Objective:To analyze the effect of endoscopic submucosal tunnel dissection on patients with large esophageal superficial neoplasms.Methods: Chosen patients with large esophageal superficial neoplasms in our hospital as research object, randomly divided into control group treated by endoscopic mucosal dissection (ESD) and observation group treated by endoscopic submucosal tunnel dissection(ESTD), compared surgery related indicators, complications and treatment outcomes.Results: 1)Observation group patients’ tumor stripping rate (23.17±4.73)/min was significantly higher than control group patients’ (12.65±2.19)/min; Intraoperative blood loss(9.14±0.67)ml, total length of hospital stay (7.34±1.89) d, were significantly less than control group patients with intraoperative blood loss(21.38±3.14)ml, total length of hospital stay (13.21±3.05)d, t value was 4.965, 5.395, 4.932, respectively(t=4.965,t=5.395,t=4.932;P<0.05); 2)Observation group patients esophageal bleeding ESTD rate(5.26%), esophageal stricture rate(31.58%), mediastinal emphysema rate(5.26%), esophageal perforation rate of 0, were significantly less than control group patients with esophageal bleeding rate(31.58%), esophageal stricture rate(5.26%), mediastinal emphysema rate(21.05%), esophageal perforation rate (26.32%), t value were 4.378, 4.378, 4.471, 5.758, (t=4.378,t=4.378,t=4.471,t=5.758;P<0.05); 3)Observation group patients with no recurrence during the follow-up period, control group patients with local recurrence rate of 21.05%, t value 8.623,P<0.05(t=8.623, P<0.05).Conclusion: Endoscopic tunnel mucosal stripping technique can effectively improve the complete tumor removal rate, during the process of optimization operation at the same time reduce the occurrence of complications, to the improvement of the prognosis of patients with positive clinical significance.

Objective:To investigate the possible mechanism of mesenchymal stem cells (MSC) secreting hepatocyte growth factor (HGF).Methods:① C57BL/6 mouse mesenchymal stem cells (mMSC) were cultured in vitro, and mMSC with high expression of chemokine receptor 7 (CXCR7) were transduced by lentivirus plasmid. Blank control group and empty carrier control group were set at the same time. After 20 generations of cell culture, the transfection efficiency was identified by fluorescence microscopy and flow cytometry. The mRNA expression levels of CXCR7 in mMSC were detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). ② mMSC with passage number 4-6 were divided into MSC control group [MSC-blank group, 100 μg/L lipopolysaccharide (LPS) was added to wild-type MSC], highly expressed CXCR7 group (MSC-OE-CXCR7 group, 100 μg/L LPS was added to mMSC transduced by lentivirus plasmid with high expression of CXCR7), highly expressed CXCR7 control group (MSC-OENC-CXCR7 group, 100 μg/L LPS was added to mMSC transduced by no load lentivirus plasmid), CXCR4 inhibitor group (MSC-IE-CXCR4 group, 100 μg/L LPS was added to mMSC after 0.1 mg/L CXCR4 inhibitor TC14012 pretreatment for 24 hours), and CXCR4 inhibitor control group (MSC-IENC-CXCR4 group, 100 μg/L LPS was added to mMSC after DMEM culture medium with equal amount of TC14012 pretreatment for 24 hours). Cells in each group were collected after treatment with LPS, and mRNA expression of inhibitor of differentiation-1 (ID-1) was detected by RT-PCR. The cell supernatant was collected, and the levels of HGF were detected by enzyme linked immunosorbent assay (ELISA). Results:① The high expression of CXCR7 for mMSC which were transduced through lentivirus plasmid were successfully constructed detected by fluorescence microscope and flow cytometry. Compared with the blank control group, the expression of CXCR7 mRNA in the lentivirus with high expression of CXCR7 group was significantly increased (2 -ΔΔCt: 5.81±0.97 vs. 1.02±0.12, P < 0.05). There was no significant difference in CXCR7 mRNA expression between the empty carrier control group and the blank control group (2 -ΔΔCt: 0.95±0.22 vs. 1.02±0.12, P > 0.05). ②Compared with the MSC-blank group, high expression of CXCR7 in MSC-OE-CXCR7 group or inhibition of CXCR4 in MSC-IE-CXCR4 group could induce high expression of ID-1 mRNA in mMSC (2 -ΔΔCt: 5.56±0.66, 2.47±0.58 vs. 1.00±0.10, both P < 0.05) and increase HGF exocrine level (ng/L: 632.02±149.98, 217.21±40.53 vs. 108.53±24.62, both P < 0.05). However, there were no significant differences in ID-1 mRNA expression and HGF exocrine level of mMSC among MSC-OENC-CXCR7 group, MSC-IENC-CXCR4 group and MSC-blank group [ID-1 mRNA (2 -ΔΔCt): 1.01±0.27, 1.21±0.32 vs. 1.00±0.10, HGF (ng/L): 133.56±25.19, 107.11±25.30 vs. 108.53±24.62, both P > 0.05]. Conclusion:High expression of CXCR7 or inhibition of CXCR4 in MSC can increase the expression of ID-1 and promote the secretion of HGF, thus promoting pulmonary microvascular endothelial repair.

