Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Malnutrition is a common complication of cancer patients, and solving nutrition problems is still one of the challenging tasks in clinical practice. The incidence of malnutrition in head and neck cancer patients during the peri-radiotherapeutic period is high, which is not only related to disease-mediated metabolic disorders, complications and psychological factors, but also associated with the toxic and side effects induced by radiotherapy. Malnutrition will reduce the tolerance, accuracy, and therapeutic effects of radiotherapy, which in turn lowers the quality of life and even adversely affects the prognosis of disease. Medical nutrition therapy can improve the nutritional status of the body, ensure smooth progress of radiotherapy, and improve the efficacy of comprehensive cancer treatment. It is necessary and urgent to deliver standardized nutrition therapy and management of head and neck cancer patients during the peri-radiotherapeutic period. Nutritional risk screening, nutritional assessment, and acute radiation injury assessment are required to develop an individualized nutrition treatment plan and make dynamic adjustment. In this article, relevant literature of nutrition therapy for head and neck radiotherapy at home and abroad was summarized, and the standardized nutrition therapy for head and neck cancer patients during the peri-radiotherapeutic period was reviewed.

Objective: To evaluate the cognitive impairment in elderly patients with minor ischemic stroke and to analyze risk factors for stroke recurrence. Methods: This was a retrospective case-control study.Ninety-five elderly patients with acute ischemic stroke hospitalized in the neurology department of Second People's Hospital of Liaocheng were enrolled from January 2016 to January 2017.Based on the National Institutes of Health Stroke Scale(NIHSS), all cases were divided into the minor stroke group(NIHSS score≤3, n=62)and the medium-severe stroke group(NIHSS score>3, n=33). After 12-month follow-up, the NIHSS, modified Rankin scale(mRS)and Montreal cognitive assessment(MoCA)were used to evaluate the study subjects. Results: Of the 95 patients, there were 62 males(65.3%)and 33 females(34.7%), with age of(68.3±6.7)years.No significant differences were found in baseline characteristics of age, male ratio, subtypes and history between two groups(all P>0.05). But, the treatment rate of intravenous thrombolysis was lower in minor stroke group than in medium-severe stroke group[6.5%(4 cases)vs.42.4%(14 cases)(P<0.01)]. The scores of NIHSS[(1.0±0.5)vs.(3.2±1.1), P<0.01], mRS[(1.6±0.7)vs.(2.4±1.1), P<0.01]were lower in the minor stroke group than in the medium-severe group.After a mean follow-up of(12.6±1.9)months, the rate of cognitive impairment was comparable between the two groups(P>0.05), while the rate of post stroke depression had a significant difference between two groups(P<0.05). Furthermore, there was lower rate of mortality and stroke recurrence in the minor stroke group than in the medium-severe group(0.0% or 0/62 vs.30.3% or 10/33, and 21.0% or 13/62 vs.42.4% or 14/33, P<0.05). Cox proportional hazard model showed that baseline NIHSS score, diabetes and stroke history were the risk factors for stroke recurrence in patients with minor stroke(P<0.05). Conclusions The treatment rate of intravenous thrombolysis with rt-PA, mortality rate and stroke recurrence rate are lower in patients with minor stroke than in patients with medium-severe stroke, while the incidence of post stroke cognitive impairment is high.High score of baseline NIHSS, diabetes and stroke history are risk factors for stroke recurrence in elderly patients with minor stroke.

Objective To observe the effect of remote post-ischemic conditioning(RPIOC)on the cerebral blood flow,neural function and prognosis of patients with acute cerebral infarction and the risk factors for short-term prognosis.Methods 133 patients with acute cerebral infarction in the Second Hospital of Beijing from January 2016 to December 2017 were selected,and randomly divided into the RIPOC group(66 cases,with RPIOC)and the control group(67 cases,without RIPOC).In the first day after hospital,patients in the RIPOC group were given RIPOC,which was tightening the left aim with a tonometer bandage for 5 minutes per time and 2 times a day at an interval of 5 minutes.All patients were provided routine treatment.All patients' cerebral blood flow,neural function and survival data were recorded.Recovery was assessed by modified Rankin Scale(mRS)180 d after stroke.Logistic regression was used to evaluate the risk factors for prognosis.Results Of the 133 patients enrolled,there were 67 males.The mean age was (73.1 ± 10.1)year.Basic clinical characteristics,neural function and cerebral blood flow were similar between groups(P＞0.05).After 10 d treatment,cerebral blood flow and neural function was significantly increased (P＜0.05)in the RIPOC group.After 180 d follow up,the RIPOC group had significantly higher rate of adverse cerebrovascular events(P＜0.05).Logistic regression analyses demonstrated that advanced age(P =0.003),hypertension(P =0.03)and high NIHSS score(P =0.005)were all risk factors for prognosis.Conclusions RIPOC can enhance the cerebral blood flow,activities of daily living,limb function and prognosis.However,it does not reduce the risk of mortality.Advanced age,hypertension and high NIHSS score are risk factors for short-term prognosis.

