BACKGROUND:It is wel-known that vitamin E holds antioxidant capacity, but whether other growth factors have the same effect on endplate chondrocytes has not yet been reported. OBJECTIVE:To observe the effect of different growth factors on the antioxidant ability of endplate chondrocytes in the intervertebral disc. METHODS:Endplate chondrocytes were primary cultured, and then divided into four groups, including blank control, serum deprivation, hydrogen peroxide stimulation and hydrogen peroxide stimulation combined with different growth factors groups. The 4th group was subdivided into insulin-like growth factor-1, basic fibroblast growth factor, transforming growth factorβ, forskolin and vitamin E groups. The expression levels of caspase-3, matrix metal oproteinase 13 and 3, inhibitor of metal oproteinase 1 as wel as thrombin 4 and 5 were detected by real-time PCR. Cel apoptosis was analyzed through apoptosis kit and flow cytometry. Cel synthesis and secretion were detected by western blot assay. The total antioxidant capacity and the hydrogen peroxide content were determined by kit, and then statistical y analyzed. RESULTS AND CONCLUSION:Different growth factors had significant differences in the endplate chondrocyte apoptosis, secretion and antioxidant capacity. To conclude, transforming growth factorβand forskolin do further damage to the cel s stimulated by hydrogen peroxide, while insulin-like growth factor-1 and vitamin E expose protective effect on the injured cel s.

Objective: To explore the clinical and anatomical characteristics of coronary slow lfow (CSF) in relevant patients.
Methods: We summarized the patients without coronary angiography (CAG) proved coronary stenosis (stenosis < 40%) while with TIMI indicated CSF in our hospital from 2013-01 to 2015-01. The patients were divided into 2 groups: CSF group, n=56 patients having at least 1 major coronary artery with TIMI frame counts > 27 and Control group,n=55 patients with normal coronary lfow. The related laboratory indexes were examined and relationship between MCV and CSF was studied by multi-logistic regression analysis.
Results: In CSF group, MCV 90.4 (87.48, 92.65) fL and RDW-CV 12.5 (12.30, 13.18) % were lower than those in Control group 92.3 (90.1, 94.3) fL and 13(12.7, 13.4) %,P<0.05; while MCHC 337 (332, 347) g/L and the number of left circumlfex distal braches involved 3 (2, 4) were higher than those in Control group 327.5 (322, 338) g/L and 2 (2, 3),P<0.05. Multi-logistic regression analysis showed that MCV was negatively related to CSF (partial regression coefficient= -0.138, P=0.015), Spearman rank correlation analysis presented that MCV was negatively related to TIMI frame counts (r= -0.201, P=0.009).
Conclusion: Deformability of red blood cells might be involved in pathogenesis of CSF in relevant patients.

Alcohol liver disease (ALD) is the most common disease resulting in liver injury in the world. Inflammatory response is an important reason for liver injury in ALD. After being absorbed into the intestines, alcohol can increase the amount of intestinal endotoxin which enters the bloodstream through enterohepatic circulation and activates Toll-like receptor 4 in liver Kupffer cells to release inflammatory factors. The inflammatory factors including tumor necrosis factor-α induce liver injury, while interleukin-6 (IL-6) and interleukin-10 (IL-10) protect the liver through regulating inflammatory response. IL-6 can increase the expression of various anti-injury genes in hepatocytes through activating signal transducer and activator of transcription 3 (STAT3), and IL-10 can inhibit liver inflammatory response through activating STAT3 in Kupffer cells. The processes of imbalance and rebalance between proinflammatory factors and anti-inflammatory factors are the development and prognosis of ALD. This article systematically reviews the role of inflammatory factors in the development and progression of ALD from the perspective of inflammatory response.

OBJECTIVETo observe the effect of Huogu II formula compatible with different channel ushering drugs on the homing of bone marrow stem cells of osteonecrosis of the femoral head (ONFH) induced by liquid nitrogen freezing in rabbits and discuss the mechanism for preventing and treating ONFH.

