Objective In order to explore the mechanism of repetitive transcranial magnetic stimulation rTMS) on neuropathic pain,we observed the effect of different frequencies of rTMS on neuropathic pain and the expression of neuronal nitric oxide synthase (nNOS) in the dorsal root ganglion (DRG).Methods A total of 28 male Sprague-Dawley rats were used and divided into a control group,in which sham-operation was performed,and an experimental group which was further divided into a sham-rTMS group,a 1 Hz group and a 20 Hz group after successful neuropathic pain model was established by operation to ligate the left sciatic nerves,with 7 rats in each group.Three days after the operation,rTMS was applied to the primary motor cortex (M1) contralateral to the pain once dai ly for 10 consecutive days.The pain behavior and nNOS expression in the DRG were measured before and after 10 days of rTMS intervention.Results All the neuropathic pain model rats demonstrated pain-related behaviors 3 days postoperation,the mechanical pain thresholds were significantly lower than those in the control group (P ＜ 0.05).After rTMS treatment,the mechanical hyperalgsia was significantly relieved in 20 Hz group but not 1 Hz group as demonstrated by a comparison with the sham-rTMS group (P ＜ 0.05).The expression of nNOS in DRG ipsilateral to the neuropathic pain was significantly increased in sham-rTMS group and 1 Hz group (P ＜ 0.05) when compared with the control group.Meanwhile,it was shown that expression of nNOS was down-regulated in 20 Hz group but not 1 Hz group (P ＜ 0.05).The degree of pain relief in 20 Hz group was negatively correlated with the expression of nNOS in DRG (P ＜0.05).Conclusions Neuropathic pain induced by peripheral nerve injury is associated with elevated expression of nNOS in the DRG.High-frequency rTMS can relieve neuropathic pain through down-regulating the overexpression of nNOS in the DRG,but the low-frequency rTMS has no such effect.

Objective To observe the effects of repeated low and high-frequency transcranial magnetic stimulation (rTMS) on neuropathic pain and the expression of specific activation markers of astrocytes and glial fibrillary acidic protein (GFAP) in the lumbar spinal cord.Methods Twenty-eight male Sprague-Dawley rats were randomly divided into a sham-operated group,a sham-rTMS group,a 1 Hz group and a 20 Hz group,with 7 in each group.The rats in the sham-operated group had their sciatic nerve exposed without ligation,while the other groups underwent sciatic nerve ligation to induce neuropathic pain.Three days after the operation,rTMS was applied to the primary motor cortex (M1) contralateral to the pain once a day for 10 consecutive days.Pain-related behavior and thermal pain response were tested before the operation and before and after the course of rTMS therapy.The expression of GFAP in the lumbar spinal cord was examined.Results All of the rats which underwent sciatic nerve ligation showed pain-related behavior and significantly decreasing thermal pain latency compared with the sham-operated group.After the rTMS therapy the thermal hyperalgia was significantly attenuated in the 20 Hz group but not in the 1 Hz group compared with the sham-rTMS group.The expression of GFAP in the dorsal horn of the lumbar spinal cord ipsilateral to the neuropathic pain was significantly increased in the sham-rTMS group and the 1 Hz group compared with the sham-operated group.Compared with the sham-rTMS group,GFAP levels were significantly lower in the 20 Hz group but not in the 1 Hz group.The pain relief in the 20 Hz group was negatively related to the expression of GFAP.Conclusions Neuropathic pain induced by peripheral nerve injury is associated with increased activity and proliferation of astrocytes in the dorsal horns of the spinal cord.High-frequency rTMS can relieve neuropathic pain through inhibiting the activity and proliferation of astrocytes in the dorsal horns,but low-frequency rTMS has no clinically significant effect.

