BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Osteoarthritis(OA)mainly lies in the lesions of articular cartilage and surrounding tissues,pro-ducing osteophytes and bone sclerosis,resulting in damage to the articular cartilage.The main pathological mechanism of OA rests with a large number of inflammatory cytokines and inflammatory mediators produced by joint synovial lesions as well as pathological vascular growth at the junction of the synovium and cartilage,which may be one of the key reasons for promoting synovitis and cartilage damage.The OA mainly occurs in the knees,hips,hands and the spine.It is mainly manifested by chronic joint pain,swelling and stiffness,and limitation of motion seriously affects the functional activities of patients.The treatment of OA mainly relies on oral administration or intraarticular injection of drugs to relieve symp-toms.When OA develops to the middle and late stages,the action and life of patients will be seriously affected.There-fore,surgical replacement of joints is considered to ensure the basic life demands of patients.Studies show that traditional Chinese medicine(TCM)treatment has attracted widespread attention and application due to its unique advantages in pre-vention and treatment of OA.Janus kinase(JAK)/signaling transduction and transcriptional activator(STAT)signaling pathway may be one of the important signaling pathways that regulate the chondrocyte proliferation,differentiation and apoptosis.Moreover,it is closely associated with intra-articular inflammatory response.The JAK/STAT signaling pathway regulates the expression of inflammatory factors and related proteins through TCM so as to reduce the inflammatory re-sponse and decrease the chondrocyte damage.It has an important reference value for OA treatment.In this paper,the roles and mechanisms of the TCM monomers and active ingredients and the Chinese herbal compounds in OA by regulating JAK/STAT signaling pathway and affecting related cytokine and protein expression levels have been reviewed,providing a new method and direction for TCM treatment of OA.

N1-methyladenosine(m1A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels.Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.

Objective:To provide references for the application of finite element model in the study of cervical vertebra by statistically analysing the frequency, numerical value, properties, and boundary setting of the finite element model and the corresponding material features as well as boundary settings in the literature.Methods:The literature on cervical vertebra-related finite element models was collected from CNKI, Wanfang, VIP, PubMed, Web of Science, and Embase databases from January 2013 to December 2023. The quality assessment was followed by manual screening. The data sources, application classification, material properties (Young’s modulus and Poisson’s ratio), and boundary conditions of cervical vertebra, cervical intervertebral, and cervical ligaments were statistically analyzed.Results:A total of 102 papers were included. The finite element models of the cervical vertebra were derived from medical image reconstruction modeling techniques, predominantly CT plain scan and magnetic resonance imaging. Among the 102 cervical vertebra models, the C3-C7 (lower cervical segment) model appeared with the highest frequency (19). The Young’s modulus of the cortical bone, cancellous bone, and posterior structure of cervical vertebrae were set at about 12 000 or 10 000, 440, and 3 600 MPa, respectively, and the Poisson’s ratios were mainly set at about 0.29 or 0.30, 0.29, and 0.29. The Young’s modulus of the cervical intervertebral disc endplate, nucleus pulposus, and annulus fibrosus were concentrated around 500 or 2 000, 1, and 100 MPa, respectively, and the Poisson’s ratios were set at about 0.40, 0.50, and 0.40, respectively. The Young’s modulus of the anterior longitudinal ligament, posterior longitudinal ligament, transverse ligament, ligamentum flavum, interspinous ligament, capsular ligament, and articular cartilage of the cervical spine were set around 30, 20, 20, 6-10, 4-8, 10 or 20, 10 MPa, and the Poisson’s ratios were set at aoubt 0.30, 0.30, 0.30, 0.30, 0.30, 0.40, and 0.30, respectively. The Young’s modulus of the upper cervical interdental ligament, lamina, cruciate ligament, nuchal ligament, and pterygoid ligament were set at about 10, 10, 10 or 20, 20, and 5 MPa, respectively, and the Poisson’s ratios were set at about 0.30. Head weight settings were more common at 50, 74, and 100 N.Conclusions:The finite element model of the cervical vertebra has great value in the study of cervical spondylosis, but further optimization is still needed in the assignment of material properties, mesh division, and model verification to improve the accuracy and clinical applicability of the model.

