[ABSTRACT]OBJECTIVETo investigate the change of fibrinogen, soluable intercellular adhesion molecules-1 (sICAM-1), soluable vascular cell adhesion molecule-1 (sVCAM-1) in the blood of elderly patients with sudden sensorineural hearing loss (SSHL) and the difference between different type of SSHL.METHODS40 elderly patients with SSHL were subdivided into different types according to the newest guideline of diagnosis and treatment of Chinese medical association.They were subdivided into two groups with or without comorbidities.The control group were made of 40 healthy elderly people.The expression of fibrinogen, sICAM-1 and sVCAM-1 in the blood serum were detected and statistically analysed.RESULTSThe expression of fibrinogen, sICAM-1 and sVCAM-1 in SSHL patients were higher than that of the control group with statistical significance.There is no significant difference between different types of SSHL,though significant difference were found between groups with and without comorbidities. CONCLUSIONThere is increased expression of fibrinogen, sICAM-1 and sVCAM-1 in elderly SSHL patients;microcirculation dysfunction may play an dominant role in the pathogenesis of elderly patients with SSHL.

Objective To study the predictive value of evaluation in oxygen partial pressure[p(O2)] and carbon dioxide partial pressure[p(CO2)] of pleural cavity to the closure of visceral pleura in primary spontaneous pneumothroax (PSP) pa-tients. Methods Seventy-six hospitalized pneumothroax patients were divided into two groups:closed pneumothroax group (n=40) and open pneumothroax group (n=36), according to the radiographic information.To collect the expiratory gas by the device which we designed and produced, to collect the gas in the pleural cavity by thoracentesis. To detect the p(O2)and p(CO2)respectively, and the blood gas analysis of radial artery was done at same time. Results There was significantly low-er value of p(O2)of the gas in the pleural cavity in patients of closed pneumothroax than that of open pneumothroax (P <0.05). The level of p(CO2)was higher in patients of closed pneumothroax than that of open pneumothroax ( P<0.05). There were no significant differences in values of p(O2)and p(CO2)in expiratory gas and the blood gas analysis between two groups (P>0.05). There was significantly higher value of the expiratory gas/the pleural cavity gas p(O2) and a significantly lower value of p(CO2), in closed pneumothroax group than those of open pneumothroax group (P<0.05). Logistic regression analy-sis showed that values of the expiratory gas/the pleural cavity gas p(O2) and p(CO2) were the effective factors for the closure of visceral pleura. ROC curve showed that the areas under ROC curve (AUC) for the expiratory gas/the pleural cavity gas p(O2) and p(CO2) was 0.985 and 0.867, the sensitivities were 92.5% and 77.8%, the specificities were 100%and 85.0%and the reference values were 1.81 and 0.97. Conclusion To utilize the evaluation of gas partial pressure can predict whether the leakage of the visceral pleura is closed.

Objective To evaluate the positive rate, reliability and safety of thoracoscope pleural brushing for diagnosing malignant pleural effusion. Methods Seventy patients with unexplained pleural effusion were performed with medical thoracoscopy:(1) Observe the visceral and parietal pleura then use disposable cell brush to obtain specimens from suspect areas and take cytological examination. (2) Observe the parietal pleura then use biopsy forceps to forceps specimens from suspect areas and take histological examination. (3) Compare the positive rate of diagnosis, coincidence rate of pathological type and complication between two methods individual and combination in diagnosis. Results In 51 patients diagnosed as malignant pleural effusion, the diagnosis-positive rate of biopsy was 88.24%(45/51) and the diagnosis-positive rate of pleural brushing cytology was 90.20%(46/51). The diagnosis-positive rate of pleural brushing combined with biopsy was 96.08%(49/51), but there was no significant difference in diagnosis-positive rate between two methods individual and combination for malignant pleural effusion (P>0.05). In 51 patients, pathological type determination rate was 76.47%(39/51) evaluated by pleural brushing, 88.24% (45/51) by biopsy, and there was no significant difference in pathological type determination rate between two methods (P>0.05). Biopsy was performed for 168 times, more bleeding was found in 5 cases (2.98%), feeling pain in 134 cases (79.76%). Pleural brushing examination was performed for 198 times, no significant bleeding and pain were found. Conclusion Medical thoracoscopic pleural brushing under direct vision is a safe and reliable method, which can be use as an effective diagnostic method for malignant pleural effusion.

