Objective Previous study found TGF-βpathway might be the molecular pathway influencing the prognosis of colo-rectal cancer, while it was uncertain whether Chinese population is associated with the disease.The article was to evaluate the genetic factors associated with prognosis in colorectal cancer. Methods 52 cases patients with colorectal cancer were followed-up for 36 months in our hospitals from January 2013 to August 2014.Their DNAs were extracted and stored and gene typing were carried out in 5 candidate genes to detect the association between SNPs and the prognosis in colorectal cancer. Results The results showed that within the TGF-βsignaling pathway, after adjusting for Bonferroni multiple testing, allele A of SNP rs10749971 located in gene POU2AF1 was associated with the recurrence of patients with stage III disease under additive and recessive genetic models ( HR =1.968, P=0.004;HR=2.174, P=0.010).Allele C of SNP rs961253 in the gene BMP2 could increase the recurrence risk (HR=1.992, P=0.005) and the death risk (HR=3.161, P=0.007) of patients with stage III disease under recessive genetic models.Allele A of SNP rs4464148 in SMAD7 gene could significantly decrease the death risk of patients with stage II and III colorectal cancer under dominant genetic model (HR=0.382, P=0.017;HR=0.230, P=0.006).In addition, accumulated effects of several adverse genes showed gene high risk group could increase the risk of death for patients with stage III colorectal cancer significantly ( HR=15.512, P=0.036;95%CI:1.611-149.360). Conclusion In different genetic models, SNP locus mutation within gene POU2AF1, BMP2 and SMAD7 on TGF-βpathway was associated with the prognosis of patients with colorectal cancer.With the increase of the number of unfavorable genes, the death risk increases accordingly.

Objective To explore the variation and clinical value of the degradation of endothelial glycocalyx in the patients with septic shock. Methods A prospective case control study was conducted. Patients of 18 years or older diagnosed with septic shock and admitted to Department of Critical Care Medicine of Affiliated Hospital of Binzhou Medical University from June 2014 to May 2015 were enrolled. The levels of degradation products, including hyaluronic acid (HA) and heparin sulfate (HS), at 0, 6, 12, 24, 48 hours were determined, while 20 healthy people were enrolled and served as controls. The changes of HA and HS were analyzed in the patients with septic shock. The differences of HA and HS between survival group and death group after 28 days were also analyzed. The relationships between HA, HS and tumor necrosis factor-α (TNF-α), sequential organ failure assessment (SOFA) score, arterial blood lactate (Lac), platelet, albumin were analyzed by Pearson correlation analysis. The receiver-operating characteristic (ROC) curve was plotted to assess the prognostic value of HA and HS for patients with septic shock. Results Thirty-one patients diagnosed as septic shock were enrolled, among whom 17 patients died after 28 days, with a mortality of 54.8%. The levels of HA and HS in patients with septic shock were increased significantly as compared with those of health control group, peaked at 48 hours, and the levels of HA and HS at 48 hours were significantly higher than those at 0 hour [HA (μg/L): 119.47±32.44 vs. 94.84±23.63, HS (μg/L): 72.83±19.03 vs. 58.83±16.63, both P < 0.05]. The levels of HA and HS at 0 hour and 48 hours in death group were significantly higher than those of the survival group [HA (μg/L): 130.42±27.67 vs. 93.29±29.80, 105.14±19.18 vs. 70.82±13.24; HS (μg/L): 67.23±25.01 vs. 39.23±14.58, 79.74±19.84 vs. 56.17±14.53, all P < 0.05]. The levels of HA and HS in patients with septic shock were remarkably positively correlated with the levels of TNF-α, SOFA score, Lac, and platelet, but were remarkably negatively correlated with albumin levels (r value of HA was 0.595, 0.462, 0.545, 0.466, -0.534, respectively; r value of HS was 0.607, 0.468, 0.563, 0.547, -0.455, respectively; all P < 0.05). It was demonstrated by ROC curves that the areas under ROC curve (AUC) of HA and HS at 0 hour and 48 hours for predicting the prognosis of patients with septic shock were 0.881, 0.940 and 0.833, 0.821, respectively, the sensitivities of HA and HS were 87.5%, 100.0% and 83.3%, 81.3%, respectively, and the specificities of HA and HS were 82.6%, 78.3% and 91.3%, 78.3%, respectively. Conclusions The concentrations of degradation products generated by endothelial glycocalyx in the blood of the patients with septic shock are remarkably increased. The elevated levels of the degradation products are closely associated with the severity of septic shock, microcirculation disturbance, and the levels of inflammatory factors.

