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.

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.

Objective:To evaluate the safety and efficacy of Toumai ? endoscopic robotic system in radical prostatectomy. Methods:This study was a single-center phase Ⅲ randomized controlled study. From June 2020 to January 2021, patients with prostate cancer who met the inclusion criteria in Changhai Hospital Affiliated to Naval Military Medical University were divided into the experimental group and the control group by random table method. Inclusion criteria included aged 18 to 80 years, pathologically diagnosed as prostate cancer, clinical stage ≤T 2N 0M 0. Exclusion criteria included patients requiring emergency surgery, having serious cardiovascular diseases and cannot tolerate surgery, having participated in other investigational drug or device clinical trials within the last 3 months. The experimental group used Toumai ? laparoscopic robotic system, and the continence group used the Da Vinci robotic system. The patients in both groups underwent radical prostatectomy via a transabdominal approach, which was performed by two surgeons. The clinical characteristics between the two groups were compared, related adverse events were recorded, and PSA and urinary continence were followed up one month after the operation. Results:A total of 44 patients were enrolled in this study, including 22 cases in the experimental group and 22 cases in the control group. The mean age of patients in the trial group and the control group was (67.7±7.5) years and (66.4±6.3) years, respectively. The median PSA at diagnosis was 10.5 (7.7, 23.7) ng/ ml and 13.5 (8.9, 24.7) ng/ ml, respectively. Biopsy Gleason score of 6, 7, 8 and 9 in experimental group were 13.6% (3/22), 68.2% (15/22), 4.5% (1/22) and 13.6% (3/22), respectively, and in the control group were 4.5% (1/22), 59.1% (13/22), 22.7% (5/22) and 13.6% (3/22) respectively. The middle risk and high risk group in the experimental group was 50.0% (11/22), 50.0% (11/22), and the control group was 36.4% (8/22), 63.6% (14/22). There was no statistical difference between the two groups.The operations in both groups were successfully performed. There were no conversions to open or laparoscopic surgeries, and no Clavien-Dindo grade Ⅲcomplications. There was no significant difference in the estimated blood loss during the operation [(109.1±51.6)ml vs.(94.5±51.6)ml] and the blood transfusion rate [9.1%(2/22)vs. 4.5%(1/22)] in both groups. The operation time was significantly higher in the experimental group than that in the control group [164.5(130.5, 214.3) min vs. 88.0(65.3, 110.5)min, P<0.001]. The positive rate of surgical margin was 13.6% (3/22) in the experimental group and 36.4% (8/22) in the control group, respectively, showing no significant difference. The pathologic stages of pT 2, pT 3a and pT 3bin experimental group were 63.6% (14/22), 13.6% (3/22) and 22.7% (5/22), respectively, while those in control group were 36.3% (8/22), 40.9% (9/22) and 22.7% (5/22), respectively, showing no significant difference. The recovery rates of urine control in the experimental group and the control group were 22.7% (5/22) and 22.7% (5/22), respectively. The median PSA in the experimental group and the control group were 0.055 (0.021, 0.103) ng/ ml and 0.032 (0.010, 0.089) ng/ ml, respectively, with no statistical difference. Conclusions:The Toumai ? endoscopic robotic system can successfully perform radical prostatectomy, based on insignificant difference from Da Vinci robotic system in safety and efficacy. The short-term follow-up showed that tumor control and urinary continence have recovered well in the test group. The long-term effect of the new system on tumor control and functional recovery after radical prostatectomy needs further multi-center studies.

The main form of fetal long bone development is endochondral ossification. In recent years, studies have shown that the mother during pregnancy with bad environmental exposure to high levels of endogenous glucocorticoid (GC) and premature use of artificial synthetic GC can go through the placenta into the fetal body, cause fetal blood GC levels, leading to intrauterine retardation, and affect fetal cartilage ossification. This effect can extend beyond birth and even into old age, leading to susceptibility and heritability of osteoporosis in offsprings. This review summarizes the current status of glucocorticoid exposure during pregnancy, summarizes the short-term and long-term effects of intrauterine GC exposure on long bone development in offsprings, and explains the possible mechanism of intrauterine endocrine programming, which lays a theoretical foundation for the prevention and treatment of fetal bone diseases caused by GC exposure during pregnancy and the future research direction of developmental diseases.