Objective:To investigate the effect and mechanism of obstructive sleep apnea hypopnea syndrome(OSAHS) on nocturnal angina in patients who undergo coronary artery bypass grafting(CABG).Methods:According to the inclusion criteria and exclusion criteria, this prospective observational study included 76 patients who underwent CABG at Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to December 2018. Patients included 60 males and 16 females, mean aged(61.4±7.3) years, BMI(25.7±2.3) kg/m 2. Portable sleep respiration monitoring and bedside ECG monitoring were performed before surgery. According to the apnea index(AHI), patients were divided into mild or no OSAHS group(AHI<15, 35 patients) and moderate to severe OSAHS group(AHI≥15, 41 patients). Baseline data, hematologic examination, degree of coronary stenosis, sleep breathing examination, night time heart rate and incidence of atrial fibrillation, and nocturnal angina were compared between the two group. Results:Combined with mild or no OSAHS group, moderate to severe OSAHS group had a significantly higher syntax-score(47.3±10.6 vs 35.1±6.8), a significantly higher proportion of coronary diffuse lesions(53.7% vs 31.4%), a significantly faster heart rate[(94.3±21.5)times/min vs(74.8±10.0) times/min], a significantly higher proportion of nocturnal angina(29.2% vs 2.9%). The differences were statistically significant( P<0.05). Binary logistic regression analysis showed that the fastest heart rate at night significantly affected the occurrence of nocturnal angina in CABG patients( OR=1.320, 95% CI: 1.084-1.607, P=0.006), the syntax-score, the fastest heart rate at night significantly affected the degree of OSAHS in CABG patients( OR=1.269, 95% CI: 1.094-1.473, P=0.002; OR=1.066, 95% CI: 1.004-1.131, P=0.036). Two linear regression showed a significant linear correlation between AHI with the fastest heart rate and syntax-score at night( R2=0.576, P<0.001; R2=0.658, P<0.001). Conclusion:OSAHS can significantly aggravate the degree of coronary artery stenosis in CABG patients, and further increase the incidence of nocturnal angina by significantly increasing nighttime heart rate.

Objective To explore the effects of TRAF6 inhibition on autophagy,myocardial inflammation and cardiac function in septic mice.Methods Twenty-four male Kunming mice were randomly divided into 4 groups:sham,sham + C25-140(sham+C),cecal ligation and puncture(CLP),and cecal ligation and puncture+C25-140(CLP+C)group.Sham+C group and CLP+C group were intraperitoneally injected with C25-140 after operation.LVEF and LVFS were evaluated by ultrasound 24 hours after operation.Serum TNF-α and IL1-β were measured by ELISA.HE staining was used to evaluate myocardial inflammatory response.Autophagosomes and mitochondrial microstructure of cardiomyocytes were observed by transmission electron microscopy.TRAF6 mRNA in myocardial tissue was detected by qPCR.The expression of TRAF6,P62,Beclin-1 and LC3B protein was detected by W-B.The effect of C25-140 on myocardial injury in the septic mice was observed by inhibiting autophagy with 3-MA.Results Compared with the sham group,the levels of TRAF6 mRNA and TRAF6 in the myocardial tissue in the CLP group were significantly increased(P<0.05)and the serum TNF-α and IL1-β concentrations were signifi-cantly increased(P<0.05).Meanwhile,the myocardial tissue HE staining showed inflammatory cell infiltration and the LVEF and LVFS levels were significantly decreased in the CLP group(P<0.05).Compared with CLP group,the CLP+C group showed that the expression of TRAF6 mRNA and TRAF6 protein decreased(P<0.05),serum TNF-α and IL1-β decreased(P<0.05),myocardial histopathological myocardial inflammatory cell infiltration decreased,the LVEF and LVFS levels increased(P<0.05).Electron microscopy showed that the mitochondrial swelling decreased,autophagosomes increased,expression of Beclin-1 and LC3Ⅱ/Ⅰ increased,and P62 expression decreased(P<0.05).As compared with CLP+C group,the CLP+C+3-MA group showed that obvious inflamma-tory cell infiltration in the myocardial pathology and the LVEF and LVFS levels decreased after 3-MA inhibited autophagy(P<0.05).Conclusion Inhibition of TRAF6 can not only ameliorate myocardial inflammatory injury and cardiac dysfunction in septic mice,but promote the involvment of cardiomyocyte autophagy in provention from sepsis-induced myocardial injury.