Objective To evaluate the efficacy of adductor canal combined with interspace between the popliteal artery and the capsule of the posterior knee (IPACK) block for multimodal analgesia after total knee arthroplasty (TKA).Methods Sixty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients of both sexes,aged 55-78 yr,scheduled for elective unilateral TKA under combined spinal-epidurai anesthesia,were assigned into 2 groups (n =30 each) using a computer random number method:adductor canal combined with IPACK block group (group A+Ⅰ) and adductor canal block group (group A).Preventive multimodal analgesia was applied as follows:preoperative pain management education was performed;flurbiprofen 50 mg was intravenously injected before induction of anesthesia,and celecoxib 200 mg was taken orally after surgery,twice a day,to control inflammatory pain;ultrasound-guided adductor canal combined with IPACK block was performed in group A+Ⅰ,and ultrasound-guided adductor canal block was performed in group A to inhibit incisional pain;nalbuphine 0.08 mg/kg was intravenously injected to inhibit breakthrough pain.Postoperative numeric rating scale (NRS) scores at rest (NRSr) and on movement (NRSm) were maintained ＜ 5 within 48 h after surgery.The area under the curve (AUC) of NRSr and NRSm (AUCNRsr and AUCNSm) were calculated within 48 h after surgery.The requirement for nalbuphine as rescue analgesic was recorded.The maximum number of ambulatory steps and maximum range of knee motion were recorded on 1 and 2 days after surgery.The development of nerve block-and postoperative rehabilitation training-related adverse events and postoperative length of hospitalization were also recorded.ResuRs Compared with group A,AUCNRSr and AUCNRSm were significantly decreased,the consumption of nalbuphine was reduced,and the maximum number of ambulatory steps and maximum range of knee motion were increased (P＜0.05),and no significant change was found in the requirement for nalbuphine or length of hospitalization in group A+Ⅰ (P＞0.05).No nerve block-and postoperative rehabilitation training-related adverse events were found in neither group.Conclusion Adductor canal combined with IPACK block can provide a relatively perfect efficacy when used for multimodal analgesia after TKA and is helpful for patient's recovery.