Objective To study the curative effect of limited-acupotomy therapy on chronic lumbosacral osteo-fascial compartment syndrome. Methods 59 patients were randomly recruited into a control group (with 29 patients) and a treatment group (with 30 patients). The control group was treated with general-acupotomy therapy, and treatment group was treated with limited-acupotomy therapy. Evaluate the curative effects before the first and the second therapy, and 3 months after the therapy respectively, as well as VAS pain, JOA and CODI scores. Results The curative effect was 96.56% and 100% respectively in the control group and the treatment group 3 months after the treatment. The difference between the two groups was not statistically significant(χ2＝0.19,P＞ 0.05). As to VAS pain scores, JOA and CODI scores, the difference among the three stages of the treatment were significant (in control group F＝165.70, 99.90, 106.60 respectively, in treatment group F＝279.76, 154.34, 67.36 respectively, P＜0.01)in both groups respectively, but the difference between the two groups were not significant(P＞0.05) in each stage. Conclusion Limited-acupotomy therapy was safe and effective in treating chronic lumbosacral osteo-fascial compartment syndrome.

Objective To evaluate the test-retest and inter-rater reliability of the hand-held pressure algometer as a measuring instrument of pressure pain threshold(PPT).Method A total of 37 healthy subjects were recruited for reliability test.Three raters measured the PPT at 12 body sites of the subjects.Each rater conducted three trials on each site.In the validity test,10 patients with active trigger points in the upper trapezius were recruited and measured by one rater using the pressure algometer for PPT,the visual analogue scale(VAS)was also used to evaluate the pain intensity induced by the trigger point.The intraclass correlation coefficient and Spearman correlation coefficient were calculated to reflect the reliability and validity.Results The test-retest and inter-rater reliabilities were both high(ICC＞0.95),with the measurements by one rater were more reliable than measurements by multiple raters.The inter-rater reliability of PPT measurement obtained by using the mean value of 3 trials was higher than any of the 3 trials alone.The PPT values of the trigger points were higher than those of the normal points,and there was a significantly negative correlation between the PPT values of the trigger points and the VAS scores.Conclusion The intra-and inter-rater PPT measurements in healthy subjects obtained with the hand-held pressure algometer were highly reliable.The algometer was valid for quantifying myofascial trigger point sensitivity.

Objective To evaluate the clinical efficacy and safety of domestic Sirolimus-eluting stents (Firebird) and imported Zotalimus-eluting stents ( Resolute) in the treatment of patients with unprotected left main coronary artery disease ( ULMCA) . Methods We retrospectively enrolled 76 patients with ULMCA treated by percutaneous coronary intervention (PCI) under the guidance of IVUS in our hospital. According to the different stents used in the procedure, the patients were divided into two groups: Domestic Sirolimus-Eluting Stents group (Firebird group, n = 42) and Imported Zotarolimus-Eluting Stents group (Resolute group, n = 34) . We analyzed the baseline characteristics, coronary artery lesion characteristics, stenting strategies and any changes in left ventricular ejection fraction ( LVEF) in both groups and investigated the long-term clinical outcomes. Results There were no significant differences in the baseline characteristics, the SYNTAX scores of the coronary artery lesion and the rate of complete revascularization between the two groups. Compared with that in Firebird group, there were more cases involving the distal left main (79. 4% vs. 45. 2% , P ﹤ 0. 05) and more patients using two stents strategies (29. 4% vs. 7. 1% , P ﹤ 0. 05) in the Resolute group. The change in LVEF post-PCI had no difference between the two groups. The patients were followed up for a mean of (23. 3 ± 10. 7) months. During the follow-up period, the occurrence of MACCE had no significant difference between the two groups. In the Firebird group, there were one sudden cardiac death, one nonfatal myocardial infarction, one stroke and five patients with recurrence of angina pectoris. In the Resolute group there were one sudden cardiac death, one target lesion revascularization and four patients with recurrence of angina pectoris. Conclusions Compared with the imported Zotalimus-Eluting Stents, the domestic Sirolimus-Eluting Stents are safe and effective in the treatment of patients with unprotected left main lesions under the guidance of IVUS. The two kinds of stent showed similar long-term clinical outcomes.