Objective:To retrospectively analyze the early mortality and related risk factors in adult patients with maintenance hemodialysis (MHD).Methods:Adult MHD patients from 2008 to 2018 were enrolled and divided into training data group and validation data group. In training data group, multivariate logistic regression was used to analyze the risk factors of early death within 120 days after hemodialysis and establish a prediction model. The receiver operating characteristic (ROC) curve was applied to evaluate the prediction ability of the model.Results:A total of 4 885 patients were included. The cumulative mortality within 120 days was 20.97/100 person years, and that within 365 days was 12.25/100 person years. A total of 3 603 patients in the training data group were analyzed. The following risk factors were correlated with early mortality (all P<0.05), including age at start of dialysis over 60 years old ( OR=1.792), non-chronic glomerulonephritis ( OR=2.214), cardio-cerebrovascular disease ( OR=2.695), plasma albumin less than 35 g/L ( OR=1.358), platelet count less than 120×10 9/L ( OR=2.194), serum creatinine less than 600 μmol/L ( OR=1.652), blood urea nitrogen over 30 mmol/L ( OR=1.887), blood phosphorus less than 1.13 mmol/L ( OR=1.783), pulse pressure over 55 mmHg(1 mmHg=0.133 kPa) ( OR=1.656), low density lipoprotein less than 1.5 mmol/L ( OR=1.873), and blood calcium over 2.5 mmol/L ( OR=1.876). Risk prediction model was established. The other 1 282 cases in the validation data group were verified. The area under ROC curve was 0.810, with sensitivity 85.7%, and specificity 62.5%. Conclusion:The mortality rate of adult MHD patients within 120 days after dialysis is high. The established prediction model can effectively predict the risk of early death.

Objective: To establish a rat model of paraquat (PQ) -induced pulmonary fibrosis and observe the changes in thrombospondin-1 (TSP-1) and its receptor CD47 in lung tissue, and to investigate their roles in the pathogenesis of PQ-induced pulmonary fibrosis. Methods: Fifty-four clean adult male Sprague-Dawley rats were randomly divided into normal control group (n=6) and 2 h, 12 h, 1 d, 3 d, 7 d, and 14 d PQ poisoning groups (n=8 per group). A rat model of PQ poisoning was established by a single gavage of 20 wt.% PQ solution (50 mg/kg). Flow cytometry was used to determine the concentration of reactive oxygen species (ROS) in blood and lung tissue. Enzyme-linked immunosorbent assay was used to determine the concentrations of hydroxyl radicals, malondialdehyde, and hydroxyproline in lung tissue. HE staining and Masson staining were used to observe the pathological damage of lung tissue after PQ poisoning. The expression of TSP-1 and CD47 in lung tissue was measured by Immunohistochemistry. Results: Compared with the normal control group, the 2 h to 7 d PQ poisoning groups showed significant increases in ROS fluorescence intensity in red blood cells and lung tissues and the concentrations of malondialdehyde and hydroxyl radicals in lung tissue (P<0.05) , and the 14 d PQ poisoning group had a significant increase in the concentration of hydroxyproline in lung tissue (P<0.05). HE staining showed that the 2 h to 7 d PQ poisoning groups had significantly higher semiquantitative pathological scores of pulmonary alveolitis than the normal control group (P<0.05). The Masson staining showed that the 7 d and 14 d PQ poisoning groups had significantly higher semiquantitative pathological scores of pulmonary fibrosis than the normal control group (P<0.05). Compared with the normal control group, all PQ poisoning groups (except the 12 h group) had significantly increased expression of TSP-1 in lung tissue (P<0.05) , and all PQ poisoning groups (except the 1 d group) had significantly increased expression of CD47 in lung tissue (P<0.05). Within 2 h after PQ poisoning, the expression of TSP-1 and CD47 was positively correlated with the concentrations of ROS, hydroxyl radicals, and malondialdehyde and the degree of pulmonary alveolitis (P<0.01) ; at 1 d after PQ poisoning, the expression of TSP-1 and CD47 was positively correlated with the concentration of hydroxyproline in lung tissue (P<0.01) . Conclusion The expression of TSP-1 and CD47 is closely related to oxidative stress and subsequent pulmonary fibrosis, and they may be involved in the development and progression of pulmonary alveolitis and subsequent pulmonary fibrosis in rats with PQ poisoning.

