Objective To explore the changes of Th17 cells in the pathogenesis and aggravation of chronic hepatitis B (CHB).Methods Thirty-two CHB patients,44 hepatitis B virus (HBV)related acute-on-chronic liver [ailure (ACLF) patients and 20 healthy controls (HC) were involved in our research. The frequencies of circulating Th17 cells were detected by flow cyrometry. The interleukin 17 (IL-17) mRNA expressions in the peripheral blood mononuclear cells (PBMC) were detected by quantitative real-time polymerase chain reaction (PCR).Immunohistochemical staining was performed to determine the expressions of IL-17+ cells in the liver tissues.The serum IL-17 concentrations were detected by enzyme-linked immunosorhent assay (ELISA),and the dynamic changes in ACLF patients with different prognosis were also observed.Normal distribution data were used by analysis of variance and non-normal distribution data were used by Kruskal-Wallis H test or Mann-Whitney U test.Results In CHB,ACLF and healthy control groups,Th17 cells frequencies in PBMC were (1.47 ± 0.60) ％,(3.20 ± 1.08) ％ and (0.86 ± 0.43) ％,respectively ; IL-17 mRNA were 4.32±11.77,18.32±8.21 and 1.00,respectively; IL-17+ cells in the liver tissues were (10.6±4.8),(21.1±6.6) and (0.5±0.2)/high power field; the level of IL-17 in serum were (15.88±6.51),(35.03±11.54) and (10.04±4.06) ng/L,respectively (all P＜0.05).Moreover,the frequencies of circulating Th17 cells and the levels of serum IL-17 in medium-stage and end-stage ACLF patients were higher than that in early-stage ACLF patients (both P ＜ 0.01). In ACLF patients,the circulating Th17 cells frequencies were positively correlated with international normalized ratio (INR,r=0.44,P＜0.01) and model of end-stage liver disease (MELD) score (r=0.44,P＜0.01).And the frequencies of circulating Th17 cells were positively associated with the serum alanine transaminase (ALT) levels in CHB patients (r=0.51,P＜0.01).Moreover,the survival ACLF patients had an initially lower serum IL-17 level compared with the non-survivors,and the serum IL-17 level showed a gradually decreasing trend during the course of medical treatment.In contrast,the nonsurvival group exhibited a gradually increasing trend.Conclusions Th17 cell and its cytokine IL-17 may contribute to liver injury in the pathogenesis of CHB and promote the occurrence and the development of HBV-related ACLF. Moreover,the elevated levels of Th17 cells and IL-17 may indicate poor short-term prognosis in ACLF patients.

Objective To investigate the clinical role of central venous pressure(CVP) to evaluate fluid responsiveness in septic shock patients. Methods 66 septic shock patients were studied, every patient was administered a volume challenge, before and after it, CVP, intrathoracic blood volume index (ITBVI),global end-diastolic volume index(GEDVI), cardiac index(CI), stroke volume index(SVI) were measured by PiCCO method. All the obtained values were analyzed by statistics method. Results Initial CVP in responders is significantly different from that in nonresponders; △ITBVI, △GEDVI, △CI, △SVI, △HR (△:changes) before and after volume challenge in responders were significantly different from those in nonresponders; the significance of △ITBVI, AGEDVI to predict volume responsiveness was strong indicated by high values of areas under the receiver operating characteristic curves (0.674 and 0.700, respectively).If patients were regrouped by CVP≤11 mm Hg(1 mm Hg=0.133 kPa) and CVP > 11 mm Hg, initial ITBVI and GEDVI in responders were not significantly different from that in nonresponders; △ITBVI,△GEDVI, △CI, △SVI before and after volume challenge in responders were significantly different from those in nom'esponders. Conclusion In septic shock patients, CVP play a guidance role to predict and evaluate volume responsiveness and when CVP was > 11 nun Hg, a positive response will be less likely. Initial volumetric parameters(intrathoracic blood volume and global end-diastolic volume) play a questionable role in predicting and evaluating volume responsiveness, changes before and after volume challenge maybe helpful.

