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Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.
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Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.
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Objective: To explore whether acupuncture can improve sleep disturbance, cognitive impairment and emotional disorders caused by sleep deprivation, and its association with the attenuation of oxidative stress injury in prefrontal cortex. Methods: Fifty-two male Sprague-Dawley rats were randomly divided into a control group (n=10), a model group (n=14), a manual acupuncture (MA) group (n=14), and a sham-MA group (n=14). All the groups were established as sleep deprivation models via the modified multiple platform method, except for the control group. Rats in both the MA group and the sham-MA group received corresponding intervention, respectively. After modeling and intervention, the four groups received three behavioral tests, namely sleep monitoring, by comprehensive lab animal monitoring system (CLAMS), Morris water maze (MWM) test and open-field test (OFT), followed by oxygen free radical level test and Western blot (WB) detection for the expression levels of Bax and Bcl-2. Results: The MA group derived more sleep time within 24 h than either the model group or the sham-MA group (both P<0.05). On MWM orientation navigation test day 1, there were no significant differences in escape latency among the control, MA and sham-MA groups (P>0.05), and the escape latency was significantly shorter in these three groups than that in the model group (all P<0.05). On test day 4, the escape latency was markedly shorter in the MA group than that in either the model group or the sham-MA group (both P<0.05); meanwhile, the MA group showed significantly better performance compared with these two groups in space probe test (both P<0.05). In OFT, compared with the control group, there was a significant decline in the horizontal movement score in the other three groups (all P<0.05), and the decrease was more significant in the model group and the sham-MA group than that in the MA group (both P<0.05). The superoxide dismutase (SOD) content was markedly higher and the malondialdehyde (MDA) content was markedly lower in the MA group than those in the model group and the sham-MA group (all P<0.05). Compared with the model group and the sham-MA group, the expression of Bax was significantly lower and the expression of Bcl-2 was significantly higher in the MA group (all P<0.05). Conclusion: MA therapy can lengthen the sleep time in sleep-deprived rats and improve learning and memory impairments induced by sleep deprivation, and the underlying mechanism may be associated with the enhancement of antioxidant capacity in the prefrontal cortex and the inhibition of hippocampal neuronal apoptosis.
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Objective: To investigate the effects of electroacupuncture (EA) on the behaviors of rat with anxiety disorder, and the expressions of hippocampal neurotransmitters including 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), and the expressions of hippocampal B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax).Methods: Forty-six male Wistar rats were randomly divided into a control group (n=10), a model group (n=12), an EA group (n=12), and a drug group (n=12). Except the control group, the other three groups were established into rat models of anxiety disorder using uncertain empty bottle stimulation. Rats in the EA group and the drug group received corresponding interventions for 15 consecutive days [EA group was given EA at Baihui (GV 20) and Sanyinjiao (SP 6); the drug group was given aqueous solution of alprazolam via intragastric administration]. After intervention, all four groups received open-field test (OFT) and elevated plus-maze (EPM) for behavioral evaluations. The expressions of 5-HT, NE and DA in hippocampus were determined by fluorescence spectroscopy (FS) while the expressions of Bcl-2 and Bax proteins in hippocampus were determined by Western blot (WB). Results: The OFT horizontal scores in the control group, EA group and drug group were significantly higher than that in the model group (all P<0.05), and the difference between the EA group and the drug group was statistically insignificant (P>0.05); the OFT vertical scores in the model group, EA group and drug group were significantly lower than the score in the control group (all P<0.05). The EPM percent of open-arm entries (OE％) in the control group, EA group and drug group was higher than that in the model group (P<0.05), and the differences among these three groups were statistically insignificant (P>0.05); though the percent of open-arm total time (OT％) in the EA group was lower than that in the control group (P<0.05), the difference was statistically insignificant when compared with the drug group (P>0.05), and it was significantly higher than that in the model group (P<0.05). The expression of 5-HT in the EA group was higher than that in the control group (P<0.05); the expression of 5-HT in the EA group was significantly lower than that in the model group (P<0.05); the difference between the EA group and the drug group was statistically insignificantly (P>0.05). The expression of NE in the model group was significantly higher than that in the other three groups (P<0.05), and there was no significant difference among these three groups (P>0.05). The expression of DA in the EA group was significantly higher than that in the control group and the drug group (both P<0.05), while the difference between the EA group and the model group was statistically insignificant (P>0.05). The expression of Bax in the model group was significantly higher than that in the other three groups (all P<0.05), whereas the expression of Bcl-2 in the model group was significantly lower than that in the other three groups (all P<0.05), and the differences in both Bax and Bcl-2 among the other three groups were statistically insignificant (all P>0.05). Bax/Bcl-2 in the EA group was significantly higher than that in the control group (P<0.05) and lower than that in the model group (P<0.05), and the difference was statistically insignificant when compared with the drug group (P>0.05). Conclusion: EA shows promising effects in attenuating rats' anxiety disorder, which may be achieved by the down-regulation of the expressions of 5-HT and NE in the hippocampus and/or inhibition of hippocampal neuronal apoptosis. The efficacy is comparable to that of intervention with alprazolam.
