BACKGROUND:Intervertebral disc degeneration is the main pathological factor causing low back pain,which is closely related to macrophage-mediated immune inflammation.Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration,but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue.OBJECTIVE:To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats,as well as its mechanisms for the treatment of intervertebral disc degeneration.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,and Tongdu Huoxue Decoction group,with eight rats in each group.An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups.On the 1st postoperative day,10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group,and the same dose of saline was given by gavage in the sham operation group and the model group,once a day.After 4 weeks of intervention,histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin.Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68,CD206,interleukin 1β,interleukin 10,type II collagen,and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height,disorganized annulus fibrosus structure with fissures,and unclear demarcation between the nucleus pulposus and the annulus fibrosus.The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis.(2)Immunohistochemical results demonstrated that,compared with the model group,the Tongdu Huoxue Decoction group had significantly lower expressions of CD68,interleukin 1β,and matrix metalloproteinase 13,and significantly higher expressions of CD206,type II collagen and interleukin 10(P<0.05 or P<0.01).(3)qPCR results showed that there were significant differences in the mRNA expression of CD68,CD206,interleukin 1β,matrix metalloproteinase 13,type II collagen,and interleukin 10 between the three groups(P<0.001).To conclude,Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration,and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs.

BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.

BACKGROUND: Whether adherence to a healthy lifestyle is associated with a lower risk of developing pneumonia and a better long-term prognosis remains unclear. This study aimed to investigate associations of individual and combined lifestyle factors (LFs) with the incidence risk and long-term prognosis of pneumonia hospitalization. METHODS: Using data from the China Kadoorie Biobank study, we used the multistate models to investigate the role of five high-risk LFs, including smoking, excessive alcohol drinking, unhealthy dietary habits, physical inactivity, and unhealthy body shape, alone or in combination in the transitions from a generally healthy state at baseline to pneumonia hospitalization or cardiovascular disease (CVD, regarded as a reference outcome), and subsequently to mortality. RESULTS: Most of the five high-risk LFs were associated with increased risks of transitions from baseline to pneumonia and from pneumonia to death, but with different risk estimates. The greater the number of high-risk LFs, the higher the risk of developing pneumonia and long-term mortality risk after pneumonia, with the strength of associations comparable to that of LFs and CVD. Compared to participants with 0-1 high-risk LF, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for transitions from baseline to pneumonia and from pneumonia to death in those with five high-risk LFs were 1.43 (1.28-1.60) and 1.98 (1.61-2.42), respectively. Correspondingly, the respective HRs (95% CIs) for transitions from baseline to CVD and from CVD to death were 2.00 (1.89-2.11) and 1.44 (1.30-1.59), respectively. The risk estimates changed slightly when further adjusting for the presence of major chronic diseases. CONCLUSION In this Chinese population, unhealthy LFs were associated with an increased incidence and long-term mortality risk of pneumonia.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/etiology* ; China/epidemiology* ; Life Style ; Pneumonia/etiology* ; Prognosis ; Risk Factors ; Smoking

BACKGROUND:Intervertebral disc degeneration is the main pathological factor causing low back pain,which is closely related to macrophage-mediated immune inflammation.Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration,but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue.OBJECTIVE:To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats,as well as its mechanisms for the treatment of intervertebral disc degeneration.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,and Tongdu Huoxue Decoction group,with eight rats in each group.An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups.On the 1st postoperative day,10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group,and the same dose of saline was given by gavage in the sham operation group and the model group,once a day.After 4 weeks of intervention,histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin.Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68,CD206,interleukin 1β,interleukin 10,type II collagen,and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height,disorganized annulus fibrosus structure with fissures,and unclear demarcation between the nucleus pulposus and the annulus fibrosus.The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis.(2)Immunohistochemical results demonstrated that,compared with the model group,the Tongdu Huoxue Decoction group had significantly lower expressions of CD68,interleukin 1β,and matrix metalloproteinase 13,and significantly higher expressions of CD206,type II collagen and interleukin 10(P<0.05 or P<0.01).(3)qPCR results showed that there were significant differences in the mRNA expression of CD68,CD206,interleukin 1β,matrix metalloproteinase 13,type II collagen,and interleukin 10 between the three groups(P<0.001).To conclude,Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration,and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs.

Objective To investigate the distributions of vitamin K1 and K2 in infants of different age groups by comparing the serum levels of vitamin K1 and K2 in them.Methods 1177 infants from 0 to 3 months were divided into 6 age groups.Those born/treated in the subject units(pediatrics,neonatology,child health care,obstetrics)were selected as the study subjects and grouped by age:0～3 days(591 cases),4～7 days(255 cases),8～5 days(104 cases),1 month(118 cases),2 months(40 cases),and 3 months(69 cases).General data of the infants were collected,and the serum vitamin K1 and K2 levels were determined by HPLC-mass spectrometry(LC-MS)on a unified platform,and analyzed from the distribution of vitamin K1 and K2 at different ages.Results The distributions of vitamin K1 and K2 levels were statistically significant(P<0.001);newborns were highly vulnerable to vitamin K1 deficiency,and vitamin K2 deficiency was higher than vitamin K1 with age.Conclusion Maintaining the normal growth of vitamin K1 and K2 is crucial for the normal growth and development of infants of all ages,so we should pay close attention to the monitoring and supplement of vitamin K1 and K2.