BACKGROUND:Sepsis complicated by myocardial injury is characterized by a high mortality.Metformin can prevent sepsis-induced myocardial dysfunction by exerting anti-inflammatory effects,improving oxidative stress,and reducing apoptosis.However,it is unclear whether metformin-induced autophagy plays an important role in the protective effect against sepsis-induced myocardial injury. OBJECTIVE:To explore the effect of metformin pretreatment on myocardial injury in septic mice. METHODS:A total of 40 male Kunming mice were randomly divided into sham operation group,model group,metformin group,and metformin+ 3-methyladenine group,with 10 mice in each group.The latter two groups were intraperitoneally injected with metformin for 14 days at a fixed time every day,and the metformin+3-methyladenine group was intraperitoneally injected with 3-methyladenine 1 hour before modeling.Twenty-four hours after the last injection of metformin,cecal ligation and perforation were used to construct a model of myocardial injury in septic mice.The sham operation group was not ligated and perforated.All mice were sacrificed 24 hours after surgery,and blood and myocardial specimens were collected.The levels of inflammatory factors and myocardial injury markers in serum were detected by ELISA.The mRNA expression of autophagy markers LC3B and p62 in myocardial tissue was detected by RT-qPCR.The protein expression of LC3B,Beclin-1,p62,p-AMPK,and AMPK in myocardial tissue was detected by western blot.The pathological changes in myocardial tissue were detected by hematoxylin-eosin staining. RESULTS AND CONCLUSION:Autophagy was inhibited in septic mice with myocardial injury.Compared with the sham operation group,the levels of serum tumor necrosis factor-α,interleukin-1β,interleukin-6,creatine kinase isoenzyme,and troponin T were increased in the model group(P<0.05),but there was no significant difference in p62,LC3Ⅱ/LC3Ⅰ,and p-AMPK/AMPK between the two groups(P>0.05).Compared with the model group,the levels of tumor necrosis factor-α,interleukin-6,creatine kinase isoenzyme,troponin T,and p62 were decreased in the metformin group(P<0.05),while LC3Ⅱ/LC3Ⅰ,p-AMPK/AMPK and Beclin-1 level were increased(P<0.05).Compared with the metformin group,the levels of tumor necrosis factor-α,interleukin-6,creatine kinase isoenzyme,troponin T,and p62 were increased in the metformin+3-methyladenine group(P<0.05),while LC3Ⅱ/LC3Ⅰ and Beclin-1 level were decreased(P<0.05).Myocardial hematoxylin-eosin staining indicated that myocardial fibers arranged normally in the sham operation group,but disorderedly in the model group,with interstitial edema and a large number of infiltrated inflammatory cells.A small amount of vacuolar changes were observed in the metformin group.The arrangement of myocardial fibers in the metformin+3-methyladenine group was slightly disordered,with more vacuolar changes.To conclude,metformin pretreatment may reduce myocardial injury in septic mice by activating the AMPK signaling pathway and inducing autophagy.

Objective To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

Objective To explore the role of Nogo-A receptor antagonist NEP1-40 in regulating regeneration of neural cells and related Wnt signaling pathway in neonatal rats with hypoxic ischemic encephalopathy (HIBD).Methods A total of 40 HIBD rats were divided into HIBD group and HIBD + NEP1-40 group,20 rats in each group.PCR Test,Western Blot Analysis,IHC test for cell proliferation and 8-isoprostane detection were used to evaluate regulation of NgR transcription factors in Wnt signaling pathway and proliferation of neural cells.Results The expressions of c-Jun and cMyc,at the protein level,were up-regulated after treatment with Nogo-A receptor antagonist NEP1-40 for 7 days,and the same change was observed at gene expression and Ki-67.There was no significant change of 8-isoprostane.Conclusion The c-Jun and c-Myc are the main transcription factors in Wnt signaling pathway by inhibition of NgR,and meanwhile the proliferation of nerve cells in subventricular zone increase.

