Cu-Catalyzed N-Arylation of Prolinamides: Access to Enantioenriched DMAP Analogues and Its Application in Black Rearrangement.

A CuI-catalyzed C-N coupling reaction of 3-bromo-DMAP with l-prolinamides was conducted at 80 °C in 12-16 h, where the prolinamide's structure had an accelerating effect on the Ullmann-type reaction. This reaction was used to construct chiral 3-amino DMAP catalysts. Furthermore, enantioenriched DMAP analogue C8 was applied in an asymmetric Black rearrangement of 2-benzofuranylcarbonates, affording 3,3-disubstituted benzofuran-2-ones in up to 96% yield and 97% ee.

Cobalt(II)-Catalyzed Enantioselective Propargyl Claisen Rearrangement: Access to Allenyl-Substituted Quaternary ß-Ketoesters.

Highly enantioselective propargyl Claisen rearrangement of O-propargyl ß-ketoesters was achieved under 2.5 mol % of the chiral cobalt complex as the catalyst under mild reaction conditions. With Co(OTf)2 as the Lewis acid and C1-symmetric imidazoline-pyrroloimidazolone pyridine as the ligand, diverse chiral allenyl-substituted all-carbon quaternary ß-ketoesters were obtained in good yields (up to 97% yield) and high enantioselectivities (up to 98% ee).

Kidney Mesenchymal stem cells alleviate cisplatin-induced kidney injury and apoptosis in rats.

OBJECTIVE: This experiment was designed to demonstrate Mesenchymal stem cells (MSCs) derived from kidney can alleviate cisplatin-induced kidney injury and renal cell apoptosis through paracrine pathway. METHODS: Firstly, MSCs were isolated from kidney of young rats, and their surface-specific markers were identified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunofluorescence staining. Self-renewal ability of Kidney Mesenchymal Stem Cells (KMSCs) was observed by cell counting and 5-Bromo-2'-deoxyuridine (BrdU) fluorescence staining. KMSCs at logarithmic growth stage were traced and injected into rat through tail vein. RESULTS: The results showed that KMSCs homed in the kidney tissues, decreased the secretion of inflammatory factors (CRP, TNFα, IL-1ß, IL-6), and alleviated renal function. Hematoxylin and Eosin (H＆E), Masson and Periodic Acid-silver Methenamine (PASM) staining showed that KMSCs could alleviate pathological damage in rats. Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) assay showed that KMSCs could reduce the apoptosis of rat kidney cells induced by cisplatin. Finally, Immunohistochemistry (IHC) results showed that cisplatin could induce higher expression of the pro-apoptotic protein Bax and lower expression of anti-apoptotic Bcl-2 in kidney tissues. However, KMSCs could reverse the pro-apoptotic effect of cisplatin on kidney cells and improve the survival rate of rats. CONCLUSIONS: In conclusion, KMSCs were successfully isolated from kidney tissues, and KMSCs have therapeutic effects on rat kidney injury induced by cisplatin.

Establishment of a chronic insomnia rat model of sleep fragmentation using unstable platforms surrounded by water.

Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear and a corresponding rat model has not been reported for this purpose at present. The present study aimed to establish a rat model of chronic insomnia with sleep fragmentation using self-made multiple strings of unstable platforms surrounded by shallow water. During the establishment of the models, changes in body weight and differences in food and water intake in the daytime and at night were acquired. The rat models were assessed using several tests, including the Morris water maze test, pentobarbital sodium-induced sleep, infrared monitoring and electroencephalogram/electromyography during sleep. The expression levels of certain inflammatory factors and orexin A were detected in the serum and brain tissues using ELISAs, immunohistochemistry and immunofluorescence. The expression levels of orexin 1 receptor (orexin 1r) were also detected in the brain. Polysomnography indicated that the model rats were successfully prepared with reduced non-rapid eye movement (non-REM) sleep in the daytime, which was increased at night, and considerably lower REM duration during the day and night. The number of instances of sleep arousals were also increased in the day and at night, and the average duration of each sleep bout was decreased in the daytime. The body weights of the model rats increased at a normal rate. However, the reduction of body weight in the daytime and increased in body weight at night were significantly less than those of the control rats. The daytime food and water consumption of the model rats increased significantly compared with that of the control rats, but was similar to that of the control group at night. The Morris water maze test indicated that the model rats were slow to learn to escape the platforms and performed a lower number of target crossings. The pentobarbital-induced sleep experiment confirmed that the model rats exhibited a longer sleep latency and shorter sleep time. The serum IL-1ß, IL-6, TNF-α and orexin A levels of the model rats were significantly increased, whereas their serum IL-10 levels were significantly decreased compared with those of the control rats. The expression levels of IL-1ß, IL-6, orexin A and orexin 1r in the brain tissues of the model rats were also significantly increased. In conclusion, these data indicate that learning and memory function, sleep time, arousal times, diurnal and nocturnal body weight changes, food and water intake, and expression levels of the specific inflammatory factors orexin A and orexin 1r were altered in the model rats. This suggests the chronic insomnia rat model with sleep fragmentation was successfully established using multiple strings of unstable platforms surrounded by water.