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Objective: To investigate the effect of electroacupuncture (EA) on cognitive function in D-galactose (D-gal)-induced aging rats, and the correlation between the effect and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3)-ASC-Caspase-1 signaling pathway. Methods: Forty-six male Sprague-Dawley (SD) rats were randomly divided into a control group (n=10), a model group (n=12), an EA-7 d group (n=12) and an EA-21 d group (n=12). Except the control group, the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction. The control group received the same amount of normal saline via intraperitoneal injection. Two EA groups were given EA therapy for 21 consecutive days (began from the 22nd day of modeling) or 7 consecutive days (began from the 36th day of modeling) accordingly at Dazhui (GV 14), Baihui (GV 20), Shenshu (BL 23) and Zusanli (ST 36). After modeling/ intervention, all four groups received behavioral evaluations by Morris water maze (MWM) test, novel object recognition (NOR) test and step-down passive avoidance (SDPA) test followed by the Western blot (WB) detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3, ASC and Caspase-1. Results: MWM (place navigation test, PNT) results showed that the escape latency in the model group was significantly longer than that in the other three groups (P<0.05), and there was no significant difference among the other three groups on the 1st day of the test (P>0.05). From the 2nd day to the 4th day of the test, there was no significant difference between the EA-21 d group and the control group (P>0.05) in the escape latency; the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group (P<0.05). MWM (spatial probe test, SPT) results showed that the time spent in the target quadrant was significantly shorter and platform crossover number was significantly lower in the model group than in the other three groups (P<0.05). The time spent in the target quadrant was longer in the EA-7 d group than in the model group (P<0.05), but was shorter than that in the control group and the EA-21 d group (P<0.05). There was no significant difference in the swimming speed among the four groups (P>0.05). NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group (P>0.05), and the recognition ratio was significantly higher in the two EA groups than in the model group (P<0.05), but was lower than in the control group (P<0.05). SDPA results showed that the electric shock number was higher in the model group than in the other three groups (P<0.05), and the differences among the other three groups were statistically insignificant (P>0.05). The model group had the shortest step-down latency, followed by the EA-7 d group, the EA-21 d group and the control group in order (P<0.05). The WB results indicated that the expression level of NLRP3 was significantly lower in the control group and the EA-21 d group than in the model group and the EA-7 d group (P<0.05). The expression levels of ASC and Caspase-1 were significantly higher in the model group than in the other three groups (P<0.05), and there was no significant difference among these three groups (P>0.05). Conclusion: NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats; 7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited; 21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via downregulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.
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Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.