Objectlve To research and analyze the hemod)rnamic status of refractory septic shock associated cardiac dysfunction.Methods 70 refractory septic shock patients were studied.In the duration of pulmonary artery catheter(PAC)-directed hemodynamic optimization,the patients were divided into a cardiac dysfunction group and a control group.Hemodynamic parameters,arterial blood lactate concentration and APACHE II scores were obtained instantly after the placement of a PAC,then lactate clearance in 24 hours was surveyed and calculated.Subsequently the two groups of patients were regrouped by nonsurvivor and survivors respectively.All the obtained values were analyzed with statistic methods.Results 37% of the refractory septic shock patients was complicated with cardiac dysfunction.The age of the patients complicated with cardiac dysfunction was significantly higher than that of the patients of the control group.Central venous pressure(CVP),pulmonary artery obstruction pressure(PAOP),pulmonary artery pressure (PAP),systemic vascular resistance index(SVRI),pulmonary vascular resistance index(PVRI)and oxygen extraction ratio(O2ext)in the cardiac dysfunction group were significantly different from those in the control group.Cardiac output(CO),cardiac index(CI),oxygen delivery index(DO2I)and mixed venous oxygensaturation(S-v O2)were significantly lower than those of the patients in the control group.S -v O2 had a strong correlation witIl CI.If the patients were regrouped by nonsurvivors and survivors.in the patients complicated with cardiac dysfunction APACHE II scores were significantly higher in the nonsurvivors than survivors:the lactate clearance in 24 hours(median-25%)of the nonsurvivors was significantly lower than that of nonresponders(median 22%),P＜0.05.Conclusion (1)In refractory septic shock patients,cardiac dysfunction maybe the main reason leading to bad outcome.(2)Higher CVP and PAOP and lower S -v O2 indicate the onset of cardiac dysfunction.(3)The patients with significantly high initial arterial blood lactate level and the low lactate clearance in 24 hours had bad outcome.

Objective To investigate the efficacy of interferon α(IFNα)and adefovir dipivoxil (ADV)combination therapy in HBeAg positive chronic hepatitis B(CHB)patients and to explore the optimized strategy for individualized treatment.Methods A total of 156 HBeAg positive CHB patients were enrolled in the study from January 2005 to June 2009 in the Third Affiliated Hospital of Hebei Medical University.Fifty-six CHB patients with hepatitis B virus(HBV)DNA≥1 X 107copy/mLand/or liver fibrosis stage≥S3,or previous monotherapy failure(relapse)were treated with initial IFNα and ADV combination therapy.Fifty-two patients who didn't meet any of the above baseline characteristics received initial IFNα monotherapy.The remaining 48 patients treated with IFNα monotherapy for full treatment duration were considered as control.At week 24 of treatment,the treatment regimens were adjusted according to quantitative changes of HBV DNA,HBeAg and HBsAg:16 patients who achieved early response in group of initial IFNα and ADV combination therapy subsequently received IFNα monotherapy,the other patients in group of initial combination therapy together with patients who did not achieved early response in group of initial IFNα monotherapy subsequently received IFNα and ADV combination treatment.The HBV DNA levels,HBeAg and HBsAg titers were detected at the end of 48 weeks of treatment to determine the treatment duration.The treatment efficacy,safety,drug resistance and relapse rates were finally evaluated at week 72.All data were analyzed using chi square test.Results At week 24,the early response rate in group of initial combination therapy was 28.6%,and the HBV DNA negative rate and alanine aminotransferase(ALT)normalization rate were significantly higher than those in groups of initial IFNα monotherapy and control(53.6%vs 32.7%vs 27.1%and 62.5%vs 40.4%vs 37.5%,respectively,P<0.05);in addition,HBeAg loss rate was higher than control group(39.3%vs 18.8%,x2=7.48;P<0.05).At week 48,five of 16 patients who achieved early response developed HBeAg reversion and three cases accompanied with virological breakthrough in group of initial combination therapy after switching to IFNα monotherapy,while the rates of HBV DNA negative,HBeAg seroconversion and HBsAg clearance were 73.2%,41.1%and 12.5%,respectively.The HBV DNA negative rate,HBeAg seroconversion rate and HBsAg clearance rate in 96 patients Who had received different combination treatment regimens were 65.6%,33.3%and 8.3%,respectively.At week 72,the relapse rate in individualized treatment group was comparable to those in control group,while HBsAg clearance rate increased 2.7%in individualized treatment group.Conclusions IFNα and ADV combination treatment could improve early biochemical and virological responses.Individualized treatment strategy based on baseline characteristics and treatment responses may be helpful for optimizing antiviral treatment in CHB patients.

