Structure modification and anti-tumor activity evaluation on sesquiterpene lactones TBA and TBB from Sphagneticola trilobata.

Thirteen sesquiterpene lactone derivatives were designed and synthesised using the sesquiterpene lactone epimers TBA and TBB as the parent molecules, isolated from Sphagneticola trilobata. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. Furthermore, the structures of 1a, 4b and 5a were confirmed by X-ray single-crystal diffraction analyses. All of the compounds were further examined for their in vitro antiproliferative activity against human cancer cell lines HeLa and MCF-7. Unfortunately, the activity of all derivatives were weaker than that of the parental compounds.

Isoperistaltic side-to-side anastomosis for the surgical treatment of Crohn disease

Purpose@#Increasing evidence has shown an association of surgical technique, particularly anastomotic configuration, with postoperative recurrence of CD. This pilot study aimed to evaluate short-term outcomes of isoperistaltic side-to-side anastomosis (ISSA) employed on Crohn disease (CD) patients. @*Methods@#Data were retrieved from a prospectively maintained database. Postoperatively, all patients were followed up with close endoscopic (ileocolonoscopy) surveillance. @*Results@#From January 2017 to May 2021, 30 patients diagnosed with CD who underwent ISSA were compared with 45 CD patients who underwent antiperistaltic side-to-side anastomosis (ASSA). The 2 groups were comparable in baseline demographics and clinical characteristics. No significant differences were observed between groups regarding postoperative safety issues, including anastomotic leak, abdominal/pelvic abscess, length of hospital stay, readmission rate within 30 days, etc. At postoperative 24th month, reduced endoscopic recurrence was observed in the ISSA group compared with that in the ASSA group (18 of 24, 75.0%, vs. 36 of 38, 94.7%; P = 0.024). Regarding surgical recurrence, there was 0% in the ISSA group vs. 4.4% (2 of 45) in the ASSA group (P = 0.510). @*Conclusion@#In this study, we aimed to explore the influence of ISSA on postoperative recurrence in CD patients, and the preliminary results show that ISSA was technically safe and feasible, and appears to be effective in reducing postoperative recurrence in CD patients. However, our conclusion was underpowered due to small sample size and inadequate followup. We proposed ISSA be considered as another alternative option in the toolbox of inflammatory bowel disease surgeons when performing anastomosis on CD patients.

Association of CXCR6 with COVID-19 severity: Delineating the host genetic factors in transcriptomic regulation

BackgroundThe coronavirus disease 2019 (COVID-19) is an infectious disease that mainly affects the host respiratory system with [~]80% asymptomatic or mild cases and [~]5% severe cases. Recent genome-wide association studies (GWAS) have identified several genetic loci associated with the severe COVID-19 symptoms. Delineating the genetic variants and genes is important for better understanding its biological mechanisms. MethodsWe implemented integrative approaches, including transcriptome-wide association studies (TWAS), colocalization analysis and functional element prediction analysis, to interpret the genetic risks using two independent GWAS datasets in lung and immune cells. To understand the context-specific molecular alteration, we further performed deep learning-based single cell transcriptomic analyses on a bronchoalveolar lavage fluid (BALF) dataset from moderate and severe COVID-19 patients. ResultsWe discovered and replicated the genetically regulated expression of CXCR6 and CCR9 genes. These two genes have a protective effect on the lung and a risk effect on whole blood, respectively. The colocalization analysis of GWAS and cis-expression quantitative trait loci highlighted the regulatory effect on CXCR6 expression in lung and immune cells. In the lung resident memory CD8+ T (TRM) cells, we found a 3.32-fold decrease of cell proportion and lower expression of CXCR6 in the severe than moderate patients using the BALF transcriptomic dataset. Pro-inflammatory transcriptional programs were highlighted in TRM cells trajectory from moderate to severe patients. ConclusionsCXCR6 from the 3p21.31 locus is associated with severe COVID-19. CXCR6 tends to have a lower expression in lung TRM cells of severe patients, which aligns with the protective effect of CXCR6 from TWAS analysis. We illustrate one potential mechanism of host genetic factor impacting the severity of COVID-19 through regulating the expression of CXCR6 and TRM cell proportion and stability. Our results shed light on potential therapeutic targets for severe COVID-19.