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Objective:To observe the efficacy and safety of dexzopiclone plus auricular acupressure in intervening primary insomnia.Methods:A total of 72 participants who met the inclusion criteria were enrolled in a randomized controlled trial,with 36 cases allocated to a treatment group and 36 cases allocated to a control group.Both groups were given dexzopiclone as the routine treatment.Patients in the treatment group were given auricular acupressure with Wang Bu Liu Xing (Semen Vaccariae) seeds at the auricular acupoints related to sleep and emotion based on meridian theory,whereas for patients in the control group,the medical plasters with Wang Bu Liu Xing (Semen Vaccariae) seeds were only gently stuck to acupoints unrelated to sleep without stimulation.Patients in both groups were required to visit the hospital once a week for replacing the seeds and plasters.The course of intervention lasted for 8 weeks and the patients were followed up for another 4 weeks.Pittsburgh sleep quality index (PSQI) and Karolinska sleep diary (KSD) were used to evaluate the outcomes.Meanwhile,adverse effects were monitored and recorded.Results:In the enrolled 72 cases,4 patients (one in the treatment group and three in the control group) reported thirst and a bitter taste,and one case in the control group reported nausea and vomiting.At last,3 cases in the control group dropped out for adverse reactions,and 69 cases completed the clinical trial.After 8 weeks of treatment,the global scores of PSQI in both treatment and control groups decreased significantly compared with the baseline (both P＜0.001).Furthermore,the global score of PSQI in the treatment group was lower than that in the control group (P＜0.01).The global scores of PSQI in both groups at the follow-up were significantly different from the baseline (both P＜0.001),but insignificantly different compared with the post-treatment results (both P＞0.05).According to KSD,both treatment protocols could prolong the total sleep time,shorten sleep-onset latency,improve sleep efficacy and sleep quality significantly,and the changes in the treatment group were more significant.The total effective rate was 88.9％ in the treatment group,higher than 81.8％ in the control group,though the difference was statistically insignificant (P＞0.05).Conclusion:Dexzopiclone plus auricular acupressure is effective and safe for patients with primary insomnia both in short and long terms,and it is more effective than monotherapy of dexzopiclone.
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Objective: To observe the effectiveness and safety of electroacupuncture (EA) plus Luohua Anshen oral liquid for patients with perimenopausal insomnia. Methods: A total of 66 participants who met the inclusion criteria were enrolled in the randomized controlled trial and allocated to a treatment group and a control group at a ratio of 1:1, with 33 cases in each group. Both groups were given Luohua Anshen oral liquid as a basic treatment. The treatment group was additionally given EA every other day, three times a week. Both groups were treated for four weeks and a four-week follow-up was conducted. The scores of Pittsburgh sleep quality index (PSQI), Kupperman index (KI) and traditional Chinese medicine sleep syndrome scale (TCMSSS) were recorded at pre- and post-treatment, and at the follow-up. Meanwhile, adverse effects were monitored and recorded. Results: After four-week treatment, the global scores of PSQI, KI and TCMSSS in both groups declined significantly (all P<0.05), and the decreases in the treatment group were more significant than those in the control group (allP<0.05). The global scores of PSQI, KI and TCMSSS in both groups at the follow-up visit were significantly different from the corresponding baseline (allP<0.05), while insignificantly different from those assessed at post-treatment (allP>0.05). The total effective rate was 93.9％ in the treatment group, significantly higher than 72.2％ in the control group (P<0.05). No significant adverse event was reported in this trial excepted one patient experienced slight dizziness in the first acupuncture treatment. Conclusion: EA plus Luohua Anshen oral liquid is safe for perimenopausal insomnia with satisfactory short- and long-term effectiveness, and it shows certain advantage compared with using Luohua Anshen oral liquid alone.
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Objective:To investigate the effectiveness and safety of manual acupuncture for memory loss and sleep quality in chronic insomniacs.Methods:A total of 60 eligible participants were enrolled and randomized into either a treatment group or a control group,with 30 cases in each group.The treatment group was intervened by manual acupuncture whereas the control group was given sham acupuncture.In the two groups,the interventions were offered once every other day and three times a week,for 8 weeks in total.Before and after the treatment,Pittsburgh sleep quality index (PSQI) and eventrelated potentials (ERPs) were used to assess the patients' sleep quality and memory,respectively.Meanwhile,adverse events were monitored and recorded.Results:After 8-week treatment,both the treatment group and the control group showed a significant decrease in the PSQI global score (P＜0.001,P＜0.01),and the decrease in the treatment group was more significant than that in the control group (P＜0.001).The intra-group comparisons of ERPs indicated that,the latencies of N1 and P3 were shortened and the amplitudes of N1 and P3 were increased in the treatment group after the intervention,and the differences were statistically significant (P＜0.05,P＜0.001);in the control group,there were no significant changes in the latency and amplitude after the treatment (P＞0.05).The between-group comparisons of ERPs showed that the treatment group was more effective than the control group in shortening the latency of P3 (P＜0.01).Conclusion:Acupuncture can be a safe and effective treatment option for chronic insomnia coupled with memory impairment.