METHODThe ONFH model was established by liquid nitrogen freezing of 84 rabbits. They were randomly assigned to the model group and the Huogu II formula group and groups of Huogu II formula combining with Achyranthis Bidentatae Radix, Asari Radix et Rhizoma, Angelicae Pubescentis Radix, Platycodonis Radix. The remaining 14 rabbits were sham-operated. During the course of ONFH modeling, all of the rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor (rhG-CSF)(30 microg x kg(-1) x d(-1), for consecutively 7 days). Meanwhile, normal saline and decoction of the formulae were orally administrated respectively. WBC was counted in peripheral blood before and after the injection of rhG-CSF. HE stainings at the 2nd and the 4th weeks after the modeling were adopted to observe histopathological changes, vascular morphology was observed by ink perfusion, BrdU and SDF-1 were determined by immunohistochemical assay in femoral heads of the left hind leg.

RESULTCompared with the sham-operated group, the Huogu II formula group showed decrease in the ratio of empty lacuna and increase in vessel area, number of BrdU positive cells and SDF-1 level. In comparison with the model group, the Achyranthis Bidentatae Radix group displayed decreasing empty lacuna ratio and increasing vessel area at the 4th week and increasing SDF-1 at the 2nd week; the Platycodonis Radix group revealed a notably increasing empty lacuna ratio and a sharp decrease in the number of BrdU positive cells at 4th week; Asari Radix et Rhizoma and Angelicae Dubescentis Radix groups showed no remarkable change.

CONCLUSIONHuogu II formula can promote the directional homing of bone marrow stem cell to the necrosis area. Channel ushering drug achyranthes can further boost above effects of Huogu II formula.

Animals ; Bone Marrow Cells ; cytology ; Bromodeoxyuridine ; metabolism ; Chemokine CXCL12 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Femur Head Necrosis ; blood ; drug therapy ; metabolism ; pathology ; Gene Expression Regulation ; drug effects ; Humans ; Leukocyte Count ; Male ; Rabbits ; Stem Cells ; cytology ; drug effects

Elucidating the active components of traditional Chinese medicine(TCM)is essential for understanding the mechanisms of TCM and promote its rational use as well as TCM-derived drug development.Recent studies have shown that surface plasmon resonance(SPR)technology is promising in this field.In the present study,we propose an SPR-based integrated strategy to screen and analyze the major active components of TCM.We used Radix Paeoniae Alba(RPA)as an example to identify the compounds that can account for its anti-inflammatory mechanism via tumor necrosis factor receptor type 1(TNF-R1).First,RPA extraction was analyzed using an SPR-based screening system,and the potential active in-gredients were collected,enriched,and identified as paeoniflorin and paeonol.Next,the affinity con-stants of paeoniflorin and paeonol were determined as 4.9 and 11.8 μM,respectively.Then,SPR-based competition assays and molecular docking were performed to show that the two compounds could compete with tumor necrosis factor-α(TNF-α)while binding to the subdomain 1 site of TNF-R1.Finally,in biological assays,the two compounds suppressed cytotoxicity and apoptosis induced by TNF-α in the L929 cell line.These findings prove that SPR technology is a useful tool for determining the active in-gredients of TCM at the molecular level and can be used in various aspects of drug development.The SPR-based integrated strategy is reliable and feasible in TCM studies and will shed light on the eluci-dation of the pharmacological mechanism of TCM and facilitate its modernization.