Objective To investigate the changes of Th1/Th2 cells and related cytokine levels in chronic hepatitis B (CHB) fibrosis.Methods Forty-six patients with CHB fibrosis underwent liver biopsy during March and October,2011.According to the stage of fibrosis,the patients were divided into S0-1 group (n =15),S2-3 group (n =20) and S4 group (n =11).Ten healthy subjects served as controls.The frequencies of circulating Th1,Th2 cells were detected by flow cytometry.The expressions of interferon-γ (IFN-γ) and interleukin 4 (IL-4) mRNA in peripheral blood mononuclear cells (PBMCs) were detected by real-time quantitative PCR.The serum IFN-γand IL-4 concentrations were determined by enzyme-linked immunosorbent assays.Intrahepatic expressions of IFN-γ and IL-4 were detected by immunohistochemical staining.Differences between groups were analyzed using non-parametric Kruskal-Wallis H test,followed by Mann-Whitney U test for multiple comparisons.Logistic regression was used for multivariate analysis.Results With the degree of liver fibrosis exacerbations,the peripheral Th1/Th2 cells frequencies ratio,IFN-γ/IL-4 mRNA ratio in PBMCs,serum IFN-γ/IL-4 ratio and intrahepatic IFN-γ/IL-4 ratio were declined (x2 =36.259,40.822,26.321 and 31.852,respectively,all P ＜ 0.05).Serum and intrahepatic IFNγ/IL-4 ratio were negatively associated with the stage of liver fibrosis (r =-0.616 and-0.531,P ＜0.01).Logistic regression analysis showed that AST,PT and the serum IFNγ/IL-4 ratio were the risk factors for significant liver fibrosis (S2-4) (OR =5.933,95％ CI:1.324-26.586,P =0.02; OR =12.866,95％CI:1.746-94.788,P =0.01; OR=4.755,95％CI:1.034-21.862,P =0.04).Conclusions The CHB patients has imbalanced Th1/Th2 ratio.With the degree of liver fibrosis exacerbations,Th1/Th2 cytokines drift into Th2 lymphocyte sub-cluster,which suggests that Th1/Th2 imbalance may be involved in the pathogenesis of CHB fibrosis.

The chitosan scaffolds with different deacetylated degree were prepared in this study. The morphology of scaffolds were observed using SEM, and the porosity, the water absorbing swelling ratio and the degradation were examined both in vitro and in vitro. The results showed that the chitosan scaffolds with different deacetylated degree exhibited three-dimensional structure with high porosity. With increasing of deacetylated degree, their porosities were 93.46%, 90.02% and 86.71%, respectively. The swelling ratios of chitosan scaffolds were 820%, 803% and 772%, respectively. At the fourth week, the degradation rates were 30.44%, 22.08% and 17.10% in vitro, respectively; while the corresponding rates were 57.48%, 40.23%, 29.53% in vivo respectively. The degradation rate of chitosan scaffold was negatively correlated to deacetylated degree. Furthermore, it showed that the speed of degradation in vivo was faster than that in vitro. We concluded that controlling the deacetylated degree of chitosan can provide a well-matched degradable scaffold material for the reparation of cartilage defects.
Absorbable Implants ; Acetylation ; Animals ; Biocompatible Materials ; Chitosan ; analogs & derivatives ; chemical synthesis ; chemistry ; Female ; Male ; Materials Testing ; Rats ; Rats, Sprague-Dawley ; Tissue Engineering ; Tissue Scaffolds ; chemistry

