Objective:Human papilloma virus(HPV)E6/E7mRNA in situ hybridization detection technology was used to explore whether high-grade squamous intraepithelial lesion(HSIL)of cervix with negative high-risk human papilloma virus(HR-HPV)typing test was caused by HPV infection,so as to provide new insights for the accurate diagnosis and treatment of cervical HSIL.Methods:305 tissue samples were collected from patients with HSIL who underwent cervical biopsy or surgical treatment in the Department of Gynecology,Affiliated Hospital of Shandong Second Medical University,from January 2020 to October2022.Patients with negative HR-HPV genoty-ping results(15 cases)were assigned to the study group,while those with positive results(290 cases)served as the control group.RNAscope in situ hybridization was used to detect the expression of HPV E6/E7 mRNA in the two groups,and the expression of HPV E6/E7 mRNA was analyzed by semi-quantitative scoring of staining inten-sity.Immunohistochemistry(IHC)was used to detect the expression of p16 and Ki-67.Results:①Among 305 pa-tients with HSIL,15 patients had negative HR-HPV typing test,with an incidence of 4.9％(15/305).②73.3％(11/15)of the study group showed positive expression of HPV E6/E7 mRNA,which was statistically significant compared with 100.0％(290/290)of the control group(P＜0.001).③The positive expression rate of p16 in the study group was significantly lower than that in the control group(93.3％vs.100.0％,P=0.049),while there was no significant difference in the positive expression rate of Ki-67 between the two groups(100.0％vs.100.0％).④In the samples with histopathological type cervical intraepithelial neoplasia(CIN)2,the overall score of HPV E6/E7 mRNA in the study group was significantly lower than that in the control group,which was statistically significant(P=0.004).In CIN3 samples,although the overall score of HPV E6/E7 mRNA in the study group was lower than that in the control group,there was no statistically significant difference(P=0.158).Conclusions:4.9％of pa-tients with HSIL in cervical cancer screening may be missed or misdiagnosed due to negative HR-HPV typing test.HPV E6/E7 mRNA in situ hybridization detection technology was helpful to reduce the false negative rate of HR-HPV typing test in HSIL,and it may assist in predicting the progression of cervical lesions,so as to provide a new idea for individualized precise treatment.

Objective:Human papilloma virus(HPV)E6/E7mRNA in situ hybridization detection technology was used to explore whether high-grade squamous intraepithelial lesion(HSIL)of cervix with negative high-risk human papilloma virus(HR-HPV)typing test was caused by HPV infection,so as to provide new insights for the accurate diagnosis and treatment of cervical HSIL.Methods:305 tissue samples were collected from patients with HSIL who underwent cervical biopsy or surgical treatment in the Department of Gynecology,Affiliated Hospital of Shandong Second Medical University,from January 2020 to October2022.Patients with negative HR-HPV genoty-ping results(15 cases)were assigned to the study group,while those with positive results(290 cases)served as the control group.RNAscope in situ hybridization was used to detect the expression of HPV E6/E7 mRNA in the two groups,and the expression of HPV E6/E7 mRNA was analyzed by semi-quantitative scoring of staining inten-sity.Immunohistochemistry(IHC)was used to detect the expression of p16 and Ki-67.Results:①Among 305 pa-tients with HSIL,15 patients had negative HR-HPV typing test,with an incidence of 4.9％(15/305).②73.3％(11/15)of the study group showed positive expression of HPV E6/E7 mRNA,which was statistically significant compared with 100.0％(290/290)of the control group(P＜0.001).③The positive expression rate of p16 in the study group was significantly lower than that in the control group(93.3％vs.100.0％,P=0.049),while there was no significant difference in the positive expression rate of Ki-67 between the two groups(100.0％vs.100.0％).④In the samples with histopathological type cervical intraepithelial neoplasia(CIN)2,the overall score of HPV E6/E7 mRNA in the study group was significantly lower than that in the control group,which was statistically significant(P=0.004).In CIN3 samples,although the overall score of HPV E6/E7 mRNA in the study group was lower than that in the control group,there was no statistically significant difference(P=0.158).Conclusions:4.9％of pa-tients with HSIL in cervical cancer screening may be missed or misdiagnosed due to negative HR-HPV typing test.HPV E6/E7 mRNA in situ hybridization detection technology was helpful to reduce the false negative rate of HR-HPV typing test in HSIL,and it may assist in predicting the progression of cervical lesions,so as to provide a new idea for individualized precise treatment.

Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline; the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.

OBJECTIVE: To analyze the clinical features and prognosis of cervical adenocarcinoma (AC) and adenosquamous carcinoma of cervix (ASC). METHODS: The clinical data of 237 patients, including 201 cases of AC and 36 cases of ASC (FIGO stage ⅠB1-ⅡA), who underwent surgery in Qilu Hospital between September 2007 and September 2016 were reviewed. Clinical features of two groups were compared, and Kaplan-Meier survival analysis was performed to evaluate the prognosis. RESULTS: A larger proportion of ASC patients had lymphovascular space invasion compared with AC patients (<0.01), but no significant differences were observed in the age, FIGO stage, size of tumor, depth of stromal invasion, parametrial invasion, lymphatic metastasis and risk grade between two groups (all >0.05). The 5-year overall survival rates of AC and ASC groups were 79.4% and 78.3%, and the 5-year recurrence-free survival rates were 77.4% and 73.0%. Among patients received concurrent chemoradiotherapy, the 5-year overall survival rates were 71.0% and 61.4%, and the 5-year recurrence-free survival rates were 68.8% abd 61.1%, respectively. No significant differences were observed in 5-year overall survival rates and recurrence-free survival rates between AC and ASC patients (all >0.05). CONCLUSIONS Lymphovascular space invasion was more likely to occur in patients with ASC, but there was no significant difference in the prognosis between AC and ASC patients.
Adenocarcinoma ; diagnosis ; mortality ; Carcinoma, Adenosquamous ; diagnosis ; mortality ; Female ; Humans ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms ; diagnosis ; mortality

Objective To investigate the clinical features and risk factors on outcomes of patients with cardio-renal syndrome (CRS) in surgical intensive care unit (SICU). Methods The clinical data of the patients admitted to SICU of Peking University People's Hospital from January 1st 2017 to December 31st 2017 were analyzed retrospectively, including gender, age, severity of the disease, underlying diseases, type of CRS, precipitating factors of CRS, cardiac and renal function [cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), serum creatinine (SCr), glomerular filtration rate (eGFR)], outcomes [secondary outcomes, duration of mechanical ventilation, the length of ICU stay, the length of hospital stay, 28-day mortality and hospital mortality]. Patients were grouped according to CRS classification or hospitalization prognosis, the clinical features within different CRS types were analyzed, and risk factors on outcomes of the CRS patients were analysed by Logistic regression. Results 86 (7.3%) of the 1 172 patients during the study period had CRS. ①CRS clinical features: CRS 1-5 type patients accounted for 24.4% (21 cases), 1.2% (1 case), 20.9% (18 cases), 1.2% (1 case) and 52.3% (45 cases) respectively, CRS type 1, 3 and 5 were the main types (i.e. acute cardiac and renal dysfunction), while type 5 CRS was the highest (i.e. organ dysfunction caused by simultaneous involvement of cardiac and renal functions secondary to systemic diseases was the most common). Baseline BNP (Z = 11.365, P =0.023), SCr peak (Z = 13.405, P = 0.009) and baseline eGFR (F = 2.648, P = 0.037) were significantly different within the CRS 5 types. The basic cardiac function of type 1 CRS patients was significantly worse than that of type 3 and type 5 CRS patients [baseline BNP (μg/L): 434.2 (187.0, 1 252.0) vs. 154.9 (66.4, 272.5), 268.5 (124.1, 486.6), both P <0.05]. The basic renal function of type 3 CRS patients was significantly worse than that of type 5 CRS patients [baseline eGFR (mL/min): 71.0±30.3 vs. 88.3±29.0, P < 0.05]. The severity of acute kidney injury (AKI) in type 3 CRS patients was significantly higher than that in type 1 and type 5 CRS patients [SCr peak (μmol/L): 285.0 (171.5, 420.6) vs. 143.0 (99.5, 213.5), 189.0 (105.5, 280.5), both P < 0.01]. There were no significant differences in gender, age, department, acute physiology and chronic health evaluationⅡ (APACHEⅡ), intraoperative blood loss, basic cTnI and SCr levels, BNP peak, AKI staging and prognostic indicators among patients with various types of CRS. ② Death risk analysis:43 (50%) of the 86 CRS patients died during the hospital stay. Compared with the survival patients, CRS death patients were older [years old: 72 (57, 80) vs. 62 (50, 73)] and had higher APACHEⅡ score [22 (17, 29) vs. 18 (15, 21)], with higher proportion of cerebrovascular disease (9.3% vs. 0). Regarding to precipitating factors of CRS, sepsis/septic shock (41.9% vs. 18.6%) and surgery stress (9.3% vs. 0) were remarkably increased in death patients. Death patients had higher cTnI and SCr peak [cTnI peak (μg/L): 1.155 (0.192, 5.125) vs. 0.122 (0.045, 0.610), SCr peak (μmol/L): 208 (143, 295) vs. 146 (101, 289)] and also high proportion of AKI stage 3 (41.9% vs. 20.9%), higher rate of secondary infection (67.4% vs. 30.2%), prolonged duration of mechanical ventilation and the length of ICU stay [hours: 179 (61, 470) vs. 37 (7, 134);days: 10 (4, 24) vs. 5 (2, 11)], with statistically significant differences (all P < 0.05). Logistic regression analysis showed that the elderly [odds ratio (OR) = 1.053, 95% confidence interval (95%CI) = 1.003-1.094, P = 0.010], high APACHE Ⅱscore (OR = 1.165, 95%CI = 1.057-1.285, P = 0.002), sepsis/septic shock (OR = 4.561, 95%CI = 1.351-15.391, P = 0.014) and AKI stage 3 (OR = 5.468, 95%CI = 1.457-20.530, P = 0.012) were independent risk factors for hospital death in CRS patients. Conclusions Surgical ICU patients with CRS are characterized by acute cardiac and renal dysfunction. CRS type 5 is the most common and has a high fatality rate. Age, severity of illness, sepsis/septic shock and AKI stage 3 are independent risk factors of death.

Objective The aim of this case-control study is to explore clinical objective variables for diagnosing delirium of intensive care unit (ICU) patients.Methods According to the method of prospective case-control study, critical adult postoperative patients who were transferred to ICU of Peking University People's Hospital from October 2015 to May 2016 and needed mechanical ventilation were included. After evaluating the Richmond agitation sedation scale score (RASS), the patients whose score were -2 or greater were sorted into two groups, delirium and non-delirium, according to the confusion assessment method for the ICU (CAM-ICU). Then these patients were observed by domestic multifunctional detector for electroencephalographic (EEG) variables such as brain lateralization, brain introvert, brain activity, brain energy consumption, focus inward, focus outward, cerebral inhibition, fatigue, sleep severity, sedation index, pain index, anxiety index, fidgety index, stress index and the cerebral blood flow (CBF) index which was named of perfusion index. Other variables including indexes of ICU blood gas analysis, which was consisted of variables of blood gas analysis, routine blood test and biochemistry, previous history and prognostic outcome was recorded. Binary logistic regression was used for multivariate analysis.Results Forty-three postoperative patients, who needed intensive care, were included. Eighteen were in delirium group and twenty-five in control group. Excluding the trauma, variables like gender, age, temperature, heart rate, respiratory rate, mean arterial pressure, acute physiology and chronic health