2 cm) according to the size of lesions. Large wound sections were sutured with metal clips. Results Histopathologic investigation showed that among 54 lesions,there were 13 cases of adenoma,38 cases of adenoma with atypical hyperplasia (10 cases with mild dysplasia,23 with moderate dysplasia and 5 with severe dysplasia )and 3 cases of mucosal cancer. We followed forty cases,local recurrence was found in none of 29 cases after 6 months of EMR. However,the recurrence was found in 2 of 11 cases after 1 month of EPMR and 1 each after 3 and 6 month of EPMR. There was no recurrence after further endoscopic re-treatment. Among 3 cancer patients,2 patients shifted to surgery due to patient's preference and 1 patient was followed up for 6 months. All of them were found without local recurrence by endoscopic biopsies or surgical results. Conclusions Chromoscopy,magnifying colonoscopy and EUS have benefits in diagnosis of early large bowel tumors,and it is also helpful in selecting the proper treatment so as to reduce the complication and recurrence.

Objective To investigate the effects of δ-opioid receptor agonist DADLE (D-Ala2-D-Leu5-enkephalin) on the hemodynamics and oxygen metabolism in rats with sepsis. Methods Eighty healthy male SD rats were randomly divided into 4 groups ( n = 20 each) : sham operation group (group S), sepsis group (group SEP) ,DADLE, group and DADLE2, group. Sepsis was induced by cecum ligation and puncture (CLP) in SEP, DADLE,and DADLE2 groups. In DADLE1 and DADLE2 groups, 0.5 mg/ml DADLE 10 mg/kg was injected intraperitoneally (IP) 0.5 h before CLP and immediately after CLP respectively. Mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and ± dp/dtmax were recorded at 0, 2, 4 and 6 h after CLP (T1-4). Blood samples from left common carotid artery and right external jugular vein were collected at T4 for blood gas analysis. The cardiac index (CI), O2 delivery (DO2), O2 consumption (VO2) and O2 extraction rate (ERO2) were calculated.Results Compared with group S, MAP and LVSP were significantly increased at T2, while decreased at T3,4, and ± dp/dtmax was significantly increased in group SEP, MAP was significantly increased at T2, while decreased at T3,4, LVSP was significantly increased at T2,3, while decreased at T4 , and ± dp/dtmax was significantly increased in DADLE, and DADLE2 groups, and CI, DO2 and VO2 were significantly decreased and ERO2 was increased in SEP, DADLE, and DADLE2 groups (P＜0.05). Compared with group SEP, MAP, LVSP and ± dp/dtmax at T3,4 and CI, DO2 and VO2 were significantly increased, while ERO2 was significantly decreased in DADLE1 and DADLE2 groups (P ＜ 0.05). There was no significant difference in the parameters mentioned above between DADLE1 and DADLE2 groups ( P ＞ 0.05). Conclusion δ-opioid receptor agonist DADLE can obviously improve the hemodynamics and oxygen metabolism in septic rats.

Objective To investigate the effect of δ-opioid receptor agonist D-Ala2-D-Leu5-enkephalin (DADLE) on the celluar immune function in septic rats. Methods One hundred and fifty healthy male SD rats weighing 154-198 g were randomly divided into 3 groups (n = 50 each):group Ⅰ sham operation (group S);group Ⅱ sepsis (group SEP) and group Ⅲ DADLE. Sepsis was induced by cecum ligation and punture (CLP) in group Ⅱ and Ⅲ. In group Ⅲ 0.5 rmg/kg DADLE 10 ml/kg was injected intraperitoneally (IP) immediately after CLP operation. Seven day survival rate was calculated. Blood samples were collected from 10 animals at 4, 8 and 12 h after operation (T1-3) respectively in each group for determination of serum TNF-α and IL-10 concentrations by ELISA and changes in T-cell subsets by flow cytometry. Results CLP significantly increased serum TNF-α and IL-10 concentrations and TNF-α/IL-10 ratio at T1-3 and decreased CD4+ and CD4+/CD8+ ratio and increased CD8+ at T3 in group Ⅱ as compared with group S (group Ⅰ). DADLE treatment significantly attenuated the CLP-induced above changes. Seven-day survival rate was significantly higher in DADLE group than in CLP group.Conclusion δ-opioid receptor agonist DADLE can improve the celluar immune function of rats with sepsis and increase the survival rate.

Objective To study the protective effects of DADLE on pulmonary function in rats with sepsis and the mechanism.Methods Seventy-two SD rats were randomly divided into sham operated group(SO),septic group(SEP),and DADLEtreated group (DADLE).Sepsis model was induced by cecal ligation and puncture(CLP).In SO group,the abdomen was opened without any other treatment.In DADLE-treated group,DADLE(0.5 mg/ml) was administerd at a dose of 5 ml/kg by intravenous injection after CLP.Rats were sacrificed at the 2nd,6th and 10th h after CLP.Arterial blood was collected for blood gas analysis.The wet-to-dry lung weight ratio was measured,and the levels of TNF-a and IL-6 in blood were detected.The levels of MPO,MDA and ATP in lung tissue were determined.The pathologic changes of the lungs were examined under a light microscope.Results As compared with SEP group,PaCO_2,and PaO_2 were significantly increased(P<0.05),while the wet-to-dry ratio and levels of serum TNF-a and IL-6 were significantly reduced(P<0.05),and levels of MPO and MDA were significantly reduced(P<0.05) and content of ATP in lung tissue was significantly increased (P<0.05)in DADLE group.More severe pathological changes were found in SEP group than in DADLE group.Conclusion DADLE has pulmonary protective effects in rats with sepsis.

