[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Comparative study of next generation sequencing and immunohistochemistry on molecular classification of endometrial carcinoma].

Objective: To investigate the differences in molecular classification of endometrial carcinoma (EC) between various technical methods and to explore molecular classification schemes suitable for Chinese population. Methods: The study used a comprehensive scheme of next generation sequencing (NGS) and immunohistochemistry for molecular classification of 254 EC cases that were obtained at Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from April 2021 to March 2022. According to the recommended threshold of Sanger sequencing which was approximate-20% variant allele fraction (VAF), NGS data were extracted to simulate the results of Sanger sequencing. Results: The 254 EC patients had a mean age of 51 years (range, 24 to 89 years). Combination of POLE (9-14 exons), TP53 total exons and microsatellite instability (MSI) detection was a better single scheme than NGS alone, while combination of MSI fragment analysis and conventional immunohistochemistry was the best solution and seemed best aligned with TCGA data and recent studies. POLE ultramuted type, mismatch repair defect type, TP53 mutant type and non-specific molecular characteristic type accounted for 11.4% (29/254), 31.5% (80/254), 22.4% (57/254) and 34.6% (88/254) of the cases, respectively. If Sanger sequencing was adopted for POLE and TP53 detection, the frequencies of these EC types were 9.1% (23/254), 31.5% (80/254), 12.9% (33/254) and 46.6% (118/254), respectively, with greatly increasing non-specific molecular characteristics cases. If POLE was detected by Sanger sequencing and others by immunohistochemistry, they were 9.1% (23/254), 42.2% (92/218), 13.8% (35/254) and 40.9% (105/254), respectively, with increasing the false positive rates of the mismatch repair defect group. Conclusions: Small and medium-sized NGS panels with MSI detection is a better solution than NGS alone. Sanger sequencing is currently available for POLE mutation detection, which is not sensitive enough for TP53 mutation detection, and seems equivalent to the efficiency of TP53 by immunohistochemistry. Further optimization of small and medium-sized NGS panels covering MSI detection and POLE and TP53 full exons may be the best choice for the future to meet national conditions.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

[Relationship of operation manner and postoperative recurrence of hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) owns the high morbidity and mortality rates. Surgical resection is still the major pathway for the longer survival of HCC patients. Postoperative recurrence and metastasis have become the key impairment of prognosis of HCC patients. The relationship between tumor recurrence and surgical manner underwent by HCC patients is complicated and multiple factors are included. When the liver tumor was pressured during operation, tumor cells could be squeezed into blood flow via the broken vessels, which resulted in tumor metastasis. Besides, ischemia-reperfusion injury induced by Pringle maneuver during the liver blood blockade resulted in the immune destruction of liver and induced tumor recurrence.The destruction of physical barriers consisted of interstitial cells and normal liver cells was also a key factor for tumor recurrence. This paper summarizes the possible relationship between postoperative recurrence and surgical manner in HCC patients to provide the preventive suggestions for the postoperative recurrence of HCC patients.

[Angiopoietin-2 regulates vessels encapsulated by tumor clusters positive hepatocellular carcinoma nest-type metastasis via integrin α5ß1].

Objective: To investigate the molecular mechanism of nest metastasis in blood vessels encapsulated by tumor clusters (VETC) positive hepatocellular carcinoma (HCC). Methods: A total of 72 paraffin embedded HCC tissue samples were collected. Immunohistochemistry staining with CD34 (vascular endothelial cell marker protein) was used to observe the morphological manifestations of VETC cancer nests in primary tumors, bile duct cancerous thrombi and portal vein cancerous thrombi, and to study the characteristics of hematogenous metastasis of VETC cancer nests. Bioinformatics was used to predict the key proteins closely related to VETC cancer nest formation. Immunohistochemistry was used to detect the expression of angiogenin-2 (Ang-2), integrin α5, Integrin ß1, and cyclooxygenase-2 (COX-2) proteins in HCC. Transwell cell migration assay was used to detect the effect of Ang-2/integrin α5ß1 protein on the migration ability of endothelial cells and HCC cells. Western blotting was used to detect the effect of Ang-2/integrin α5ß1 protein on the activity of focal adhesion kinase (FAK) protein. Results: Of the collected HCC specimens, 27 cases (27/72) were VETC (+), including 3 cases with biliary duct cancerous thrombus, 5 cases with portal vein cancerous thrombus, and 3 cases with both biliary duct cancerous thrombus and portal vein cancerous thrombus. VETC (+) HCC could metastasize to portal vein, bile duct, and liver in the form of cancer nest, and the nests retain their intact structure. Ang-2, integrin α5 and integrin ß1 were overexpressed in tumor cells and endothelial cells of VETC (+) HCC nests, while COX-2 was only overexpressed in tumor cells of VETC (+) HCC nest. Ang-2 could promote the migration of HCC cell [(121±12) vs (186±11), P<0.01] and endothelial cells [(81±7) vs (163±14), P<0.01]. Integrin α5ß1 activation antagonist ATN-161 could significantly block the ability of Ang-2 to promote the migration of HCC cells [(185±10) vs (135±9), P<0.05] and endothelial cells [(156±14) vs (103±6), P<0.05]. ATN-161 could significantly block the phosphorylation of FAK in HCC and endothelial cells induced by Ang-2. Conclusions: VETC (+) HCC could metastasize as a whole in a nested form, and possesses a specific regulatory protein. Ang-2/α5ß1/FAK might be potential protein targets in the treatment of VETC (+) HCC nest-type metastasis.

