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BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.
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BACKGROUND:The impact of anterior cervical surgery on the sagittal balance parameters of the cervical spine is gradually being paid attention to.Currently,there is a lack of clear and feasible clinical guidelines for the selection of surgical methods for two-level cervical spondylosis,aiming to find the most suitable fixation method that is more beneficial for this type of patient. OBJECTIVE:To compare the effects of different fusion devices for anterior cervical decompression on the changes of cervical sagittal parameters after surgery for adjacent two-level cervical spondylotic myelopathy. METHODS:A total of 44 patients with adjacent two-level cervical spondylotic myelopathy underwent anterior cervical discectomy and fusion from March 2018 to September 2020 in Liaocheng People's Hospital were retrospectively analyzed in the study,and they were divided into zero-p group(23 cases)and cage group(21 cases).All patients underwent anteroposterior X-ray,three-dimensional CT reconstruction and MRI examination before operation.At the last follow-up,the anteroposterior X-ray films of cervical spine were taken.The sagittal balance parameters of the cervical spine were measured before and after surgery,including cervical lordotic angle(C2-7 Cobb),C2-C7 sagittal vertical axis,segmented lordotic angle and T1 slope.The surgical time,intraoperative bleeding,last follow-up intervertebral fusion,and postoperative swallowing disorders were recorded,and Japanese Orthopaedic Association score on the patient was evaluated before and after surgery.The changes in cervical sagittal parameters before and after surgery were calculated and their differences were compared between the two groups. RESULTS AND CONCLUSION:(1)Both groups of patients successfully completed the surgery and received follow-up.The zero-p group had shorter surgical time and less intraoperative bleeding compared to the cage group,but the difference was not statistically significant(P>0.05).(2)The incidence rate of postoperative swallowing disorders in the cage group(7/21,33%)was higher than that in the zero-p group(3/23,13%),and the difference was statistically significant(P<0.05).(3)At the last follow-up,the clinical efficacy of the two groups was the same;all patients had bone fusion.Comparison within the group showed that the sagittal parameters of the cervical spine in both groups improved compared to before surgery(P<0.05).There was no statistically significant difference in sagittal parameters between groups(P>0.05),and there was no statistically significant difference in changes in C2-C7 sagittal vertical axis,C2-7 Cobb angle,and T1 slope between the two groups(P>0.05).However,the segmented lordotic angle changes in the zero-p group were smaller than those in the cage group,and the difference was statistically significant(P<0.05).(4)It is indicated that the use of zero-p and titanium plate combined with cage during anterior cervical discectomy and fusion surgery can effectively improve cervical sagittal balance.Titanium plate combined with cage intervertebral fusion can better reconstruct the patient's cervical lordosis and curvature.The selection of fusion devices should also comprehensively consider the occurrence of surgical complications.
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Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.
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Objective: To observe the effects of electroacupuncture (EA) pretreatment on M1 polarization of alveolar macrophages (AMs) in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to explore the potential protective mechanism of EA.Methods: Forty Sprague-Dawley rats were randomly divided into a normal group, a model group, and three groups of EA pretreatment [including a Chize (LU5) group, a Zusanli (ST36) group and a Chize (LU5) plus Zusanli (ST36) group], with eight rats in each group. The model rats of ALI were established by instilling LPS [2 mg/(kg·bw)] into the trachea of rats for 3 h. The rats in each EA pretreatment group were pretreated with EA for 30 min per day at the corresponding bilateral acupoints 6 d before instilling LPS. Three hours after modeling, the pulmonary function of the rats was tested, and the lung tissue was taken to calculate the ratio of lung wet weight to dry weight (W/D). The pathological lung changes and the injury score were observed