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This study is aim to determine the predominant prevailing nontuberculosis mycobacteria (NTM) in Hangzhou and to understand the predisposing factors and drug resistance of NTM.PNB/TCH growth tests were used to preliminarily identify the NTM in the mycobacterium-positive culture samples from 1 972 patients.The species of NTM isolates were con firmed using mycobacterium molecular linear probe method and sequencing of PCR product of 16S rRNA gene.The influence of sex and age on predisposing factors of NTM was subsequently analyzed.Concentration proportional method was applied to de tect the susceptibility of NTM isolates to armazide,rifampicin,streptomycin,ethambutol,ofloxacin and kanamycin.Results of PNB/TCH growth tests showed that 9.8％ (193/1 972) of the 1 972 mycobacterium-positive culture samples were positive.The mycobacterium molecular linear probe hybridization and PCR product sequencing confirmed that in the 193 samples with positive results of PNB/TCH growth tests,66.3％,18.1％,8.3％ and 7.3％ were infected with NTM alone,two mycobacteria,Mycobacterium tuberculosis and bacteria that not belonging to the genus of Mycobacteria,respectively.In the 173 NTM isolates (128 with single infection and 45 with mixed infection),57.8％ were identified as Mycobacterium intracellulare,followed by Mycobacterium abscessus (12.1％),Mycobacterium kansasi i (9.8％),Mycobacterium chelonei (9.8％) and Mycobacterium avium (5.8％).In the 35 mixed infection samples,28.5％ and 20.0％ were the co-infection of M.intracellulare and M.chelonei with M.tuberculosis,respectively.Male patients infected with NTM were more than female patients (1.67 ∶ 1) and the infection rate (80.4％) of populations with age over 50 years old was significantly high than that with lower than 50 years old (P＜0.01).Pulmonary infection proportion (95.1 ％) of NTM was significantly higher than other positions of body (P＜0.01).100％ of NTM isolates were resistant to armazide while the resistance rates of the isolates against the other 5 antituberculosis drugs were as high as 70.3 ％ 90.6 ％.As the conclusion of this study,M.intracellulare is the predominant prevailing NTM species in the recent years in Hangzhou,NTM mainly causes pulmonary infection and middle-aged and old people are easily infected by NTM.Moreover,NTM isolates have high resistance against commonly used antituberculosis drugs.
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Objective To investigate the efficacy of an anti-vascular endothelial growth factor (VEGF) antibody,MIL60,in inhibiting corneal neovascularization (CoNV) formation in a rat model of alkali cauterization and its involved mechanisms.Methods Rat CoNV model induced by alkali burn was founded in the right eyes,and then 72 cases were randomly divided into four groups according to the subconjunctival administration of medicine next day after the successful establishment of this model:25mg· mL-1 MIL60 group,dexamethasone group,MIL60 solvent group and NaCl group.Then CoNV was observed for recording the its length and the involved area using digital photograph.Next the rats were sacrificed on day 7,14,21 and 28,followed by the collection of rats' cornea for HE and immunohistochemical staining to analyze the protein expression of VEGF,VEGF receptor-1 (VEGFR-1),VEGFR-2 and matrix metallopeptidase-9 (MMP-9).Results At each time point,the area and length of CoNV in the 25 mg· mL-1 MIL60 and dexamethasone group were significantly less than those in the MIL60 solvent and NaC1 group,and the differences were statistically significant (all P ＜0.01),and 25 mg· mL-1 MIL60 group had the similar CoNV area and length with the dexamethasone group (all P ＞ 0.05).Moreover,HE and immunohistochemical staining showed that MIL60 could inhibit the protein expression of VEGF,VEGFR-1,VEGFR-2 and MMP-9,which could explain its effective anti-angiogenic activity.Conclusion Subconjunctival administration of MIL60 can significantly inhibit corneal neovascularization formation and alleviate the inflammation in rats suffered from alkali burn.
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There are tens of thousands of microbiota in the intestine, and the balance of these microbiota is essential to maintain intestinal stability and body metabolism. Once the intestinal flora structure is disordered, a variety of metabolic diseases will follow. In recent years, the international scientific researches focus on the relationship between intestinal flora and metabolic diseases, especially type 2 diabetes mellitus (T2DM). And the probiotics, as a kind of active microorganism that regulate the micro-ecological balance of the host's gut, can change the intestinal flora and their metabolites, and thus improve the host energy metabolism and reduce low level chronic inflammation and oxidative stress. Therefore, its intake has gradually become an usual method of preventing and controlling T2DM. This review provides an overview of the effects of probiotics on host intestinal flora and the mechanisms of improving T2DM, as well as a theoretical reference for the clinical application of probiotics.