[Meta-analysis of external fixator and open reduction and internal fixation for the treatment of distal radius fracture].

OBJECTIVE: To compare clinical efficacy and safety of plate internal fixation (ORIF) and external fixator (EF) in treating distal radius fractures by Meta-analysis. METHODS: From establishment of database to August, 2019, randomized controlled trial (RCT) about open reduction and internal fixation (ORIF) and external fixation (EF) in treating distal radius fractures was conducted by using computer-based databases, including CNKI, VIP, Wanfang Data, Medline, Cochrane library databases. Data extraction and quality evaluation of included study according to inclusion and exclusion criteria, RevMan 5.3 software was used to perform Meta-analysis. Palm angle, ulnar deflection angle, radius height, grip strength, ulnar variation, disabilities of arm, shoulder and hand (DASH) score, total complication rate, infection rate and tendon rupture between two groups were compared. RESULTS: Totally 19 RCT were included with 1 730 patients, 873 patients in ORIF group and 857 patients in EF group. Meta analysis result showed that after operation at 12 months, there were no significant difference in radial height [MD=0.04, 95%CI (-0.90, 0.99), P=0.93], tendon rupture [RR=1.82, 95%CI (0.71, 4.67), P=0.21], carpal tunnel syndrome [RR=2.15, 95%CI(0.98, 4.70), P=0.06], complex regional pain syndrom [RR=0.63, 95%CI(0.31, 1.27)P=0.78] between two groups. While there were significant difference in palm inclination angle [MD=1.38, 95%CI (0.83, 1.93), P< 0.000 01], ulnar deflection angle[MD=0.99, 95%CI(0.54, 1.45), P<0.000 1], ulna variability[MD=0.66, 95%CI(0.21, 1.12), P=0.005], DASH score[MD=2.42, 95%CI(0.37, 4.46), P=0.02], incidence of complications[RR=0.83, 95%CI(0.71, 0.96), P=0.01], infection rate[RR=0.20, 95%CI(0.11, 0.36), P<0.000 1]between two groups. There was statistical difference in tendinitis incidence between two groups [MD=3.88, 95%CI (1.56, 9.64), P<0.003]. CONCLUSION: Compared with EF in treating distal radius fracture, ORIF has better clinical effects in postoperative complications, palm angle, ulnar deviation angle, ulnar variation rate and infection rate. While there were no significant difference between in DASH score, radial height, tendon rupture and carpal tunnel syndrome better EF and ORIF. For the patient pursue rapid recovery of function, ORIF is better choice.

Establishment of a rat model with ageing insomnia induced by D-galactosef and para-chlorophenylalanine.

The current study aimed to establish a rat model of ageing insomnia induced by D-galactose and/or para-chlorophenylalanine. Following establishment of the model, body weights were measured, and Morris water maze and pentobarbital-induced sleep tests were performed. The serum levels of inflammatory mediators and the neural levels of neurotransmitters were detected. The results demonstrated that the body weights of PCPA+D-gal-induced ageing insomnia rats decreased significantly. Ageing insomnia rats exhibited longer latencies to the platform in the Morris water maze tests and fewer target crossings. The sleep latency of the model rats was longer and sleep time was shorter by contrast. The relative expression of hippocampal IL-6, TNF-α, NF-κB and mGluR2 mRNA of the PCPA+D-gal-induced ageing insomnia group was higher, while the relative expression of 5-HT1AR and GABAARa1 mRNA were lower. The serum levels of IL-1ß, IL-6, TNF-α and brain level of glutamate increased in the PCPA+D-gal-induced ageing insomnia group, while the levels of 5-HT and GABA decreased. In conclusion, memory function, sleep time, expression of inflammatory factors and neurotransmitters are altered in ageing insomnia rats induced by D-galactose and para-chlorophenylalanine, indicating the successful establishment of a murine model of ageing insomnia.

