Objective To investigate the effect of poractant alfa injection(PS) on neonatal respiratory distress syndrome(NRDS).Methods According to the digital table,80 cases of NRDS were randomly divided into the control group (40 cases) and the treatment group (40 cases).Both two groups were treated by mechanical ventilation and conventional symptomatic,supportive treatment.The treatment group was given PS intratracheal injection,the control group was given 0.9％ sodium chloride injection intratracheal injection.The clinical symptoms,blood gas analysis and the improvement of X-ray chest film were dynamicly observed,the clinical efficacy was compared between the two groups.Results In the treatment group,PaO2 returned to ＞ 60mmHg time,PaCO2 returned to ＜ 50mmHg time,mechanical ventilation time were (2.13 ± 0.21) h,(12.56 ± 0.11) h,(18.2 ± 0.33) h,which were shorter than those in the control group [(12.41 ± 0.13) h,(89.87 ± 0.26) h,(76.13 ± 0.65) h,t =2.632,2.403,1.895,all P ＜ 0.05] ;39 cases in the treatment group were cured(97.5％),30 cases in the control group were cured(75.0％),the difference of cure rate between the two groups was statistically significant(x2 =8.53,P ＜ 0.05).The incidence rate of comnplications such as pulnonary hemorrhage,pneumothorax,intracranial hemorrhage in the treatment group was 7.5％,which was significantly lower than 32.5％ in the control group (x2 =7.81,P ＜ 0.05).Conclusion PS in the treatment of NRDS has obvious curative effect and less adverse reactions,it can be used in clinical application.

Objective To investigate the effects of total flavonoids of litchi chinensis sonn (TFL) on cell proliferation and the molecular mechanism in rat hepatic stellate cells (HSC-T6) activated by growth factor-β1 (TGF-β1). Methods HSC-T6 cells were treated by 0.25%Trypsin-EDTA and then were digested into single cell suspension by DMEM (10%FBS included), which were mixed with TGF-β1 (5μg/L). (1) MTT method was used to detect the proliferation of HSC-T6 cells. Cells were cultured in 96-well plate and were treated by different concentrations of TFL including TGF-β1 group, the control group (5‰DMSO included), and different concentrations of TFL groups (80, 160, 320, 640 and 800 mg/L TFL). Each group has three wells. The absorbance (A) value was measured by enzyme standard meter at the 490 nm wavelength after 24 h, 48 h and 72 h treatment. The cell inhibitory rate was calculated. The subsequent experimental drug concentration and drug treatment time were determined according to half inhibitory concentration (IC50). (2) The expression levels of NF-κB andα-SMA mRNA were detected by PCR (for mRNA) and Western blot assay (for protein). Cells were cultured in the 10 cm culture dish and were divided into different TGF-β1 groups, including TGF-β1 group, the control group (5‰DMSO included), and different concentrations of TFL groups (125, 250 and 500 mg/L TFL). After 48 h, related indicators were measured. Results At the same treatment time point, with the increased concentrations of TFL, A values were gradually decreased, and the cell inhibitory rates were gradually increased. There were no significant differences in the expressions of NF-κB andα-SMA mRNA between TGF-β1 group and control group. And there were no significant differences in the expressions of NF-κB andα-SMA mRNA between TFL125 group, TGF-β1 group and control group. There was a gradually decrease in the expressions of NF-κB andα-SMA mRNA and protein with the increased concentrations of TFL. Conclusion TFL can inhibit TGF-β1-induced HSC-T6 cell proliferation, which is involved in the inhibited expressions of NF-κB andα-SMA to anti-fibrotic effects in liver fibrosis.

OBJECTIVETo investigate the correlation of expressions of STAT3 and p-STAT3 with epithelial mesenchymal transition(EMT)-associated protein E-cadherin in colorectal cancer, and to examine the association of above expressions with tumor invasion and metastasis of colorectal cancer.

