This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.
Antifungal Agents/pharmacology* ; Fungi ; Natamycin ; Streptomyces

COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.

Objective Revascularization of the distal segment of the anterior cerebral artery (ACA) using extracranial donors requires long interposition grafts.A novel bypass procedure which uses the two main branches of the superficial temporal artery (STA) to reach the A3 segment of the anterior cerebral artery with a single skin incision was designed.Methods Ten cadaveric specimens were dissected through a single skin incision to harvest the frontal and parietal branches of the STA from June,2017 to September,2017.An anterior interhemispheric approach provided access to the middle internal frontal artery (MIFA).The parietal STA was used as an interposition graft between the frontal STA and MIFA.Lengths and calibers of the distal branches of STA and MIFA were measured at the anastomotic sites.All data was statistical analysis by t-test.Results The average caliber of MIFA was (1.4±0.2) mm,which matched the caliber of both frontal and parietal branches of STA.The mean distance for an end-to-side bypass from STA to MIFA was (144.5±7.4) mm and the average harvested donor-graft complex length was (203.1±27.9) mm.This bypass construct provided around 140％ donor graft length.Conclusion Using the parietal branch of the STA as an interposition graft enabled a successful tension-free STA-MIFA bypass.The advantages of this technique over existing approaches include sufficient graft length,caliber match and relative technical ease.

Objective To analyze the donor specific antibody (DSA) in liver transplantation,and discuss the therapeutic schemes.Methods We retrospectively analyzed prospectively collected samples from 139 cases of liver transplantation from September 1,2013 to July 1,2015.Luminex assays were applied to determine human leukocyte antigen,panel reactive antibody (PRA).For PRA positive cases,DSA,C1q and C4d were detected,and liver biopsy was done.Results Of 139 cases enrolled,there were 12 cases positive for DSAs,including 2 cases of PreDSA:1 case of Ⅰ DSA (HLA-A mismatch),and 1 case of Ⅱ DSA (HLA-DQ mismatch).Ten cases of de novo DSA (including 1 case of PreDSA) all were HLA-DQ mismatch.The liver biopsy on 5 cases showed hepatic fibrosis,early rejection and intrahepatic cholestasis,and only 2 cases showed positive C4d.Of 6 cases of DSA,5 cases showed positive C1q.In the patients positive for DSA,tacrolimus dose was adjusted postoperatively,adding mycophenolatemofetil or increasing its dose,or methylprednisolone and immunoglobulin given.Conclusion DSAs are important indicators of sensitized recipients in liver transplantation,associated with trends toward worse outcomes in patients or allografts.The monitoring of DSA is requisite in order to adjust the immunosuppressant.

Objective To investigate the clinical effect of microsurgical resection combined with preoperative interventional embolization in the treatment of solid intracranial hemangioblastomas, and to analyze the effect of pre-operative embolization on tumor resection,and to discuss the surgical technique and perioperative management of mi-crosurgery. Methods From September, 2010 to September, 2015, the clinical signs, preoperative embolization, mi-crosurgery and prognosis of 18 patients with solid hemangioblastomas were retrospectively analyzed. The patients were examined by CTA and MRI,18 patients underwent DSA tumor arterial embolization and tumor microsurgery. Results The tumor diameter was 2.5-4.0 cm, the proportion of preoperative embolization tumor was 100% in 4 cases, 80% -95% in 9 cases,60%-70% in 3 cases and 60% in 2 cases.16 cases(88.9%)were subtotal tumors,2 cases(11.1%) were subtotal resection, 1 case died. No patients with intraoperative blood transfusion.followed up for 2 years without tumor recurrence. Conclusion The risk of postoperative hemangioblastomas is high, and the intervention of em-bolization for tumor artery will reduce the risk of operation.Microsurgery is the preferred treatment,and skilled micro-surgery is the key to treatment.

Objective To explore the clinicopathological features,imaging manifestation and treatment of solitary fibrous tumor in the central nervous system(cSFT),in order to improve the diagnosis and treatment.Methods Fourteen cases of cSFT that had been received microsurgery treatment from June,2010 to July,2016 were analyzed retrospectively.The clinicopathological features,treatment and prognosis were concluded and analyzed.Results In 14 patients with cSFT treated with microsurgery,and 1 case in the foramen magnum region for the first time,and enriched the understanding of this disease.Of 14 patients with cSFT,12 received total resection and 2 subtotal or part.The cSFT were pathologically diagnosed as benign tumors in 11 patients and low grade cSFT in 3.The microscopical presence of spindle-shaped tumor cells arranged in fascicles that alternate hypocellular and hypercellular areas separated from each other by collagenous fibre.Immunohistochemistry was positive for Vimentin,and CD34,Bcl-2 of 14 patients,and positive for CD99 in 12 patients.Followed-up time was from 6 to 49 months.Twelve cases had good prognosis to total resection and 2 recurrence due to subtotal or part resection.Conclusion cSFT is extremely rare,and it has some characteristics on MRI,final diagnosis should be depended on pathological and immunohistochemical examination.There are good prognoses in the patients with cSFT after the total removal of cSFT,but when the lesion could not be totally resected,radiotherapy should be considered,the curative effect of chemotherapy on cSFT is not definitive.

Objective To explore the feasibility of occipital artery(OA) to anterior inferior cerebellar artery (AICA) through the extended retrosigmoid approach,also perform a systemic microanatomical study of OA and AICA with the exposure of extended retrosigmoid approach,find the easy way to perform the procedure.Methods From September,2016 to January,2017,5 adult cadaveric heads injected with colored latex (total 10 sides) were performed the extended retrosigmoid approach,and measured the caliber of distal occipital artery (OA),the final length of the OA harvest,the reliable landmark of the OA harvest,and the distance from the flocculonodular segment of anterior inferior cerebellar artery (AICA) to the OA,the diameter of AICA flocculonodular segment branch.Whole procedure of OA to IACA bypass also be performed.Statistical analysis was performed.Results By the extended retrosigmoid approach,AICA flocculonodular segment could be easily exposure,the average diameter was 1.2 mm,the OA branch could be harvested in average was (72.3±3.3)mm in length from the occipital sulcus,and the average distance between occipital sulcus and AICA flocculonodular segment was (47.6±l.9)mm.The bypass procedure also could be performed through the proper corridor.Conclusion The Extended retrosigmoid approach is a safe and efficient way to perform the OA-AICA bypass procedure,and the procedure is easier to be performed than other surgical approaches.