Sedative and Hypnotic Effects and Transcriptome Analysis of Polygala tenuifolia in Aged Insomnia Rats.

OBJECTIVE: To study the sedative and hypnotic effects and underlying mechanisms of Polygala tenuifolia (PT) on treating aged insomnia rats. METHODS: Sixty Sprague-Dawley male rats were divided into 6 groups by a random number table, including control group, model group, diazepam group (0.92 mg/kg), as well as PT low-, medium- and high-dose groups (0.0875, 0.175, 0.35 g/kg, respectively), 10 rats in each group. Aged insomnia rat model was established with subcutaneous injection of D-galactose for 42 days and then intraperitoneal injection of para-chlorophenylalanine for 3 days. PT and diazepam were respectively given to aged insomnia rats by intragastric administration for 7 days after model establishment. Then the rats were investigated by body weight, Morris water maze test, pentobarbital test, enzyme-linked immunosorbent assay, and transcriptome sequencing. RESULTS: Compared with the model group, PT increased the body weight, improved memory ability, and prolonged pentobarbital-induced sleep time of aged insomnia rats (P<0.01 or P<0.05). The medium dose of PT also increased the neurotransmitter levels of 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA), and decreased the level of Glu in the hippocampus of aged insomnia rats (P<0.05 or P<0.01). Twenty-four differentially expressed genes (DEGs) were overlapped among model group, medium-dose PT group, and diazepam group in transcriptome analysis. Fuom and Pcp2 were down-regulated by the treatment of medium-dose PT (P<0.01 or P<0.05). The metabolic pathways of PT were relatively less than diazepam (91 vs. 104). CONCLUSIONS: The sedative and hypnotic effects of PT in aged insomnia rats might be related to neuro, metabolism pathways, especially through GABAergic signaling pathway. It provided more effective herb choice for the treatment of senile insomnia.

[Establishment of grading model of knee osteoarthritis based on clinical research system].

OBJECTIVE: The factors influencing the grade of knee osteoarthritis were screened by ordered Logistic regression analysis. The classification model of knee osteoarthritis was established, which provided tool for the evaluation of clinical classification of knee osteoarthritis. METHODS: A total of 753 cases of knee osteoarthritis from Wangjing Hospital, China Academy of Chinese Medical Sciences were treated with single factor and multivariate Logistic regression analysis from September 18, 2014 to April 26, 2016. The model formula was constructed and evaluated. RESULTS: In this study, it was found that 13 factors associated with knee osteoarthritis grading. Old age, obesity, long course of disease, recurrence, lower limb deformity, quadriceps muscle atrophy, WOMAC index, TCM syndrome score, VAS score and grading degree were positively correlated. One knee pain, limited pain range, knee activity and grading degree were negatively correlated. The knee osteoarthritis grading model was constructed and the evaluation test was effective(Training set AUC=0.860, test set AUC=0.879). CONCLUSIONS: In this study, a classification model of knee osteoarthritis was established which has a good ability to predict the classification of knee osteoarthritis under preliminary evaluation.

[Case-control study on tibetan Baimai ointment (see symbol in text) for the treatment of wrist-dysfunction after distal radius fracture].

