Enantioselective Synthesis of Planar-Chiral Sulfur-Containing Cyclophanes by Chiral Sulfide Catalyzed Electrophilic Sulfenylation of Arenes.

An efficient catalytic asymmetric electrophilic sulfenylation reaction for the synthesis of planar-chiral sulfur-containing cyclophanes has been developed for the first time. This was achieved by using a new Lewis base catalyst and a new ortho-trifluoromethyl-substituted sulfenylating reagent. Using the substrates with low rotational energy barrier, the transformation proceeded through a dynamic kinetic resolution, and the high rotational energy barrier of the substrates allowed the reaction to undergo a kinetic resolution process. Meanwhile, this transformation was compatible with a desymmetrization process when the symmetric substrates were used. Various planar-chiral sulfur-containing cyclophanes were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities (up to 97 % yield and 95 % ee). This approach was used to synthesize pharmaceutically relevant planar-chiral sulfur-containing molecules. Density functional theory calculations showed that π-π interactions between the sulfenyl group and the aromatic ring in the substrate play a crucial role in enantioinduction in this sulfenylation reaction.

[Clinical and genetic analyses of Joubert syndrome in children]. / 儿童Joubertç»¼åˆå¾ä¸´åºŠåŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the clinical and genetic features of Joubert syndrome (JS) in children. METHODS: A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022. RESULTS: Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes. CONCLUSIONS: For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

Atroposelective Sulfenylation of Biaryl Anilines Catalyzed by Chiral SPINOL-Derived Selenide.

The atroposelective electrophilic sulfenylation of biaryl anilines has been realized for the first time. The reaction is enabled by a new chiral 6,6'-dianisole substituted SPINOL-derived selenide. A variety of axially chiral sulfur-containing biaryl aniline compounds were obtained in moderate to excellent yields with moderate to excellent enantioselectivities. The experimental results suggest that catalyst rigidity is important for the high atroposelectivity.

[Application of intermittent flap opening in L-shaped surgical incision of calcaneal fracture].

OBJECTIVE: To explore clinical effect of intermittent flap opening technique in L-shaped incision of calcaneal fracture. METHODS: From January 2017 to January 2019, 48 patients with Sanders typeⅡ to Ⅳ calcaneal fractures were treated by open reduction and internal fixation. According to different flap opening techniques, the patients were divided into control group and observation group, 24 patients in each group. In observation group, there were 17 males and 7 females, aged from 20 to 60 years old with an average of(45.12±9.56) years old;7 patients were typeⅡ, 10 patients were type Ⅲ and 7 patients were type Ⅳ according to Sanders classification;3 patients were C0, 16 patients were C1 and 5 patients were C2 according to Tscherne-Gotzen soft-tissue assessment;treated with intermittent flap technique. In control group, there were 19 males and 5 females aged from 20 to 60 years old with an average of (47.32±10.67) years old;7 patients were typeⅡ, 11 patients were type Ⅲ and 6 patients were type Ⅳ according to Sanders classification;2 patients were C0, 18 patients were C1 and 4 patients were C2 according to Tschemc-Gotzen soft-tissue assessment;treated with static flap opening technique. Operation time, flap retraction time, changes of Böhler angle and Gissane angle before and after operation at 3 days, and occurrence of incision complications were observed and compared between two groups. RESULTS: All patients were followed up from 3 to 6 months with an average of(4.52±1.01) months. There were no significant differences in operation time, changes of Böhler angle and Gissane angle before and after operation at 3 days between the two groups(P>0.05);there was statistical difference in flap retraction time between two groups(P<0.05). Occurrence of incision complications in observation group was significantly lower than that in control group (P<0.05). CONCLUSION: Intermittent flap opening technique is superior to static opening technique in reducing incision complications of lateral "L" approach of calcaneus. Single Kirschner wire opening does not affect the exposure, reduction and fixation of fracture during operation.

Atroposelective Electrophilic Sulfenylation of N-Aryl Aminoquinone Derivatives Catalyzed by Chiral SPINOL-Derived Sulfide.

Atroposelective electrophilic sulfenylation of N-aryl aminoquinone derivatives has been achieved for the first time. This transformation is enabled by a new chiral 6,6'-disubstituted SPINOL-derived sulfide catalyst, which was first synthesized and then successfully explored for catalyzing enantioselective reactions. Various axially chiral sulfur-containing diarylamine derivatives were readily obtained in moderate to excellent yields with moderate to excellent enantioselectivities. A class of relatively flexible stereogenic C-N axes was easily constructed. The experimental results and a computational study suggested that an intramolecular N-H⋅⋅⋅S hydrogen bond is important for the stability of the C-N axis, which is consistent with our hypothesis. Density functional theory calculations revealed the origin of atroposelectivity and underscored the importance of catalyst rigidity in this sulfenylation reaction.