Objective:To identify the risk factors for myocardial injury after non-cardiac surgery.Methods:The medical records of adult patients admitted to the intensive care unit of Peking University First Hospital after non-cardiac surgery from June 2017 to June 2018 were retrospectively collected.Myocardial injury was defined as serum cardiac troponin I concentration>0.06 μg/L within 3 days after operation, and the patients were divided into myocardial injury group and non-myocardial injury group.The perioperative data of patients were obtained through searching the electronic medical record system.The variables of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factors for myocardial injury after non-cardiac surgery. Results:A total of 752 patients were included in the study, and the incidence of myocardial injury occurred after non-cardiac surgery was 15.7%.Emergency operation and highest lactic acid concentration during operation were the independent risk factors for myocardial injury after non-cardiac surgery.Conclusion:Emergency operation and highest lactic acid concentration during operation are the independent risk factors for myocardial injury after non-cardiac surgery.

Objective To simulate dynamic response of cervical spine of the pilot during typical maneuver flight movements using finite element method, as well as make analysis and prediction on damage failure of the pilot neck during flight by impact injury and fatigue injury model of biological tissues.Methods A geometrically accurate finite element model of the neck was constructed, and validity of the model was verified by relevant examples. Then, the acceleration curves of centrifugal trainer under different modes were loaded for numerical simulation, and impact injury and fatigue injury of tissues were predicted by using the universal cervical injury criterion and the fatigue damage model of biological tissues.Results The maximum stress of the vertebrae and intervertebral disc caused by overload impact was 66.53 MPa and 58.63 MPa respectively during typical maneuver flight. According to the Nij injury criteria, the maximum Nij was 0.096, which was lower than the injury tolerance threshold of 1, and would not cause direct acute injury to cervical tissues. Based on fatigue damage model of biological tissues, it was found that cancellous bone suffered fatigue failure under the condition of uninterrupted repeated loading for more than 40 000 times. Considering the limited flight career of the pilot, the vertebral tissues would not be fractured due to the accumulation of fatigue damage.Conclusions To a certain extent, the results can contribute to formulating pilot training and flight plans, and also provide data support for the development of its protective equipment.

Objective Based on construction and verification of the lumbar finite element model, the simulation calculation and injury prediction on dynamic response of normal lumbar model and L5 unilateral and bilateral spondylolysis models of the pilot were carried out, so as to explore the influence of persistent flight overload on normal and spondylolysis lumbar vertebrae of the pilot. Methods The precise finite element model of lumbavertebrae was established using reverse engineering software and computer-aided engineering (CAE) technology based on CT images. The validity of the lumbar vertebrae model was verified by static and dynamic in vitro experiments. The biomechanical simulation analysis on normal and spondylolysis lumbar vertebrae of the pilotunder persistent overload was carried out, and the spinal injury was predicted and analyzed by dynamic response index (DRI) injury evaluation and prediction method. Results The maximum isthmus stress of L5 vertebra in unilateral and bilateral spondylolysis models were 105. 29 MPa and 126. 32 MPa, respectively, which were significantly higher than those in normal model. The L4-5 and L5-S1 intervertebral discs of the spondylolysis model were more prone to premature degenerative changes than those of normal model. Combined with DRI spinal injury prediction method, the probability of spinal injury in normal lumbar vertebrae, lumbar vertebrae with L5 unilateral and bilateral spondylolysis were 0. 001 4% , 2. 26% and 3. 21% , respectively, and the probability of spinal injury was significantly increased after the occurrence of spondylolysis. Conclusions The spondylolysis increases the load of lumbar isthmus under flight overload. The results provide more accurate data support for the formulation of training programs and the development of protective devices to ensure flight safety

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.
Humans ; Osteoclasts ; Alveolar Bone Loss/therapy* ; Cell Differentiation ; MicroRNAs ; Periodontitis/therapy* ; Extracellular Vesicles ; Apoptosis ; Mesenchymal Stem Cells