Objective To analyze the differential expression of D2 and D3 alternative splicing sites of human kinectin in human hepatocellular carcinoma (HCC) tissues, adjacent non-cancerous tissues and normal liver tissues, and to investigate a possible relationship between alternative splicing sites of kinectin and hepatocarcinogenesis. Methods The cDNA was obtained by RT-PCR in 45 coupled HCC cancerous and adjacent tissues, and 10 normal liver tissues. The difference in the expression of D2 and D3 alternative splicing sites in cDNA was examined by semi-quantitative PCR, and statistical analysis was performed. Results The ratio of D2L (long segment contains of the D2 region)/D2S (short segment that does not contain a D2 zone) in hepatocellular cancerous tissues was 2.709 ± 1.025, the ratio of D2L/D2S in adjacent non-cancerous tissues was 1.564 ± 0.357, and the ratio of D2L/D2S in normal liver tissues was 1.507 ± 0.499. The differences were statistically significant (F=29.698, P<0.05);the ratio of D2L/D2S in hepatocellular cancerous tissues was higher than that of adjacent non-cancerous tissues and normal liver tissues (P<0.05). The ratio of D3L (long segment contains of the D3 region)/D3S (short segment that does not contain a D3 zone) in hepatocellular cancerous tissues was 1.232 ± 0.041, the ratio of D3L/D3S in adjacent non-cancerous tissues was 1.156 ± 0.309, and the ratio of D3L/D3S in normal liver tissues was 1.282 ± 0.343. The ratio of D3L/D3S was not significantly different among hepatocellular cancerous tissues, adjacent non-cancerous tissues and normal liver tissues (F = 0.989, P > 0.05). Conclusion Variant containing D2 is over expressed in cancerous tissues and this alteration may be tumor associated.

Based on the known IRAK4 inhibitors MK-32 and AU-5,we designed and synthesized 12 pyridine-based target compounds by adopting open-ring and hybrid strategies,and combining molecular docking technology.The bioassays determined by radioisotope labeling demonstrated that the target compounds displayed good inhibitory activity against IRAK4.Among them,the IC50 value of 5 compounds was less than 1 μmol/L,suggesting that these compounds may be candidates for further investigation.

BACKGROUND:Studies have shown that Schwann cells form a Bunger band in the basement tube and guide the extension of regenerating axons after peripheral nerve injury, but the exact mechanism remains to be explored.
OBJECTIVE:To explore the effect of Wal erian degeneration on biological characteristics and secretory function of Schwann cells in rats with sciatic nerve injury.
METHODS:A rat model of sciatic nerve injury was established and divided into two groups:sciatic nerve transection group and surgical control group. Schwann cells were isolated and cultured from sciatic nerve segments by one enzyme digestion. The cellmorphology was observed under light microscope and S-100 protein expression was determined by immunofluorescence staining. After subculture, the first generation of Schwann cells were chosen to draw the growth curve by the counting method within 14 days. The cellactivity was detected by MTT assay. The adhesion of Schwann cells was examined by acid phosphatase analysis and the concentration of nerve growth factor was detected by ELISA method.
RESULTS AND CONCLUSION:At 14 days after primary culture, a great number of Schwann cells were observed near the edges of nerve segments in the sciatic nerve transection group, but only smal number of Schwann cells scattered around nerve segments in the control group. Schwann cells in both groups showed S-100 positive expression. At 3 days after subculture, Schwann cells reached the logarithm proliferative phase, the cellnumber and proliferation absorbance values in both groups were increased along with time extension. Furthermore, the number of Schwann cells and absorbance value in the sciatic nerve transection group were significantly higher than those of control group (P<0.05). The adhesion ability in the sciatic nerve transection group was also significantly higher than those in the control group (P<0.05). ELISA results showed that, the concentrations of nerve growth factor in the sciatic nerve transection group were significantly higher than those in the control group at 4, 6, 8, 10, 12 and 14 days (P<0.05). After sciatic nerve injury, Wal erian degeneration can induce Schwann cells dedifferentiate into the precursors, significantly influence the biological function of Schwann cells, promote the proliferation of Schwann cells within the short term, secrete large amounts of neurotrophic factors, enhance celladhesion, and provide a suitable microenvironment for regenerated axons. In addition, it creates the necessary microenvironment for peripheral nerve regeneration.

Objective To investigate the effects of sevoflurane postconditioning on intestinal ischemiareperfusion (I/R) injury in rats.Methods Thirty-six adult male Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 4 groups (n =9 each):sham operation group (group Sham),group I/R,ischemic postconditioning group (group Ipo) and sevoflurane postconditioning group (group Sevo).Intestinal I/R was induced by clamping the superior mesenteric artery (SMA) for 60 min followed by 120 min of reperfusion in groups I/R,Ipo and Sevo.In group Ipo the animals were subjected to 3 cycles of 30 min reperfusion-30 min ischemia starting from the beginning of reperfusion.The animals inhaled 1.15％ sevoflurane for 30 min starting from the beginning of reperfusion in group Sevo.The animals were sacrificed at 120 min of reperfusion and then the small intestines were removed for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by colorimetric method) and caspase-3 protein expression in intestinal tissues (by Western blot).The density of apoptotic cells was calculated by TUNEL.Results Compared with group Sham,the intestinal injury score,density of apoptotic cells and MDA content were significantly increased,SOD activity was decreased,and caspase-3 protein expression was up-regulated in groups I/R,Ipo and Sevo (P ＜ 0.05).Compared with group l/R,the intestinal injury score,density of apoptotic cells and MDA content were significantly decreased,SOD activity was increased,and caspase-3 protein expression was down-regulated in groups Ipo and Sevo (P ＜ 0.05).There was no significant difference in the intestinal injury score,density of apoptotic cells,SOD activity,MDA content and caspase-3 protein expression between Sevo and Ipo groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can attenuate intestinal I/R injury through reducing lipid peroxidation and cell apoptosis in rats,and the protective effect is similar to that of ischemic post-conditioning.

ObjectiveTo introduce a simple and quick method of adherent monoculture to primary neural stem cells depending on the mainly peptic characteristic of collagenase. MethodsThe fetus rat telencephalons of a pregnant 14-day-old SD rat were isolated, and tissues were treated with collagenase type Ⅰ contained EDTA following trituration. The cells were raised in polylysine culture plates with serum-free medium, and assessed with Nestin immunofluorescence. ResultsThe Nestin positve cells were obtained, and the purity was over 99%. ConclusionThis method may simply and quickly yields the primary neural stem cells that are monolayer and adherent.

BACKGROUND: Schwann cells are the seed cells of neural repair, and it is a key to harvest a large number of Schwann cells with high purity and activity. OBJECTIVE: To compare the in vitro culture, purification, and morphology of Schwann cells between neonatal and adult rats, and investigate a simple and feasible culture method to harvest high-purity Schwann cells. METHODS: Totally 30 Sprague-Dawley rats, comprising 20 neonatal (1-3 days after birth, neonatal group) and 10 adult (weighing 150-200 g, adult group) rats, were included. Following double-enzyme digestion and two incubations, Schwann cells were isolated and purified by differential attachment. Cell morphology and attaching speed were determined through the use of inverted microscope. Cells were counted and cell purity was calculated. Cell proliferative ability was detected by MTT microcolorimetry. Curves of cell proliferation in each group were depicted to determine proliferative speed. Schwann cells were identified by S-100 immunochemistry.RESULTS AND CONCLUSION: Compared with fibroblasts, neonatal rat Schwann cells exhibited faster, while adult rat Schwann cells showed slower, attaching speed. Both neonatal and adult groups yielded over 96% cell purity. MTT microcolorimetry results revealed that Schwann cells proliferated actively in neonatal and adult groups. Cell proliferative curves show that neonatal rat Schwann cells proliferated faster than adult rat Schwann cells (P < 0.05). S-100 immunochemistry results showed positive results in both groups. All these findings suggest that double-enzyme digestion and two incubations followed by differential attachment is a satisfactory method to harvest considerable Schwann cells with high purity and activity. Neonatal rat Schwann cells show stronger proliferative, attaching capacities than adult rat Schwann cells.