by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) in rat's bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of M1 macrophage markers clusters of differentiation 86 (CD86), inducible nitric oxide synthase (iNOS), and its signaling pathway factor Toll-like receptor (TLR) 4, and nuclear factor-κB (NF-κB) p65 in the alveoli were detected by fluorescence quantitative polymerase chain reaction and Western blot, respectively. Results: After being induced by LPS, the pulmonary function of the model rats showed that the forced expiratory volume in 0.1 s (FEV0.1), forced expiratory volume in 0.3 s (FEV0.3), and their respective ratios of FEV to forced vital capacity (FVC) (including FEV0.1/FVC and FEV0.3/FVC) were significantly decreased (P<0.01), while the W/D of lung tissue was increased (P<0.01). The score of lung injury was significantly higher (P<0.01). The contents of TNF-α, IL-1β, and MPO in the BALF and the mRNA and protein expression levels of CD86, iNOS, TLR4, and NF-κB p65 in the lung tissue were significantly increased (P<0.01). After EA pretreatment, the FEV0.1, FEV0.3, FEV0.1/FVC, and FEV0.3/FVC were significantly increased, the lung injury score decreased significantly, and the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs and proteins in the alveoli decreased significantly (P<0.05 or P<0.01). Compared with the other two single acupoint groups, the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs in the alveoli in the Chize (LU5) plus Zusanli (ST36) group were significantly lower (P<0.01). Conclusion: EA pretreatment at Chize (LU5) and Zusanli (ST36) can inhibit inflammation and reduce pulmonary injury in ALI rats induced by LPS. The effect of the combination of Chize (LU5) and Zusanli (ST36) is better than that of using these two acupoints separately, and its mechanism may be related to the inhibition of AMs' M1 polarization by down-regulation TLR4/NF-κB signaling pathway.
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【Objective】 The purpose of this study was to perform bioinformatics analysis of infliximab （IFX） treatment of rheumatoid arthritis （RA） non-responders and responders gene data chip based on autophagy， and to screen out the characteristic autophagy-related genes， carry out a preliminary experiment on the role of characteristic genes， and explore the possible mechanism of IFX treatment of RA non-response. 【Methods】 R language was used to analyze the differential expressions of autophagy-related genes on the selected gene expression omnibus database （GEO） data set. Univariate logistic regression， least absolute shrinkage and selection operator （Lasso） regression， and multiple logistic regression analyses were made to screen out the characteristic autophagy-related genes； receiver operating characteristic curve （ROC） was used to assess the diagnostic value of the characteristic autophagy-related genes. Real-time PCR was used to detect the expressions of characteristic autophagy-related genes in RA clinical samples， and Western blot was used to detect the role of characteristic autophagy-related genes in autophagy in RA synovial cell line MH7A cells. 【Results】 Part of autophagy-related genes were differentially expressed between non-responders and responders to IFX treatment of RA （P<0.05）， and autophagy-related gene sets were mainly expressed in non-responders. Hepatocyte growth factor-regulated tyrosine kinase substrate （HGS） and autophagy related 4 homolog B （ATG4B） were screened out as characteristic genes of non-response to IFX treatment of RA. The ROC showed that the predictive model constructed using the selected markers had good discrimination ability in the internal validation data set GSE78068 （AUC=0.708， P<0.05） and the external validation data set GSE58795 （AUC=0.719， P<0.05）. The Real-time PCR results showed that the expression of HGS was increased in peripheral blood leukocytes in the non-responders. After overexpression of HGS in MH7A cells， the ratio of LC3BⅡ/LC3BⅠ was increased while the expression of P62 was decreased， indicating that autophagy increased. 【Conclusion】 The autophagy-related gene expression profiles were different between IFX-treated RA non-responders and responders， suggesting that the non-response of IFX treatment of RA may be related to autophagy. The prediction model constructed with HGS and ATG4B had a certain ability to predict IFX-treated RA non-response， and HGS promoted autophagy in MH7A cells， which provides a new idea for future research on the molecular mechanism of IFX in treating RA non-response.
