ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective:To conduct a retrospective study on the treatment outcomes of patients who underwent artificial temporomandibular joint (TMJ) replacement surgery and to evaluate the effectiveness of artificial TMJ treatment.Methods:This study selected 62 patients who received standard Biomet artificial TMJ treatment at Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University from May 2010 to September 2023 as the study subjects. Among them, there were 15 male patients and 47 female patients. The average age was 33.5 years old(ranging from 18 to 67 years). This study statistically analyzed postoperative indicators, including maximum mouth opening, forward jaw movement, lateral movement, postoperative pain scores, and patient satisfaction.Results:This study included a total of 62 patients with 99 TMJ joints. No infections occurred postoperatively. The average follow-up period was 33.7 months (ranging from 7 to 170 months). At 6 months postoperatively, the mean mouth opening was (36.1±6.2) mm, lateral movement was (2.1±0.9) mm, and forward jaw movement was (1.0±0.9) mm. The pain visual analog scale score at 6 months postoperatively was (2.8±0.6), and patient satisfaction with the surgery was (8.8±1.1). Spiral CT scans conducted after surgery showed no joint dislocation or migration, and the artificial joint remained stable during the follow-up period.Conclusions:Artificial TMJ replacement is a valuable method for effectively restoring TMJ structure and essential functions related to mouth opening and chewing. It is worthy of promotion as a reconstructive approach for the temporomandibular joint

Objective:To observe the long-term effect of repairing soft tissue defect of the digital palmar with medial plantar artery perforators flap.Methods:From January, 2012 to February, 2015, 15 cases of digital palmar soft tissue defect were selected clinically, including 8 cases with phalangeal fracture, 5 cases with flexor tendon injury, and 9 cases with digital artery and nerve injury. The soft tissue defect area was 7.0 cm×2.5 cm-2.4 cm×3.0 cm. The medial pedis perforators flap with deep branch of medial plantar artery as pedicle and terminal cutaneous branch of saphenous nerve was cut out. The artery of the flap was anastomosed with the digital artery or common digital artery, 1 accompanying vein or superficial vein was selected to anastomose with the dorsal digital vein, and the cutaneous nerve was anastomosed with the digital nerve or common digital nerve. The perforating point, number, source of perforating vessels and the length of vessel pedicle were observed during the operation, and the color, shape, stability and TPD of the flap were observed through long-term followed-up. The good and excellent rate of the affected finger was evaluated and whether there was obvious scar, abnormal sensation and abnormal walking gait in the donor area.Results:All flaps survived and the wounds healed in one stage. All 15 patients were followed-up for 36-72 months, with an average of 48.5 months. The color and thickness of the flap were similar to that of the normal digital palmar, and the flap was wear-resistant, stable and strong in holding. The TPD was 9-12 mm. Twelve patients had transverse finger striations at the interphalangeal joint. According to the Trial Standard of the Function Evaluation of the Upper Limb of the Hand Surgery Society of Chinese Medical Association, 10 cases were excellent, 4 cases were good, 1 case was acceptable, and the good and excellent rate was 93.3%. There was no painful scar or abnormal sensation in the donor area. The ankle and foot function was good, and the gait was normal.Conclusion:The thickness, color and texture of the medial pedis perforator flap are similar to that of the palmar skin, and it is an ideal choice for repairing the palmar skin defect.