Strategies against blood collection and supply during the COVID-19 epidemic, Hainan Province / 中国输血杂志

【Objective】 To investigate the strategies against blood collection and supply in Hainan Province during the COVID-19 epidemic, so as to provide theoretical and technical support for ensuring blood balance and safety under epidemic situation. 【Methods】 Countermeasures of blood collection and supply against the COVID-19 epidemic, taken by blood centers in Hainan, were reviewed, and data from 2016 to 2020 were collected and analyzed to evaluate the effectiveness of countermeasures by comparison. 【Results】 During the COVID-19 epidemic, the total units of blood collected and issued continued to grow and the annual growth rate reached 10.3% in 2020. The proportion of blood donation by groups increased by 0.3%. The number of blood donations by soldiers and medical personnel has increased significantly, reaching 91.2% and 24.7%, respectively. 【Conclusion】 The countermeasures in Hainan during the COVID-19 epidemic achieved remarkable effects and ensured blood safety in the whole province, which provided references and experience for blood collection and supply under public emergencies.

De Novo and Inherited SETD1A Variants in Early-onset Epilepsy / 神经科学通报·英文版

Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first 2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1A gene (SET domain-containing 1A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations (R913C, Q269R, G1369R, and R1392H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913C mutation also affected the migration of cortical neurons in the mouse brain. We further identified two common genes (Neurl4 and Usp39) affected by mutations of SETD1A. These results suggested that the mutations of SETD1A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.

Establishment of orthotopic colorectal cancer model by colonoscopy with submucosal injection in living mice / 国际生物医学工程杂志

Objective To set up a living mice colonoscopy platform to establish an orthotopic model of colorectal cancer in mice under direct vision,and to observe its biological behavior such as metastasis.Methods Eighteen-week-old male C57/BL mice were anesthetized,and the intestinal lumen of the mice was examined by a self-developed living mice colonoscopy and Olympus URF-P5 ureteroscopy,respectively.The imaging effects of the two methods were compared.Human colon cancer HT-29 cells were injected into the colonic mucosa of BALB/c-nu mice under direct vision.The colonoscopy was performed on the 3rd,7th and 15th day after the injection to observe the tumor formation in the intestinal lumen.The mice were sacrificed when the body weight decreased significantly or cachexia appeared,and then the abdominal cavity was examined including the tumor formation and metastasis.Results The self-developed living mice colonoscopy platform can provide clear vision of enteric cavity,and no mice died in the colonoscopy examination.In vivo subcutaneous injection of HT-29 cells in mice was performed with a perforation rate of 15％,a mortality rate of 33.3％,a tumor formation rate of 62.5％,an abdominal metastasis rate of 60％,a liver metastasis rate of 25％,and an abdominal wall transfer rate of 25％.Conclusion The self-developed mice colonoscopy platform can be used for the study of colorectum in living mice.The imaging effect is no less than that of Olympus URF-P5 ureteroscopy.In addition,an orthotopic colorectal cancer model can be established by this platform combing with submucosal injection technology.