Objective To analyze and summarize the cases of pregnancy on maintenance hemodialysis (MHD),and review the literature.Methods Seven cases of pregnancy and childbirth in patients on MHD in the First Affiliated Hospital of Zhejiang University from Jan 2009 to Dec 2017 were analyzed,and the literature about pregnancy in patients on MHD reported in Pubmed and Web of Science database was retrieved.Both maternal and fetal outcome were studied.Results There are seven pregnant MHD patients in this center,among whom six patients went through a smooth pregnancy and one patient had intra-uterine fetal death at 14 weeks of pregnancy.The six patients had preterm labor.Among six fetuses,four grew in good health and developed well,one had physical development retardation and one had heart malformation at born.In the literature,169 cases reported pregnant patients and 182 fetuses were evaluated,of which 145 live infants were delivered,79.67％ overall fetal survival rate,with gestational age of (32.94±3.34) weeks.In 164 delivered fetuses,147 were preterm labor (89.63％).The weight of live births was (1824±609) g.There were no maternal deaths.Fetal survival rate was zero in ＜ 20 weeks of gestational age,20-24 weeks was 14.29％,25-27 weeks was 45.45％,≥28 weeks was 94.44％.The fetal survival rate was higher in pregnant woman receiving hemodialysis≥28 hours weekly compared to women receiving ＜ 16 hours weekly (92.31％ vs 52.94％,P=0.02).Conclusions There are still a very high matemal and fetal complication rate in hemodialysis patients,especially in fetus.Gestational age≥28 weeks has a high fetal survival rate.Intensive dialysis during pregnancy may benefit higher fetal survival rate.

Objective:To investigate the association of early serum potassium level with all-cause mortality in adult maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. The data of patients newly entered MHD in the registration system of Zhejiang province dialysis quality control center from January 1, 2010 to December 31, 2019 were collected. Follow-up was conducted until December 31, 2020. The average value of predialysis serum potassium within the first 3 months starting hemodialysis was defined as early serum potassium, and patients were divided into 6 groups according to their early serum potassium levels. Death within 1 year of MHD patients was defined as short-term death. Kaplan-Meier method was used to compare the long-term and short-term survival rates of the six groups. Cox regression model was used to analyze the association of different serum potassium levels with the short-term all-cause mortality of adult MHD patients.Results:A total of 27 362 patients aged (61.2±14.4) years old were included, including 16 775 males (61.3%), 1 303 patients (4.8%) with hypokalemia (serum potassium<3.5 mmol/L) and 10 034 patients (36.7%) with hyperkalemia (serum potassium≥5.0 mmol/L). Among them, there were 5 145 patients (18.8%) with serum potassium≥5.5 mmol/L. According to the early serum potassium levels, the patients were divided into group 1 (serum potassium<3.5 mmol/L), group 2 (3.5≤ serum potassium<4.0 mmol/L), group 3 (4.0≤serum potassium<4.5 mmol/L), group 4 (4.5≤serum potassium<5.0 mmol/L), group 5 (5.0≤serum potassium<5.5 mmol/L) and group 6 (serum potassium≥ 5.5 mmol/L), respectively. Until the end of follow-up, the follow-up time was (40.7±27.8) months and 5 400 patients died. Cardiovascular and cerebrovascular diseases [1 551 cases (28.7%)] and infections [366 cases (6.8%)] were the main causes of death. Kaplan-Meier survival analysis showed that the long-term and short-term cumulative survival rates in the serum potassium<3.5 mmol/L group were the lowest among the 6 groups (Log-rank test, χ2=119.0, P<0.001; χ2=74.6, P<0.001, respectively). Multivariate Cox regression analysis showed that early serum potassium<3.5 mmol/L was an independent influencing factor for short-term all-cause death in MHD patients (with 4.5≤serum potassium<5.0 mmol/L as reference, HR=1.54, 95% CI 1.26-1.89, P<0.001). In the subgroup of age≥65 years, multivariate Cox regression model showed that serum potassium<4.5 mmol/L was independently associated with short-term death in MHD patients (with 4.5≤ serum potassium< 5.0 mmol/L as reference, serum potassium<3.5 mmol/L, HR=2.16, 95% CI 1.69-2.75, P<0.001; 3.5≤serum potassium<4.0 mmol/L, HR=1.40, 95% CI 1.14-1.72, P=0.001; 4.0≤serum potassium< 4.5 mmol/L, HR=1.46, 95% CI 1.21-1.75, P<0.001), while in the subgroup of age<65 years, serum potassium level was not significantly associated with short-term mortality risk in MHD patients. The early serum potassium level was associated with the risk of short-term all-cause death in a "U" shape, and both low and high potassium levels increased the risk of short-term all-cause death. The optimal early blood potassium level was about 4.75 mmol/L. Conclusions:The prevalence of hypokalemia at early stage of dialysis in adult MHD patients is about 4.8%. There is a U-shaped association between early serum potassium level and short-term (1 year) all-cause mortality risk, and early serum potassium<3.5 mmol/L is an independent risk factor for long-term and short-term all-cause mortality in MHD patients.

【Objective】 To clarify the role and molecular mechanism of Tanshinone ⅡA (TanⅡA) in the pathological integration of granule cells in the dentate gyrus (DG) by using the mouse model of temporal lobe epilepsy (TLE). 【Methods】 Status epilepticus (SE) was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg. After two months, Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures. The DG was removed for staining of Timm, Prox-1, DCX and SynⅠ. PTEN, p-AKT, and p-S6 expressions were observed by Western blotting. 【Results】 TanⅡA decreased Timm score, SynⅠ, PSD-95 and pS6 levels, and increased the level of PTEN in the DG, and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells. Video surveillance showed that TanⅡA reduced the frequency of Racine’ grade 5 seizures. 【Conclusion】 TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.