HCl/DMSO/HFIP-Mediated Chlorination of Pyrrolo[2,1-a]isoquinolines and Other Electron-Rich Heteroarenes.

An efficient oxidative chlorination of pyrrolo[2,1-a]isoquinolines has been established using HCl (aq) as the chlorine source and DMSO as the terminal oxidant in HFIP at ambient temperature. A variety of chlorinated pyrrolo[2,1-a]isoquinoline derivatives have been prepared readily in 23 to 99% yields. This chlorination strategy can be expanded to the functionalization of other electron-rich heteroarenes including substituted pyrroles, indoles, and naphthols.

Function and biomedical implications of exosomal microRNAs delivered by parenchymal and nonparenchymal cells in hepatocellular carcinoma.

Small extracellular vesicles (exosomes) are important components of the tumor microenvironment. They are small membrane-bound vesicles derived from almost all cell types and play an important role in intercellular communication. Exosomes transmit biological molecules obtained from parent cells, such as proteins, lipids, and nucleic acids, and are involved in cancer development. MicroRNAs (miRNAs), the most abundant contents in exosomes, are selectively packaged into exosomes to carry out their biological functions. Recent studies have revealed that exosome-delivered miRNAs play crucial roles in the tumorigenesis, progression, and drug resistance of hepatocellular carcinoma (HCC). In addition, exosomes have great industrial prospects in the diagnosis, treatment, and prognosis of patients with HCC. This review summarized the composition and function of exosomal miRNAs of different cell origins in HCC and highlighted the association between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC. Finally, we described the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC.

The changing pattern of enteric pathogen infections in China during the COVID-19 pandemic: a nation-wide observational study.

BACKGROUND: Non pharmaceutical interventions (NPI) including hand washing directives were implemented in China and worldwide to combat the COVID-19 pandemic, which are likely to have had impacted a broad spectrum of enteric pathogen infections. METHODS: Etiologically diagnostic data from 45 937 and 67 395 patients with acute diarrhea between 2012 and 2020, who were tested for seven viral pathogens and 13 bacteria respectively, were analyzed to assess the changes of enteric pathogen infections in China during the first COVID-19 pandemic year compared to pre-pandemic years. FINDINGS: Test positive rates of all enteric viruses decreased during 2020, compared to the average levels during 2012-2019, with a relative decrease of 71•75% for adenovirus, 58•76% for norovirus, 53•50% for rotavirus A, and 72•07% for the combination of other four uncommon viruses. In general, a larger reduction of positive rate in viruses was seen among adults than pediatric patients. A rebound of rotavirus A was seen after September 2020 in North China rather than South China. Test positive rates of bacteria decreased during 2020, compared to the average levels during 2012-2019, excepting for nontyphoidal Salmonella and Campylobacter coli with 66•53% and 90•48% increase respectively. This increase was larger for pediatric patients than for adult patients. INTERPRETATION: The activity of enteric pathogens changed profoundly alongside the NPIs implemented during the COVID-19 pandemic in China. Greater reductions of the test positive rates were found for almost all enteric viruses than for bacteria among acute diarrhea patients, with further large differences by age and geography. Lifting of NPIs will lead to resurgence of enteric pathogen infections, particularly in children whose immunity may not have been developed and/or waned. FUNDING: China Mega-Project on Infectious Disease Prevention; National Natural Science Funds.

[Application of tunable guide device in prominent mandibular angle osteotomy].

OBJECTIVE: To discuss the application and therapeutic effect of tunable guide device in correction of prominent mandibular angle. METHODS: Since 2007, 50 cases with prominent mandible angle underwent mandible angle osteotomy with the tunable guide device. The patients were followed up for 3-6 months. RESULTS: No severe complication happened. Local seroma occurred in one case. Improved esthetic results were achieved at both frontal and oblique view. CONCLUSIONS: The mandibular angle osteotomy with the tunable guide device makes the procedure safe and easily performed.