evaluationⅡ(APACHEⅡ) score, organ failure, dementia and emergency surgery didn't show any statistical significance between two groups. The trauma in delirious patients increased obviously compared with the control group (33.3% vs. 4.0%,P = 0.031). Except for the brain activity [122.47 (88.62, 154.21) vs. 89.40 (86.27, 115.97),P = 0.034], there were no statistical differences in any other EEG and CBF variables. In ICU blood gas analysis, only pH value (7.43±0.42 vs. 7.47±0.31,P =0.003), chloride concentration [Cl- (mmol/L): 114.66±4.32 vs. 111.90±3.08,P = 0.019], magnesium concentration [Mg2+ (mmol/L): 0.60±0.10 vs. 0.54±0.06,P = 0.035] and blood osmolality [mmol/L: 290.10 (284.15, 306.35) vs. 282.70 (280.20, 286.75),P = 0.014] were statistically significant. Compared with control group, the prognostic variables in delirium group such as duration of mechanical ventilation [days: 125.0 (49.0, 293.0) vs. 149.5 (32.0, 251.3)], length of stay in ICU [days: 216.5 (50.5, 360.8) vs. 190.0 (72.0, 330.5)] and mortality rate (22.2% vs. 24.0%) didn't appear to be statistically significant either (allP > 0.05). It was shown by multivariate logistic regression analysis that pH [odds ratio (OR) = 1.446, 95% confidence interval (95%CI) = 1.116-1.875,P = 0.005] and Cl- (OR= 0.708, 95%CI =0.531-0.945,P = 0.019) were potential risk factors of delirium.Conclusions The brain activity of HXD_Ⅰ may contribute to the clinical diagnose of delirium, but it still remained to be proved further. The pH and Cl- are potential risk factors of delirium.

Objective To evaluate the difference and correlation between ultrasonic cardiac output monitor (USCOM) and pulse indicated continuous cardiac output (PiCCO) monitor on determination of hemodynamic parameters in critical patients.Methods A prospective observation self-control study was conducted.The critical patients who need hemodynamics monitoring,and admitted to Department of Critical Care Medicine of Peking University People's Hospital from March 2013 to December 2015 were enrolled.Cardiac output (CO),cardiac index (CI),stroke volume (SV),and stroke index (SI) were determined by PiCCO using thermodilution method at immediately (0 hour) and 24 hours after successful location of PiCCO catheter for 3 times then the above indexes were measured with USCOM,and the average values were chosen for statistical analysis.The differences in above parameters between the two methods,and the correlation of the parameters monitored by two methods were evaluated by Pearson linear correlation method,the consistency test was conducted by Bland-Altman method.Results In 31 critical patients enrolled,there were 18 males and 13 females,aging 29-89 years old with the mean of (48.1 ± 36.3) years,body mass of (68.7 ± 17.5) kg,and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score of 21.2 ± 3.1.CO,CI,SV,and SI detected by USCOM were significantly higher than those detected by PiCCO [CO (L/min):6.32 ± 1.98 vs.5.86 ± 1.72,t =4.887,P =0.000;CI (mL· s-1· m-2):61.68 ± 20.17 vs.56.84± 17.34,t =5.189,P =0.000;SV (mL):61.9 ± 19.7 vs.57.0± 16.9,t =3.977,P =0.000;SI (mL/m2):36.84 ± 12.67 vs.33.33 ± 10.79,t =4.278,P =0.000].It was shown by correlation analysis that CO,CI,SV,and SI monitored by USCOM and PiCCO was positively correlated (R2 value was 0.795,0.798,0.837,and 0.827,respectively,all P =0.000).It was shown by Bland-Altman analysis that the mean CO change (ΔCO) from 0 hour to 24 hours was 0.1 L/min,and the 95％ confidence interval was-0.62 to 0.80.Conclusion There was significant difference in the comparison of hemodynamics parameters monitored by USCOM and PiCCO respectively in critical patients,the overall values monitored by USCOM were higher than those monitored by PiCCO monitoring,but the correlations were good.