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

Objective To analyze the level of post-traumatic stress disorder(PTSD)and its risk factors in patients with ischemic stroke.Methods A total of 183 cases of patients with ischemic stroke treated in Putuo District People's Hospital of Zhoushan City from May 2020 to June 2022 were selected as the observation objects.Basic information of patients was collected by self-made questionnaire,including gender,age,personality characteristics,family per capita monthly income,education level,marital status,ability of daily living,duration of ischemic stroke,family function,type of medical insurance,whether there was swallowing dysfunction,whether there was underlying disease(heart disease,hypertension,hyperlipidemia and diabetes),whether there is anxiety,coping style,level of social support.PTSD self-rating scale(PTSD-SS)was used to determine the complications of PTSD in ischemic stroke patients,and the incidence of PTSD was calculated.To compare the difference in basic information between the two groups of patients with PTSD.Factors with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to screen out the risk factors affecting the development of PTSD in patients with ischemic stroke,and receiver operator characteristic curve(ROC curve)was drawn to evaluate the predictive value of each risk factor for the development of PTSD in patients with ischemic stroke.Results PTSD-SS score of 183 patients with ischemic stroke(48.76±9.21)was relatively low.Among them,37 case(20.22%)of patients developed PTSD.Compared with the non-PTSD group,the proportion of patients with introverted personality,dysfunctions of daily living,swallowing dysfunction,combined anxiety,negative coping style,and low/no social support was significantly increased in the PTSD group(all P＜0.05).Multivariate Logistic regression analysis showed that introverted personality,severe impairment of daily living ability,swallowing dysfunction,combined anxiety,negative coping style,and low/no social support were independent risk factors for PTSD in ischemic stroke patients[odds ratio(OR)and 95%confidence interval(95%CI)were 2.289(1.091-4.804),5.842(1.658-20.587),2.634(1.095-6.333),7.138(3.255-15.655),2.751(1.271-5.953),3.153(1.477-6.733),all P＜0.05].ROC curve analysis showed that introverted personality,severe impairment of daily living ability,swallowing dysfunction,combined anxiety,negative coping style,and low/no social support all had certain predictive value for the occurrence of PTSD in ischemic stroke patients,the area under the ROC curve(AUC)was 0.602,0.675,0.573,0.722,0.603,0.624,and 95%CI was 1.091-4.804,1.342-9.566,1.095-6.333,3.255-15.655,1.271-5.953,1.477-6.733,respectively,all P＜0.05.The sensitivity to predict PTSD in ischemic stroke patients was 58.2%,87.7%,87.7%,79.5%,80.1%,78.8%,and the specificity was 37.8%,67.6%,70.3%,35.1%,59.5%,54.1%,respectively.Conclusions Ischemic stroke patients have a certain risk of concurrent stress disorder after trauma,and are easily affected by stroke patients'personality characteristics,daily living ability,swallowing dysfunction,coping style and social support,etc.Targeted preventive interventions should be developed to reduce the risk of PTSD and improve the prognosis and quality of life.

Objective To analyze the changes in morphology of intervertebral foramina in patients with cervical spondylotic radiculopathy (CSR) treated with fixedpoint lateral flexion and rotation manipulation based on three-dimensional (3D) reconstruction technology, so as to provide references for the effectiveness of manipulation treatment. MethodsForty patients with CSR were treated with fixed point lateral flexion and rotation manipulation once every other day for a total of 7 times and 2 weeks as a course of treatment. CT data of the patients before and after treatment were analyzed by using multifunctional CT, Mimics 21.0, Geomagic and SolidWorks 2017. The area of the intervertebral foramen, anterior and posterior diameter of the intervertebral foramen, upper and lower diameter of the intervertebral foramen were measured before and after treatment, as well as the infrared thermal imaging temperature differences of the bilateral neck and shoulder, front and back of the upper limb, and the VAS scores of the patients were observed before treatment, 7 d after treatment, 14 d after treatment and 1 month follow-up. Results Foraminal area, anterior and posterior diameters, upper and lower diameters of 40 patients were improved after treatment, and the temperature differences of infrared thermal imaging of patients before and after treatment were statistically significant. The VAS score of the patients decreased progressively. Conclusions Fixed point lateral flexion manipulation can significantly improve the shape of the intervertebral foramen in patients with CSR, so as to achieve the treatment purpose of relieving nerve compression.