Objective:To investigate the role of neurite outgrowth inhibitor (Nogo)-oligodendrocyte myelin glycoprotein (Omgp)/Ras homologous (Rho)-Rho-associated coiled-coil forming protein kinase (Rock) signaling pathway in acute brain injury of carbon monoxide (CO) poisoning rats and treatment feasibility with Rho kinase inhibitor hydrochloride fasudil.Methods:According to random number table method, 135 healthy male SD rats were divided into three groups: a normal control group, a CO poisoning group and a fasudil treatment group ( n=45). Rat models of acute severe CO poisoning were established in the CO poisoning group and fasudil treatment group by inhalation method in a hyperbaric oxygen chamber. All rats received hyperbaric oxygen therapy for two weeks. Rats in the farsudil treatment group were intraperitoneally injected with hydrochloride farsudil for intervention (15 mg/[kg·d], once a d for 2 weeks), while those in the CO poisoning and normal control groups received the same volume of normal saline. The ultrastructures of rat brain tissues were observed by transmission electron microscopy one week after modeling. Staining intensities of Nogo- and OMgp-positive cells were detected by immunohistochemistry, and those of Rock-positive cells were analyzed by immunofluorescence one d, one week, one month and two months after modeling. The protein expressions of Nogo, OMgp and Rock in brain tissues were detected by Western blotting one d, one week, one month and two months after modeling. Results:In the CO poisoning group, the ultrastructures of brain tissues and blood-brain barrier were damaged obviously, and the changes in nucleus, mitochondria and synaptic structure were obvious; while fasudil treatment could effectively maintain the integrity of ultrastructures and functions of brain tissues, and reduce brain edema. One d, one week, one month and two months after modeling, the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the CO poisoning group were significantly higher than those in the normal control group at the same time point ( P<0.05); the staining intensities of Nogo, OMgp and Rock positive cells and protein expression levels of Nogo, OMgp and Rock in the fasudil treatment group were significantly lower than those in the CO poisoning group at the same time point ( P<0.05). Conclusion:The activation of Nogo-OMgp/Rho-Rock signaling pathway related molecules (Nogo, OMgp and Rock) is closely related to acute brain injury caused by CO poisoning; hydrochloride fasudil can effectively down-regulate the protein expressions of Nogo, OMgp and Rock, therefore obviously alleviate brain injury after CO poisoning.

Objective To explore the effects of N-butylphthalide on the expressions of ZO-1 and claudin-5 in blood-brain barrier (BBB) in rats with acute carbon monoxide (CO) poisoning. Methods A total of 144 adult healthy male Sprague-Dawley (SD) rats were randomly divided into normal control group, CO poisoning group, and NBP treatment group, with 48 rats in each group. The acute CO poisoning model was reproduced in hyperbaric oxygen chamber, and all model rats were given hyperbaric oxygen therapy once daily. The rats in the normal control group were free to breathe fresh air. The rats in NBP treatment group were administered orally NBP 60 mg/kg twice a day at 2 hours after poisoning until death. The rats in normal control group and CO poisoning group were treated with equal amount of pure olive oil. Four rats were sacrificed from each group at 1, 3, 7, 14 days after model reproducing, respectively. The changes in ultrastructure of BBB were observed under transmission electron microscope. The expressions of ZO-1 and claudin-5 proteins were determined by immunofluorescence staining and Western Blot. The localization of the two target proteins was observed by immunofluorescence double staining. The correlation between the two proteins was analyzed by linear regression. Results The ultrastructure of BBB was normal in normal control group, some ZO-1 and a large number of claudin-5 positive cells were observed. The ultrastructure of BBB was seriously injured, ZO-1 and claudin-5 positive cells in brain tissue were significantly decreased, and the expressions of ZO-1 and claudin-5 proteins in brain tissue at 1 day after poisoning in CO poisoning group were significantly lower than those of normal control group (ZO-1 protein:3.38±0.30 vs. 24.50±5.62, claudin-5 protein: 11.38±0.93 vs. 46.35±6.88, both P < 0.05), and although gradually restored, they were maintained at relatively lower levels until 14 days as compared with those in normal control group (ZO-1 protein: 10.35±0.80 vs. 24.63±3.57, claudin-5 protein: 32.35±3.11 vs. 46.43±7.20, both P < 0.05). NBP treatment could significantly alleviate the ultrastructure injury of BBB induced by acute CO poisoning, the amount of ZO-1 and claudin-5 positive cells in brain tissue were significantly increased, as well as the expressions of ZO-1 and claudin-5 proteins were significantly increased, which were significantly higher than those of CO poisoning group from 1 day and 3 days on, respectively (1-day ZO-1 protein: 7.57±0.69 vs. 3.38±0.30, 3-day claudin-5 protein:20.46±1.42 vs. 11.43±0.86, both P < 0.05), and which showed an increase tendency with time prolongation. The results of immunofluorescence double staining showed that ZO-1 and claudin-5 proteins could not only coexist in the same cell, but also could be expressed separately in different cells. Linear regression analysis showed the positive correlation between the expressions of ZO-1 and claudin-5 proteins in brain tissue of rats with acute CO poisoning (R2= 0.917, P = 0.022). Conclusion NBP could markedly improve the ultrastructure and functional integrity of BBB through up-regulating the expressions of ZO-1 and claudin-5 proteins, and then reduce brain damage caused by CO poisoning.