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There are tens of thousands of microbiota in the intestine, and the balance of these microbiota is essential to maintain intestinal stability and body metabolism. Once the intestinal flora structure is disordered, a variety of metabolic diseases will follow. In recent years, the international scientific researches focus on the relationship between intestinal flora and metabolic diseases, especially type 2 diabetes mellitus (T2DM). And the probiotics, as a kind of active microorganism that regulate the micro-ecological balance of the host's gut, can change the intestinal flora and their metabolites, and thus improve the host energy metabolism and reduce low level chronic inflammation and oxidative stress. Therefore, its intake has gradually become an usual method of preventing and controlling T2DM. This review provides an overview of the effects of probiotics on host intestinal flora and the mechanisms of improving T2DM, as well as a theoretical reference for the clinical application of probiotics.
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ObjectiveTo investigate the neuroprotective mechanism of edaravone for cerebral ischemia-reperfusion injury in rats.MethodsThirty-six healthy adult male SD rats were randomly divided into three groups: a sham operation group, an ischemic model group, and an edaravone group (n=12 in each group).A focal cerebral ischemia model was induced by the suture method.Reperfusion was resumed after 2 h of ischemia;then the animals were sacrificed at 24 h after reperfusion.Edaravone 3 mg/kg was injected intraperitoneally immediately after cerebral ischemia-reperfusion in the edaravone group.The rats in the model group were injected equal volume normal saline.HE staining was used to observe the pathological changes.TUNEL staining was used to detect apoptotic cells in the ischemic cortex.Western blot and immunofluorescent staining were used to detect the expression levels of LIM domain protein 4 (LMO4) and LMO4 positive cells.Results HE staining showed that cellular morphology was basically normal in the sham operation group;both the model group and edaravone group had cell necrosis, but the latter was less severe.The number of morphologically normal cells in the edaravone group was significantly more than that in the model group (P<0.01).TUNEL staining showed that no TUNEL positive cells in the sham operation group were observed.The TUNEL positive cells in the edaravone group was significantly less that in the model group (P<0.01).Immunofluorescence staining showed that the expression level of LMO4 in the ischemic cortex in the edaravone group was significantly higher than that in the model group (P<0.01).ConclusionsEdaravone can alleviate the cerebral ischemia-reperfusion injury and inhibit neuronal apoptosis.Its mechanism may be associated with the upregulation of LMO4 expression.
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<p><b>OBJECTIVE</b>To accurately define the injury position of medial patellar retinaculum with acute injury under the guiding of high frequency ultrasonography, and to study therapeutic effects of suture operation on medial patellar retinaculum in the injuried position.</p><p><b>METHODS</b>From June 2009 to March 2014, there were 17 patients with acute patellar dislocation, 6 males and 11 females with average age of (16.2±6.2) years old. The duration time of patellar dislocation was 2 weeks. Before operation, the medial patellar retinaculum of all patients were examined with the high frequency ultrasonography, and the skin with the non-continuous fiber was iudicated as the surface mark under the high frequency ultrasonography. The injury position of medial retinaculum was in the middle of 5 patients who were treated with suture operation of arthroscopic medial retinaculum. The injury position was in the patellar edge in 12 patients who were treated with fixing bone anchor on patella and arthroscopic suture operation of medial retinaculum. The CT examination and Kujala scores, patellar tilt angle on CT film, measured maximal angles of passive or active knee flexion and apprehension test were observed before treatment and postoperative 18 months.