Objective:To observe the effects of "pushing patella and extending knee" manipulation on the protein and mRNA expression levels of integrin β1 (ITGβ1) and phosphorylated adhesion plaque kinase (p-FAK) in rabbit knee osteoarthritis (KOA) model, and to investigate the mechanism of manipulations in the treatment of KOA.Methods:Twenty healthy 6-month-old New Zealand rabbits were divided into the normal group, the model group, the acupuncture group, and the manipulation group according to the random number table method. Among them, the model group, the acupuncture group, and the manipulation group were modeled using the modified Hulth method for KOA. After 7 d of successful modeling, the normal group and the model group did not receive any intervention, while the acupuncture group and the manipulation group received one acupuncture intervention and one "pushing patella and extending knee" manipulation intervention daily, respectively. After 2 weeks of treatment, the rabbit KOA model was executed by air embolization, and the protein and mRNA expression levels of ITGβ1 and p-FAK in knee cartilage were measured by Western blot and real-time polymerase chain reaction (PCR), respectively.Results:Compared with the normal group, the ITGβ1 protein expression level was decreased ( P<0.05) and p-FAK protein expression level was increased ( P<0.05), and the mRNA expression levels of ITGβ1 and p-FAK did not change significantly (all P>0.05) in the model group. Compared with the model group, the ITGβ1 protein expression level was increased ( P<0.05), the p-FAK protein expression level decreased ( P<0.05), and the mRNA expression levels of both ITGβ1 and p-FAK increased (all P<0.05) in the acupuncture group. Compared with the acupuncture group, ITGβ1 protein expression level increased ( P<0.05), p-FAK protein expression level decreased ( P<0.05), and mRNA expression levels of both ITGβ1 and p-FAK increased (all P<0.01) in the manipulation group. Conclusions:The "pushing patella and extending knee" manipulation can optimize the protein and mRNA expression levels of ITGβ1 and p-FAK in the articular cartilage of the rabbit KOA model.

Objective:To explore the application value of the method of judging the density of small shadows in the lung area by using CT and CT reference films for pneumoconiosis.Methods:The chest imaging data of 244 employees of a large copper company in Tongling City, Anhui Province who underwent occupational physical examination at Tongling Municipal Hospital in Anhui Province from January 2016 to December 2019 were retrospectively analyzed. Totally 244 cases underwent chest CT scan and chest DR radiography at the same time. The shape and size of the small shadows (the size of the circular and quasi-circular nodules in the lung area were represented by p, q, r, and the size of the irregular small shadows were represented by s, t, u), the overall density, the density of small shadows in each lung area, the large shadows, and the diagnosis stage were observed and compared. The small shadow density of each lung area was judged by the method of judging the small shadow density of CT lung area and the reference film, and other observation indicators were judged according to GBZ70-2015 Diagnosis of Occupational Pneumoconiosis. Results:There was a significant difference between CT and DR in judging s-shaped small shadows and no small shadows ( P<0.05), and there was no statistically significant difference in judging p, q, r, t, and u-shaped small shadows ( P>0.05). CT and DR had medium to high consistency in the judgment of the overall density of small shadows (Kappa=0.692, P=0.001), and the diagnostic coincidence rate was 82.38% (201/244). There was moderate to high agreement between CT and DR in the density of small shadows shown in the right upper, right lower, left upper, left middle, and left lower lung regions (Kappa ranged from 0.40 to 0.75, P<0.05), and the consistency in the right middle lung region was poor (Kappa=0.381, P=0.001). Eleven large shadows were detected in 8 cases by DR, 31 large shadows were detected in 23 cases by CT, and 20 (8.20%) large shadows were detected more frequently by CT than DR. The agreement between CT and DR for the diagnosis and staging of silicosis was excellent (Kappa=0.843, P=0.001), and the diagnostic coincidence rate was 91.80% (224/244). Conclusion:Applying the method of determining the density of small shadows in the lung area of pneumoconiosis and reference films, combined with GBZ70-2015 Diagnosis of Occupational Pneumoconiosis, can make a more accurate diagnosis of silicosis.