Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNTT） against adjuvant-induced arthritis （AA） in rats with wind-dampness-heat arthralgia （FSR） based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal （control） group， FSR group， low-， medium-， and high-dose DGNTT （5.67， 11.34， 22.68 g·kg^-1） groups， and methotrexate （MTX） group （1.35 mg·kg^-1）， with 10 rats in each group. The rats， except the control group， were injected with Mtb adjuvant and then exposed to artificial climatic chamber （hot and humid with wind） for 64 h for modeling. The rats were treated with water， DGNTT or MTX for 28 days from the day of injection. Arthritis index （AI） of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin （HE） staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes， Lactobacillus， Prevotella 9， and Alloprevotella decreased （P<0.05， P<0.01） and the relative abundance of Bacteroidetes and Bacteroides increased （P<0.01） in FSR group compared those in the control group. Compared with the FSR group， all DGNTT groups and MTX group had high relative abundance of Lactobacillus （P<0.05， P<0.01） and low relative abundance of Bacteroidetes （P<0.01） and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes， Prevotella 9， and Alloprevotella and low abundance of Bacteroides （P<0.05， P<0.01）. Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI （P<0.05）， while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI （P<0.01， P<0.05）. There was a negative correlation between the abundance of Prevotella 9 and paw volume （P<0.01）， and the abundance of Ruminococcaceae NK4A214 group， Christensenellaceae R-7 group， and Bacteroides was in negative correlation with spleen index （P<0.05）. The abundance of Prevotella 9 was in negative correlation with spleen index （P<0.01）. ConclusionDGNTT is effective for arthritis with FSR， as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.

Objective To investigate the effect of carrimycin on the biological function of pancreatic cancer cells. Methods Pancreatic cancer cell lines MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 were treated with carrimycin at concentrations of 0 (control group), 2, 4, 8, and 16 μmol/L for 24, 48, and 72 hours. MTT assay was used to measure cell viability; EdU cell proliferation assay was used to observe the effect of carrimycin on DNA replication of pancreatic cancer cells; colony formation assay was used to observe the effect of carrimycin on the proliferation of pancreatic cancer cells; flow cytometry was used to analyze the effect of carrimycin on the cell cycle of pancreatic cancer cells; wound healing assay was used to analyze the effect of carrimycin on the migration of pancreatic cancer cells; Western blot was used to measure the expression levels of the markers such as epithelial-mesenchymal transition (EMT) and cell cycle-dependent protein kinase inhibitor 1A (P21); immunofluorescence assay were used to measure the expression levels of EMT-related markers. An analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, carrimycin significantly inhibited the proliferative activity of MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 cells in a concentration- and time-dependent manner (all P < 0.01); carrimycin at concentrations of 4, 8, and 16 μmol/L significantly reduced DNA replication in MIA PaCa-2 cells ( t =2.378, 4.984, and 18.970, all P < 0.05) and BxPC-3 cells ( t =4.879, 6.089, and 9.521, all P < 0.01); after treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, colony formation ability significantly decreased with the increase in drug concentration in MIA PaCa-2 cells ( t =5.889, 11.240, and 15.840, all P < 0.001) and BxPC-3 cells ( t =6.717, 15.800, and 18.850, all P < 0.001). After treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, there was a significant increase in the proportion of cells in G1 phase in MIA PaCa-2 cells ( t =9.071, 12.280, and 19.360, all P < 0.0001) and BxPC-3 cells ( t =3.061, 4.962, and 8.868, all P < 0.05), and there was a significant reduction in the proportion of cells in S phase in MIA PaCa-2 cells ( t =2.316, 4.165, and 5.562, all P < 0.05) and BxPC-3 cells ( t =2.424, 3.264, and 5.744, all P < 0.05). Western blot further demonstrated that compared with the control group, the expression level of the cell cycle-related protein P21 gradually increased with the increase in the concentration of carrimycin in MIA PaCa-2 cells ( t =5.437, 6.453, and 8.799, all P < 0.001) and BxPC-3 cells ( t =25.130, 44.750, and 52.960, all P < 0.000 1). Wound healing assay showed that after treatment for 12, 24, and 48 hours, carrimycin at concentrations of 0, 4, 8, and 16 μmol/L significantly reduced the lateral migration of MIA PaCa-2 cells (all P < 0.05) and BxPC-3 cells (all P < 0.05). Western blot showed that compared with the control group, carrimycin treatment at concentrations of 4, 8, and 16 μmol/L significantly upregulated the expression of the epithelial marker E-cadherin in MIA PaCa-2 cells ( t =2.388, 4.899, and 5.819, all P < 0.05) and BxPC-3 cells ( t =2.533, 5.836, and 6.774, all P < 0.05) and significantly downregulated the expression of the interstitial marker Snail in MIA PaCa-2 cells ( t =12.440, 14.830, and 16.800, all P < 0.000 1) and BxPC-3 cells ( t=5.039, 5.893, and 7.725, all P < 0.01), and it also significantly downregulated the expression of the interstitial marker Vimentin in MIA PaCa-2 cells ( t =3.105, 7.752, and 11.200, all P < 0.05) and BxPC-3 cells ( t =2.555, 4.883, and 9.153, all P < 0.05). Conclusion Carrimycin can effectively inhibit the proliferation, migration, and EMT process of pancreatic cancer cells, thereby exerting an antitumor biological activity.

