[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

[Single-cell RNA sequencing deciphers transcriptional profiles of hepatocytes in mouse with hepatic alveolar echinococcosis].

OBJECTIVE: To investigate the cell composition and the transcriptional characteristics in microenvironments of hepatic tissues in mice at late stage of Echinococcus multilocularis infection at a single-cell level. METHODS: Peri-lesion and paired distal hepatic specimens were collected from two BALB/c mice (6 to 8 weeks old) infected with E. multilocularis for single-cell RNA sequencing. The Seurat package in the R software was employed for quality control of data, multi-sample integration and correction of batch effects, and uniform manifold approximation and projection (UMAP) algorithm was used for cell clustering. Cell types were annotated using classical marker genes. Differentially expressed genes were screened in each cell type through differential gene expression analysis, and the biological roles of cells were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: A total of 43 710 cells from peri-lesion and distal hepatic tissues of E. multilocularis-infected mice were analyzed, and were classified into 11 cell types, including neutrophils, T cells, macrophages, granulocyte-monocyte progenitor cells, B cells, plasma cells, basophils, hepatic stellate cells, endothelial cells, hepatocytes, and platelets. T cells were the largest population of immune cells in the microenvironment of hepatic tissues, including five CD4+ T cell subsets, two CD8+ T cell subsets and phosphoantigen-reactive γδT cells. The proportions of CD4+ helper T cells and cytotoxic CD4+ T cells decreased and the proportion of T helper 2 (Th2) cells increased in peri-lesion tissues relative to distal hepatic tissues. In addition, the differentially expressed genes in Th2 cells were associated with negative regulation of the immune system, and the highly expressed genes in cytotoxic CD4+ T cells correlated with activation of the immune system. CONCLUSIONS: Single-cell RNA sequencing deciphers the cell composition and distribution in microenvironments of hepatic tissues from mice infected with E. multilocularis, and the increased proportion of Th2 cells in peri-lesion hepatic tissues may be associated with formation of immunosuppressive microenvironments.

[Analysis of prognosis and related factors in oldest-old patients with left-side or right-side colon cancer after hemicolectomy].

Objective: This study aimed to explore the difference of prognosis in oldest-old colon cancer patients between the left-side and right-side hemicolectomy. Methods: A total of 238 oldest-old (≥75 years old) colon cancer patients who received surgical treatment in Gastrointestinal Surgery Department of Beijing Hospital from December 2010 to December 2020 were retrospectively collected. They were divided into right-side hemicolectomy (RCC) group (130 cases) and left-side hemicolectomy (LCC) group (108 cases) by surgical methods. The difference in postoperative short-term complications and long-term prognosis was compared between the two groups, and the related factors of postoperative death was analyzed using multivariate Cox regression model. Results: The age of 238 oldest-old patients with colon cancer ranged from 75 to 93 years old (80.5±3.7). There were 128 males and 110 females. The ages of patients in the LCC group and RCC group were (80.4±3.7) and (80.6±3.7) years old (P=0.699), respectively. There was no significant difference in gender, body mass index (BMI) and co-existing chronic diseases between two groups (P>0.05). The proportion of the duration of surgery exceeding 170 min in the LCC group was significantly higher than that in the RCC group (56.5% vs 43.1%, P=0.039). The incidence of postoperative short-term complications in RCC group was slightly higher than LCC group (P>0.05), and there was no significant difference in overall survival (OS), tumor-specific survival (CSS) and disease-free survival (DFS) between two groups. However, the two groups had different prognostic risk factors, pathological Ⅳ stage (HR=28.970,95%CI:1.768-474.813,P=0.018), intraoperative bleeding (HR=2.297,95%CI:1.351-3.907,P=0.002) and cancer nodules (HR=2.044,95%CI:1.047-3.989,P=0.036) were independent prognostic risk factors in LCC group. Underweight (HR=0.428,95%CI:0.192-0.955,P=0.038), overweight(HR=0.316,95%CI:0.125-0.800,P=0.015),obesity (HR=0.211,95%CI:0.067-0.658,P=0.007), lymph node metastasis (HR=2.682,95%CI:1.497-4.807,P=0.001), tumor nodule (HR=2.507,95%CI:1.301-4.831,P=0.027) and postoperative length of stay of 9 days (HR=1.829,95%CI:1.070-3.128,P=0.006) were independent risk factors for poor prognosis in RCC group. Conclusions: The duration of surgery of oldest-old colon cancer patients in the LCC group was longer than that in the RCC group. However, there was no significant difference in the incidence of postoperative complications between the two groups. High pathological stage, more intraoperative bleeding and cancer nodules were independent prognostic risk factors in the LCC group. Abnormal BMI, lymph node metastasis, cancer nodules and postoperative length of stay were independent risk factors for poor prognosis in the RCC group.