Objective To observe the dynamic characteristics of protein kinase ,casein kinase II α (CK2α) ,expression during hepatic fibrogenesis in rats ;and the effects of a matrine derivative ,13-methylamino-18-thione-matrine (M ASM ) ,on CK2αexpression when it is used for anti-fibrotic treatment .Methods Hepatic fibrosis model was established in SD rats by dimethylnitrosamine (DMN) injection or by bile duct ligation (BDL) .The established fibrotic rats were given 50 mg/kg MASM or saline as a control by gavage for three weeks .The level of hepatic fibrosis was evaluated by histopathology examina-tion using hematoxylin-eosin staining ,and using the sirius red and Masson's trichrome staining for collagen determination in fi-brosis .The expressions of CK2αandα-smooth muscle actin (α-SMA) in hepatic tissues were detected by immunohistochemis-ry .Results CK2α is mainly expressed in the stellate cells of fibrotic livers induced by DM N or BDL comparing the control group .Along with the development of hepatic fibrosis as evidenced by α-SMA expression ,increased CK2α-positive cells in liver were detected while injecting DMN in the rats for one to four weeks .MASM treatment significantly inhibited the hepatic fibro-sis and suppressed the expression of CK2αcomparing the model group .Conclusion The expression level of CK2α,and hepatic fibrosis formation are positively correlated .The matrine derivative ,MASM ,can significantly inhibit hepatic fibrosis and sup-press the CK2αexpression .These results suggest CK2αmay be a potential target for hepatic fibrosis therapy .

Objective To investigate the clinical outcomes using posterior percutaneous endoscopic cervical discectomy (PECD) for single level cervical spondylotic radiculopathy (CSR).Methods From October 2015 to June 2016,33 patients (23 men,10 women,mean age 54.0 years,range from 30 to 85 years) who had single level CSR were treated by PECD,and the medical records were reviewed.All patients were followed up for an average of 13.5±4.6 months (range from 12 to 22 months).The operation related parameters (operation time,estimated blood loss,length of hospitalization,complications) and clinical parameters,including neck visual analog scale (Neck-VAS),ann visual analog scale (Arm-VAS),neck disability index (NDI) and the modified Macnab criteria were assessed at 3,6,and 12 months postoperatively and last follow-up.Disc height,shell angle,C2-C7 Cobb angle and range of motion were recorded preoperatively and at 3 months,6 months,12 months and last follow-up postoperatively.Results The mean operation time was 76.4±26.6 minutes (range from 40 to 120 minutes),the mean estimated blood loss was 30.2±15.6 ml (range from 20 to 80 ml),and the mean length of hospitalization was 3.5± 1.1 days (range from 2 to 8 days).There was significant decrease at different time points postoperatively in Neck-VAS,Arm-VAS,and NDI when compared with preoperatively (P＜ 0.05).According to the modified Macnab criteria,there was excellent concordance in 20 patients (60.6％),good in 7 patients (21.2％) and fair in 6 patients (18.2％) at the last follow-up.The disc height was significantly decreased at postoperative 3 months and 1 year compared with at preoperative (F=95.1,P＜0.01).The shell angle of index level (F=35.4.,P＜0.01),upper adjacent level (F=30.1,P＜0.01),lower adjacent level (F=1 1.7,P＜0.01) as well as spinal function units (F=22.2,P＜0.01) were increased significantly at postoperative compared with at preoperative.The range of motion of index level (F=8.1,P＜0.01) and upper adjacent level (F=64.0,P＜0.01) increased significantly at postoperative compared with at preoperative.The range of motion in lower adjacent level (F=1.5,P=0.23),spine functional unit of index level (F=2.9,P=0.06),as well as C2-C7 (F=0.6,P=0.56) had no significant difference between preoperative and postoperative 1 year (P＞0.05).One patient turned into traditional ACDF procedure because of hemorrhage limiting the vision during PECD operation.Upper extremity numbness and pain deteriorated in one case after a PECD procedure and was revised with ACDF at last.No other complications,like spinal cord injury,cervical root injury,cerebral spinal fluid leakage,infection as well as recurrence were found.Conclusion PECD,which can maintain normal cervical range of motion and intervertebral disc height,is a minimally invasive and essential procedure for CSR treatment with minor trauma,excellent outcome and quick recovery.Surgeon's experience,however,is needed in case of turning into open surgery for good outcome.

