OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists （TPO-RA） approved in China， providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection， Eltrombopag olamine tablets， Herombopag olamine tablets， Avatrombopag maleate tablets， and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions （Second Edition）， 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions： pharmacological characteristics， efficacy， safety， cost-effectiveness， and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points， with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative， the overall rankings of the five TPO-RA were as follows： Lusutrombopag tablets （75.50 points）， Eltrombopag olamine tablets （75.10 points）， Avatrombopag maleate tablets （70.40 points）， Romiplostim for injection （63.93 points）， and Herombopag olamine tablets （63.52 points）. Lusutrombopag tablets scored relatively high in pharmacological characteristics， safety， and cost-effectiveness， while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value， with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores， these two drugs should be prioritized in drug selection and formula optimization by medical institutions.

Objective:To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL.Methods:53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis.Results:The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different ( P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom′s macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions:Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.

Objective:To investigate the application value of triangular modal construed for planning approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients who underwent local laparoscopic resection of liver tumors located in superior part of central liver lobe at the Affiliated Hospital of Qingdao University from January to June 2020 were collected. There were 6 males and 4 females, aged from 41 to 63 years, with a median age of 54 years. Preoperative triangular model was constructed for all patients to plan approach of laparoscopic local resection of liver tumors located in superior part of central liver lobe. Observation indicators: (1) preoperative general situations of patients; (2) surgical situations; (3) follow-up. Follow-up was conducted by outpatient examination or telephone interview to detect tumor recurrence and survival of patients up to February 2021. Measurement data with normal distribution were expressed as Mean± SD. Count data were expressed was absolute numbers. Results:(1) Preoperative general situations of patients: hepatocellular carcinoma was found in 7 cases, inthahepatic cholangiocarcinoma was found in 2 cases and ovarian cancer with liver metastasis was found in 1 case. Three cases had tumors located in S4a segment, 2 cases had tumors located in ventral subsegment of S8 segment, 2 cases had tumors located in dorsal subsegment of S8 segment, and 3 cases had tumors across the ventral segment of S4a+S8. The diameter of tumors was (3.4±1.0)cm. (2) Surgical situation: all the 10 patients underwent R 0 resection successfully, with no intraoperative blood transfusion or conversion to open surgery. The operation time of 10 patients was (149±59)minutes, the volume of intraoperative blood loss was (294±163)mL, the minimum surgical margin of specimen was (1.1±0.2)cm. The alanine aminotransferase was (324±151)U/L on the postoperative first day, the aspartic aminotransferase was (401±113)U/L on the postoperative first day, and the duration of postoperative hospital stay was (9±4)days. No bile leakage, hemorr-hage, reoperation or other complications occurred in all patients. (3) Follow-up: 10 patients were followed up for 7?13 months, with a median follow-up time of 11 months. All patients had no margin recurrence or distant metastasis. Conclusion:It is safe and feasible to construct triangular modal for planning approach of local laparoscopic resection of liver tumors located in superior part of central liver lobe.

Objective:To explore the value of FibroScan in liver grafts from brain-dead donors (DBD) prior to liver transplantation (LT).Methods:Liver grafts from 52 DBD were examined using ultrasound and FibroScan before LT. The causes of death were cerebral hemorrhage ( n=25), brain trauma ( n=21) and ischemic-hypoxic cerebropathy ( n=6). Blood samples were tested before LT and a biopsy was performed pre- or intra-operation for determining pathology. The diagnostic accuracy of FibroScan results was compared with that of pathological examinations. The latter is a gold standard for evaluating liver grafts. The eligible donors were grouped by stage of liver fibrosis (F0-F4) and steatosis (S0-S3) based upon Kleiner's scoring system of nonalcoholic fatty liver disease. Results:The value of liver stiffness (LS) significantly rose in group F1 as compared with group F0 (8.74±1.32) kPa and (5.93±1.64) kPa respectively ( P<0.01). The value of LS had a significantly positive correlation with liver graft fibrosis stage ( r=0.73, P<0.01). The area under receiver operating characteristic curve (AUROC) was 0.93 for F1 stage fibrosis ( P<0.01). Significant differences existed in controlled attenuation parameter (CAP) among groups S0, S1 and S2 (173.30±38.36), (230.29±23.27) and (250.00±57.01) dB/m respectively ( F=12.41, P<0.01). CAP was correlated with liver graft steatosis stage ( r=0.64, P<0.01). And AUROC for S1/S2 stage steatosis in liver grafts was 0.89 ( P=0.002) and 0.83 ( P=0.007) respectively. Conclusions:With a high diagnostic accuracy, FibroScan quantifies fibrosis and steatosis in liver grafts from DBD and provides further imaging evidence for assessing liver grafts.