</p><p><b>RESULTS</b>Eighteen months after treatment, Kujala scores were 92.2±11.1 and patellar tilt angle were(11.5±4.2) °, and there was no statistical difference between post-operation and pre-operation. The difference between maximal angles of passive knee flexion(133.5±4.2) ° and normal had no statistically significance. Maximal angles of active knee flexion were(153.5±4.6) °. Ultrasonography showed the continuous fiber of medial retinaculum. A patient showed positive apprehension test and no patient had the recurrence patella instability after operation.</p><p><b>CONCLUSIONS</b>The injury position of medial patellar retinaculum was accurately shown by high frequency ultrasonography and treated with arthroscopic suture operation. Knee immobilization time after operation was shorten. Eighteen months after operation, knee joint function was good, and no patient had the recurrence patella instability.</p>
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Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
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Humans , Amyotrophic Lateral Sclerosis , Genetics , Metabolism , Therapeutics , Cell Line , Clustered Regularly Interspaced Short Palindromic Repeats , Genetic Therapy , Genome-Wide Association Study , Induced Pluripotent Stem Cells , Metabolism , Mutation, Missense , RNA-Binding Protein FUS , Genetics , Metabolism , Superoxide Dismutase-1 , Genetics , MetabolismABSTRACT
BACKGROUND:Co-culture technique makes different kinds of ceils cultured in the same system.The trans-differentiation from osteoblasts to adipocytes is usually analyzed under the action of adipogenesis inducers in vitro,but the cellular interactions in vivo are neglected.OBJECTIVE:To investigate the trans-differentiation from osteoblasts to adipocytes in indirect co-culture using Transwell system.METHODS:Mouse preadipocytes 3t3-l1 were induced to adipocytes.There were three groups:group A:mature adipocytes in the lower chamber of Transwell system;group B:mouse osteoblasts MC3T3-E1 in the upper chamber of Transwell system according to a ratio of 1:4 (MC3T3-E1:3t3-l1);group C:mouse osteoblasts MC3T3-E1 alone.At 7,14,and 21 days the cell morphology was observed under inverted phase contrast microscope,the relative level of triglyceride,expression of peroxisome proliferator-activated recoptor y2 in each group were detected,and red oil O staining and alizarin red staining were performed.The cell proliferation inhibition rate in the groups B and C were detected at 0,24 and 36 hours.RESULTS AND CONCLUSION:At 2 weeks after culture,spindle-shaped 3t3-l1 coils changed into round,the light and round lipid droplets in the cytoplasm were increased and were reserved after identified by oil red O staining.In the group B,the cells presented with spindle shape with no transparent lipid droplets after 7-day co-culture until black granules and small round lipid droplets appeared on day 14;and the cells changed from spindle shape to oval or round,and larger lipid droplets were found on day 21.Alizarin red staining results:the staining region in the group B was on a decline with time,while the group C showed no significant changes at each time point and all appeared with large staining region.Oil red O staining results:the staining region in the group B increased gradually in a time-dependant manner,while the group C was negative for oil red O staining and showed no significant changes at different time points.The relative level of triacylglycerol in the group B was increased with time,and there was significant difference between groups A and B (P ＜0.05),and the group C showed no significant differences (P ＞ 0.05).The coll proliferation inhibiting rate in the group B was increased with time,which showed significant difference from the group C (P ＜ 0.05).The expression level of peroxisome proliferator-activated recoptor y2 in the group B was on a rise with time,which had significant difference compared with the groups A and C (P ＜ 0.05).These results indicate that the trans-differentiation from osteoblasts to adipocytes appears in the Transwell system,and metabolic products and cytokines of adipocytes obviously inhibit the proliferation of osteoblasts,but all above conclusions need to be studied in depth.