Objective To investigate the prognostic effects and failure patterns of different clinical target volumes of IMRT in definitive chemoradiotherapy for cervical and upper-thoracic esophageal cancer,in order to provide a reference for radiotherapy target area delineation.Methods A retrospective analysis was performed on the clinical data of 132 patients with cervical and upper-thoracic esophageal cancer who received definitive IMRT and concurrent chemotherapy in our hospital from 2010 to 2014.Seventy-one patients received elective nodal irradiation (ENI) and the other 61 patients received involvedfield irradiation (IFI).The Kaplan-Meier method was used to calculate local control (LC),progressionfree survival (PFS) and overall survival (OS) rates.The significant difference was evaluated by the logrank test.The prognostic factors were determined by Cox univariate and multivariate analyses.Results The last follow-up time was December 2017,the median follow-up time was 59.5 (14.2-95.8) months.Follow-up rate was 99.2％.For the ENI and IFI groups,the 1-,3-,5-year LC were 77.5％,58.8％,48.8％ vs.64.3％,29.1％,26.2％ (x2=9.68,P=0.002),PFS were 68.6％,37.7％,25.9％ vs.47.5％,17.2％,3.6％ (x2=11.39,P=0.001),OS were 81.7％,53.9％,31.3％ vs.70.5％,31.9％,16.3％ (x2=7.70,P =0.006),respectively.In multivariate analysis,T stage,N stage,and RT field were independent factors for LC,PFS and OS(P＜0.05).The total failure rates,local-regional recurrent rate in ENI group were lower than those in IFI group (x2 =13.23,5.24,P＜0.05).No significant differences were found in acute radiation esophagitis,pneumonitis and myelosuppression (Grades ≥ 3) between the two groups(P＞0.05).Conclusions Compared with IFI,ENI can significantly reduce local-regional recurrence and distant metastasis and improve the long-term survival for cervical and upper-thoracic esophageal cancer patients who received definitive chemoradiotherapy.

Objective:To investigate the relationship between Onodera′s prognostic nutritional index (PNI) and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy or radiotherapy, aiming to provide a convenient, effective and accurate predictive indicator for evaluating the long-term survival of patients after treatment.Methods:Clinical data of 231 ESCC patients treated with definitive chemoradiotherapy or radiotherapy at the Fourth Hospital of Hebei Medical University from 2013 to 2015 were retrospectively analyzed. The PNI values of each patient at different radiotherapy periods were calculated and the ROC curve was used to determine the optimal cutoff value of PNI before radiotherapy, 231 patients were divided into the better-nourishment group ( n=86) and worse-nourishment group ( n=145). Kaplan- Meier method was used for survival analysis. Cox proportional hazards model was utilized to analyze the relationship between different nutritional status and prognosis. The short-term clinical efficacy and incidence of acute toxicities were statistically compared between two groups. Results:The mean values of PNI before, at week 3, week 6 and 1 month after radiotherapy were48.68±5.08, 39.68±4.87, 43.74±4.89 and48.31±4.92, respectively. The optimal cutoff value of pretreatment PNI was 49.25, the area under the curve (AUC) was 0.655, the sensitivity and specificity were 68.6% and 60.9%, respectively. The 5-year overall survival (OS) and progression-free survival (PFS) rates in the better-nourishment group (PNI≥49.25) were 36.0% and 31.3%, significantly better than 19.3% and 18.6% in the worse-nourishment group (PNI<49.25)( P=0.001, P=0.039). Multivariate analysis showed PNI before the therapy was an independent prognostic factor for OS ( P=0.021). Stratified analysis demonstrated that Stage Ⅰ/Ⅱ and concurrent chemotherapy patients in the better-nourishment group all obtained significantly better OS than their counterparts in the worse-nourishment group ( P=0.007, P=0.004). In addition, the objective response rate in the better-nourishment group was significantly higher than that in the worse-nourishment group ( P=0.047), whereas the incidence of ≥3 grade radiation esophagitis was lower than that in the worse-nourishment group ( P=0.060). Conclusions:Pretreatment PNI is a convenient and reliable indicator for predicting the long-term survival of ESCC patients after definitive chemoradiotherapy or radiotherapy. Patients with higher PNI have relatively better prognosis and radiotherapy tolerance, especially in those with early stage or concurrent chemotherapy.