Objective: To retrospectively analyze the differential diagnosis and treatment strategy of neonatal intestinal perforation caused by neonatal necrotizing enterocolitis (NEC) and Hirschsprung′s disease (HD). Methods: The clinical data of 42 cases with NEC and 22 cases with HD combined with intestinal perforation from Ja-nuary 2012 to January 2017 admitted at Fujian Provincial Maternity and Children′s Hospital were collected, the proportion of premature infants, and the proportion of low birth weight infants, age of onset, preoperative clinical symptoms and surgical treatment was compared between the two groups. Results: The proportion of premature infants[95.23%(40/42 cases) vs.27.27%(6/22 cases)], the proportion of low birth weight infant[90.48%(38/42 cases) vs.45.45%(10/22 cases)]and the age of onset [(14.48± 10.51) d vs.(3.18±3.43) d]were statistically different between the NEC group and the HD group, and the differences were statistically significant(all P<0.05). There were significant differences in the presence of normal defecation before the operation[71.4% (30/42 cases)vs.27.3%(6/22 cases)], and in the the defecation characteristics at the onset[95.2% (40/42 cases)vs.9.1%(2/22 cases)]between the NEC group and HD group(all P<0.05). Among 42 cases of NEC patients, 8 cases underwent intestinal anastomosis, and 34 cases underwent enterostomy because of the high risk of anastomosis.All of 22 patients with HD underwent double-lumen enterostomy. Conclusions The general conditions, preoperative manifestations and intraoperative fin-dings of the children should be comprehensively analyzed for identification.Enterostomy is recommended for NEC intestinal perforation, but if the risk of anastomosis is high, then fistula should be performed.Double-lumen fistula should be recommended for HD intestinal perforation, and enterostomy should be recommended if the two cannot be clearly distinguished.

Objective To investigate the application value of contrast enhanced ultrasound (CEUS) for postoperative monitoring after split liver transplantation. Methods Ten recipients undergoing split liver transplantation received conventional two-dimensional ultrasonography, color Doppler ultrasound (CDU) and CEUS. Clinical prognosis of 10 recipients undergoing split liver transplantation was summarized. The findings of postoperative conventional two-dimensional ultrasonography, CDU and CEUS were analyzed. Results Among 10 recipients, 8 cases obtained favorable clinical prognosis, one died from the recurrence and metastasis of malignant tumors and multiple organ failure, and one died from sudden cardiac arrest. CDU detected the hepatic artery in 8 of 10 recipients(80%). CEUS revealed hepatic artery embolism in one recipient and normal hepatic artery in the other case. Conventional two-dimensional ultrasonography demonstrated abnormality of the hepatic parenchyma in 5 recipients including hyperecho in S5 segment in 1 case, hypoecho in S7 segment in 1 case, hyperecho in S4 segment in 1 case, hypoecho followed by hyperecho in S5 and S6 segments in 1 case and multiple hypoecho and slight hyperecho in 1 case. CEUS revealed significant asynchrony in the microcirculation blood perfusion between the normal and abnormal echo regions, manifested with imaging features of early perfusion and early regression, which was considered to be associated with hepatic venous back-flow obstruction. Evident asynchrony in microcirculation blood perfusion between the normal and abnormal echo regions was observed in 1 case, manifested with the imaging features of early perfusion and synchronous regression,suggesting that congestion and edema on the hepatic resection surface caused by hepatic venous back-flow obstruction and myocardial infarction. Multiple intrahepatic abnormal blood perfusion region of 'fast-in and fast-out' echo was noted in 1 case, which was probably correlated with postoperative recurrence of malignant tumors. Conclusions CEUS is an effective supplement of conventional two-dimensional ultrasonography and CDU for postoperative monitoring after split liver transplantation, which contributes to understanding of hepatic blood flow and blood perfusion and identifying early postoperative complications after split liver transplantation.

