Copper-Catalyzed Borrowing Hydrogen Reaction for α-Alkylation of Amides with Alcohols.

We report the first example of copper-catalyzed α-alkylation of acetamides with alcohols via a borrowing hydrogen strategy. Catalyzed by the in situ-generated copper particles, acetamides and various substituted benzyl or alkyl alcohols were transformed into functionalized amides in good yields with excellent selectivity. Compared with previous work, this process is simple using commercially available Cu(OAc)2 as a precatalyst, without an additional ligand or a metal complex, and easier. Mechanistic studies revealed that aldehyde and α,ß-unsaturated amides were the intermediates of this reaction and also disclosed the role of copper in alcohol dehydrogenation and C═C bond hydrogenation.

Association between cervical length and massive intraoperative bleeding in patients with suspected placenta accreta spectrum combined with placenta previa: A retrospective cohort study.

Purpose: Abnormal placentation is a spectrum disorder that includes creta, increta, and percreta; the term placenta accreta spectrum (PAS) disorders is used as a broad term to describe all of these conditions. PAS can lead to life-threatening hemorrhage. The predictive value of cervical length (CL) in patients with PAS remains controversial. Thus, this study investigated the relationship between CL and the probability of major bleeding in patients with PAS and placenta previa. Methods: This retrospective cohort study was conducted at a comprehensive tertiary hospital in Chongqing, China, between January 2018 and December 2020. The target independent and dependent variables were CL and intraoperative massive bleeding, respectively. The covariates included demographic, clinical, and ultrasound characteristics. Logistic regression was used to explore the association between CL and massive bleeding. Results: In total, 317 participants were enrolled, in whom the prevalence of massive bleeding was 41.9% (133/317). The threshold of CL associated with massive bleeding (≥1,000 ml) was 33 mm based on a receiver operating characteristic curve. In the fully adjusted model for each additional unit of CL, the risk of massive bleeding decreased by 7% [95% confidence interval (CI), 0.88-0.98]. The risk of major bleeding was reduced by 44% in patients with a CL greater than 33 mm (95% CI, 0.33-0.97) compared with patients with a CL less than 33 mm. Conclusions: CL was negatively associated with massive intraoperative bleeding in patients with PAS combined with placenta previa. When the CL was greater than 33 mm, the risk of bleeding decreased by 44%. Thus, CL can be used as a standalone parameter to identify the risk of massive intraoperative bleeding in patients with suspected PAS.

Association of the placenta accreta spectrum score and estimated blood loss in placenta accreta spectrum patients with placenta previa: a retrospective cohort study.

PURPOSE: The placenta accreta spectrum (PAS) score calculated by the scoring system may predict patients with PAS. We aim to find the relationship between estimated blood loss and the PAS score. Further, find the inflection point, identify PAS patients with placenta previa who were at risk for major bleeding. METHODS: The PAS patients with placenta previa, as diagnosed by color Doppler ultrasound, were divided into two groups according to their PAS scores using a new scoring system. Blood loss, transfusion requirements, the rate of Intra-Abdominal Balloon Occlusion (IABO), and other indicators were analyzed between groups. RESULTS: The estimated blood loss, intraoperative transfusion, postoperative transfusion, operation time, and hospitalization time significantly increased in the group with a PAS score ≥ 9 (P < 0.05). The inflection point analysis revealed that a significant increase in estimated blood loss occurred when the PAS score was beyond 10 (crude) or 6 (adjusted for age, body mass index, and IABO). CONCLUSION: There was a non-linear relationship between estimated intraoperative blood loss and PAS score. When the PAS score was greater than 9, hemorrhage, the risk of major bleeding, the need for transfusions, and the placement of an abdominal aortic balloon all increase significantly.

Molecular characterization of human respiratory syncytial virus subtype B: a novel genotype of subtype B circulating in China.

Human respiratory syncytial virus (HRSV) is major pathogen of lower respiratory tract infections in infants and young children worldwide. There have been many studies regarding HRSV subgroup A (HRSV-A) G protein genetic variability but little information about HRSV subtype B (HRSV-B) G protein genetic diversity and molecular evolution in China. Thus, a survey of the molecular epidemiology and evolution of the G protein in China is of high importance. In this study, the circulation and genetic diversity of HRSV in Chongqing, Southwestern China, from June 2009 to May 2013, were investigated. A total of 3,167 nasopharyngeal aspirates were obtained in this study, and it was found that HRSV-B predominated in the 2009-2010 and 2012-2013 epidemic seasons. This study identified the genetic variability of the glycoprotein G gene among 102 HRSV-B strains isolated by cell culture from Chongqing nasopharyngeal aspirates, and 68 Chinese HRSV-B sequences were deposited in GenBank. Genotyping and phylogenetic analysis revealed that the HRSV-B strains were clustered into three genotypes: BA (n = 111, 65.29%), GB3 (n = 5, 2.94%), and a new GB genotype (n = 54, 31.77%) named GB5. The GB5 strains varied from other genotypes in the central conserved region and N-glycosylation sites. The estimated evolutionary rate of Chinese HRSV-B was 2.01 × 10(-3) nucleotide substitutions/site/year, which is similar to the reports from Belgium and the Netherlands with 1.95 × 10(-3) and 2.78 × 10(-3) nucleotide substitutions/site/year, respectively. This study provides data on the circulating pattern and molecular characterization of HRSV-B genotypes in China during four consecutive years and may contribute to HRSV vaccine development.

The genetic variability of glycoproteins among respiratory syncytial virus subtype A in China between 2009 and 2013.

Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and children under 5years of age. The novel genotype ON1 has a 72-nucleotide duplication, which is the largest duplicated genome portion of RSV. Whether the ON1 genotype will follow the pattern of the BA genotype, which has a 60-nucleotide duplication, and become the predominant RSV-A strain is a global concern. To obtain information regarding the prevalence of the ON1 genotype in Chongqing in Southwestern China, we examined the circulation pattern of RSV-A identified over four consecutive years (June 2009 to August 2013). In this study, 312 (12%) RSV-A strains were isolated from 2601 nasopharyngeal aspirates, and partial G gene was sequenced successfully in 250 isolates. Of the sequenced Chongqing RSV-A isolates, 237 (94.8%) strains were the NA1 genotype, 4 (1.6%) strains were the NA3 genotype, 4 (1.6%) strains were the NA4 genotype, 1 (0.4%) strain was the GA1 genotype, and 4 (1.6%) strains were identified as the ON1 genotype. Analysis of the distribution, phylogeny, and evolution of the ON1 strains that were collected globally until December 2013 revealed that the ON1 genotype has rapidly disseminated across the world under positive selection pressures. Future studies will determine whether this new genotype will continue to spread and become the dominant strain of RSV-A worldwide. These findings may contribute to the understanding of RSV evolution and to the potential development of a vaccine against RSV.

Detection of respiratory syncytial virus fusion protein variants between 2009 and 2012 in China.

Respiratory syncytial virus (RSV) causes respiratory tract infection, particularly acute lower respiratory tract infection (ALRTI), in early childhood. The RSV fusion protein (F protein) is an important surface protein, and it is the target of both cytotoxic T lymphocytes (CTL) and neutralizing antibodies; thus, it may be useful as a candidate for vaccine research. This study investigated the genetic diversity of the RSV F protein. To this end, a total of 1800 nasopharyngeal aspirates from hospitalized children with ALRTI were collected for virus isolation between June 2009 and March 2012. There were 333 RSV-positive cases (277 cases of RSV A, 55 of RSV B, and 1 with both RSV A and RSV B), accounting for 18.5 % of the total cases. Next, 130 clinical strains (107 of RSV A, 23 of RSV B) were selected for F gene sequencing. Phylogenetic analysis revealed that the F gene sequence is highly conserved, with significant amino acid changes at residues 16, 25, 45, 102, 122, 124, 209, and 447. Mutations in human histocompatibility leukocyte antigen (HLA)-restricted CTL epitopes were also observed. Variations in RSV A F protein at the palivizumab binding site 276 (N→S) increased between 2009 and 2012 and became predominant. Western blot analysis and microneutralization data showed a substitution at residue 276 (N→S) in RSV A that did not cause resistance to palivizumab. In conclusion, the RSV F gene is geographically and temporally conserved, but limited genetic variations were still observed. These data could be helpful for the development of vaccines against RSV infection.

Correlation between nucleotide mutation and viral loads of human bocavirus 1 in hospitalized children with respiratory tract infection.

The human bocavirus 1 (HBoV1) parvovirus causes respiratory disease and primarily affects children. Despite its worldwide prevalence, the mechanisms of HBoV1 replication and pathogenesis remain largely undefined. In this study of 846 children hospitalized at the Children's Hospital of Chongqing Medical University in China for respiratory tract infection between June 2009 and May 2011, HBoV1 was detected in 112 (13.2%) by real-time quantitative PCR. The median age of HBoV1-positive patients was 10 months old. Forty-five (40.2%) of the HBoV1 cases were monoinfections, and 67 (59.8%) were viral co-infections. Genotyping of all 112 HBoV1-positive cases yielded 27 full HBoV1 sequences, as well as two NS1 gene sequences, 15 NP1 gene sequences and 10 VP1/VP2 gene sequences harbouring 24, 10 and 43 mutations, respectively. Statistical analysis revealed no relationship between genetic mutations and clinical manifestations of HBoV1-positive patients. However, the viral loads were significantly lower in samples with mutations G236A or A447G in NP1, or G1461A in VP1/VP2, than in samples with wild-type HBoV1. Future studies should investigate whether these mutations in the HBoV1 gene may represent useful markers of disease pathogenesis.

Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection.

BACKGROUND: Regulatory T cells (Treg cells), which are essential for regulation of immune response to respiratory syncytial virus (RSV) infection, are promoted by pharyngeal commensal pneumococcus. The effects of pharyngeal microflora disruption by antibiotics on airway responsiveness and relative immune responses after RSV infection have not been clarified. METHODS: Female BALB/c mice (aged 3 weeks) were infected with RSV and then treated with either oral antibiotics or oral double distilled water (ddH(2)O) from 1 d post infection (pi). Changes in pharyngeal microflora were analyzed after antibiotic treatment for 7 d and 14 d. At 8 d pi and 15 d pi, the inflammatory cells in bronchoalveolar lavage fluid (BALF) were investigated in combination with tests of pulmonary histopathology, airway hyperresponsiveness (AHR), pulmonary and splenic Treg cells responses. Pulmonary Foxp3 mRNA expression, IL-10 and TGF-ß1 in BALF and lung homogenate were investigated at 15 d pi. Ovalbumin (OVA) challenge was used to induce AHR after RSV infection. RESULTS: The predominant pharyngeal commensal, Streptococcus, was cleared by antibiotic treatment for 7 d. Same change also existed after antibiotic treatment for 14 d. After RSV infection, AHR was promoted by antibiotic treatment at 15 d pi. Synchronous decreases of pulmonary Treg cells, Foxp3 mRNA and TGF-ß1 were detected. Similar results were observed under OVA challenge. CONCLUSIONS: After RSV infection, antibiotic treatment cleared pharyngeal commensal bacteria such as Streptococcus, which consequently, might induce AHR and decrease pulmonary Treg cells.