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Objective To explore the incidence of dysphagia and its potential risk factors.Methods From January 2014 to December 2015,a total of 187 patients who underwent single-level anterior cervical spine surgery were recruited in this retrospective analysis study.Specific perioperative data including age,gender,smoking,alcohol use,BMI,estimated blood loss,surgical segment,length of incision,and length of hospital stay were recorded respectively.The Bazaz grading system and the swallowing quality of life (SWAL-QOL) score were used to assess the presence and severity of dysphagia.According to the Bazaz grading system,the patients were divided into dysphagia group and non-dysphagia group 1 week after operation.One-factor x2 test and one-sample t test were used to univariate analyze the two groups of related factors,and select the potential variables for multivariate logistic regression analysis to identify the risk factors leading to dysphagia.Results The number of dysphagia patient was 99 (52.94％) at 1 week after surgery,and 16 (8.56％) at 1 year.The preoperative mean SWAL-QOL score was 65.62±4.41 points,which decreased to 58.72±7.54 points after surgery and rose up to 64.66±5.26 points at the 12-month follow-up.The SWAL-QOL score at 1 week after surgery was correlated with the operative time (r=-0.474;P ＜ 0.001).Multivariate analysis indicated that preoperative tracheal exercise (OR=0.302,95％CI:0.131,0.748),operation time ＜ 60 min (OR=0.407,95％CI:0.190,0.878),and arthroplasty (OR=0.211,95％CI:0.102,0.425) were the independent factors to reduce the incidence of postoperative dysphagia.Conclusion The incidence and severity of dysphagia symptoms after single-level anterior cervical spine surgery gradually decreased with the extension of follow-up time.Preoperative tracheal exercise,shortened operative time and manual artificial disc replacement may be helpful to reduce the postoperative occurrence of dysphagia.
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Objective To evaluate the diagnostic efficacy of magnetic resonance(MR)-guided prostate biopsy based on abnormal diffusion weighted imaging for prostate cancer in elder men.Methods From July 2014 to Dec 2016,56 patients (age≥ 65 years) with diffusion weighted imaging (DWI)abnormalities undergoing MR-guided prostate biopsy were retrospectively evaluated.According to pathological diagnosis,patients were divided into prostate cancer and non-prostate cancer groups.The clinical data of two groups were analyzed.The correlation of Gleason score,prostate specific antigen(PSA),and the location and number of biopsy were compared.Results Among 56 cases,32 (57.1％)were diagnosed as prostate cancer,and 24 (42.9％)as chronic prostatitis and prostatic hyperplasia (non-prostate cancer).There were statistically significant differences between prostate cancer and non-prostate cancer in age[(73.0±5.7)vs.(70.1±4.3)year]and PSA[(9.3±6.0)μg/L vs.(6.0± 3.9)μg/L] (both P＜0.05),and no statistical differences in biopsy location and biopsy number(t =2.08,2.37,P＞ 0.05).Gleason score had no correlation with PSA level and biopsy location and biopsy number(r=0.189、-0.183、0.082,P＞0.05).Conclusions MR-guided prostate biopsy based on MR-DWI has some merits,such as accurate positioning,fewer numbers of biopsy,and lower false-negative rate.
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Objective To explore the reliability and validity of poly ether ether ketone (PEEK) rods and pedicle screw system for lumbar degenerative diseases.Methods Sixty-three patients,including 23 men and 40 women with the mean age of 56.2±5.1 years (range,35-75 years),treated by PEEK rods pedicle screw system from September 2012 to March 2013 were retrospectively recruited.Fusion procedure were performed in 10 patients,with 2 cases at L3,4,5 cases at L4,5,3 cases at L5S1; nonfusion procedure were performed in 17 patients,with 4 cases at L3,4,10 cases at L4,5,3 cases at L5S1; hybrid procedure were performed in 36 patients,with 22 case fusion at L4,5 and nonfusion at L3,4,with 2 cases fusion at L3,4 and nonfusion at L4,5,with 12 cases fusion at L5S1 and nonfusion at L4,5.Clinical effects were evaluated via Japanese Orthopedics Association (JOA) score and Oswestry disfunction index (ODI) at 3 months,6 months and 24 months postoperatively.Disc heights were measured by disc height index on lateral lumbar radiograph.Range of motion (ROM) was measured by extension-flexion lumbar X-ray.Three-dimensional CT reconstruction was achieved to observe the integrity of PEEK rods at the final follow-up.Results The mean follow-up were 23.4±3.3 months.The mean operation time were 110±17 min in the fusion group,98±22 min in the non-fusion group and 121±25 min in the hybrid group.The mean blood loss were 270±85 ml in the fusion group,255±72 ml in the non-fusion group and 316±80 ml in the hybrid group.The JOA score improved from 10.5±2.6 preoperatively to 24.0±3.1 at the final follow-up in the fusion group,from 10.3±2.2 to 24.3±3.4 in the non-fusion group and from 11.1±2.3 to 23.9±3.3 in the hybrid group (P＜0.05).The ODI decreased from 51.8％±10.3％ preoperatively to 14.1％±3.7％ at the final follow-up in the fusion group,from 52.2％±11.1％ to 13.2％±3.2％ in the non-fusion group and from 53.4％±9.2％ to 13.8％±2.5％ in the hybrid group.There was no significantly statistical difference in the disc height index at 3 months,6 months and 24 months postoperatively compared with that at preoperative.The ROM decreased from 8.8°±1.8° preoperatively to 2.2°±0.3° at the final follow-up (P＜0.05).One case demonstrated cage migration at one month follow-up,bony fusion in situ at 3 months follow-up,and the patient had no related symptoms during the follow-up.No screw loosening or breakage and rods breakage was observed during the follow-up.Conclusion PEEK rods and pedicle screw system for lumbar degenerative diseases by fusion,non-fusion and hybrid procedure can achieve considerable clinical outcome with low complication rate.