[Selective U-shaped osteotomy of lateral tibial condyle for the treatment of collapse and comminuted fracture of lateral tibial plateau].

OBJECTIVE: To explore methods and clinical effects of selective U-shaped osteotomy of lateral tibial condyle in treating collapse and comminuted fracture of lateral tibial plateau. METHODS: From January 2014 to October 2019, 15 patients with collapse and comminuted fracture of lateral tibial plateau were treated by selective U-shaped osteotomy of lateral tibial condyle, including 9 males and 6 females. The age of patients ranged from 25 to 70 years old, with an average age of (38.5±7.7) years old. According to ABC classification of condyle fracture of tibial plateau lateral, there were 2 cases of type A, 6 cases of type B, 4 cases of type BC and 3 cases of type C. Five patients were combined with medial plateau fracture, 8 patients were combined with left knee fracture and 7 patients of right knee fracture. The time of treatment after injury ranged from 1 day to 14 days with an average of (3.4±1.2) days. CT of all patients showed that lateral tibial plateau collapsed more than 2 mm, more than 2 pieces of bones were crushed and broken, and lateral tibial condyle cortex was intact. At follow-up of 12 months after operation, Rasmussen's anatomical grading system was used to evaluate fracture reduction. Rasmussen's functional grading system were used to evaluate knee joint function. RESULTS: Selective U-shaped osteotomy was successfully complated in 15 patients at one time, and operation time ranged from 55 to 110 min, with an average time of (85.6±20.0) min. The lateral plateau operation ranged from 20 to 60 min with an average time of(30.5±10.5) min. All patients were followed up for 12 to 24 months with an average of (14.6±2.5) months. Fracture healing time was 12 to 24 weeks, with an average of (13.6±3.6) weeks. At follow-up 12 months after operation, by Rasmussen's grading system, anatomical score of knee joint ranged from 14 to 18 points, with an average score of (17.5±0.3) points, of which 13 cases were excellent and 2 cases were good. The functional score ranged from 13 points to 30 points, with an average score of (26.8±2.5) points. Among them, 12 cases were excellent, 1 case was good, 2 cases were fair. Two patients suffered 2 mm and 4 mm loss of lateral tibial plateau, 1 case of knee joint 5 ° valgus, 1 case of stiff joints (10 ° to 100 °). No common peroneal nerve injury, important vascular injury, postoperative infection, internal fixation failure and other serious complications was found. CONCLUSION: The use of selective lateral tibial condyle "U"- shaped osteotomy approach is an effective and reliable method to treat the collapse and comminuted fracture of the lateral tibial plateau. It has the advantages of simple surgical incision, direct fracture exposure, accurate repositioning and fixation, short operation time and few complications.

Alkaloids from the stem of Ephedra equisetina.

Two new cyclotrypyamine alkaloids equisetinines A and B, as well as three known alkaloids (3-5) were isolated from the stems of Ephedra equisetina Bunge. Their structures were characterized by spectroscopic methods, and the absolute configurations of the new compounds were determined by interpretation of their electronic circular dichroism. Anti-asthmatic activities of compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells, and compound 5 exhibited significant anti-asthmatic activities.

Lignans and terpenoids from the stem of Ephedra equisetina Bunge.

Seven undescribed lignans, equiselignan A-F, and six undescribed terpenoids, equiseterpenoid A-E (including two pairs of enantiomers, (+/-)-equiselignan A and (+/-)-equiseterpenoid E), were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, and the absolute configurations of the undescribed compounds were determined by interpretation of their electronic circular dichroic (ECD) and optical rotation data. In ß-hexosaminidase (ß-Hex) release assay, anti-asthmatic activities of all of the compounds were evaluated by releasing ß-Hex in C48/80-induced RBL-2H3 cells. The ß-Hex release rates of equiselignan B and equiseterpenoid B were 0.86 ± 0.094 and 0.86 ± 0.012 by comparing with model group, whereupon equiselignan B and equiseterpenoid B exhibited significant anti-asthmatic activities.

Chiral Selenide/Achiral Sulfonic Acid Cocatalyzed Atroposelective Sulfenylation of Biaryl Phenols via a Desymmetrization/Kinetic Resolution Sequence.