Learning curve of transanal total mesorectal excision for rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the learning curve of transanal total mesorectal excision (taTME) for rectal cancer.</p><p><b>METHODS</b>Clinical data of 60 rectal cancer patients undergoing taTME from July 2014 to April 2016 were retrospectively analyzed. According to the sequence of operation date, 60 patients were divided into four groups (A, B, C, D) with 15 cases in each group. General information and perioperative, especially the operative indexes were compared among four groups.</p><p><b>RESULTS</b>There were no significant differences in age, sex, preoperative staging, BMI, tumor size among four groups (all P>0.05). The distance from tumor to anal verge in A group was(6.7±2.5) cm, which was significantly different with B group (4.6±1.2) cm, C group (4.5±1.0) cm and D group (4.0±1.0) cm (P=0.000, P=0.000, P=0.001). Ratio of receiving neoadjuvant therapy was 0, 60.0%(9 cases), 26.7%(4 cases) and 26.7%(4 cases) in A, B, C, D groups respectively with significant difference (P=0.004). Ratio of receiving complete taTME was 73.3%(11/15) in A group, 26.7%(4/15) in B group, 13.3%(2/15) in C group and 26.7%(4/15) in D group, while other patients underwent laparoscopy-assisted procedures. This ratio of A group was significantly higher as compared to B, C, D groups (P=0.003). The operation time was significantly different among four groups [A group (223.0±105.2) minutes, B group (299.0±131.0) minutes, C group(278.0±44.8) minutes, D group (246.0±34.0) min, P=0.035]. Fluctuation of operation time was more common in A and B groups, which became stable in C and D groups. Though intra-operative blood loss was not significantly different among four groups [A group (249.0±559.6) ml, B group (288.0±568.1) ml, C group (87.0±43.3) ml, D group (69.0±64.5) ml, P=0.225], but it presented a decline trend in C and D groups. Number of harvested lymph node from postoperative pathological specimen was 10.9±5.9 in A group, 9.6±2.7 in B group, 15.8±4.8 in C group, and 14.2±5.1 in D group, with significant difference among groups (P=0.008; A group vs. C group, P=0.010; B group vs. C group, P=0.002; B group vs. D group, P=0.021). There were no significant differences in specimen length, postoperative complication rate, distal margin distance and hospital stay.</p><p><b>CONCLUSION</b>A well-skilled laparoscopic colorectal surgeon, by following the standard surgical procedures, are likely to overcome the learning curve smoothly after performing approximately 30 cases of taTME for rectal cancer.</p>

Experience of treatment for common bile duct stones by laparoscope combined with choledochoscope / 局解手术学杂志

Objective To summarize the effect of treatment for common bile duct stones by laparoscope combined with choledocho-scope, and to assess the feasibility in judgment the patency of common bile duct by stone basket. Methods To review and analyze the clini-cal data of 32 patients who were given choledocholithiasis operation through laparoscope combined with choledochoscope,and the operation method,effect and complications were compared. Results In this research,32 choledocholithiasis operations were carried out using laparo-scope combined with choledochoscope from January 2013 to January 2014. The stones of 31 patients were taken out completely,and there were no stone in the other patient. All 32 patients recovered without any complication. After operation,all 32 patients showed unrestricted inferior bile common duct and no residual stone by T-tube cholangiography. Conclusion It showed satisfactory effect in treatment of choledocholithi-asis by laparoscope combined with choledochoscope. Compared to traditional laparotomy,which showed less injure and faster recovery. It is a simple and feasible method to judge the patency of common bile duct using large size stone basket combined with methylene blue injection.

The experimental study of VEGF inhibitor (bevacizumab) on the treatment of retinopathy of premature rats / 中国医师杂志