Objective To explore the neuroprotective effect of targeted regulation Nrf2 gene on rats with brain injury caused by acute severe carbon monoxide ( CO ) poisoning. Methods A total of 180 healthy adult SD rats were divided into 4 groups at random:normal control group( NC group) ,CO poisoning group(CO group),lentivirus group(LV group) and Nrf2 gene therapy group(Nrf2 group),and 45 rats in each group. An acute CO toxic rat model was established by inhalation in a hyperbaric oxygen tank. The lentivirus group was directly injected with lentivirus dilution (4×106 TU/μl) into striatum with a microsy-ringe guided by a stereotactic apparatus,and the Nrf2 gene therapy group was administrated the same dose of recombinant Nrf2 gene lentivirus dilution,while rats in the normal control group and the CO poisoning group were received the same amount of normal saline. Five rats were taken and decapitated at day 1,day 7 and week 2 from each group,respectively. The mitochondrial membrane potential (MMP) of neurons in brain tis-sue was detected by JC-1 method,and the expressions of Nrf2 and GCLC proteins were observed by immuno-histochemistry and Western Blot. Results Compared with the NC group (cortex:(75. 3±6. 8);hippocam-pus:(76. 4±7. 1);striatum:(73. 8±7. 3)) at the same time point,the MMPs of neurons in CO group (cor-tex:(34. 5±6. 7);hippocampus:(30. 3±5. 6);striatum:(41. 5±6. 1) and LV group (cortex:(36. 8±6. 2);hippocampus:(30. 8±6. 0);striatum:(42. 7±6. 3)) were significantly decreased,and the difference was sig-nificant(P<0. 05). However,there was no significant difference between the CO poisoning group and the lentivirus group (P>0. 05). A small amount of Nrf2 protein (0. 22±0. 05) and GCLC protein (0. 24±0. 04) were expressed in the brain tissue of normal control rats. The expressions of Nrf2 protein (0. 31±0. 06,0. 31 ±0. 05) and GCLC protein (0. 30±0. 04,0. 31±0. 07) in CO group and LV group were slightly increased (P<0. 05). Similarly,there was no significant difference between the CO poisoning group and the lentivirus group (P>0. 05). The MMPs value of nerve cells in the Nrf2 group (cortex:(53. 3±5. 3);hippocampus:(56. 9±6. 1);striatum:(60. 6±6. 0)) also decreased,but it was significantly higher than that in the CO group and the LV group at the same time point (P<0. 05) . The expression of Nrf2 in brain tissue was signifi-cantly increased (0. 59±0. 05),and there was significant difference between CO group and LV group at the same time point (P<0. 05);GCLC protein increased slightly (0. 37±0. 06),but there was no statistical difference compared with CO poisoning group and lentivirus group (P>0. 05). Conclusion CO poisoning could induce oxidative stress and damage mitochondrial function of nerve cells. The active state of targeted regulation Nrf2 could significantly enhance the antioxidant capacity of rats and positively protect rats against brain injury induced by acute severe CO poisoning.