Objective : To investigate the possible mechanism of metformin (Met) -induced cardiomyocyte autoph- agy in protecting myocardial injury in septic mice． Methods : The model of myocardial injury in septic mice was es- tablished by cecal ligation and puncture ( CLP) ．Sixty Kunming mice were randomly divided into sham operation group (Sham group) ，model group ( CLP group) ，model + dimethyl sulfoxide ( DMSO) group ( CLP + DMSO group) ，model + metformin (Met) group (Met group) ，model + Met + 3-methyladenine (3-MA) group (Met + 3- MA group) ，model + Met + compound C ( CC) group (Met + CC group) ，with 10 mice in each group．The Met， Met + 3-MA and Met + CC groups were intraperitoneally injected with Met (200 mg / kg) once a day for 2 weeks be- fore modeling．The Met + 3-MA group was intraperitoneally injected with 3-MA ( 10 mg / kg) 1 h before surgery. The Met + CC group was intraperitoneally injected with CC (20 mg / kg) 30 min before surgery．The model was es- tablished 24 h after the last injection of Met．The heart and blood of all mice were collected 24 h after surgery．The Western blot technique was employed to assess the relative expression levels of microtubule-associated protein 1 light chain 3 (LC3) isoforms，namely LC3 I and LC3 II，autophagy effector protein 1 (Beclin-1) ，ubiquitin-bind- ing protein 62 (p62) ，B-cell lymphoma / leukemia-2 (Bcl-2) ，Bcl-2-associated X protein (Bax) ，adenosine mono- phosphate (AMP) kinase (AMPK) and phosphorylated AMPK (p-AMPK) ．Myocardial pathological changes were observed by hematoxylin-eosin (HE) staining．The changes of myocardial mitochondria and autophagosomes were observed by electron microscopy．Hematoxylin-eosin (HE) staining was used to observe the pathological changes of myocardium． Electron microscopy was used to observe the changes of myocardial mitochondria and autophago- somes. Results : Compared with Sham group，the relative protein expression of Beclin-1，p62，p-AMPK / AMPK and LC3 II / LC3 I in CLP and CLP + DMSO groups had no statistical significance，but Bax increased and Bcl-2 de- creased in CLP group (P＜0. 01) ．Compared with CLP group，the relative expression of Beclin-1 protein and LC3 II / LC3 I in Met group increased and p62 decreased (P＜0. 01) ，Bax decreased and Bcl-2 increased (P＜0. 01) . Compared with Met group，the relative protein expression of Beclin-1 and LC3 II / LC3 I in Met + 3-MA group de- creased and p62 increased (P＜0. 05) ，Bax increased and Bcl-2 decreased (P＜0. 05) ．Besides，the relative pro- tein expression of p-AMPK / AMPK in Met + CC group decreased (P＜0. 05) ．HE staining showed that there was no disorder in myocardial fibers in Sham group，and a large number of inflammatory cells infiltrated the myocardial fibers of CLP group in a clear disorder．The Met group showed vacuolar changes in the myocardium，while the Met + 3-MA group showed disordered arrangement of myocardial fibers and a small amount of inflammatory cell infiltra- tion．Under electron microscopy，the morphology of myocardial mitochondria in the Sham group was normal，while in the CLP group，the arrangement of mitochondrial cristae was disordered with vacuolar changes，and occasional autophagosomes were observed．Mitochondria in Met group showed slight swelling and a large number of autophago- somes．The mitochondria in the Met + 3-MA group showed significant swelling with a small amount of autophago- somes． Conclusion The protective effect of metformin on myocardial injury in septic mice can reduce cardiomyo- cyte apoptosis and improve mitochondrial damage by activating AMPK signaling pathway to induce autophagy.

Objective:To simulate the neuroendoscopy assisted contralateral cervical 7 (C 7) nerve transfer via prespinal route and measure its relevant anatomical landmarks to explore the clinical feasibility and efficacy of this surgical approach for central upper limb spastic paralysis. Methods:(1) Six fresh cadaver specimens of the head and neck were obtained. Linear incisions of approximately 5 cm were made above the midpoint of the bilateral clavicles to simulate neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. With the superior margin of midpoint of the clavicle as central point, distance to the distal bifurcation of the C 7 nerve, distances to the superior or inferior trunks of the proximal brachial plexus nerves, and distances to the exit of the intervertebral foramina of the C 6, C 7, and C 8 nerves were measured. (2) One patient with upper limb spastic paralysis after intracerebral hemorrhage accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route; the clinical data and efficacy of the patient were retrospectively analyzed. Results:(1) The C 7 nerve, the upper trunk of brachial plexus formed by the C 5 and C 6 nerves and the lower trunk of brachial plexus formed by the C 8 and T 1 nerves could be exposed after neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route. The distance between the superior margin of midpoint of the clavicle and the distal bifurcation of the C 7 nerve is (2.20±0.11) cm, and its distance to the superior trunk of the proximal brachial plexus is (2.62±0.10) cm, and its distance to the inforior trunk of the proximal brachial plexus nerve is (2.72±0.11) cm. The distance between the superior margin of midpoint of the clavicle and the proximal C 7 nerve (at the exit of the intervertebral foramen) is (7.22±0.15) cm, its distance to the proximal C 6 nerve (at the exit of the intervertebral foramen) is (7.84±0.12) cm, and its distance to the proximal C 8 nerve (at the exit of the intervertebral foramen) is (6.96±0.12) cm. (2) The patient with central upper limb spastic paralysis accepted neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route successfully, with surgical time lasting for 2 h and bleeding amount of 20 mL. After surgery, the incision healed well, and the patient experienced pain and numbness in the healthy side of the upper limb with subsided symptoms one month after surgery. The spasticity symptoms of the affected upper limb obviously improved after surgery with decreased muscle tone. Follow-up after discharge was performed for 14 months, and the muscle strength of the affected upper limb recovered to level 1 +. Conclusion:Neuroendoscopy assisted contralateral C 7 nerve transfer via prespinal route can expose the proximal and distal C 7 nerves, with minimal invasion; this clinical study has preliminarily confirmed the safety and effectiveness of this transfer via prespinal route in central upper limb spastic paralysis.