotoxin (5), imperatorin (6) and β-sitosterol (7). It was concluded that chemical constituents 3-7 were isolated from this genus for the first time. And chemical constituents 1-7 were isolated from this plant for the first time.

Cost-minimization Analysis of Prostaglandins Drugs in the Treatment of Glaucoma / 中国药房

OBJECTIVE:To investigate the curative effect and economics of prostaglandins drugs in the treatment of glauco-ma,and to provide reference for clinical medication. METHODS:In retrospective study,a total of 790 glaucoma patients were di-vided into latanoprost group(62 cases),travoprost group(356 cases)and bimatoprost group(372 cases)according to therapy regi-men. They were given relevant medicine. Total effective rate of 3 groups were calculated,and the cost-minimization method was used for pharmacoeconomics evaluation. RESULTS:The total effective rate of 3 groups were 87.10%,84.27%,76.08% respective-ly,without statistical significance(P>0.05). The cost of them were 208.00 yuan,225.00 yuan and 173.00 yuan,and that of bima-toprost group was the lowest. The results of sensitivity analysis was in line with that of cost-minimization analysis. CONCLU-SIONS:For glaucoma,bimatoprost is more economical than latanoprost and travoprost.

Meta-analysis of long-term outcomes of percutaneous coronary intervention or coronary artery bypass graft surgery in coronary artery disease patients with multi-vessel and/or left main stem disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the long-term outcomes of coronary artery disease patients with left main stem and/or multi-vessel disease receiving percutaneous coronary intervention (PCI) or coronary artery bypass graft(CABG).</p><p><b>METHODS</b>PubMed, EMBase, Cochrane central register of controlled trials were searched to identify randomized controlled trials concerning the long-term outcomes of PCI and CABG in coronary artery disease patients with left main stem and/or multi-vessel disease before May 2013.Keywords included "angioplasty", "coronary", "coronary artery bypass surgery" and "stent". The data were analyzed by STATA 12.0.</p><p><b>RESULTS</b>Six randomized controlled trials (5 071 patients) were enrolled for analyses.Five years all-cause mortality (RR = 1.13, 95% CI: 0.88-1.44, P = 0.35), incidence of myocardial infarction (RR = 1.20, 95% CI: 0.69-2.07, P = 0.53), and angina (RR = 1.17, 95% CI: 0.88-1.57, P = 0.28) were similar between PCI and CABG groups. Major adverse cardiac and cerebrovascular event (RR = 1.85, 95% CI: 1.38-2.48, P < 0.01) and repeat revascularization (RR = 3.48, 95% CI: 2.20-5.53, P < 0.01) were significantly higher in PCI compared to CABG.</p><p><b>CONCLUSIONS</b>The present analysis suggests that 5 years all-cause mortality is similar between PCI and CABG strategies.However, PCI is associated with higher major adverse cardiac and cerebrovascular event and repeat revascularization rate compared to CABG in patients with unprotected left main stem and/or multi-vessel disease.</p>

Impact of percutaneous coronary intervention versus medical therapy on mortality in stable coronary artery disease: a meta-analysis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the impacts of percutaneous coronary intervention (PCI) and medical therapy on mortality in patients with stable coronary artery disease.</p><p><b>METHODS</b>We searched PubMed,Embase, Cochrane central register of controlled trials, Wanfang data and CNKI to find relevant randomized controlled trials on PCI versus medical therapy for treating patients with stable coronary artery disease, which were reported before December 2013. Publications were selected according to inclusion and exclusion standard. Meta-analyses was performed with the software of STATA 12.0.</p><p><b>RESULTS</b>Five randomized controlled trials and 5 567 patients were enrolled for this analysis. Compared with medical therapy, PCI could not significantly decrease the long-term all-cause mortality (RR = 0.96, 95%CI 0.80-1.15), the cardiac death rate (RR = 1.02, 95%CI 0.77-1.36), the myocardial infarction rate (RR = 1.05, 95%CI 0.89-1.23), the acute coronary syndrome (RR = 0.70, 95%CI 0.27-1.82), the rate of freedom from angina (RR = 1.09, 95%CI 0.98-1.21), and the rate of stroke (RR = 1.27, 95%CI 0.75-2.15).However, the revascularization rate was significantly lower for patients in PCI group (RR = 0.60, 95%CI 0.42-0.86).</p><p><b>CONCLUSIONS</b>Long-term mortality is similar for patients with stable coronary artery disease underwent PCI or medical therapy.</p>

Analysis of Eye Drops for External Use in the Outpatient of Our Hospital Between 2004 and 2006 / 中国药房

OBJECTIVE:To investigate the application structure and tendency of eye drops for external use so as to provide references for the research & development,production and use of this preparation.METHODS:Data including variety,classification,consumption amount and sales volume of the eye drops from 2004 to 2006 in the outpatient were analyzed retrospectively by hospital information system.RESULTS & CONCLUSION:The application structure of eye drops in our hospital was basically stable,but control on the use of anti-infective drugs needs to be tightened;the amount of anti-xeroma and anti-asthenopia drugs increased to a large extent;the imported variety takes an excessively large proportion.The use of anti-infective drugs should be standardized and the market share of domestic drugs remains to be further enlarged.