Enantioselective synthesis of axially chiral sulfur-containing biaryl derivatives through the electrophilic sulfenylation of biaryl phenols has been achieved for the first time. This catalytic asymmetric system, which involves sequential desymmetrization and kinetic resolution, is enabled by a combination of a novel 3,3'-disubstituted BINOL-derived selenide catalyst and an achiral sulfonic acid. Control experiments and computational studies suggest that multiple noncovalent interactions between the cocatalysts and substrate, especially a network of hydrogen bond interactions, play a crucial role in determining the enantioselectivity and reactivity.

[Effect of rehabilitation treatment based on the ICF-CY Core Sets on activities of daily living in children with cerebral palsy: a prospective randomized controlled study].

OBJECTIVE: To study the effect of rehabilitation treatment based on the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY) Core Sets on activities of daily living in children with cerebral palsy. METHODS: The children with cerebral palsy were divided into an observation group (n=63) and a control group (n=59) using a random number table. The children in the observation group were evaluated using the brief ICF-CY Core Sets for children under 6 years to identify intervention targets and develop rehabilitation plans and goals, and then specific methods were selected for rehabilitation treatment. The children in the control group were evaluated and treated with the traditional rehabilitation mode. The scores of the Functional Independence Measure for Children (WeeFIM) and the Infants-Junior Middle School Students' Social-Life Abilities Scale were assessed for both groups before treatment and after three courses of treatment. The intervention of environmental factors was compared between the two groups. RESULTS: There was no significant difference in the scores of the WeeFIM and Social-Life Abilities scales between the two groups before treatment (P > 0.05). After treatment, both groups had significant increases in the scores of the WeeFIM and Social-Life Abilities scales (P < 0.001). The observation group had significantly higher scores of WeeFIM and Social-Life Abilities scales than the control group after treatment (P < 0.05). There was no significant difference in the use rate of orthosis between the two groups (P > 0.05), but the use rate of assistive devices for self-help, transfer and communication, the rate of facility renovation, and the rate of family rehabilitation guidance in the observation group were significantly higher than those in the control group (P < 0.05). CONCLUSIONS: The rehabilitation treatment regimen for cerebral palsy based on the CF-CY Core Sets pays more attention to the influence of environmental factors in the process of rehabilitation and can effectively improve the activities of daily living of children with cerebral palsy.

Reduction of essential amino acid levels and sex-specific alterations in serum amino acid concentration profiles in children with autism spectrum disorder.

BACKGROUND: Existing evidence has shown that metabolic disturbances may be involved in the pathological process of autism spectrum disorder(ASD). This study aimed to investigate the alterations of serum amino acid concentration profiles in Chinese Han children with ASD. METHODS: Serum amino acid levels were measured using tandem mass spectrometry in 60 children with ASD and 30 typically developing (TD) controls. The Chinese Wechsler Young Children Scale of Intelligence (C-WYCSI) was used to evaluate the ASD subjects' intelligence quotient (IQ). RESULTS: The serum levels of essential amino acids and some non-essential amino acids (glutamine, glycine, alanine, citrulline, cysteine, serine, tyrosine, and proline) in the ASD group were significantly lower than those in controls. The serum glutamate/glutamine (Glu/Gln) ratio was elevated in the ASD PIQ≥70 group, while serum levels of alanine, cysteine, phenylalanine, methionine and proline were significantly higher in male children with ASD than that in the female group. CONCLUSION: The study revealed that children with ASD exhibit alterations in the serum levels of certain amino acids, and the divergence can be sex-related or associated with different cognitive function, which might provide clues for further etiological research of ASD.

Selenium-Catalyzed Trifluoromethylsulfinylation/Rearrangement of Allylic and Propargylic Alcohols: Access to Allylic and Allenic Triflones.

A selenium-catalyzed trifluoromethylsulfinylation/rearrangement of allylic and propargylic alcohols for synthesizing triflones was developed for the first time. Various allylic and allenic triflones were delivered in moderate to excellent yields. After numerous control experiments were performed, it was suggested that this transformation includes an unusual [+SCF3] group disproportionation process that forms [+SOCF3] that is in-situ-catalyzed by selenium, and H2O was used as an oxygen source. This reaction features mild reaction conditions and good compatibility of substrates, and it is transition-metal-free.

[Clinical effectiveness of Subjective Global Nutritional Assessment in hospitalized children with cerebral palsy].