Objective To study the impact of splenectomy and esophagogastric devascularization on the nutritional status of patients with cirrhosis and portal hypertension.Methods Sixty consecutive patients with cirrhosis and portal hypertension who underwent splenectomy and esophagogastric devascularization at the Beijing YouAn Hospital from April 5,2015 to January 23,2017 were included in this study.The body mass index (BMI),albumin (Alb),prealbumin (PA) and lymphocyte counts were prospectively collected at the end of 1-week,1-month,3-month,6-month and 1-year after surgery.The postoperative results were compared with the preoperative results in these patients.Results The BMI results obtained at 1-week and 1-month after surgery were significantly lower than the preoperative level [(22.14 ± 3.08)kg/m2 vs.(22.85 ± 3.14) kg/m2,(21.72 ± 3.05) kg/m2 vs.(22.86 ± 3.16) kg/m2,P ＜ 0.05].The BMI result at the end of 1-year after surgery was significantly elevated when compared with the preoperative level [(23.24 ± 3.64) kg/m2 vs.(22.68 ± 3.47) kg/m2,P ＜ 0.05].The ALB levels at 1-month and 3-month after surgery were significantly higher than the preoperative level [(39.87 ± 4.22)g/L vs.(35.35 ±5.15) g/L,(39.35 ± 4.75) g/L vs.(34.82 ± 5.50) g/L,P ＜ 0.05].The PA obtained at 1-week after surgery was significantly lower than the preoperative levels [(79.59 26.52)mg/L vs.(121.77 ±39.96)mg/L,P ＜ 0.05].The lymphocyte counts at all the points after surgery were significantly higher than the preoperative level (P ＜ 0.05).Conclusion Short term and long term nutritional status improved in patients with cirrhosis and portal hypertension after splenectomy and esophagogastric devascularization.

Objective To analyze the law of the mid﹣term hepatic hemodynamics after liver transplantation and to investigate its relationship with liver function. Methods A total of 56 recipients underwent liver transplantation in the Affiliated Hospital of Qingdao University from February 2014 to October 2015 were studied,and divided into normal group (n =24)and abnormal group (n =32)according to the liver function.General information and liver function of both groups were recorded.Furthermore,hepatic artery peak velocity (HAP),portal vein peak velocity (PVP)and portal vein flow (PVF)before the liver transplantation and on postoperative day 1,30 and 90 were measured through ultrasonic detection;hepatic arterial buffer capacity (BC)and adjustment BC were calculated.The univariable and multivariable analysis were performed to analyze the relationship between hepatic hemodynamics and liver function in two groups,and the receiver operating curve (ROC)was drawn. Results The PVP and PVF on postoperative day 30 in abnormal group were significantly higher than those of normal group (P =0.014,0.049).The BC and adjustment BC in normal group were significantly higher than those of abnormal group (P =0.048,0.011).The multivariable analysis showed that adjustment BC was the independent risk factor (P =0.047),with the area under the curve (AUC)of ROC of 0.705,sensitivity of 0.652 and specificity of 0.750. Conclusions PVP,PVF,BC and adjustment BC on postoperative day 30 may be related to abnormal liver function,of which adjustment BC can be used as one of the indicators for diagnosis and intervention of abnormal liver function.

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Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adult ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; surgery ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diagnosis, Differential ; Electrosurgery ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; Keratin-7 ; metabolism ; Mesonephros ; metabolism ; pathology ; surgery ; Neprilysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology