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Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

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Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of Csp2-H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.

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@#Objective To explore the predictive value of slow apparent diffusion coefficient(ADCslow),fast apparent diffusion coefficient(ADCfast)and perfusion fraction(f)value of intravoxel incoherent motion in body diffusion-weighted imaging(IVIM-DWI)sequence in early lumbar disc degeneration in young people.Methods The IVIM-DWI technique was used as quantitative magnetic resonance imaging for 120 patients(596 lumbar intervertebral discs)with lower back pain included in Wenzhou People's Hospital.The ADCslow,ADCfast and f values of all lumbar intervertebral discs were measured,and then they were divided into 3 groups according to the Pfirrmann grading standard.SPSS 20.0 statistical software was used to analyze the data.Results The ADCfast value has statistical significance in distinguishing the lumbar intervertebral discs of each group:The area under the curve(AUC)of the normal group vs.the early degenerative group was 0.766,with a sensitivity of 64.2%and a specificity of 78.5%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.822,with a sensitivity of 67.9%and a specificity of 91.3%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.797,with a sensitivity of 62.1%and a specificity of 92.1%.The ADCslow value has statistical significance in distinguishing the lumbar intervertebral discs of each group:AUC=0.707 in the normal group vs.the early degenerative group,with a sensitivity of 83.6%and a specificity of 61.0%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.701,with a sensitivity of 84.5%and a specificity of 58.6%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.668,with a sensitivity of 86.6%and a specificity of 51.0%.The f value cannot distinguish between different groups of lumbar intervertebral discs.Conclusion ADCslow and ADCfast of IVIM-DWI sequence have certain accuracy and specificity in distinguishing the early degeneration of lumbar intervertebral disc in young people,which provides a reliable basis for early clinical treatment.

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Six-membered N-containing heterocycles, such as 2-piperidinone derivatives, with diverse substitution patterns are widespread in natural products, drug molecules and serve as key precursors for piperidines. Thus, the development of stereoselective synthesis of multi-substituted 2-piperidinones are attractive. However, existing methods heavily rely on modification of pre-synthesized backbones which require tedious multi-step procedure and suffer from limited substitution patterns. Herein, an organophotocatalysed [1 + 2 + 3] strategy was developed to enable the one-step access to diverse substituted 2-piperidinones from easily available inorganic ammonium salts, alkenes, and unsaturated carbonyl compounds. This mild protocol exhibits exclusive chemoselectivity over two alkenes, tolerating both terminal and internal alkenes with a wide range of functional groups.

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Aliphatic trifluoromethyl ketones are a type of unique fluorine-containing subunit which play a significant role in altering the physical and biological properties of molecules. Catalytic methods to provide direct access to aliphatic trifluoromethyl ketones are highly desirable yet remain underdeveloped, partially owing to the high reactivity and instability of trifluoroacetyl radical. Herein, we report a photocatalytic synthesis of trifluoromethyl ketones from alkyl bromides with trifluoroacetic anhydride. The reaction features dual visible-light and halogen-atom-transfer catalysis, followed by an enabling radical-radical cross-coupling of an alkyl radical with a stabilized trifluoromethyl radical. The reaction provides straightforward access to aliphatic trifluoromethyl ketones from readily available and cost-effective alkyl halides and trifluoroacetic anhydride (TFAA).

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Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

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Three-membered cyclic structures are widely existing in natural products and serve as enabling intermediates in organic synthesis. However, the efficient and straightforward access to such structures with diversity remains a formidable challenge. Herein, a general and practical protocol to aziridines and cyclopropanes synthesis using free XH2 (X=C or N) with alkenes by thianthrenation is presented. This metal-free protocol features the direct aziridination and cyclopropanation with unprotected XH2 . Free sulfonamides, amides, carbamates, amines, and methylene with acidic protons, are good precursors, providing an attractive alternative for straightforward synthesis of aziridines and cyclopropanes from easily available starting materials.

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ß-Thiolated-α-arylated ketones are perversive in bioactive molecules and serve as potential bidentate ligands for catalysis. Herein, a straightforward protocol to access ß-thiolated ketones from aldehydes, alkenes, and disulfides enabled by the combination of photocatalysis and N-heterocyclic carbene catalysis is reported. The sequential radical addition to alkenes and subsequent radical-radical coupling cascade process simultaneously forge C-S and C-C bonds. The mild conditions allow for radical relay coupling with a broad functional group tolerance.

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Selective functionalization of allylic C-H bonds into other chemical bonds is among the most straightforward and attractive, yet challenging transformations. Herein, a transition-metal-free protocol for direct allylic C-H nitrogenation, oxygenation, and carbonation of alkenes by thianthrenation was developed. This operationally simple protocol allows for the unified allylic C-H amination, esterification, etherification, and arylation of vinyl thianthrenium salts. Notably, the reaction furnishes multialkyl substituted allylic amines, ammonium salts, sulfonyl amides, esters, and ethers in good yields. The reaction proceeds under mild conditions with excellent functional group tolerance and could be applied to late-stage allylation of natural products, drug molecules and peptides with excellent chemoselectivity.

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An efficient and mild Zn-mediated decarboxylative/defluorinative alkylation of α-trifluoromethyl alkenes using N-hydroxyphthalimide esters as radical precursors was developed. Several α-trifluoromethyl alkenes were readily coupled to a wide range of primary, secondary, and tertiary radicals, affording the desired gem-difluoroethylenes in moderate to excellent yields. This reaction protocol was also successfully applied to the construction of complex molecules such as the bioactive natural dehydroabietic acid and glycosyl groups bearing the gem-difluoroethylene moiety.

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In this study, a facile and efficient method to synthesize monofluoroalkenes by photoredox catalytic defluorinative alkylation of gem-difluoroalkenes with 4-alkyl-1,4-dihydropyridines under mild conditions (room temperature) is described. This novel strategy is applicable for a broad range of gem-difluoroalkene substrates with good functional group tolerance and a variety of 4-alkyl-1,4-dihydropyridines (including primary, secondary, and even tertiary alkyl radicals). Moreover, it also allows the challenging radical coupling with glycosyl-based 4-alkyl-1,4-dihydropyridines (DHPs) to synthesize monofluoroalkenylated saccharides.

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OBJECTIVE@#To evaluate the clinical effects of debridement and bone grafting with internal fixation via anterior approach in treatment of tuberculosis of lower cervical vertebrae.@*METHODS@#The clinical data of 15 patients with tuberculosis of lower cervical vertebrae who accepted the treatment of one-stage debridement and bone grafting with internal fixation from June 2010 to December 2018 were retrospectively analyzed. There were 9 males and 6 females, aged from 39 to 72 years with an average of (54.67±10.75) years. The lesion segment was C to C. Pre- and post-operative neurologic functions were evaluated by ASIA grade. All the patients underwent the X-ray films of positive and lateral of cervical spine before and after the operation and accepted the periodic review of CT to evaluate the bone grafting.@*RESULTS@#All the 15 operations were successful, no neurological or vascular injury occurred during the operation, and all patients were followed up for 18 to 52 months. The clinical symptoms improved significantly during the follow-up period and CT showed good bone grafting fusion. One patient suffered a relapse of the illness 3 years later, but was healed during the follow-up visit by strengthening the anti tuberculosis therapy.@*CONCLUSION@#For the patients with vertebral destruction and loss of cervical stability, one-stage debridement and bone grafting with internal fixation via anterior approach has definite curative effects. On the basis of standard anti tuberculosis treatment before operation, the long-term standard anti-tuberculosis treatment after operation is the key to healing the tuberculosis of lower cervical vertebrae.

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Objective:To analyze the MRI features of hepatic epithelioid hemangioendothelioma (HEHE).Methods:The data of patients with HEHE managed in the Wenzhou People's Hospital of Zhejiang Province and the First Affiliated Hospital of Wenzhou Medical University from April 2000 to April 2019 were retrospectively analyzed. Among the 26 patients with HEHE, there were 12 males and 14 females, aged from 23 to 65 years (average 44.4 years). The quantity, size, shape and type of the lesions were observed and the MRI features were analyzed.Results:Of the 382 nodules detected by MRI in the 26 patients, the size varied from 0.5cm to 12.0 cm, with 16 nodules being more than 5.0 cm in diameter (average of 2.2 cm). Four patients with a single nodular type presented with low signal on T 1 weighted imaging (T 1WI), high signal on T 2 weighted imaging (T 2WI), high signal on diffused weighted imaging (DWI), and high central signal and low peripheral annular signal on apparent diffusion coefficient (ADC). After enhancement, the lesions presented with annular centripetal enhancement or continuous annular enhancement. Fourteen patients with multiple nodules had a total of 147 lesions, presenting with low signal on T 1WI, high signal on T 2WI, high signal on DWI, and high central signal and low peripheral annular signal on ADC. After enhancement, the lesions presented with annular centripetal enhancement and continuous annular enhancement. There were 24 lesions in 6 patients who had a " double-ring sign" , 21 lesions in 7 patients who had a capsule " shriveled sign" , 16 lesions in 7 patients who had a " lollipop sign" and 18 lesions in 5 patients who had an " intravascular sign" . There were 231 lesions in 8 patients of the fusion type. The lesions showed low signal on T 1WI, high signal on T 2WI , high signal on DWI, and high central signal and low peripheral signal on ADC. After enhancement, the lesions presented with flocculent or annular centripetal enhancement. In 8 patients, 87 lesions had a " target sign" , 55 lesions had a " lollipop sign" and 42 lesions had a capsule " shriveled sign" , and 36 lesions in 5 patients had an " intravascular sign" . Conclusion:MRI signs of HEHE have certain characteristics, such as lesions being distributed near the capsule, and fusing with each other; a " target sign" on T 2WI; a capsule " shriveled sign " ; and a " double-ring sign" , a " lollipop sign" , an " intravascular sign" in the portal phase. These features are helpful in diagnosing HEHE.

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Objective:To summarize the imaging and pathological features of primary central nervous system lymphoma in special sites, and analyze some misdiagnosed cases to provide help for clinical diagnosis.Methods:Thirty-nine patients with primary central nervous system lymphoma diagnosed by pathology from 2000 to 2019 in Wenzhou People′s Hospital and the Second Affiliated Hospital of Wenzhou Medical University were retrospectively analyzed. The imaging and pathological features of primary central nervous system lymphoma in special sites were summarized, and the misdiagnosed cases in these special sites were analyzed.Results:Primary central nervous system lymphoma in special sites included one case of primary dural lymphoma, with thickening of dura mater and obvious enhancement; two cases with lesions in lateral ventricle, with homogeneous enhancement, involving ependyma and spreading to medulla oblongata; two cases with lesions in middle cerebellar peduncle, with patchy abnormal signals and no specific masses, mild to moderate enhancement after enhancement, and one misdiagnosed as demyelinating lesions; one case with lesions in the sellar region which obviously enhanced with a typical “dent sign”, misdiagnosed as invasive pituitary tumor. All the pathological findings indicated diffuse large B cell lymphoma.Conclusions:It is difficult to diagnose primary central nervous system lymphoma in special sites, which is easy to cause misdiagnosis. Understanding its imaging characteristics and pathology can help to diagnose the disease.

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OBJECTIVE@#To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD).@*METHODS@#The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34 cells, and CD3 cells were 14.6×10/kg, 5.86×10/kg, and 2.13×10/kg respectively.@*RESULTS@#The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively.@*CONCLUSIONS@#Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.