Objective To evaluate perioperative fluid infusion strategies in retroperitoneal tumor patients.Method Data of 89 retroperitoneal tumor patients in Peking University People's Hospital and Peking University International Hospital were collected and devided into intraoperative minor haemorrhage group (761 ml) and massive haemorrhage group (4 813 ml),including postoperative fluid treatment,input and output volume,serum brain natriuretic peptide level and postoperation complications.Results Fluid input on the 1st day after operation,the 2nd day,the 3rd day respectively were (7 565 ±4 757),(3 869 ± 727),(3 289 ± 897),(3 096 ± 567) ml in the minor haemorrhage group,and (13 927 ± 5 612),(5 192 ± 1 274),(3 786 ± 1 137),(3 797 ± 719) ml in the massive haemorrhage group (t =-4.637,-3.117,-2.460,-2.982,P =0.04,0.048,0.36,0.038).BNP level respectively were (33 ±25),(82 ±66),(116 ± 54),(145 ± 75) ng/ml in the minor haemorrhage;respectively,(70 ± 65),(165 ± 153),(256 ± 220),(442 ± 412) ng/ml in the massive haemorrhage group (t =-4.637,-3.117,-2.460,-2.982,P =0.041,0.038,0.046,0.04).The accumulative percentage of negative fluid balance was 100％ in 3 days after operation.Acute kidney injury (AKI),cardiac,respiratory events,major intraabdominal complications deep venous thrombosis developed in minor and massive haemorrhage group were 4.7％,7.1％,4.7％,14.3％,9.5％ vs.25.1％,27.6％,46.8％,10.6％,17.0％ respectively (x2 =2.89,5.89,19.96,0.044,0.674,P=0.049,0.015,0.001,0.834,0.412).Conclusions Multiple goals directed fluid strategy leads to a better outcome by decreasing the AKI rate.BNP level could be used as a goal marker in fluid treatment.

Objective To investigate the influence of hydroxyethyl starch solution on exogenous coagulation and active protein C (APC) in the patients with septic shock.Methods A single-center prospective study was conducted.Eighty-four consecutive patients with septic shock admitted to intensive care unit (ICU) of Peking University People's Hospital from November 2009 to October 2014 were enrolled.The patients were randomized into two study groups by random digits table:Ringer lactate solution group (RL group,n =40) and hydroxyethyl starch group (HES group,n =44),and Ringer lactate solution or hydroxyethl starch 130/0.4 was used for resuscitation respectively.Peripheral blood was collected at four time points:before resuscitation,6,12,and 24 hours after resuscitation.The prothrombin time (PT),tissue factor (TF),tissue factor pathway inhibitor (TFPI) and APC were determined,and the length of ICU stay and the mortality were recorded.Results There were no significant differences in PT,TF,TFPI,and APC before and after resuscitation in RL group.No change in PT was found after resuscitation in HES group,and no significant difference was found as compared with RL group.TF after resuscitation in HES group was decreased gradually,and the level at the 24 hours after resuscitation was significantly lower than that before resuscitation (U/L:15.80±7.32 vs.31.40±2.75,P ＜ 0.05); but there was no significant difference at all time points when compared with that of RL group (all P ＞ 0.05).TFPI at 12 hours and 24 hours after resuscitation in HES group was increased when compared with before resuscitation (μg/L:1.32±0.22,1.14±0.09 vs.0.63±0.54).TFPI in HES group was significantly higher than that in RL group (μg/L:0.84 ± 0.69,0.95 ± 0.30),but there was no significant differences between two groups (both P ＞ 0.05).APC after resuscitation in HES group was decreased gradually,which was significantly lower than that in RL group at 6,12,24 hours after resuscitation (mg/L:3.38±3.00 vs.5.98±4.12,3.31 ± 1.94 vs.5.33 ± 3.71,3.42 ± 2.64 vs.7.53 ± 4.67,P ＜ 0.05 or P ＜ 0.01).The length of ICU stay in HES group was significantly shorter than that in RL group (days:12.50 ± 8.83 vs.17.10± 16.60,t =9.037,P ＜ 0.001),but there was no significant difference in mortality between HES group and RL group [40.9％ (18/44) vs.60.0％ (24/40),x 2=2.339,P =0.126].Conclusions Both RL and hydroxyethyl starch fluid resuscitation did not affect the PT of the patients.The use of hydroxyethyl starch probably inhibits excessive activation of the exogenous coagulation and hyper-coagulation in the early stage of sepsis,and inhibits activation of protein C as well.