[Experience of midfacial distraction osteogenesis in upper airway stenosis].

OBJECTIVE: To investigate the therapeutic effects of upper airway stenosis after Le Fort III osteotomy and midfacial distraction osteogenesis (DO). METHODS: Eleven cases (age, 5-16 yrs) with severe midface dysostosis complicated with exophthalmos, anterior crossbite and upper airway stenosis were treated by using Le Fort III osteotomy and midfacial DO from August 2000 to February 2007. The 3D reconstruction of the upper-airway from CT data was used to evaluate the upper airway volume before and after the operation. And meanwhile polysomnography was carried out to demonstrate the upper airway functional changes. RESULTS: There was a 64.3% mean increase [mean, (9.13 +/- 6.94) ml, P < 0.05] in upper airway volume in the 11 cases after the operations. It showed that there was significant improvements in the indexes of polysomnography after the operations, such as apnea and hypopnea index, average SaO2, minimum oxygen saturation and snore index. CONCLUSIONS: The Le Fort III osteotomy and midfacial distraction osteogenesis can efficiently relieve the symptoms of upper-airway stenosis in severe midfacial dysostosis.

[Changes of different section area at different parts of upper-airway after Le Fort III osteotomy].

OBJECTIVE: To observe the therapeutic effects of Le Fort III osteotomy and midface distraction osteogenesis (DO) on the upper-airway narrow. METHODS: Since 2000, 11 cases (10 cases of Crouzon syndrome and 1 case of Apert syndrome) with severe midface deficiency were treated with Le Fort III osteotomy and midface DO. The section area of different parts of upper-airway were tested by computer assistants image measurement preoperatively and postoperatively. Some patients received sleep function monitoring. RESULTS: The face appearance and the function of upper-airway improved significantly after Le Fort III osteotomy and Midface DO. The section area at the level of posterior nasal spine and uvula increased obviously after treatment (P < 0.05), however the section area at the level of epiglottis and separation between airway and esophagus were not obviously enlarged (P > 0.05). CONCLUSIONS: Midface DO after Le Fort III osteotomy can effectively improve the upper-airway narrow, especially the upper part from uvula.

[3-dimensional position changes of periorbital structures after midface distraction osteogenesis].

OBJECTIVE: To evaluate the 3-D position changes of periorbital structures after midface distraction osteogenesis in patients with Crouzon syndrome. METHODS: The CT data of 8 cases who had accepted the midface distraction osteogenesis following Le Fort III osteotomy were retrospectively analyzed. The patients were averagely 11.9 years old, and the CT was performed before and one year after operation. After 3-D image reconstruction, a right-hand coordinate system based on the preoperational Frankfurt Plane was then established. The pre- and post-operative positions of the superior orbit point (SOr), inferior orbit point (IOr), median orbit point (MOr), lateral orbit point (LOr), anterior ocularis point (AO), ocularis eyeball point (PO) and the four insertion ocularis rectus were documented and compared. The positions of these marked points in normal controls were also documented and compared with those in patients. RESULTS: After midface distraction osteogenesis, the position of AO was not changed significantly on the y-axis and z-axis, but the distance between two AO points on x-axis was reduced by 3.40 mm; IOr moved averagely 12.24 mm on y-axis and 4.25 mm on z-axis, MOr moved averagely 10.11 mm on y-axis and 2.80 mm on z-axis, LOr moved averagely 9.86 mm on y-axis and 2.31 mm on z-axis. The Inferior Rectus attachment moved averagely 3.63 mm on y-axis and 2.98 mm on z-axis. No other significant change was observed on other marked points. CONCLUSIONS: Midface distraction osteogenesis following Le Fort III osteotomy can significantly move the medial, lateral and inferior peri-orbital bone structure anteriorly and inferiorly. The eyeballs have no markedly sagittal position changes after distraction except slight medial, downwards movements and anterior-upwards rotations.