Objective To establish hyperoxia retinopathy in premature rat model with SpragueDawley (SD),observe the pathological changes of angiogenesis and expression of vascular endothelial growth factor (VEGF),and compare the effect of bevacizumab periocular injection and intravitreal injection of retinopathy of premature rats.Methods Ninety preterm rat retinopathy models were randomly divided into 3 groups:high oxygen group,retrobalbar injection group,and vitreous cavity group (n =30 per group);36 healthy rats were chosen as the normal control group.Each group were randomly selected 10 rats 'right eyes to make retinal flat mount to observe the right eye retina vascular morphology;10 resections of right eyes were embedded in paraffin,and stained with hematoxylin eosin (HE);the number of right eye of retinal neovascularization was observed;the right eye RNA was extracted,and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect the expression of VEGF.Results The normal group showed retinal vessels were around a reflection of distribution,good branch,shape rules,and clear structure.Intravitreous neovascularization occurred in the high oxygen group and peribulbar injection group.Retinal vascular endothelial cells in the high oxygen group were increased significantly compared to the normal group (P ＜ 0.05).The visible clusters of red blood cells in the periocular injection group and vitreous group were decreased compared to the high oxygen group (P ＜ 0.05),but no significant difference between the periocular injection group and vitreous group (P ＞ 0.05).The expressions of VEGF mRNA and HE staining had a consistent trend.Conclusions Bevacizumab inhibited the expression of VEGF that was increased in premature rats in hyperoxia retinopathy.The effects of bevacizumab periocular injection and intravitreal injection were similar,but the former was more secure than the latter.

Effect of chronic high-fat diet on predation behavior in rats / 中南大学学报(医学版)

Objective: To observe the eff ect and mechanism of chronic high-fat diet on predation behavior in rats. Methods: Ten female SD rats with 4-week-old were randomly divided into a normal control group (NC group,n=5) and a chronic high-fat diet group (HF group,n=5). The rats in the NC group received the regular diet while rats in the HF group were fed with high-fat diet. Fitf een weeks later, the predation behavior of rats was evaluated by open if eld test and food foraging tests. At the end of experiments, the rats were killed and brain tissues were collected for evaluation of c-Fos protein expression in anterior cingulate cortex by immunohistochemical assay. Results: hT e predation behavior of rats in the HF group was signiif cantly impaired in the competitive or non-competitive food foraging test compared with the control rats (P<0.001). hT e c-fos protein expression in anterior cingulate cortex of rats from the HF group was signiif cantly decreased (P<0.001). Conclusion: Long time high-fat diet can aff ect the predation behavior of rats, which is related todysfunction of neuron in anterior cingulate cortex.

The relationship between the antipituitary antibodies (APAs) and hypopituitarism after traumatic brain injury / 中华微生物学和免疫学杂志

Objective To investigate the relationship between antipituitary antibodies (APAs) and hypopituiarism following traumatic brain injury (TBI),as well as the severity of brain injury.Methods The study included 73 patients who suffered TBI 9 to 12 months ago and were diagnosed with hypopituitarism during the follow-up.Based on their Glasgow Coma Scale (GCS) on admission they were categorized into three groups:A (3-8),B (9-12) and C (13-15).Levels of plasma pituitary hormones (GH,TT,FT3 and FSH/LH) and APAs were measured in all patients with chemiluminescence assays and ELISA,respectively.Results Patients in group A had higher levels of APAs and lower levels of hormones compared with those in group B(P＜0.001) or group C(P＜0.001),while no significant difference was found between group B and group C for levels of either APAs (P＞0.05) or hormones (P＞0.05).Levels of APAs were negatively correlated with both GH (r=-0.64071,P＜0.001) and GCS (r=-0.50132,P＜0.001).Conclusion The present investigation provides preliminary evidence that APAs may be associated with the development of TBI-induced hypopituiarism.It suggests that the severity of hypopituiarism following TBI could be predicted by measuring the level of APAs.

Pilot study on measurement of sICAM-1 and sE-selectin in patients with chronic hepatitis C to judge response to treatment / 中华检验医学杂志

Objective To investigate the levels of sICAM 1 and sE selectin in patients with chronic hepatitis(CHC) and to study their roles in judge of response to IFN ? 2b treatment. Methods sICAM 1 and sE selectin levels were measured in 32 cases of CHC before and after treatment of IFN ? 2b by enzyme linked immunosorbent assay(ELISA), levels of HCV RNA was detected by quantitative PCR and serum ALT activity was also detected. Results Levels of sICAM 1 and sE selectin in CHC patients were significantly higher than those in normal controls(P