ObjectiveTo investigate the influence of the midazolam sedation based on remifentanil analgesia on the occurrence of delirium in critically ill patients in intensive care unit (ICU).Methods A single-center prospective randomized controlled trial was conducted. 140 consecutive critically ill patients admitted to ICU of Peking University People's Hospital, undergoing mechanical ventilation longer than 24 hours, with the need of sedation, from February 2014 to January 2015 were enrolled. They were randomly divided into two groups by computer generated random numbers table, eachn = 70. The patients in observation group received midazolam 1μg·kg-1·min-1 for sedation, and 1 mg/mL remifentanil for analgesia with 0.05 mg/kg intravenous bolus, then continuous infusion of 0.02-0.10 mg·kg-1·h-1. The patients in control group received midazolam for sedation only. The data were recorded as follows: the main indices for observation included the occurrence of delirium and its duration; the second item for observation was consumption of drug for sedation, followed by the mean arterial pressure (MAP) before and after sedation, the time of wake-up, duration of mechanical ventilation, the length of ICU stay, and 28-day fatality rate. The 28-day survival was analyzed by Kaplan-Meier survival curve.Results The dosage of remifentanil used in observation group was (98.6±24.9) mg/d, the dosage of midazolam was significantly lower than that of the control group (mg/d: 160.6±33.3 vs. 178.9±43.4, t = 2.829,P = 0.005), the incidence of delirium was obviously lower than that of the control group [22.9% (16/70) vs. 57.1% (40/70),χ2 = 15.700,P< 0.001], and the time of delirium was slightly shorter than that of the control group (hours: 162.9±78.0 vs. 194.8±117.3,t = 0.947,P = 0.348). Among the patients with delirium, the dosage of dexmedetomidine used in observation group was significantly less than that of the control group (mg/d: 0.54±0.11 vs. 0.64±0.14,t = 2.112,P = 0.041). The MAP before sedation was similar as the MAP after sedation in both groups, and there was no significant difference between observation group and control group [mmHg (1 mmHg = 0.133 kPa), before treatment: 84.7±16.2 vs. 89.5±37.7, after treatment: 82.3±10.7 vs. 80.8±13.9, bothP> 0.05]. There was no significant difference in the time of waking-up between observation group and control group (hours: 2.3±0.9 vs. 2.4±0.8,t = 0.487,P = 0.627). The duration of mechanical ventilation (hours: 143.4±138.3 vs. 163.9±158.9, t = 0.812,P = 0.418), the length of ICU stay (days: 8.8±7.7 vs. 10.0±7.8,t = 0.917,P = 0.361) and 28-day fatality rate [11.4% (8/70) vs. 20.0% (14/70),χ2 = 1.941,P = 0.245] in observation group were slightly lower than those of the control group without significant difference. Kaplan-Meier survival curve showed that the cumulative 28-day survival rate in observation group was slightly higher than that of control group (χ2 = 1.647,P = 0.199). ConclusionAnalgesia based on sedation may reduce the occurrence of delirium and its severity, furthermore, even if delirium occurs, it may be less severe.