Objective:To analyze the local recurrence patterns after concurrent chemoradiotherapy (CCRT) for thoracic esophageal squamous cell carcinoma (ESCC) through image fusion, and to explore the risk factors of local recurrence and its relationships with dosimetric indices.Methods:A retrospective analysis was conducted for 209 thoracic ESCC patients who received radical CCRT in Fourth Hospital of Hebei Medical University during 2016-2019. For the patients diagnosed as the local recurrence of esophageal lesions, their CT images were fused with the original planning CT images using image registration software to identify the recurrence sites. Through 1∶1 propensity score matching (PSM) of the clinal data of patients with local recurrence (the recurrence group, nbefore = 81, nafter = 62) and those without local recurrence (the recurrence-free group, nbefore = 128, nafter=62), the dose and volume parameters of the treatment plans for the two groups were compared. Univariate and multivariate analyses were conducted using the Kaplan-Meier method and the Cox regression model to analyze the factors affecting the overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS). Results:All patients had 1-, 3-, and 5-year OS rates of 80.9%, 42.6%, and 33.0%, respectively, 1-, 3-, and 5-year PFS rates of 67.9%, 34.0%, and 27.9%, respectively, and 1-, 3-, and 5-year RFS rates of 71.3%, 39.2%, and 30.5%, respectively. T stage, N stage, and radiation dose were independent prognostic factors for the OS, PFS, and RFS ( HR = 1.42-1.87, P < 0.05) of the patients, respectively. Among 68 patients with local recurrence, 62 cases (91.2%) suffered recurrence within the gross tumor volume (GTV). The dose and volume parameters of patients with local recurrence, such as GTV- D95%, clinical target volume (CTV)- D95%, GTV- D50%, CTV- D50%, and planning target volume (PTV)- D50%, GTV- V60, CTV- V60, and PTV- V60, were significantly lower than those of patients free from the local recurrence ( t=1.90-2.15, P < 0.05). Conclusions:Local recurrence of patients with thoracic ESCC after radical CCRT occurs mainly within the GTV. Increasing radiation doses may contribute to their survival benefits. The D50% for each target volume in the radiotherapy plan may be related to local recurrence, and it is necessary to conduct further research.

Objective To investigate the application and effect evaluation of combined warming and humidification device in patients with artificial airway in high altitude area. Methods The convenient sampling method was used to select 225 hospitalized patients in the Department of Critical Care Medicine of the People′s Hospital of Tibet Autonomous Region from January to June 2018. According to the order of admission time, they were divided into two groups: observation group (125 cases) and control group (100 cases). The observation group was humidified by artificial nose, while the control group was humidified by heating and humidifying device. The phlegm properties and scab formation were observed in the two groups. The ambient temperature, humidity and airway temperature were measured at 3:00, 9:00, 15:00 and 21:00 every day. The average values of four measurements were taken. The levels of CO2 partial pressure and oxygen partial pressure were recorded by blood gas analysis. χ2was used to compare the differences between the 2 groups. Results There was no difference in sputum properties between the two groups before humidification. The incidence of grade II and grade III mucous phlegm in the observation group was 46, 48 and 65 on the first, second and third day after humidification, while that in the control group was 13, 9 and 10 respectively. The difference between the two groups was statistically significant (χ2=16.266, 25.387, 44.100, P<0.01). On the 2nd and 3rd day, the oxygen partial pressure levels of the observation group were (92.62 ± 5.73), (91.34 ± 4.82) mmHg, and those of the control group were (96.17 ± 3.60), (95.53 ± 2.96) mmHg, respectively. The difference between the two groups was statistically significant (t=5.697, 8.045, P<0.01). The sputum scab formation and airway temperature in the observation group were 41 cases and(29.89±1.95)℃ respectively after 3 days of humidification, 7 cases and(34.79±1.82)℃respectively in the control group. The difference between the two groups was statistically significant (χ2= 22.035, t =- 26.031, P < 0.01). Conclusion The combination of heating and humidifying device can effectively improve the sputum properties, reduce the formation of sputum scab, effectively improve the level of carbon dioxide, without increasing the workload.