Objective To investigate the therapeutic effects of Xingzhi Yinao (XZYN) particles combined with hyperbaric oxygen therapy on cognitive impairment and motor dysfunction in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods Sixty-seven patients with DEACMP were admitted to the Affiliated Yantai Yuhuangding Hospital of Qingdao University from January 2011 to December 2015, and they were randomly divided into a control group (given conventional treatment such as inhalation of oxygen, cytidine diphosphate cholin and vitamin B, 19 cases), a hyperbaric oxygen (HBO) treatment group (given conventional treatment + hyperbaric oxygen therapy once a day, 24 cases) and a XZYN particles treatment (XZYN group, given conventional treatment, hyperbaric oxygen and XZYN particles, 24 cases), the therapeutic course being 2 months in the three groups. Before and after treatment for 1 and 2 months, the cognitive function and motor function of the patients were evaluated by the use of activity of daily living (ADL) scale, Montreal cognitive assessment (MoCA) scale, and mini-mental state examination (MMSE) scale; the severity of cerebral white matter injury was assessed by age related white matter changes (ARWMC) scale; and the electromyographic evoked potential was used to detect the amplitude and latency of P300 to assess the severity of cognition impairment and prognosis. Results With the prolongation of therapeutic time, after treatment, the neurological function scores of ADL, MoCA, MMSE and amplitude of P300 were increased, while ARWMC was decreased and the latency of P300 was shortened gradually in the three groups, and the changes of above indexes after treatment for 2 months in XZYN group were more significant than those in either HBO group or control group[ADL score: 70.2±8.3 vs. 60.5±8.1, 23.0±6.1, MoCA score: 26.1±3.1 vs. 22.2±2.7, 18.2±3.6, MMSE score:25.9±4.1 vs. 22.4±3.5, 18.1±4.5, ARWMC score: 7.0±2.1 vs. 8.7±2.2, 15.2±3.3, latency of P300 (ms):332.9±20.4 vs. 352.5±23.6, 381.7±30.3, amplitude of P300 (μV): 6.5±1.6 vs. 5.6±1.3, 4.1±1.5, all P < 0.05]. Conclusion The hyperbaric oxygen therapy combined with XZYN particles for treatment of patients with DEACMP can significantly improve their cognitive and motor functions and ameliorate the severity of cerebral white matter injury.

Objective To explore the mechanism of ultrastructural and functional impairment of mitochondria and the protective effect of sulforaphane (SFP) at different dosages on hippocampus neurons in rats after acute carbon monoxide(CO)poisoning.Methods One hundred and fifty adult healthy SD rats were randomly divided into the normal control group,the CO poisoning group and the SFP treatment group.The rat model of CO poisoning was established through exposure to CO in a hyperbaric chamber.The uhrastructural changes of mitochondria in nerve cells of the brain tissue were observed by transmission electron microscopy (TEM).Mitochondrial membrane potential (MFI) was detected with JC-1 fluorescent probe,and the expressions of Nrf-2 and Trx-1 proteins and mRNA were evaluated by immunohistochemistry and quantitative RT-PCR before and after intervention.Results CO poisoning could induce impairment of mitochondria ultrastructure in neurocytes in the brain tissue.SFP could obviously alleviate the damage of mitochondria ultrastructure.The MFI level in the brain tissue was obviously reduced in rats after CO exposure.Though MFI level was decreased 3 to 7 days after SFP administration,its level was significantly higher than that of the CO poisoning group at the same time point (P ＜0.05).As compared with those in the normal control group,the expression levels of Nrf-2 and Trx-1 proteins as well as their mRNA in the CO poisoning group were slightly increased (P ＜ 0.05).After treatment with SFP,the expressions of both the proteins and mRNA were obviously increased,and there was significant difference when compared with that of the CO poisoning group at the same time point (P ＜0.05).Conclusion Early administration of either moderate or high dose SFP could efficiently improve mitochondrial structure and function,enhance anti-oxidative stress of cells,thus exerting a positive effect against brain damage induced by acute CO poisoning.