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Objective: To investigate the efficacy of haplotype hematopoietic stem cell transplantation in the treatment of acquired severe aplastic anemia (SAA) in children. Methods: The clinical characteristics of 59 pediatric patients with SAA, including 26 cases VSAA, 37males and 22 females, 47 cases typeⅠ and 12 cases typeⅡ, undrerwent haplo-HSCT in our hospital between December 1st, 2011 and December 1st, 2017 were retrospectively analyzed. Among 59 patients, 56 patients with a median age of 4.5 (1.2-14.8) years and median weight of 43 (12-80) kg underwent their first HSCT and 3 patients underwent their second HSCT. All patients received the following conditioning regimen: busulfan, cyclophosphamide, and rabbit ATG or Bu (-, CTX) , fludarabineand rabbit ATG. The prophylaxis of acute graft versus host disease (aGVHD) was cyclosporine (CsA) , MMF and methotrexate. All patients received bone marrow transfusion on day 01 and peripheral stem cell transfusion on day 02 from haploid donor. The median dose of donor mononuclear cell counts was 15.60 (7.74-21.04) ×108/kg of recipient weight and CD34+ cell counts was 4.86 (3.74-7.14) ×106/kg of recipient weight. Results: Neutrophils and platelets of all 59 children were implanted. The median implantation time of granulocytes and platelets were 13 (10-19) d, 19 (9-62) d, respectively. The incidence of grade Ⅰ-Ⅱ aGVHD was 45.76% (27 cases) and grade Ⅲ/Ⅳ 13.56% (8 cases) , The incidence of chronic GVHD was 8.47% (5 cases) , The incidences of CMV and EBV viremia were 59.32% (35 cases) and 28.81% (17 cases) , respectively. The median follow-up was 30 (8-80) months, 57 patients survived with disease free, 2 patients died of GVHD. Both of the estimated 5-year OS and DFS rates were (96.4±2.5) %. Conclusion: Haplo-HSCT could improve the outcomes of SAA children.

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Objective: To discuss the effect of Peiyuan Tongnao capsules on neurological impairment of patients with ischemic stroke at convalescence, and discuss the mechanism of action in microcirculation improvement, anti-inflammation and neuroprotection. Method: One hundred and thirty one patients were randomly divided into control group (66 cases) and observation group (65 cases) by random number table. Patients in control group were given aspirin enteric-coated tablets, 0.1 g/day, simvastatin tablets, 10 mg/days, and treated by percutaneous nerve electrical stimulator for 30 times, 30 min/time, 1 time/day, 5 times/week. In addition of the therapy in control group, patients in observation group were also given Peiyuan Tongnao capsules, 3 grains/time, 3 times/days. A course of treatment was 12 weeks. Before treatment, and at the 4th, 8th and 12th weeks, neurological deficits in the national institutes of health (NIHSS), activity of daily life scale (ADL), berg balance scale (BBA), fugl-meyer scale (FMA) and traditional Chinese medicine (TCM) syndromes were scored. And levels of brain-derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), homocysteine (Hcy) and serum cystatin C (Cys-C) and hemorheological indicators whole blood viscosity, high shear rate, low shear rate, reduced viscosity, plasma viscosity, platelet aggregation rate, fibrinogen (FIB) and blood sedimentation rate (ESR)were detected. Result: At the 8th and 12th week after treatment, score of NIHSS in observation group was lower than that in control group (PPPα, Hcy, Cys-C and hemorheological indices were all lower than those in control group (PPConclusion: Peiyuan Tongnao capsules can promote the recovery of neurological impairment at recovery period of ischemic stroke, regulate inflammatory factors, improve blood rheology, protect neural function, and improve the effect of routine western medicine rehabilitation therapy.