OBJECTIVE: To investigate the nutritional status of children with cerebral palsy (CP) and the clinical effectiveness of Subjective Global Nutritional Assessment (SGNA) in nutritional assessment of hospitalized children with CP. METHODS: A total of 208 children with CP, aged 1-5 years, who were hospitalized from April to October 2019 were enrolled as subjects. SGNA was used to investigate nutritional status, and the Z-score method recommended by the World Health Organization was used as a reference standard to validate the clinical effectiveness of SGNA. RESULTS: The detection rate of malnutrition in children with CP was 42.3% by SGNA and 39.4% by the Z-score method (P>0.05). The application of SGNA showed high consistency between different evaluators (κ=0.621, P<0.001). With the Z-score method as the reference standard, SGNA had a sensitivity of 80.5%, a specificity of 82.5%, a positive predictive value of 75.0%, and a negative predictive value of 86.7%, and high consistency was observed between the two evaluation methods (κ=0.622, P<0.001). SGNA was moderately consistent with weight-for-age Z-score and height-for-age Z-score (κ=0.495 and 0.478 respectively, P<0.001) and was poorly consistent with weight-for-height Z-score (κ=0.197, P<0.05). CONCLUSIONS: There is a relatively high incidence rate of malnutrition in children with CP. SGNA can be used as a tool to assess the nutritional status of children with CP.

[Autosomal dominant intellectual disability-40 caused by a de novo mutation of the CHAMP1 gene: a case report].

A boy, aged 6 months, had the manifestations of intellectual and motor developmental delay, head instability, general weakness, unawareness of grasping objects by hands, and unusual facies (slightly wide eye distance, epicanthus, esotropia, mouth-opening appearance, short philtrum, and low-set ears). Gene detection results showed a de novo heterozygous frameshift mutation of the CHAMP1 gene at the chromosomal location of chr13:115089847, and nuclear acid was changed to c.530delCinsTTT, resulting in a change in amino acid to p.S177Ffs*2. Therefore, the boy was diagnosed with autosomal dominant intellectual disability-40 caused by the mutation in the CHAMP1 gene. This case report suggests that for children with unexplained intellectual disability, especially those with generalized hypotonia and severe language disorder, the possibility of CHAMP1 gene mutation should be considered, and genetic testing should be performed as early as possible.

Divergent Synthesis of Trifluoromethyl Sulfoxides and ß-SCF3 Carbonyl Compounds by Tandem Trifluoromethylthiolation/Rearrangement of Allylic and Propargylic Alcohols.

A selenium-catalyzed trifluoromethylthiolation/[2,3]-sigmatropic rearrangement of tertiary allylic and propargylic alcohols which could provide straightforward and facile access to trifluoromethyl sulfoxides was developed. Various allylic and allenic trifluoromethyl sulfoxides were obtained with moderate to excellent yields. Meanwhile, a Lewis acid mediated trifluoromethylthiolation/1,2-rearrangement to synthesize ß-SCF3 carbonyl compounds was also accomplished. These two tandem reactions feature with mild reaction conditions and metal-free. During these two reactions, the chemoselectivity of electrophilic trifluoromethylthiolation was revealed.

Lewis-Acid-Mediated Intramolecular Trifluoromethylthiolation of Alkenes with Phenols: Access to SCF3-Containing Chromane and Dihydrobenzofuran Compounds.

A Lewis-acid-mediated intramolecular trifluoromethylthiolation of alkenes with phenols that can offer direct access to SCF3-containing chromane and dihydrobenzofuran compounds was disclosed for the first time. Numerous SCF3-containing chromanes were obtained in moderate to good yields using γ-substituted 2-allyphenols as substrates. Meanwhile, various SCF3-containing dihydrobenzofurans with oxa-quaternary centers were also delivered in moderate to good yields using ß-substituted 2-allyphenols as substrates.

Noncovalent Indocyanine Green Conjugate of C-Phycocyanin: Preparation and Tumor-Associated Macrophages-Targeted Photothermal Therapeutics.