METHODSImmunohistochemistry assay ElivisionTM plus was used to detect the expressions of STAT3, p-STAT3 and E-cadherin protein in colorectal cancer tissue samples of 50 cases and their corresponding adjacent non-tumor tissues. Association of these protein expressions with tumor invasion and metastasis was analyzed with χ(2) test. Correlation of STAT3 and p-STAT3 with E-cadherin was analyzed with Spearman method.

RESULTSPositive expression rates of STAT3, p-STAT3 and E-cadherin protein in colorectal cancer tissues were 72%(36/50), 76%(38/50) and 26%(13/50), which were significantly higher compared to adjacent normal intestinal mucosa tissues [24%(12/50), 26%(13/50) and 68%(34/50), all P<0.05]. STAT3, p-STAT3 and E-cadherin expressions were associated with tumor differentiation, tumor invasion depth, tumor size, lymph node metastasis, TNM staging (all P<0.05). In colorectal cancer tissues, STAT3 protein expression was positively correlated with p-STAT3 expression. STAT3 and p-STAT3 expressions in colorectal cancer tissues were negatively correlated with E-cadherin expression(P<0.05).

CONCLUSIONSTAT3 and p-STAT3 may be involved in tumor EMT through inhibition of E-cadherin expression, leading to the development of colorectal cancer.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Cadherins ; metabolism ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Phosphorylation ; STAT3 Transcription Factor ; metabolism

Objective To evaluate the efficacy and drug resistance profiles of nucleosides (NA) retreatment in NA experienced chronic hepatitis B (CHB) patients. Methods Totally 104 NA experienced CHB subjects were enrolled in this study.All these subjects had received at least 3 months NA monotherapy and stopped the treatment,and then received NA retreatment for at least one year.The subjects were divided into three groups according to the following criteria:reached the therapy endpoint of China guideline when they stopped NA-naive treatment (group A,n =39); did not reach the therapy endpoint when they stopped NA-naive treatment but hepatitis B virus (HBV) DNA＜1.0× 103 copy/mL (group B,n=33); and with HBV DNA＞1.0× 103 copy/mL (group C,n=32).The efficacy and drug resistance profiles of retreatment were compared among three groups. The effects of baseline alanine aminotransferase (ALT) levels,HBV DNA levels and HBeAg titers on the retreatment efficacies were analyzed. The mutations of HBV P gene were detected by nested polymerase chain reaction (PCR) and direct sequencing.The data were analyzd by Wilcoxon test and x2 test.Results The time to ALT normalization in patients with baseline ALT＜ 1.3 × upper limit normal (ULN) was shorter than that in patients with ALT≥1.3×ULN (2 months vs 4 months; Z=2.281,P=0.023).The time to virological response in patients with baseline HBV DNA＜5 lg copy/mL was shorter than that in patients with HBV DNA≥5 lg copy/mL (1 month vs 2 months; Z=2.054,P =0.040). The time to virological response and ALT normalization in baseline HBeAg negative were both shorter than those in patients with baseline HBeAg positive patents ( 1 month vs 3 months and 2 months vs 4.5 months,respectively; Z=2.580 and 2.304,respectively; both P＜0.05). The subjects in group A achieved virological response and HBeAg seroconversion after retreatment earlier compared to previous NA-naive therapy ([1.61 ± 1.76] months vs [3.48±4.066]months and [3.38 ± 3.34] months vs [9.92-11.22] months,respectively; Z=-2.854 and-1.094,respectively; both P＜0.05).The cumulative HBeAg seroconversion rate in group A was higher compared to those in group B and group C (80.0％ vs 36.8％ and 37.5％,respectively; x2 =4.368 and 5.100,respectively; both P＜0.05).Thirteen patients developed clinical resistance and four of them developed genotypic resistance proved by PCR direct sequencing.Among the patients retreated with the same regimen as previous in the C group,the cumulative resistance rate was highest compared to group A and B (44％ vs 9％ and 0,respectively; x2 =5.019 and 6.588,respectively;both P＜0.05).No resistance was detected in the 14 patients retreated with combined NA treatment without cross resistance.Conclusions For NA experienced CHB patients who fulfill the indication of antiviral therapy,the retreatment should be started as earlier as possible. Retreatment with NA combination without cross resistance can prevent (reduce) the risk of developing drug resistance.