[Research progress in the Hepatobiliary Surgery operation of hepatic hilar plate system].

An estimate of about 50% of new liver cancer cases worldwide occur in China every year.Surgical resection is still the major treatment choice for longer survival of patients with hepatocellular carcinoma. Blocking hepatic blood flow and reducing intraoperative bleeding ensure the success of the operation. Anatomic separation of hepatic hilar region is the precondition of hepatic inflow occlusion. The hepatic hilar plate system involves a thick layer of connective tissue covering the hepatic inflow ducts of hepatic hilar region. The descending part of hilar plate assists in reducing the anatomical difficulty of the hepatic hilar region. The "forth porta hepatis" that is hidden in the hepatic hilar plate system involves the accumulation area of "short hepatic portal veins" .The communicating branch vessels between the hepatic inflow vessels form the anatomical basis in reducing the indocyanine green fluorescence stain effect.The relatively fixed position of the hepatic portal plate is considered as a positioning marker for accurate liver resection. The intrahepatic Glisson sheath is connected with thick connective tissue of the hepatic portal panel system, and is regarded as the physical barrier in limiting the proliferation and hypertrophy of hepatocytes and continuation of hepatic portal panel system in the liver.This paper summarizes the anatomy and application of hepatic hilar plate system during hepatobiliary surgery.

A survey of psychiatrists' and registered nurses' levels of mental health literacy in a Chinese general hospital.

BACKGROUND: Mental health literacy (MHL) is the term used to describe people's knowledge and beliefs about mental disorders which aid in the recognition, management or the prevention of illness. Health professionals' levels of MHL will shape the therapeutic relationship in which they work in partnership with patients. Studies have been conducted in Australia and Singapore to determine levels of MHL among members of the general public and health professionals. To date, no such studies have been published in Chinese populations. AIM: The study aims to compare levels of MHL between registered nurses and psychiatrists in a Chinese general hospital. The paper reports participants' diagnosis and beliefs about interventions used to manage depression and schizophrenia. METHODS: A descriptive cross-sectional survey was undertaken among a group of psychiatrists and registered nurses in the psychiatric department of one large teaching hospital in China (n=70). Participants completed the survey by rating written vignettes related to depression and schizophrenia. RESULTS: The psychiatrists were highly accurate in correctly diagnosing both depression and schizophrenia; the registered nurses were less so for diagnosing depression. In terms of treatment options, the two groups reached a broad agreement on beliefs about the use of mental health interventions, but differed significantly in the use of some specific mental health interventions. CONCLUSIONS: This study provides preliminary information about levels of MHL among Chinese mental health professionals and describes their attitudes towards the helpfulness of interventions used to restore mental health and well-being. Future large-scale studies are required to identify factors that influence beliefs about the use of mental health interventions. The findings have implications for further education of registered nurses in the specialization of mental health nursing in China.

Characterization and partial genome sequence analysis of Clostera anachoreta granulovirus.

The morphological and biological properties as well as partial genomic sequencing of a granulovirus isolated from Clostera anachoreta (Lepidoptera: Notodontidae), C. anachoreta granulovirus (ClanGV), were carried out. The ovoidal occlusion bodies were 337 nm x 170 nm in size, and each granule contained one single rod-shape virion, with a mean size of 250 nm x 46 nm. Granulin had a molecular weight of approximately 30 kDa. ClanGV genome size was estimated as 104.34 kb based on the restriction fragments. The restriction pattern of the ClanGV genome was different from other GVs. A restriction fragment genomic library of ClanGV genome was constructed. The library consisted of nine SalI fragments, seven HindIII fragments and seven EcoRI fragments. One 4.8 kb fragment of the genome, digested by SalI, was sequenced and analyzed. This region was composed of eight unknown ORFs, two baculoviruses homologous gene (vp1054 and lef10) and partial sequence of lef-8. The unknown ORFs included three unique to ClanGV, the other five ORFs were related to baculoviruses. The ORFs, located within this restriction fragment, were compared to homologues in other GVs. The results indicated that ClanGV, CpGV, ClGV, AoGV and PoGV had similar arrangement and orientation of the homologous ORFs. Phylogenetic analysis of VP1054 proteins from 20 baculoviruses indicated that ClanGV was more closely related to CpGV, ClGV, AoGV and PoGV than to other baculoviruses.