Fabrication of a multifunctional near-infrared (NIR) theranostic nanoplatform has attracted increasing attention. Indocyanine green (ICG), a clinic-approved NIR fluorescence-imaging agent, is an excellent photothermal agent candidate. However, the stability and tumor targeting are still great obstacles for its wide application. In this work, C-phycocyanin (CPC) as a tumor-associated macrophages (TAMs) targeted vehicle was used to fabricate noncovalent ICG conjugate of CPC (ICG@CPC) via self-assembly in aqueous media. Compared to free ICG, ICG@CPC displays improved stabilities in aqueous solutions and under light irradiation and threefold increase in photothermal conversion efficiency. The in vitro results indicated that ICG@CPC could be selectively internalized into J774A.1 cells via SR-A-mediated endocytosis and lead to enhanced photocytotoxicity against J774A.1 cells. In vivo results showed that ICG@CPC had significantly improved drug accumulation in the tumor and photothermal therapeutic efficacy relative to ICG alone. This study for the first time utilizes CPC as a TAMs-targeted nanocarrier for ICG and may promote further rational design of ICG-based photothermal nanodrugs for precise and efficient cancer theranosis.

Lewis Base/Brønsted Acid Co-Catalyzed Asymmetric Thiolation of Alkenes with Acid-Controlled Divergent Regioselectivity.

A divergent strategy for the facile preparation of various enantioenriched phenylthio-substituted lactones was developed based on Lewis base/Brønsted acid co-catalyzed thiolation of homoallylic acids. The acid-controlled regiodivergent cyclization (6-endo vs. 5-exo) and acid-mediated stereoselective rearrangement of phenylthio-substituted lactones were explored. Experimental and computational studies were performed to clarify the origins of the regioselectivity and enantioselectivity. The calculation results suggest that C-O and C-S bond formation might occur simultaneously, without formation of a commonly supposed catalyst-coordinated thiiranium ion intermediate and the potential π-π stacking between substrate and SPh as an important factor in the enantio-determining step. Finally, this methodology was applied in the rapid syntheses of the bioactive natural products (+)-ricciocarpin A and (R)-dodecan-4-olide.

A new technology for reducing anastomotic fistula in the neck after esophageal cancer surgery.

BACKGROUND: To explore the risk factors and prevention methods of cervical mechanical anastomotic fistula and stenosis after the radical resection of esophageal cancer. METHODS: From March 2018 to November 2018, 128 patients undergoing mechanical anastomosis of esophageal cancer were selected from the Department of Thoracic Surgery of The First Affiliated Hospital of Zhengzhou University. All the enrolled patients were operated on using the Mckeown method, and a retrospective study was conducted. Data for preoperative and postoperative test indices, intraoperative embedding materials, postoperative complications, and preoperative and postoperative treatment were collected, and the relationship between various factors and the incidence of cervical anastomotic fistula and stenosis was analysed. Univariate analysis was conducted using t tests or Fisher's exact probability method, and multivariate analysis was conducted using logistic regression models. RESULTS: All 128 patients successfully underwent surgery without dying. The enrolled patients were evaluated using the Stooler classification, with 28 patients having grade 0, 41 patients having grade 1, 34 patients having grade 2, 21 patients having grade 3, and 4 patients having grade 4 stenosis. Patients with stenosis of grade 3 or above had obvious choking sensation, which could only be relieved by balloon dilation. Symptoms in all patients with stenosis were relieved by balloon dilation. There were no significant differences between the two groups regarding embedding materials, preoperative choking history, history of alcohol consumption, history of hypertension, history of coronary heart disease, history of diabetes, postoperative calcium concentration, average albumin concentration, average platelet concentration, body mass index, anastomotic fistula, preoperative chemotherapy, postoperative chemotherapy, or postoperative cough (P>0.05). There were significant differences in postoperative reflux (χ2=11.338, P<0.05) and scar constitution (χ2=12.497, P<0.05). The effects of embedding materials in patients with anastomotic fistula were significantly different (χ2=4.372, P<0.05). CONCLUSIONS: Postoperative reflux and scar constitution may be risk factors for postoperative anastomotic stenosis after resection of esophageal cancer. There was almost no difference in the effects on esophageal anastomotic stenosis between embedding materials and the omentum majus, but Neoveil® may have certain advantages in preventing cervical anastomotic fistula, and thus may have certain clinical application value.

Lewis base-catalyzed asymmetric sulfenylation of alkenes: construction of sulfenylated lactones and application to the formal syntheses of (-)-nicotlactone B and (-)-galbacin.

An efficient method for the preparation of chiral sulfenylated lactones has been described based on Lewis base-catalyzed enantioselective sulfenylation of unsaturated carboxylic acids. The scope of this method includes two enantioselective cyclization reactions: 5-endo and 6-exo thiolactonizations of alkenes. Two types of lactones were obtained with up to 95% ee and 99% yield. Additionally, this methodology has been applied in the formal syntheses of bioactive natural products (-)-nicotlactone B and (-)-galbacin.