Objective To explore the influence factors on hepatitis B virus (HBV) relapse after nucleos(t)ide analogues (NA) withdrawal in the chronic hepatitis B (CHB) patients who met NA cessation criteria. Methods Eighty-one consecutive CHB patients were treated with NA, 38 with lamivudine (LAM), 25 with adefovir dipivoxil (ADV), 12 with entecavir (ETV), 6 with LAM +ADV. Among recruited patients, 40 were hepatitis B virus e antigen (HBeAg) positive, 41 were HBeAg negative, 67 of them were initial treatment, 14 were retreatment due to resistance to NA at baseline. The treatment was discontinued after meeting China therapeutic end-point criteria. HBV DNA, HBV serological markers, alanine aminotransferase (ALT) were measured respectively at baseline, every month before virological response, every 3 months after virological response, every month within first 6 months and every 2 months over 6 months after drugs withdrawal. Twelve probable influence factors on relapse which were sex, age, HBV family history, baseline HBV DNA,baseline HBeAg status, baseline ALT, virological response time, total duration of treatment, duration of additional treatment, the level of hepatitis B virus surface antigen (HBsAg) at cessation therapy,initial treatment or retreatment, drug category were analyzed with univariate, multivariate Cox regression modle and stratified analysis. The cumulative relapse was calculated by the Kaplan-Meier method. Results A total of 36 patients (44. 4%) relapsed within 1 year. Initial treatment or retreatment, HBV family history, virological response time, the level of HBsAg at cessation therapy were independent risk factors. The relapse rate of retreatment was higher than that of initial treatment (78.6% vs 37. 3% , χ2 = 7. 983, P = 0. 005) , those of patients with HBV family history higher than without family history (64. 5% vs 15.0%, χ2 =12. 096,P = 0.002), those of patients obtained virological response within 3 months lower than after 3 months(34. 0% vs 64. 3% , χ2 =6. 823,P=0. 009) , those of patients with HBsAg≤150 μg/L at cessation therapy lower than >150 μg/L(27. 6% vs 53. 8%, χ2=5. 199,P=0. 023). Conclusions Retreatment, HBV family history, later virological response and higher HBsAg level at cessation therapy are risk factors of relapse after NA withdrawal. Such patients should be treated with prolonged duration after meeting end-point criteria to strengthen the efficacy.

Objective: To investigate the impact of improved AHA cardiovascular health behavior score (CHS) on short-time systemic blood pressure variability (SBPV) in elder population.
Methods: A total of 2464 participants ≥ 60 years from 3 hospitals of Kailuan area were taken for cohort study. The participants had no cardiovascular disease, not taking anti-psychotic drug, Parkinson treatment drug, anti-depression drug and analgesic drug within 2 weeks. All participants received 24-hour ambulatory blood pressure monitoring (ABPM) and the 24-hour, day-time, night-time SBPV were deifned by the standard deviation of 24-hour, day-time, night-time systolic blood pressure. The influence of CHS on SBPV was studied by multi-linear regression analysis. Improved cardiovascular health behavior and factors implied as changing the vegetable intake amount to salt amount by American Humane Association, 2010; boundary of BMI based on《Guidelines for prevention of overweight and obesity in Chinese adults》; status of exercise was deifed as the ideal status: ≥80 min/week, general status: < 80 min/week and bad status: no exercise.
Results: Finally, 1812 participants were recruited for survey and they were divided into 3 groups according to improved CHS: Group①, CHS (0-4) points,n=56, Group②, CHS (5-9) pointsn=1600 and Group③, CHS (10-14) points,n=156. The 24-hour SBPV in Groups①,②and③were 16.02 mmHg, 14.91 mmHg and 13.18 mmHg; day-time SBPV were 15.42 mmHg, 14.50 mmHg and 13.22 mmHg; night-time SBPV were 12.68 mmHg, 11.44 mmHg and 10.16 mmHg, allP<0.05. Multi-linear regression analysis indicated that with adjusted confounding factors, with 1 point of CHS elevation, the 24 hour-, day-time, night-time SBPV would reduce for 0.20 mmHg, 0.19 mmHg and 0.37 mmHg respectively, allP<0.05.
Conclusion: CHS was negatively related to short-time SBPV in elder population.