Brown goat yogurt: Metabolomics, peptidomics, and sensory changes during production.

Brown goat milk products have gained popularity for their unique taste and flavor. The emergence of chain-reversal phenomenon makes the design and development of goat milk products gradually tend to a consumer-oriented model. However, the precise mechanism of how browning and fermentation process causes characteristics is not clear. In an effort to understand how the treatments potentially lead to certain metabolite profile changes in goat milk, comprehensive, quantitative metabolomics and peptidomics analysis of goat milk samples after browning and fermentation were undertaken. An intelligent hybrid z-score standardization-principal components algorithm-multimodal denoizing autoencoder was used for feature fusion and hidden layer fusion in high-dimensional variable space. The fermentation process significantly improved the flavor of brown goat yogurt through the tricarboxylic acid-urea-glycolysis composite pathway. Bitter peptides HPFLEWAR, PPGLPDKY, and PPPPPKK have strong interactions with both putative dipeptidyl peptidase IV and angiotensin-converting enzyme, proving that brown goat yogurt can be considered as effective provider of potential putative dipeptidyl peptidase IV and angiotensin-converting enzyme inhibitors. The level of health-promoting bioactive components and sensory contributed to consumer selection. The proposed multimodal data integrative analysis platform was applicable to explain the effect of the dynamic changes of metabolites and peptides on consumer preferences.

[Clinical and genetic studies of a family with hereditary angioedema].

Objective: To diagnose a large family of patients with hereditary angioedema, and to study its inheritance pattern and gene locus. Methods: A retrospective analysis was carried out from August 2021 to February 2022 in a proband (female, 48 years old) and 12 family members who underwent medical history collection and laboratory examinations in the Department of Otorhinolaryngology and Head and Neck Surgery, the Second Hospital of Shanxi Medical University. The clinical data of members and non-affected members [including 7 males and 5 females, aged 12-78 (median 24) years old], were drawn a family map while confirming the diagnosis. Whole exome sequencing technology was used to detect the genetic sequence of the proband and to verify its family members to map the genetic pedigree of the mutation. Results: The inheritance pattern of the family was autosomal dominant, and 8 members of the family were diagnosed with hereditary angioedema by laboratory examination, including 7 cases of type I and 1 case of type Ⅱ. Whole exome sequencing analysis was performed on 2 patients with 2 phenotypes, and it was found that they both carried the same pathogenic mutation locus, which was c.890-2A>G. The family members were verified by next-generation sequencing, and it was found that all members of the family who had a history of edema contained this mutation site, while the younger brother of the proband who had no history of edema did not have this mutation. Conclusion: Both type Ⅰ and type Ⅱ phenotypes are present in this hereditary angioedema family, and the mutation of SERPING1 gene c.890-2A>G causes the onset of each patient in this family.

[Cardiometabolic disease patterns among elderly patients with colorectal cancer in China].

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

Long non-coding RNAs and small nucleolar RNA host gene 6 contribute to the depression-like behavior of hypothyroid mice by promoting methylation of the brain-derived neuropathic factor promoter that is mediated by DNA methyltransferase 1.