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.

Objective:To explore the associations between anxiety and family rearing styles and sleep habits in preschool children.Methods:From March to October 2019, a total of 100 preschool children (47 boys and 53 girls) were investigated by Spence Children′s anxiety scale, Family rearing style Evaluation scale (parents′ version) and self-made sleep habit questionnaire.Results:There was no significant difference in the total score of anxiety between girls and boys: (55.12 ± 9.89) scores vs. (53.40 ± 11.82) scores, P > 0.05. The parent′s acrasia-control was positively correlated with children′s social anxiety dimension and total score of anxiety ( r = 0.202 and 0.202, P<0.05), the parent′s reception-rejection was positively correlated with children′s generalized anxiety dimension ( r = 0.237, P<0.05), and children′s sleep duration was negatively correlated with physical injury fear dimension and the total score of anxiety ( r = -0.230 and -0.203, P<0.05). The anxiety scores in children who slept in the same bed was significantly higher than that in children who slept alone and who slept in different beds in the same room: (53.57 ± 9.75) scores vs. (50.21 ± 13.89) and (50.48 ± 11.50) scores, and there was statistical difference ( P<0.05); there was no difference in the total score of anxiety between children who slept alone and who slept in different beds ( P>0.05). Multivariate analysis result showed that children′s age, sex, sleep duration, parents′ acrasia-control and partial-rough were the predictors of children′s anxiety ( P<0.05 or<0.01). Conclusions:Different family rearing styles and children′s bed sleeping styles significantly affect the anxiety of preschool children. Parents should pay attention to the positive effects of good rearing styles and children′s separate sleep on anxiety.

In this paper, a new type of preparation for treatment of initial dry eye disease, thermosensitive in situ gel, was prepared using levocarnitine as a model drug. Poloxamer 407 and poloxamer 188 were used as the gel matrix, and sodium hyaluronate and sodium carboxymethylcellulose were used as bioadhesive materials. Gelation temperature was determined by a rotor method and the prescription was optimized by central composite design-response surface methodology. The pH value, viscosity value and gelation temperature of the optimal prescription were measured. The release of the drug in vitro was examined by dialysis membrane permeation, and retention time of the thermosensitive in situ gel preparation on the rabbit's ocular surface was observed by a slit lamp microscope. The results showed that the dosage of the poloxamer 407 and poloxamer 188 were 20.81% and 3.46%, respectively, and sodium hyaluronate was 0.02%, sodium carboxymethyl cellulose was 0.10% of the optimal formulation of levocarnitine thermosensitive in situ gel. The pH value was 6.90 ± 0.06 at room temperature and the viscosity value started to rise sharply at 27 ℃ of the optimal formulation. The gelation temperature of the optimal preparation before and after dilution by simulated tear fluid were (26.37 ± 0.06) ℃ and (33.57 ± 0.21) ℃, respectively. In the first 240 min, in vitro release rate per unit area of levocarnitine thermosensitive in situ gel was lower than that of solution (P<0.05), and after 600 min, the cumulative release rate of levocarnitine thermosensitive in situ gel could reach more than 80%. The retention time of the thermosensitive in situ gel preparation on rabbit's ocular surface reached about 25 min, at least 5 times as much as that of the solution. The animal experiment was conducted following the National Institutes of Health Guidelines for the use of experimental animals, and approved by the Ethics Committee of the Experimental Animal Center of Beijing University of Chinese Medicine. The levocarnitine thermosensitive in situ gel showed good characteristics and sustained release property and significantly improved the retention time of the drug on the rabbit's ocular surface.