Objective To explore the effect of prophylactic hepatic artery infusion chemotherapy (HAIC) on survival after curative resection in patients with primary pancreatic cancer. Methods A total of 106 patients with pancreatic cancer after pancreatectomy received 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (HAIC) or 6 cycles of sys-temic chemotherapy alone (Control). Both the HAIC and systemic chemotherapy regimen consisted of 5-fluorouracil 1000 mg/m2 on day 1 and Gemcitabine 800 mg/m2 on day 1 and 8. The treatment was started on an average of 3 weeks after surgery and repeated every 4 weeks. The disease-free survival , overall survival and liver metastases-free survival were compared. Results Significant differences were found in 3-year overall survival (HAIC, 23.08 %; Control, 14.81%;P=0.0473) and liver metastases-free survival (HAIC, 80.77%;Control, 55.56%;P=0.0014). There was no significant difference in adverse effects between two groups. Conclusion HAIC effectively and safely prevented liver metastases and improved the prognosis of patients with pancreatic cancer after pancreatectomy.

Objective To study the protective effect of δ opioid receptor agonist DADLE(D-Ala2-D-Leu5-enkephalin)on mitochondrial respiratory function in a rat model of sepsis. Methods Sixty SD rats were randomly divided in to sham operated group (SO), septic group (SEP), and DADLE group (DADLE), each of 20 cases. Sepsis model was produced by cecal ligation and puncture (CLP). In SO group,the abdomen was opened without any other treatment. In DADLE group, DADLE (0.5 mg/mL) was administer at a dose of 5 mL/kg by intra-peritoneal injection after CLP. All rats were sacrificed 8 hours after CLP. ALT and AST in blood were determined. Mitochondrial respiratory function was evaluated by the clark oxygen eletrode. The levels of ATP, ADP, AMP were determined by high performance liquid chromatogra phy (HPLC). Results RCR and ADP/O in DADLE group were much higher than that in SEP group (P<0.05). ATP in DADLE groups were much higher than SEP group (P<0.05), while ALT and AST of DADLE group were significantly lower than SEP group (P<0.05). Conclusion DADLE can protect mitochondrial respiratory function and improve the hepatocellular energy metabolism in sepsis.

Objective To evaluate the effects of preoperative regional intra-arterial infusion chemotherapy for patients with advanced gastric cancer (AGC). Methods A total of 82 patients with clinical stage Ⅲ,Ⅳ gastric cancer received two cycles of neoadjuvant regional intra-arterial infusion chemotherapy (arterial infusion group, n=42) or neoadjuvant systemic chemotherapy (systemic chemotherapy group, n=40). The operation was administrated in 10 to 15 days before chemotherapy. All patients received 6 course of systemic chemotherapy after surgery. Chemotherapy toxicity and sur-vival rate were retrospectively analyzed. Results No significant difference was found in chemotherapy toxicity between two groups. The median survival period was 25.3 months in arterial infusion group and 19.1 months in systemic chemotherapy group. 3-year survival rate was 36.4% in arterial infusion group and 21.0% in systemic chemotherapy group respectively, there were significant differences (P<0.05). Conclusion Preoperative regional intra-arterial infusion chemotherapy is well tolerated in advanced gastric cancer patients and could improve short-term survival.

SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively throughout the world since its first outbreak in December,2019.Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving,and driven by adaptation to the new host and environments is still under debate.Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,and providing guidance for disease control and treatments.Interrogating novel strategies for identifying natural selection using within-species polymorphisms and 3,674,076 SARS-CoV-2 genome sequences of 169 countries as of December 30,2021,we demonstrate with popula-tion genetic evidence that during the course of SARS-CoV-2 pandemic in humans,1)SARS-CoV-2 genomes are overall conserved under purifying selection,especially for the 14 genes related to viral RNA replication,transcription,and assembly;2)ongoing positive selection is actively driving the evolution of 6 genes(e.g.,S,ORF3a,and N)that play critical roles in molecular processes involving pathogen-host interactions,including viral invasion into and egress from host cells,and viral inhi-bition and evasion of host immune response,possibly leading to high transmissibility and mild symptom in SARS-CoV-2 evolution.According to an established haplotype phylogenetic relation-ship of 138 viral clusters,a spatial and temporal landscape of 556 critical mutations is constructed based on their divergence among viral haplotype clusters or repeatedly increase in frequency within at least 2 clusters,of which multiple mutations potentially conferring alterations in viral transmis-sibility,pathogenicity,and virulence of SARS-CoV-2 are highlighted,warranting attention.

Objective:To investigate the total radioactivity in drinking well water around the Bayanwula uranium mine.Methods:Totally 174 samples of drinking well water and 5 samples of filtered well water from residential houses were collected during dry and wet seasons in 2020 around the Bayanwula uranium mine. Total α and total β radioactivity in dry season and wet season were analyzed for detrmining whether there were differences between them and the relation between total radioactivity with different locations away from the uranium center. The radioactivity in filtered drinking well water used in residential houses was also investigated. Radioactivity were measured and analyzed using low background alpha and beta radioactivity meters, and the data were analysed using SPSS analytical statistical method.Results:In the drinking well water around Bayanwula uranium mine, the activity concentrations of total α and β measured in dry season were 0.024-2.468 Bq/L with a mean of (0.605±0.507) Bq/L and 0.125-1.395 Bq/L with a mean of (0.420±0.235) Bq/L, respectively. The values measured in wet season were 0.049-2.988 Bq/L with a mean of (0.825±0.605) Bq/L for total α and 0.059-1.623 Bq/L with a mean of (0.506±0.265) Bq/L for total β, respectively. The average value of total radioactivity in water samples was lower within 10, 30 and 20 km of the uranium mine in the descending order.Conclusions:The radioactivity in well water around the Bayanwula uranium mine is high, with the total α and β in samples greater in wet season than in the dry season and without elevated levels as compared to the pre-mining background.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.