Objective To explore the mechanism of ultrastructural and functional impairment of mitochondria and the protective effect of sulforaphane (SFP) at different dosages on hippocampus neurons in rats after acute carbon monoxide(CO)poisoning.Methods One hundred and fifty adult healthy SD rats were randomly divided into the normal control group,the CO poisoning group and the SFP treatment group.The rat model of CO poisoning was established through exposure to CO in a hyperbaric chamber.The uhrastructural changes of mitochondria in nerve cells of the brain tissue were observed by transmission electron microscopy (TEM).Mitochondrial membrane potential (MFI) was detected with JC-1 fluorescent probe,and the expressions of Nrf-2 and Trx-1 proteins and mRNA were evaluated by immunohistochemistry and quantitative RT-PCR before and after intervention.Results CO poisoning could induce impairment of mitochondria ultrastructure in neurocytes in the brain tissue.SFP could obviously alleviate the damage of mitochondria ultrastructure.The MFI level in the brain tissue was obviously reduced in rats after CO exposure.Though MFI level was decreased 3 to 7 days after SFP administration,its level was significantly higher than that of the CO poisoning group at the same time point (P ＜0.05).As compared with those in the normal control group,the expression levels of Nrf-2 and Trx-1 proteins as well as their mRNA in the CO poisoning group were slightly increased (P ＜ 0.05).After treatment with SFP,the expressions of both the proteins and mRNA were obviously increased,and there was significant difference when compared with that of the CO poisoning group at the same time point (P ＜0.05).Conclusion Early administration of either moderate or high dose SFP could efficiently improve mitochondrial structure and function,enhance anti-oxidative stress of cells,thus exerting a positive effect against brain damage induced by acute CO poisoning.

Objective To evaluate the neuroprotective effect of edaravone on brain tissues after acute carbon monoxide (CO) poisoning and explore its mechanism.Methods Ninety Sprague-Dawley rats were randomly selected as normal control group,poisoning group and treatment group (n=30).Rats in the poisoning group and treatment group were established animal models of acute CO poisoning with hyperbaric chamber method and received hyperbaric oxygen therapy.The rats in the treatment group were given intraperitoneal injection ofedaravone (10 mg/kg) additionally.TUNEL and real time-PCR were used to detect the cell apoptosis and their apoptosis-related gene expressions (Bcl-2 and Bax mRNA) in brain tissues 1,2 and 7 d after CO poisoning in each group.Immunohistochemistry and Western blotting were used to observe the positive cells and protein changes of heme oxygenase-1 (HO-1) and nuclear factor erythrocyte two related factors-2 (NRF-2).Results The apoptosis cell number in the poisoning group and the treatment group was significantly increased as compared with that in the normal control group (P＜0.05);that in the treatment group was relatively fewer than that in the poisoning group with significant differences (P＜0.05).As compared with those in the normal control group,the Bcl-2 and Bax mRNA expressions in the poisoning group were obviously up-regulated with significant difference (P＜0.05);the Bcl-2 mRNA level was significantly increased,the Bax mRNA level was signficantly down-regulated,and the ratio ofBcl-2 mRNA/Bax mRNA was notablyly increased in the treatment group as compared with those in the poisoning group (P＜0.05).The positive cells and HO-1 and NRF-2 proteins in the brain tissues of the poisoning group were significantly higher than those in the normal group (P＜0.05);those in the treatment group were obviously increased as compared with those in the poisoning group (P＜0.05).Conclusion Edaravone might be partly associated with activation of NRF-2/HO-1 pathway to counteract oxidative stress damage,inhibit neuronal apoptosis,and play a neuroprotective role in brain damage after acute CO poisoning.