Objective To investigate the effect of SP600125 on the proliferation, cell cycle, apoptosis and invasion of human cervical cancer HeLa cells. Methods CCK-8 method was used to detect the proliferation of HeLa cells treated with different concentrations of SP600125 at different time points. The 20 μmol/L of SP600125 was determined for subsequent experiments. Cell proliferation ability was detected using plate clone formation assay; nuclear morphology was observed by DAPI staining; cell cycle and apoptosis were measured by flow cytometry; cell migration and invasion were detected by cell scratch and Transwell methods; the mRNA and protein levels of p53, Mad2L1 and CDC20 were measured by qRT-PCR and Western blot after SP600125 treatment at different time points. Results Compared with control group (0.1%DMSO), cells proliferative activity were reduced by 10, 20, 30, 40 and 50 μmol/L SP600125 treatment for 24h. Compared with control group, the rate of apoptosis was significantly increased in SP600125 treatment groups, and the cell proportion in G₂/M phase increased (P < 0.001), while the cell proportion in G₀/G₁ phases cells was reduced after SP600125 treatment for 24h and 48h (P < 0.001), and the clonal number, migration and invasion ability of HeLa cells also decreased significantly (P < 0.001). qRT-PCR and Western blot results showed a significant decrease in Mad2L1 mRNA and protein expression (P < 0.05) and a significant increase in p53 and CDC20 mRNA and protein expression (P < 0.01). Conclusion SP600125 can induce cell cycle arrest of cervical cancer HeLa cells in G₂/M phase by upregulating p53 and CDC20 and downregulating Mad2L1 expression, and promote cell apoptosis to inhibit cell proliferation, migration and invasion.

Objective:To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy.Methods:It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer.Results:The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 ( P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions:SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