Objective:To investigate the prognostic factors of severe patients with bloodstream infection (BSI) caused by Enterobacteriaceae bacteria. Methods:Patients suffered from BSI caused by Enterobacteriaceae bacteria admitted to department of critical care medicine of Binzhou Medical University Hospital from October 2016 to October 2019 were enrolled. The information of gender, age, combined shock, acute physiology and chronic health evaluationⅡ(APACHEⅡ), sequential organ failure assessment (SOFA), sensitivity of initial antibiotics, as well as the baseline of procalcitonin (PCT), white blood cell count (WBC), platelet (PLT), albumin (ALB) were collected. The 72-hour PCT clearance rate (72 h PCTc) was calculated after 72 hours' treatment. According to the clinical outcome after 28 days, the patients were divided into recovery group and death group. The differences of clinical indicators between the two groups were compared, and then the statistical significant variables were further performed by Logistic regression to analyze the factors affecting the prognosis of patients. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive efficacy of the factors in severe BSI. Results:A total of 86 patients were enrolled, among whom 54 cases recovered while 32 cases died, and the 28-day mortality was 37.2%. There was no significant difference in gender, age, sensitivity of initial antibiotics, baseline levels of PCT and WBC between two groups. In the death group, the shock incidence, APACHEⅡscore, SOFA score were significantly higher than those in recovery group [shock incidence: 84.4% (27/32) vs. 46.3% (25/54), APACHEⅡ: 24.94±7.65 vs. 17.02±6.57, SOFA: 11.00±3.27 vs. 6.30±2.65, all P < 0.01]; the PLT and ALB baseline levels, 72 h PCTc were significantly lower than those in recovery group [PLT (×10 9/L): 73.38±49.15 vs. 138.69±101.80, ALB (g/L): 25.47±5.91 vs. 28.59±4.53, 72 h PCTc: -44 (-170, 27)% vs. 63 (40, 77)%, all P < 0.01]. The above 6 variables were included in Logistic regression. The results showed that SOFA score was a risk factor for death in these patients [odds ratio ( OR) = 1.930, P = 0.037], while 72 h PCTc and ALB were protective factors ( OR values were 0.043, 0.783, P values were 0.008, 0.047). The SOFA, 72 h PCTc and ALB can be used to predict the prognosis of severe BSI, and the diagnostic value of the combination of three factors was the largest [area under the ROC curve (AUC) = 0.953, 95% confidence interval (95% CI) was 0.909-0.997], the sensitivity was 100%, and the specificity was 79.6%. Conclusions:Severe patients with BSI caused by Enterobacteriaceae bacteria had a high mortality. Higher SOFA score, and lower ALB and 72 h PCTc predicted the adverse outcome. The combination of the three factors has the greatest prognostic efficacy.

Objective:To summarize the clinical manifestations, diagnosis and surgical treatment of abdominal unicentric Castleman's disease.Methods:The clinical data of abdominal unicentric Castleman's disease cases admitted to the General Surgery Department of the First Affiliated Hospital,Nanjing Medical University from Jan 2009 to Dec 2019 was retrospectively analyzed.Results:A total of 18 patients were included with definite pathological diagnosis. The main complaint was abdominal pain and discomfort (50%, 6/12), dizziness and fatigue (25%, 3/12), multiple rash with oral ulcer (16.7%, 2/12) and weight loss (8.3%, 1/12). All patients received surgical resection. Postoperative pathology showed clear vascular type in 15 patients and plasma cell type in 3 patients. There were no major complications nor mortality.Conclusion:Abdominal unicentric Castleman's disease has diverse clinical manifestations, which was difficult for preoperative diagnosis, postoperative prognosis is satisfactory.

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

【Objective】 To analyze the influence of different Inc parameters in the Monaco planning system on the left breast cancer volumetric modulated arc therapy (VMAT) planning, in the hope of providing some reference for plan design. 【Methods】 Seventeen left-breast cancer patients who were receiving radical radiotherapy were selected. The plans were enrolled in the design of VMAT with the same optimization conditions but different Inc parameters in the Monaco planning system. All plans used different Inc parameters like 10°, 20°, 30°, and 40°. The results of the plan were compared. The dosimetric parameters of the PTV and the organs at risk inquired by the plan were analyzed. The SPSS software was used for calculating the differences between the VMAT plans and evaluating the quality of the plans. 【Results】 The different Inc parameters affected the dosimetric parameters D98%, D2%, D50%, V55 Gy of PTV and CI, HI (F=10.528, F=15.154, F=15.513, F=16.979, F=4.632, F=14.277, all P<0.05). The MU of the four groups significantly differed (F=4.632, P<0.05), and the difference of V10 on the ipsilateral lung was significant (F= 3.324, P<0.05), the remaining parameters in the four groups had no statistically significant difference. 【Conclusion】 For the left-breast cancer volumetric modulated arc therapy, the smaller of Inc parameter on the plan had better dose distribution and conformity index while the monitor units increased. 40° was not suitable for the breast cancer VMAT plan, and the high amount beyond the range would increase the toxic and side effects on the skin.