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<p><b>BACKGROUND</b>Collagen VI-related myopathies are autosomal dominant and recessive hereditary myopathies, mainly including Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM). Muscle magnetic resonance imaging (MRI) has been widely used to diagnosis muscular disorders. The purpose of this study was to evaluate the diagnostic value of thigh muscles MRI for collagen VI-related myopathies.</p><p><b>METHODS</b>Eleven patients with collagen VI gene mutation-related myopathies were enrolled in this study. MRI of the thigh muscles was performed in all patients with collagen VI gene mutation-related myopathies and in 361 patients with other neuromuscular disorders (disease controls). T1-weighted images were used to assess fatty infiltration of the muscles using a modified Mercuri's scale. We assessed the sensitivity and specificity of the MRI features of collagen VI-related myopathies. The relationship between fatty infiltration of muscles and specific collagen VI gene mutations was also investigated.</p><p><b>RESULTS</b>Eleven patients with collagen VI gene mutation-related myopathies included six UCMD patients and five BM patients. There was no significant difference between UCMD and BM patients in the fatty infiltration of each thigh muscle except sartorius (P = 0.033); therefore, we combined the UCMD and BM data. Mean fatty infiltration scores were 3.1 and 3.0 in adductor magnus and gluteus maximus, while the scores were 1.3, 1.3, and 1.5 in gracilis, adductor longus, and sartorius, respectively. A "target" sign in rectus femoris (RF) was present in seven cases, and a "sandwich" sign in vastus lateralis (VL) was present in ten cases. The "target" and "sandwich" signs had sensitivities of 63.6% and 90.9% and specificities of 97.3% and 96.9% for the diagnosis of collagen VI-related myopathies, respectively. Fatty infiltration scores were 2.0-3.0 in seven patients with mutations in the triple-helical domain, and 1.0-1.5 in three of four patients with mutations in the N- or C-domain of the collagen VI genes.</p><p><b>CONCLUSIONS</b>The "target" sign in RF and "sandwich" sign in VL are common MRI features and are useful for the diagnosis of collagen VI-related myopathies. The severity of fatty infiltration of muscles may have a relationship with the mutation location of collagen VI gene.</p>
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Young Adult , Collagen Type VI , Genetics , Metabolism , Magnetic Resonance Imaging , Muscle, Skeletal , Pathology , Muscular Diseases , Genetics , Metabolism , Pathology , Mutation , Genetics , Sensitivity and Specificity , Thigh , PathologyABSTRACT
Objective To evaluate the efficacy and safety of focal fractional laser treatment(FFLT)for atrophic acne scars. Methods A randomized, self-controlled study was performed. A total of 20 patients with atrophic facial acne scars were enrolled into this study. Treatments were randomly administered in a split-face manner. Half of each subject′s face received FFLT(FFLT side), and the other half underwent full-face fractional CO2 laser resurfacing(control side), for one session. All the patients were followed up for 3 months after the treatment. Evaluation was based on the ECCA grading scale (échelle d′évaluation clinique des cicatrices d′acné)and patient satisfaction score. A VISIA skin detector was used to take photographs and evaluate skin texture. Moreover, physical parameters of the skin, including erythema index, melanin index and transepidermal water loss (TEWL), were measured. Adverse effects were recorded and evaluated. Statistical analysis was carried out by paired t test, Wilcoxon paired rank test, Fisher′s exact test and repeated-measure analysis of variance. Results The ECCA score decreased from 51.24 ± 17.61 at the baseline to 34.46 ± 14.99 at 3 months after the treatment at the FFLT side(t = 7.886, P 0.05). Compared with those before the treatment, skin texture scores decreased in both sides (both P 0.05)from 2 weeks to 3 months after the treatment(all P > 0.05). Conclusion FFLT can improve therapeutic outcomes in atrophic acne scars with reduced adverse reactions.
ABSTRACT
<p><b>OBJECTIVE</b>To compare therapeutic effects between arthroscopic medial retinaculum plication and plaster external fixation for the treatment of acute patellar dislocation.</p><p><b>METHODS</b>From February 2006 to October 2012,29 patients with acute patellar dislocation were divided into two groups: operation group and non-operation group. The patellar dislocation duration was 2 weeks. In operation group, there were 7 males and 10 females, with an average age of (16.2 ± 6.2) years old, and the patients were treated with arthroscopic medial retinaculum plication. In non-operation group, there were 5 males and 7 females,with an average age of (16.3 ± 5.0) years old,and the patients were treated with plaster external fixation. The Kujala scores, patellar tilt angle measured on CT film, apprehension test and recurrence rate of patellar instability were observed before and 1 year after treatment.</p><p><b>RESULTS</b>In operation group, the pre-treatment and post-treatment patellar tilt angles had no statistical difference, but the post-treatment Kujala score was lower than that of pre-treatment; while in non-operation group, the post-treatment patellar tilt angle was larger than that of pre-treatment, and the post-treatment Kujala score was lower than that of pre-treatment. At 1 year after treatment, the patellar tilt angle (21.2 ± 5.3) of patients in non-operation group was larger than (13.5 ± 3.5) of operation group, and the Kujala score 73.3 ± 10.5 of patient in non-operation group was lower than 84.1 ± 5.6 of operation group.</p><p><b>CONCLUSION</b>During 1 year after operation, arthroscopic medical retinaculum plication is a more effective treatment for acute patellar dislocation compared with plaster external fixation.</p>