OBJECTIVE: To evaluate efficacy and safety of Baimai ointment (see symbol in text) in the treatment of wrist-dysfunction after distal radius fracture. METHODS: From April, 2011 to June, 2012, 43 patients with distal radius fracture were treated with plaster fixation. All the patients were divided into two group: test group and control group. Twenty-one patients in test group and 22 in control group, and the baseline was balance (P > 0.05). The 21 patients in test group were treated with Baimai ointment (see symbol in text), fomentation, functional exercises. The 22 patients in control group were treated with placebo, fomentation, functional exercises. Foment affected side wrist with wet towel in 20 min before medication, with the temperature between 50 degrees C and 60 degrees C. Smear drugs uniformly in range of 3 cm in the vicinity of palm stripes after drying (about 3 g) and take functional exercises for the activities of wrist and hand. Continuous follow the program per 8 hours once and follow-up for 8 weeks. The Wrist's pain was assessed with VAS. The wrist's activities were measured with the protractor of orthopedic. Measure The grip strength was measured with dynamometer. The wrist's function were assessed with the table of Cooney. RESULTS: The test group had a significantly better results than those of control group in the extent of wrist's pain throughout the treatment (P < 0.001), and grip strength on the 28th day and the 56th day (P < 0.05), and Cooney functional assessment on the 56th day (P < 0.05). Wrist's activities had no significane difference throughout the 8 weeks (P > 0.05). There were no drug adverse reactions occurred. CONCLUSION: Tibetan Baimai ointment (see symbol in text) has the treatment of wrist-dysfunction after distal radius fracture for external use, which can reduce the extent of wrist's pain, promote grip strength recovery in the middle and late of process, promote wrist's function recovery latterly, and safety for external use.

[A case control study on the treatment of unstable distal radius fractures with internal and external fixation].

OBJECTIVE: To explore the clinical effects of diaplastic external fixator on the treatment of unstable fractures of distal radius. METHODS: A clinical data of 60 patients with unstable fractures of distal radius admitted to Wangjing Hospital from August 2005 to September 2009 were retrospectively analyzed with the paired design. According to the paired design, 60 patients were equally divided into two groups (internal fixation group and external fixation group), which were respectively treated with open reduction and steel plate internal fixation (internal fixation group) or closed reduction and external fixation (external fixation group), including 8 males and 52 females, with an average age of 60.27 years ranging from 34 to 85 years. Left side was in 33 cases and right side was in 27 cases. All fractures were closed and caused by hand supporting when falling down. According to AO classification, type A3 was in 22 cases, type B2 was in 4 cases, type B3 was in 2 cases, type C1 was in 20 cases, type C2 was in 8 cases, type C3 was in 4 cases. Palmar flexion, dorsiflexion, radial deviation, ulnar deviation, pronation, supination, grip strength, radial angle, radial length, volar tilt were observed before and after operation. RESULTS: All the patients were followed up from 12 to 18 months with an average of 15.4 months. The radial length was (4.85 +/- 2.75) mm,volar tilt (14.66 +/- 10.77) degrees, radial angle (7.90 +/- 4.70) degrees in the external fixation group,while those were (4.29 +/- 1.53) mm, (14.39 +/- 5.01) degrees, (6.19 +/- 3.15) degrees in the internal fixation group, but with no statistical significance (P>0.05). Function comparison of internal and external fixation group, P-value of every function is more than 0.05 or equal to 0.05, with no statistical significance except for supination and radial deviation. The functions of wrist joints were evaluated according to Batra scoring system at 1 year after operation. The average radiological scores of external fixation group was 86.27,in which 15 cases were excellent, 11 good, 1 fair,3 poor,while the average functional scores was 94.93, and all the cases were excellent. The average radiological scores of internal fixation group was 91.27, 16 cases were excellent, 12 good, 2 fair, while the average functional scores was 94.23, in which all the cases were excellent. CONCLUSION: Compared with the open reduction and steel plate fixation, the unstable fractures of distal radius treating by diaplastic external fixator can be achieved a similar result, with no statistical significance.

[Discussion of the mechanism of using continuous traction in treating unstable distal radius fracture].

OBJECTIVE: To explore the mechanism of continuous traction in treating unstable distal radius fracture. METHODS: Thirty patients with unstable distal radius fractures were treated by diaplastic external fixator including 4 males and 26 females with an average age of 61 years ranging from 18 to 85 years. According to AO classification, 12 cases were type A3, 3 were type B2, 8 were type C1, 4 were type C2, 3 were type C3. The distance of the processus radial malleolus and ulnar articularis were measured through X-ray examination. RESULTS: Thirty patients were followed-up for 6 to 15 months with an average of 11.2 months. The results of distance before treatment measuring in X-ray was (0.55+/-0.22) cm, and the distance after treatment was (1.07+/-0.23) cm. The distance after treatment was higher than the distance before treatment, there were significant difference between them (P<0.01). CONCLUSION: Continuous traction by diaplastic external fixator can explain by the theory of tendon reinforced bone and ligament restoration, or distraction osteogenesis.