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Objective To establish a Hr mutant knockout mouse model to study the function of Hr gene.Methods Transcription activator-like effector nucleases ( TALENs) technique was used to disrupt the mouse Hr locus,creating heritable mutations that eliminate Hr function to explore the effects of Hr on hair development and provide a good model to study the function of Hr gene.The phenotype of Hr -/- mice was observed after birth and skin histology of the transgenic mice was studied by light microscopy.Results It was shown that a F0 mouse with the 2 -bp deletion in Hr gene ranging from 86 to 87 base pairs was obtained.The male mice with clear deletion of the Hr fragment and with obvious frame shifting were mated with wild-type female mice, and F1 mice were achieved.The heterozygous males mated with females to generate the F2 homozygous mice.The first hair coat of Hr-/- mice developed normally.Beginning from 14 days after birth, however, there was a rapid hair loss.The mices were completely hairless except for a few vibrissae at 30 days. Histologically, two characteristic structures appeared, the utriculus and dermal cyst.Conclusions The results suggest that Hr -/- mice are successfully created using TALENs, and Hr is important for regulating hair development, which could explain at least in part the hair loss and be applied to study the mechanism of hair growth and development disorder.
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BACKGROUND: The incidence of the adjacent vertebral fracture after kyphoplasty is about 2.4%-23.0%, and 2/3 of new fractures occurred in adjacent vertebrae in 6 months. There is controversy addressing the reason which is the development of osteoporosis or the result of bone cement augment at present.OBJECTIVE: To determine the correlations between percutaneous kyphoplasty on adjacent vertebral endoplates stresses pressure under physiologianl load and a new fracture of adjacent vertebral body in physiological load.METHODS: Computed tomography (CT) data of an old female osteoporotic patient was selected, and a three-dimensional finite element model of the osteoporetic thoracolumbar spine T_(12)-L_1-L_2 was created by using kinds of computer aided design software.The height of vertebral L_1 was compressed by 60% to simulated the compressed fracture, and the height of L_1 became the 90% of normal to simulate the replacement, two columns-like PAMA mass (4 mL) was placed in vertebral L_1 to simulate pemutaneous kyphoplasty. The stress on inferior endplate of L_(12) and superior endplate of L_2 was compared with three models. RESULTS AND CONCLUSION: Compared to the normal vertebral body, the maximum stress in the adiacent vertebral bodies endplates increased by 76% for L_1 compress fracture model and increased by 27% for kyphoplasty model, respectively. The stress on the posterior part of vertebral body after percutaneous kyphoplasty have an average increase of 13.2%, of which 4.5% increase in the pedicle, isthmus, and 6.15% increased in the key points 25.6%, but with the wedge-shaped fracture of L_1 vertebral body compared to the model, percutaneous kyphoplasty after pedicle, isthmus and the articular process had reduced stress. The results indicate that the stress on inferior endplate of L-(12) and superior endplate of L_1 increased after percutaneous kyphoplasty under all loading conditions. Increased stress may lead endplate fracture, and increase the risk of adjacent vertebral body fracture. Further researches are needed to support the conclusion.