Objective: To investigate the effect of varying concentrations of polyethylene glycol(PEG)400 in receiving solution on in vitro transdermal test of drugs. Method: 5-Fluorouracil(5-FU) was selected as a model drug,by preparing different concentrations of PEG400-phosphate buffer solution(PBS) as the receiving solution,the receiving chamber did not add drug,the excised rat skins were treated with various additives for 12 h,then replaced by PBS and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug.Meanwhile,scanning electron microscopy(SEM) was employed to monitor the effect of PEG400 with different concentration on the stratum corneum of rat skin. Result: The 10%,15% and 40% PEG400-PBS groups had no significant effect on in vitro transdermal absorption parameters of the 5-FU.The steady transdermal rate and cumulative penetration rate of the drug in 20% and 30% PEG400-PBS groups were significantly higher than that in the PBS group(P<0.01,P<0.05).SEM indicated that wrinkle of the intact rat skin gradually disappeared and a number of flakes were desquamated from the skin when the concentration of PEG400 was above 20% in receiving solution.Meanwhile,30% PEG400-PBS group and 40% PEG400-PBS group were extremely wrinkled. Conclusion: In the rat skin transdermal test,the concentration of PEG400 in receiving solution should be controlled below 20%.

OBJECTIVETo explore the surgical method and clinical outcome of modified osteotomy of olecranon for the treatment of inter-condylar fracture of humerus.

METHODSFrom May 2007 to December 2012, 32 patients of intercondylar fracture of humerus were treated surgically through the approach of modified osteotomy of olecranon. The patients were 21 males and 11 females with a mean age of 46.3 years (ranged 18 to 65 years). Nineteen fractures occurred on the right extremity and 13 on the left extremity. According to the AO classification, type C1 fracture was found in 7, C2 in 11 and C3 in 14. Five patients suffered from open fracture (Gustilo type Iin 3, type II in 2). Other fractures occurred in 6 patients and the primary injury of nerve occurred 6. The healing of the osteotomy was evaluated with physical examination and plain X-ray film, and the function of elbow was assessed according to Cassebaum scale.

RESULTSAll the patients were followed from 9 months to 5 years(average, 1.9 years). All the osteotomies healed at 7.4 weeks averagely after operation, and no nonunion, delayed union, fracture of ulna olecranon were found. Two cases had little pain on the elbow, heterotopic ossification occurred in 2 cases and cutting bone block loosed in 1 case. The function of the elbow showed excellent in 19 cases, good in 8, fair in 4 and poor in 1.

CONCLUSIONSThe use of the approach of modified olecranon osteotomy for surgical management of intercondylar fracture of humerus has some advantages, it provides satisfactory stability with simple technical procedures avoiding inter-articular invasion, and it facilitates rehabilitation exercises and providing good results with low complication rates.

OBJECTIVETo observe the clinical effect of the treatment for complex fractures of the tibial plateau through the application of the external fixator and the locking plate.

METHODSFrom Feb. 2006 to Oct. 2008,12 patients with tibial plateau fractures were treated with external fixator and locking plate included 8 males and 4 females with an average age of 38 years ranging from 23 to 59. According to Schatzker type, 7 cases were type V and 5 cases were type VI. Using an anteromedial incision and an anterolateral approach, the locking plate were fixed in the tibia lateral. The collapse and height lossing of tibial plateau was observed through X-ray film before and after operation. The function of knee joint was evaluated according to HSS scoring.

RESULTSThese patients were followed up for 4 to 18 months (means 9.79 months). Eleven cases had bone primary union,and 1 delayed union. No deep phlebothrombosis and osteofascial compartment syndrome occurened. The average healing time was 3.1 months. Between the preoperative and postoperative X-ray film there were no second stage depression fracture of the tibial plateau,postoperative reduction loss and bad alignment. The range of knee flexion was 90 degrees to 110 degrees. The HSS knee functional scoring was(75.50 +/- 10.01)scores after operation and (21.50 +/- 11.68) scores before operation.

CONCLUSIONThe treatment with the external fixator and the locking plate for complex fractures of the tibial plateau could provid continuous stability of fixation,prevent the fracture from second stage displacement and the knee force line change, protect the soft-tissue around the knee, reduce the postoperative complications. The knee joint function is satisfied.

Adult ; Bone Plates ; External Fixators ; Female ; Humans ; Knee Joint ; physiopathology ; Male ; Middle Aged ; Tibial Fractures ; physiopathology ; surgery