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Objective Brucine and strychnine monomer reference substance as extremely toxic substance had potential threat during transportation and utilization. In this study we investigated the homogeneity, stability and assignment accuracy of the mixture reference solution of strychnine and brucine, so as to provide reference for the quality control of extremely toxic chemical reference substances for Chinese medicine. Methods Following the assay in Chinese Pharmacopoeia volume I (2015), we prepared the mixture reference solution of brucine and strychnine, and investigated the solvents and the concentration of mixutre reference solution. The stability test lasted for 12 months. F-test was used for heterogeneity assay. Three researchers were involved for collaboration. Results Methanol and chloroform solution were selected as the solvents for the stability test. Results showed the difference was not statistically significant among various mixture solutions. The results of value assignment were 0.14 mg/mL for strychnine (sR = 0.5％)and 0.10 mg/mL for brucine (sR = 1.0％). The stability of mixture solution were better under the conditions of methanol solution at 4 ℃ or -20 ℃. Conclusion The results provide a possible way to develop the mixture solution in place of the monomer reference, and the mixture reference solution is expected for the quality control in the slices of Semen Strychni and its compound preparations.

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·AIM: To evaluate the effectiveness of visian implantable collamer lens with central hole (ICL V4c) implantation for the correction of high myopia using the double- pass visual quality analysis system. ·METHODS: Totally 60 eyes of 30 high myopia patients who underwent ICL V4c implantation were enrolled into this prospective randomized control study. Myopic degree of selected patients was -6. 0D to -12. 0D, age 18 to 35 years old, best corrected visual acuity ( BCVA ) ≥0. 6, preoperative corneal astigmatism acuities ≤1. 0D. All patients were taken the temporal side transparent corneal incision. The patients were evaluated postoperatively 1wk, 1 and 3mo respectively. The evaluating items included preoperative BCVA, postoperative uncorrected visual acuity ( UCVA), objective scattering index ( OSI), and modulation transfer function ( MTF ) cut off frequency, Strehl ratio (SR), and 100%, 20%, 9% Optical Quality Analysis System ( OQAS ) Value ( OV, contrast visual acuity ). All statistical analyses were performed with SPSS19. 0 statistical software. Variance analysis of repeated measurement data was employed. ·RESULTS: The UCVA gradually improved at 1wk, 1 and 3mo after surgery. There was statistical significance compared with the preoperative BCVA ( P < 0. 01 ). The postoperative OSI, MTF cut off, SR, OV 100%, OV 20% and OV 9% at 1wk, 1 and 3mo showed statistically differences compared with the preoperative values (P<0. 05). ·CONCLUSION: ICL V4c implantation can effectively correct high myopia range from -6. 0D to -12. 0D. The postoperative OSI were smaller than the preoperative OSI. The postoperative UCVA were better than the preoperative BCVA. The value of postoperative MTF cut off, SR, and OV value of 100% , 20% and 9% improved.

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Objective At present,there are relatively few studies on the application of pepsin in the diagnosis of laryngopha -ryngeal reflux disease(LPRD)in China.This paper aimed to evaluate the application value of Peptest in the diagnosis of LPRD by measuring saliva/sputum pepsin in patients with chronic pharyngitis. Methods From January to June 2017,35 patients with chronic pharyngitis treated in our department were selected to undertake electronic laryngoscopy and evaluated by reflux finding score(RFS) and reflux symptom index(RSI)scoring.The patients'saliva/sputum samples were collected three times for pepsin concentration de-tection(PEPTEST).The first collection was before mouthwash in the morning,the second was 1h after lunch,and the third was the time of evident symptoms.Comparative research was carried out on the above results. Results The average RSI score and RFS score were11.31±6.21 and 5.97±1.98.The pepsin content in morning saliva/sputum[26.80(0,109.80)ng/mL]was significantly lower than that at 1 h after lunch[89.00(16.0,254.8)ng/mL]and that at the time of obvious symptoms[105.70(34.3,254.8)ng/mL](P<0.05).The area under ROC of Peptest in the morning[0.759(0.602, 0.917)],1h after lunch[0.824(0.670,0.978)], at the time of ob-vious symptoms were all greater than the combination of RSI and RFS, representing significant statistical differences(P<0.05). Conclusion Compared with traditional method(a combination of RSI and RFS),Peptest has more important clinical value in the diag-nosis of LPRD.