Objective:To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China.Methods:After excluding those born after 31 st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31 st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results:A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95% CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95% CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m 2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95% CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95% CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m 2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion:This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

[Objective]To explore the intervention effect of β-sitosterol,an effective monomer component of Eucommia ulmoides,on postmenopausal osteoporosis in mice and its potential mechanism.[Methods]Twenty-four female C57BL/6J mice of 12 weeks old were randomly divided into sham operation group,model group and β-sitosterol intervention group,with 8 mice in each group.The model of postmenopausal osteoporosis was established by bilateral ovariectomy.Mice in sham group and model group were given 0.9％sodium chloride solution and β-sitosterol intervention group was given β-sitosterol.Eight weeks after operation,all the mice were sacrificed and samples were collected.Micro-computed tomography(Micro-CT)was used to observe the protective effect of the β-sitosterol intervention on postmenopausal bone loss and trabecular bone breakage.Hematoxylin-eosin(HE)staining was used to analyze the bone histomorphology of the distal femur.The tartrate-resistant acid phosphatase(TRAP)staining and the alkaline phosphatase(ALP)staining were used to evaluate bone resorption and bone formation respectively.Then the expression level of β-catenin in each group was detected by immunohistochemistry.[Results]Micro-CT scanning showed that β-sitosterol could reduce bone loss and bone microstructure destruction in postmenopausal mice.HE staining also confirmed that β-sitosterol could effectively maintain the number and morphology of trabecular bone and inhibit abnormal fat accumulation caused by estrogen deficiency.TRAP staining also showed that β-sitosterol treatment did not affect osteoclast formation,while immunohistochemical results showed that β-sitosterol could significantly promote the expression of osteogenic marker ALP.Moreover,β-sitosterol can increase the expression of β-catenin in the distal femur to promote bone formation.[Conclusion]β-sitosterol treatment could enhance osteogenic differentiation and promote bone formation to relieve postmenopausal osteoporosis by upregulating β-catenin expression in vivo.

Based on the pathogenesis of “tendon off-position and joint subluxation”， combined with modern ana-tomy and biomechanics， the characteristic manifestations of “tendon off-position” and “joint subluxation” of the knee and the intrinsic connection between them are clarified. Through sorting out the relationship between “tendon off-position and joint subluxation” and knee osteoarthritis （KOA） in modern research， it is believed that “tendon off-position and joint subluxation” is the key mechanism for the occurrence and development of KOA， and accordingly， it is proposed to take the diet as the guide， use bone manipulation for external diagnosis and treatment， use traditional Chinese medicine decoction for internal treatment， and use Daoyin exercise throughout the whole process as the strategy for KOA's comprehensive traditional Chinese medicine treatment to improve the clinical effectiveness.

BACKGROUND:Mechanical stimulation has been confirmed to promote osteogenic differentiation of bone marrow stromal stem cells,but the mechanism is unknown.Primary cilia are important mechanoreceptors and regulate various signaling pathways such as TGF-β1/BMP-2/SMAD.They are likely to be important targets for mechanical regulation of bone marrow stromal stem cells. OBJECTIVE:To investigate the effect and mechanism of fluid shear stress on osteogenic differentiation of bone marrow stromal stem cells. METHODS:Rat bone marrow stromal stem cells were divided into control group,mechanical stimulation group(fluid shear mechanics intervention by shaking table),mechanical stimulation + IFT88 silencing group(mechanical stimulation + silencing IFT88 expression with siRNA).After 24 hours of intervention,qRT-PCR was utilized to determine the expression of transforming growth factor β1 and bone morphogenetic protein 2.Western blot assay was used to detect the expression of phosphorylated SMAD2/3 protein.Immunofluorescent staining of primary cilia was conducted and morphology was analyzed. RESULTS AND CONCLUSION:Shear stress stimulation could promote the transcriptional activity of transforming growth factor β1 and bone morphogenetic protein 2 genes,and increase the expression of phosphorylated SMAD2/3 protein.After siRNA interfered with primary cilia,this mechanical response effect was significantly reduced.There was a Spearman correlation between the change ratio of the primary cilium area of bone marrow stromal stem cells and the increased ratio of transforming growth factor β1 and bone morphogenetic protein 2 gene transcription.These findings indicate that primary cilia/intraflagellar transport mediates the activation of fluid shear stress-responsive transforming growth factor β1/bone morphogenetic protein 2/SMAD signaling pathway and promotes osteogenic differentiation of bone marrow stromal stem cells.

BACKGROUND:"Tendon off-position"is a disease name included in the International Classification of Diseases 11th Revision,and also a clinical indication of manipulation,acupuncture and other treatments.However,its specific mechanism is still unclear.It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of"tendon off-position,"so as to further study the mechanism of effective clinical treatments. OBJECTIVE:To establish an animal model of"tendon off-position"in rats based on isometric contraction of skeletal muscles,and to explore the changes of skeletal muscle function and morphological phenotype after"tendon off-position." METHODS:Sixty rats were randomly divided into control group,static-loading group and extra loading group,with twenty rats in each group.Rats in the control group were kept normally without treatment.In the latter two groups,the rats were fixed by the self-made static-loading modeling device and a static-loading(the body mass of each rats was applied as the static-loading)was applied to cause sustained isometric contraction of the upper limb muscles.Then,animal models of"tendon off-position"were successfully established.In the extra loading group,50%of the body mass was added to the ankle joint after modeling.The skeletal muscle samples were harvested at 2 and 4 weeks after modeling.The changes of limb grip strength,wet mass of skeletal muscle,and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured,and the changes of skeletal muscle histomorphology and ultrastructure were observed. RESULTS AND CONCLUSION:At 2 weeks after modeling,the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass,significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A,and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers.Electron microscopy results showed that the structure of myofibrils was disordered,the Z-line was distorted,and the light and dark boundaries were blurred.At 4 weeks after modeling,the grip strength of the model rats was increased compared with that at 2 weeks,the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased,and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees.It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of"tendon off-position"at 2 weeks,and can be used to study the mechanism of acupuncture and manipulation in the treatment of"tendon off-position."