Objective:To investigate the correlation of monocyte/lymphocyte ratio (MLR) with the prognosis and adverse event in critically ill patients.Methods:Basic information of patients were extracted from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ), including demographics, blood routine, biochemical indexes, systemic inflammatory response syndrome score (SIRS), sequential organ failure assessment (SOFA) score, and outcome, etc. MLR on the first day of intensive care unit (ICU) admission was calculated. The receiver operating characteristic curve (ROC curve) was applied to evaluate the prognostic value of MLR on the 30-day mortality and its cut-off value. According to the cut-off value, the patients were divided into two groups, and the differences between the groups were compared. Logistic regression model was used to analyze the relationship of MLR with 30-day mortality, continuous renal replacement therapy (CRRT), mechanical ventilation, the length of ICU stay, and total hospitalization time.Results:① A total of 43 174 critically ill patients were included. ROC curve showed that area under ROC curve (AUC) of MLR in predicting 30-day mortality was 0.655 [95% confidence interval (95% CI) was 0.632-0.687]. The cut-off value of MLR calculated according to the maximum Yoden index was 0.5. There were 16 948 patients with MLR ≥ 0.5 (high MLR group) and 26 226 patients with MLR < 0.5 (low MLR group). ② Compared with the low MLR group, the high MLR group had higher age, proportion of male, body mass index (BMI) [age (years old): 66.0 (51.7, 78.4) vs. 57.6 (27.1, 74.6), proportion of male: 57.2% vs. 52.5%, BMI (kg/m 2): 26.5 (22.5, 31.1) vs. 24.7 (14.3, 29.7)]. The high MLR group also had higher incidence of complications (hypertension: 49.2% vs. 44.6%, chronic heart failure: 32.6% vs. 21.7%, diabetes mellitus: 27.0% vs. 23.4%, chronic obstructive pulmonary disease: 21.5% vs. 16.1%, renal insufficiency: 19.3% vs. 13.1%), and higher white blood cell count (WBC), blood glucose, lactate (Lac), serum creatinine (SCr), SIRS score and SOFA score [WBC (×10 9/L): 13.8 (9.6, 19.2) vs. 11.5 (8.4, 15.6), blood glucose (mmol/L): 8.66 (6.88, 11.49) vs. 8.27 (6.55, 10.88), Lac (mmol/L): 2.2 (1.5, 3.7) vs. 2.1 (1.4, 3.3), SCr (μmol/L): 106.1 (70.7, 176.8) vs. 88.4 (70.7, 132.6), SIRS score: 3 (2, 4) vs. 2 (2, 3), SOFA score: 4 (2, 7) vs. 3 (1, 5)]. The 30-day mortality, and the proportion of patients with length of ICU stay > 5 days, total hospitalization time > 14 days, CRRT and mechanical ventilation > 5 days were significantly higher in high MLR group (30-day mortality: 20.0% vs. 8.3%, length of ICU stay > 5 days: 33.2% vs. 20.4%, total hospitalization time > 14 days: 33.7% vs. 16.2%, CRRT: 3.6% vs. 0.7%, mechanical ventilation > 5 days: 18.4% vs. 5.7%), with statistically significant differences (all P < 0.05). ③ After adjusted with the related factors, multivariate Logistic regression analysis showed that elevated MLR was an independent risk factor for increased 30-day mortality [odd ratio ( OR) = 1.54, 95% CI was 1.37-1.72, P < 0.001]. Moreover, the increased MLR was independently associated with the increased risk of usage of CRRT ( OR = 2.77, 95% CI was 2.18-3.51), mechanical ventilation > 5 days ( OR = 2.45, 95% CI was 2.21-2.72), the length of ICU stay > 5 days ( OR = 2.29, 95% CI was 2.10-2.49), and total hospitalization time > 14 days ( OR = 2.28, 95% CI was 2.08-2.49), all P < 0.001. Conclusions:Retrospective analysis of large sample shows that MLR elevation is an independent risk factor for 30-day mortality, usage of CRRT, prolonged mechanical ventilation time, prolonged hospitalization, prolonged length of ICU stay. MLR can be used for risk stratification of severe patients.

Objective: The effect of total flavonoids of litchi (TFL) on nuclear translocation of nuclear factor-kappa B (NF- kappa B) in rat hepatic stellate cell line (HSC-T6) induced by transforming growth factor - beta 1 (TGF- beta 1) in vitro was studied to explore the mechanism of action of anti-hepatic fibrosis drugs. Methods: HSC-T6 was cultured in vitro, induced by TGFβ1 for 24 h, and then treated with TFL at 125, 250 and 500 μg/ml for 48 h. The effect of TFL on NF-κB nuclear translocation in HSC-T6 was observed by confocal laser microscopy. The effects of TFL on the expression of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and Collagen I protein were detected by western blot. The expressions of TLR4 and p-NF-κB p65 were detected by immunofluorescence. Data were presented as mean±SEM. Homogeneity test of variance was performed and then followed by one-way analysis of variance (ANOVA). The multiple comparisons between groups were performed by LSD test. P < 0.05 was considered statistically significant. Results: Confocal laser scanning microscopy showed TFL inhibited the nuclear translocation of NF-κB in activated HSC-T6 in a concentration-dependent manner and TFL down regulated the protein expression levels of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and collagen I protein in HSC-T6 in a concentration-dependent manner. Conclusion The mechanism of TFL against hepatic fibrosis may be related to the inhibition of nuclear translocation of NF-κb in the activated HSC-T6 and the expression of TLR4, P-iκbɑ, P-nf-κb p65, NF-κb and collagen I protein in HSC-T6.