Objective:To explore the changes of brain network functional connection in neonates with different degrees of hypoxic-ischemic encephalopathy(HIE), and to understand its influence on brain function.Methods:Clinical data of full-term HIE children hospitalized in Neonatology Department of Changzhou Children's Hospital from January 2017 to May 2020 were collected by convenient sampling method. A total of 44 cases were scanned by conventional and functional magnetic resonance image.Twenty-four of them met the inclusion criteria, including 11 mild patients (PT1 group) and 13 moderate and severe patients (PT2 group). The amplitude of low frequency fluctuation (ALFF) was used to compare the differences of ALFF values between PT1 group and PT2 group, and the differences of functional connectivity (FC) between PT1 group and PT2 group were compared by the method of brain network connectivity analysis.Results:In the edge analysis, compared with the PT1 group, the FC of the right supplementary motor area and the right precentral gyrus ( Z1=0.39, Z2 =-0.08), the right lingual gyrus and the right hippocampus ( Z1=0.61, Z2=0.20), the left calcarine cortex and the right amygdala ( Z1=0.30, Z2=-0.02), the right pallidus and the right posterior cingulate cortex ( Z1=0.33, Z2=0.05) were decreased in the PT2 group (all P<0.001, uncorrected). In ALFF analysis, there was no significant difference between PT1 group and PT2 group ( P>0.05, FDR adjusted). Conclusion:There are changes in functional connections in some brain regions in children with moderate and severe HIE.These functional connections are related to motor function, emotional processing, language development, cognitive function, learning and memory, etcetera.

Objective To evaluate the short-term efficacy of combination of 125 I seed brachytherapy and cetuximab in postoperation recurrent rectum cancer.Methods From July 2014 to June 2018,at Affiliated Hospital of Shandong Academy of Medical Sciences,57 patients with postoperation recurrent rectal cancer were recruited.According to therapy the patients were divided into two groups:the radiotherapy group (30 cases) treated with radioactive 125I seeds alone and the combination treatment group (27 cases) treated with combination of radioactive 125I seeds and cetuximab.The tumor size,pain relief and adverse reactions were observed in both groups.Chi-square test were performed for statistical analysis.Results After treatment for six months,the total efficacy rate and local control rate of combination treatment group were 54.2％ (13/24) and 87.5％ (21/24),respectively;and which were higher than those of radiotherapy group (17.9％,5/28 and 39.3％,11/28),and the differences were statistically significant (x2 =15.01 and 2.55,both P ＜ 0.05).At one month after treatment,the pain relief rate of radiotherapy group and combination treatment group was 70.0％ (21/30) and 85.2％ (23/27),respectively,and there was no statistically significant difference between the two groups (P ＞ 0.05).After treatment for six months,the rates of adverse reactions of radiotherapy group and combination treatment group were 46.7 ％ (14/30) and 63.0％ (17/27),respectively,there was no statistically significant difference between the two groups (P ＞ 0.05).The symptoms of patients with radiation injury significantly improved after symptomatic treatment.Conclusion The short-term efficacy of combination of 125 I seed brachytherapy and cetuximab is better than that of 125 I seed brachytherapy alone in patients with postoperation recurrent rectum cancer.