Objective:To investigate the types of non-tumor diseases in patients with cancer, and to explore the effects of those dis-eases on the diagnosis and treatment of cancer patients. Methods:We collected the medical records of cancer patients from January 2013 to December 2017 in Peking University Cancer Hospital, and screened for non-tumor diseases. The clinical records of the patients in this group were analyzed retrospectively, and the effects of those diseases on the diagnosis and treatment of tumors were dis-cussed. Results:Of the 1,323 cases of inter-hospital consultation, 1,153 cases of non-tumor disease (87.2％) were selected. There were 773 men (67.0％) and 380 women (33.0％) included. The median age was 62 (14-90) years. The primary tumor types included lung can-cer, gastric cancer, lymphoma, colorectal cancer, esophageal cancer, breast cancer, malignant melanoma, liver cancer, cholangiocarci-noma/gallbladder cancer, pancreatic cancer, and other tumors. Non-neoplastic diseases included cardiovascular disease in 356 cases (30.9％), respiratory system disease (17.0％) in 196 cases, digestive system disease in 107 cases (9.3％), skin and venereal diseases in 81 cases (7.0％), nervous system lesions (6.4％) in 74 cases, urinary system disease in 72 cases (6.2％), blood disease in 70 cases (6.1％), en-docrine and metabolic diseases in 47 cases (4.1％), autoimmune disease in 23 cases (2.0％), and other diseases (11.0％) in 127 cases. Impact on tumor diagnosis and treatment was as follows:direct, 771 cases (66.9％);no influence, 313 cases (27.1％);and uncertain, 69 cases (6.0％). Conclusions:Cardiovascular disease is a major non-tumor disease associated with cancer. Non-neoplastic diseases are important factors affecting the diagnosis and treatment plans of cancer.

OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.

ObjectiveTo further assess the safety of clinical application of Shujin Jianyao pills after marketing and find its potential risk factors as early as possible， to obtain the real world medication situation of Shujin Jianyao pills and its incidence of adverse reactions and clinical characteristics， and to explore the factors affecting the occurrence of adverse drug reactions （ADR）. MethodIn this study， prospective， large-sample， multi-center and intensive whole-hospital monitoring with continuous registration was carried out， combined with telephone follow-up visits 2-4 weeks after the end of medication， for whole treatment course monitoring among patients. In addition， the three-level quality control was strictly implemented in the monitoring process. The study used a proprietary electronic data management system for data management， and SAS 9.4 and R software were used for statistical analysis. ResultFrom May 2018 to July 2020， the study completed the safety monitoring of 3 033 patients taking Shujin Jianyao pills in 30 clinical departments of 25 hospitals in China. A total of 36 ADR cases （49 times） were confirmed by expert assessment on data and supervision quality and expert interpretation of ADR. ConclusionAccording to the World Health Organization （WHO）， the symptoms of adverse reactions were mainly classified into occasional adverse reactions （0.1%≤ADR<1%： abdominal distension， oral ulcer， dry mouth， constipation） and rare adverse reactions （0.01%≤ADR<0.1%： loss of appetite， rash， fatigue， increased ALT， increased creatinine， dizziness， stomachache， stomach distension， liver discomfort， pruritus， dysphoria， acid regurgitation， numbness in mouth， abdominal pain， sore throat， earache， tinnitus）. Moreover， through the synthetic minority oversampling technique （SOMTE） combined with logistic regression， the following factors might affect ADR： taking Shujin Jianyao pills for 1-14 days， aged 46-65， 66-80 and 81 and above as well as combined use of atorvastatin， cobamamide， calcitriol capsules， Gushukang capsules， glucosamine， nifedipine， methylcobalamin， metformin， Tenghuang Jiangu pills， Bugu tablets， and diclofenac sodium sustained-release tablets. This study provided a real world basis for the safety and standardized use of Shujin Jianyao pills in clinical practice.