Objective To observe the development and progression of autophagy,and investigate the effect of autophagy on recovery of neurological dysfunction in rats after cerebral ischemia-reperfusion injury.Methods Preparation of middle cerebral artery occlusion (MCAO) models was performed by Longa method.(1) Forty-two SD rats were randomly assigned to blank control 1 group (n=9) and MCAO 1 group (n=33),and the rats of the MCAO 1 group were randomly divided into 6,12,48 and 72 h subgroups (n=6) and 24 h subgroup (n=9) according to the reperfusion times;the ultrastructural changes and autophagosome formation in hippocarnpal tissues of the blank control 1 group (n=3) and 24-h-reperfusion MCAO 1 subgroup (n=3) were observed under transmission electron microscope;the expressions of microtubule associated proteins light chain-3 (LC3)-Ⅱ,LC3-Ⅰ and Beclin-1 in the hippocampal tissues of each group (n=6) were detected by Western blotting.(2) Eighteen SD rats were randomly divided into blank control 2 group,MCAO 2 group and 3-methyladenine (3-MA,autophagy inhibitor) group (60 min prior to MCAO,injection of 10 μL [600 nmoL] 3-MA dilution into the lateral ventricle by stereotactic technique,n=6);the neurological rehabilitation of rats was analyzed by modified neurological severity scale (mNSS) one,3,5 and 7 d after reperfusion;the morphological changes and number of apoptotic cells in the hippocampal tissues were observed by HE staining 7 d after reperfusion.Results (1) The formation ofautophagy in the 24-h-reperfusion MCAO 1 subgroup was clearly observed under microscope;as compared with blank control 1 group,the ratio of LC3-Ⅱ/Ⅰ (excepted for 72-h-reperfusion MCAO 1 subgroup) and Beclin-1 expression in the hippocampus of 6,12,24 and 48-h-reperfusion MCAO 1 subgroups were significantly increased (P＜0.05);as compared with those in the 24-h-reperfusion MCAO 1 subgroup,the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 expression in the hippocampus of 6,12,48 and 72-h-reperfusion MCAO 1 subgroups were significantly decreased (P＜ 0.05).(2) As compared with those the MCAO 2 group,the mNSS scores of 3-MA group were significantly decreased 3,5 and 7 d after surgery (P＜0.05);HE staining indicated that the injury of neurons in the hippocampus of 3-MA group was alleviated,and the number of apoptotic cells in the 3-MA group was significantly smaller than that in the MCAO 2 group ([14.00±2.10]/field vs.[37.83± 2.64]/field,P＜0.05).Conclusion Cerebral ischemia-reperfusion injury can activate autophagy,by which it can alleviate brain damage and improve its neurological dysfunction in rats after cerebral ischemia-reperfusion injury.

Objective To explore the feasibility, safety and preliminary efficacy of radioactive gastric tube of 125Ⅰ seeds in the treatment of advanced esophageal carcinoma. Methods For 10 cases with advanced esophageal carcinoma, the tumor target area was outlined in the TPS system according to preoperative CT images. Prescription dose was 60 Gy with 125Ⅰ seed radioactivity of 2. 22 × 107 Bq. Accordingly, the 125Ⅰ seeds number and the appropriate gastric tube was decided. Then, depending on the location of the tumor and certain rules, 125Ⅰ seeds were fixed in the tube wall to make the radioactive 125Ⅰ seeds gastric tube. Under the C-arm X-ray fluoroscopy, the radioactive 125Ⅰ seeds gastric tubes were placed into esophageal carcinoma site of the patients. Results The radioactive 125Ⅰ seeds gastric tubes of 10 patients were successfully placed, without esophageal perforation, bleeding complications and so on. In one month after operation, all patients with dysphagia′s Stooler classification score were 2 -3 level,of which one case died of other basic diseases in three months after operation, and six cases achieved 0 -1 level while the other three cases achieved 1 -2 level in four months after operation. There were no cases of postoperative chest pain, bleeding, pneumonia and other related complications. Conclusions The radioactive 125Ⅰ seeds gastric tube could not only help to solve nutrition problems, but also the intracavitary brachytherapy inhibit the growth of tumor, which is safe and feasible in clinical use. It can be used as a palliative treatment for patients with advanced esophageal carcinoma.

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

Objective To investigate the effect of Aurora-A kinase inhibitors VX-680 on the proliferation of thyroid carcinoma cell and to study their molecular mechanism. Methods The undifferentiated thyroid carcinoma cells were divided into groups of VX-680 with different drug concentration. Drug effect was observed by MTT method to measure the changes of cell proliferation. The gene expression of Aurora-A , Bcl-2 and Bax were tested by immunofluorescence assay. Results MTT results showed cell proliferation had been suppressed obviously with the of concentration increase of drug and the duration of administration (P < 0.05). The immunofluorescence results of 48 h showed Aurora-A and Bcl-2 protein expression of 400 nmoL were lower than those of other groups (P < 0.05), and Bax protein expression was similar to that of other groups(P > 0.05). Conclusions Aurora-A and Bcl-2 protein expression of thyroid cancer are inhibited when VX-680 being used , at the same time , Bcl-2/Bax scale value loses balance to accelerate forming Bax/Bax homodimer. Thus cancer cell proliferation is blocked and cell apoptosis is induced. So VX-680 is a good target inhibitor for anaplasia thyroid cancer.

Objective To study the pros and cons of two methods of infusing itraconazole injectionand prevent the blockage of peripherally inserted central catheter (PICC) and improve patients' satisfaction with nursing technology.Methods 172 patients infusing itraconazole were divided into two groups by random digital table method.86 cases established an independent infusion pathway as the control group,another 86 cases using PICC for itraconazole injection and withdrawing plunger of the syringe about 0.5 ml before and after the infusion and then pulsing-flushing it with 10 ml normal saline as the experimental group.Then compared the blockage rate of PICC and the patients' satisfaction with nursing technology.Results The blockage rate of the two groups had no significant difference (x2 =0.206,P ＞ 0.05) while patients' satisfaction with nursing skills was distinct,and the experimental group's was 96.51％ (83/86),much higher than 16.28％ (14/86) of the control group.Conclusions Withdrawing taken before and after the infusion of itraconazole injection could effectively prevent catheter blockage and improve patients' satisfaction with nursing technology.