Long non-coding RNAs (lncRNAs) and small nucleolar RNA host gene 6 (SNHG6) have attracted extensive attention due to their involvement in various pathological processes. However, the functional role of lncRNA SNHG6 in depression-like behavior induced by hypothyroidism is still largely unknown. Our study was designed to explore the biological role of lncRNA SNHG6 in depression-like behavior induced by hypothyroidism and the underlying mechanisms. First, the depression-like behavior of hypothyroid mice was investigated after lncRNA SNHG6 knockdown. Subsequently, the regulation of the methylation levels of the brain-derived neurotrophic factor (BDNF) promoters by lncRNA SNHG6 was evaluated. To reveal the underlying mechanisms of lncRNA SNHG6 in the methylation of the BDNF promoters, RNA pull-down assays, RNA immunoprecipitation, and co-immunoprecipitation were performed. Further experiments were also conducted to investigate the roles of DNA (cytosine-5)-methyltransferase 1 (DNMT1) in the depression-like behavior induced by hypothyroidism. In this study, elevated levels of lncRNA SNHG6 were noted in the hippocampus in hypothyroid mice. Function assays proved that lncRNA SNHG6 knockdown alleviated the depression-like behavior induced by hypothyroidism. Furthermore, a mechanistic investigation validated that lncRNA SNHG6 stabilized DNMT1 by blocking UHRF1-mediated DNMT1 ubiquitination, which increased the methylation levels of the BDNF promoters. Moreover, DNMT1 was found to be involved in depression-like behavior in hypothyroid mice. Our findings revealed a novel mechanism by which lncRNA SNHG6 promotes the methylation levels of the BDNF promoters by stabilizing DNMT1 and sheds light on potential therapeutic strategies for depression-like behavior induced by hypothyroidism.

[Clinical features and survival analysis in non-M(3) acute myeloid leukemia patients with ASXL1 gene mutation].

Objective: To examine the survival rates and clinical characteristics of people with newly discovered non-M(3) acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods: From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M(3) AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results: ① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1(+)) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1(-)) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1(-) patients, while complete response after the first round of treatment (CR(1)) was lower (P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1(+) patients were higher than those in ASXL1(-) patients (P<0.05) . In the young group, the WBC of ASXL1(+) patients was higher than that of ASXL1(-) patients (z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related (P=0.018, r=0.34) . In ASXL1(+) patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients (P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1(+) patients were shorter than those of ASXL1(-) patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1(+) patients, according to multivariate analysis (P<0.05) . Conclusion: ASXL1-mutated non-M(3) AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR(1) rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.

[Clinical study of dienogest in the treatment of refractory endometriosis-associated pain].

Objective: To evaluate the efficacy and safety of dienogest (DNG) in the treatment of refractory endometriosis-associated pain (REAP). Methods: In this study, REAP was defined according to the following criteria: (1) the pain duration was ≥12 months and visual analogue scale (VAS)≥60 mm; (2) the previous treatments with over two medicines like oral contraceptives and levonorgestrel-releasing intrauterine system failed to achieve satisfactory relief of pain, with VAS reduction less than 50%; with gonadotropin-releasing hormone agonist or mifepristone, the pain could be controlled temporarily, but it recurred after discontinuation of medicines; (3) the pain could not be relieved by surgery or even repeated surgeries. In the present study, 48 patients with REAP were treated with DNG 2 mg/day orally and the clinical outcomes were retrospectively analyzed. The VAS scores, levels of CA125, estradiol, FSH, LH and changes in the size of endometriotic lesions before and after treatment were compared respectively. The side effects were also analyzed. Results: The average duration of DNG treatment was (20.1±12.8) months. After 3 months of medication, the VAS score was significantly reduced from (77.9±15.8) mm to (20.8±10.7) mm (P<0.01), and CA125 level was significantly reduced from (95±139) kU/L to (38±45) kU/L (P<0.05). The effects were maintained with continuation of DNG treatment. Endometriotic lesions tended to shrink, after 12 months of DNG treatment, the size of ovarian endometriomas was reduced significantly from (3.1±1.0) cm to (1.9±1.2) cm (P<0.05). The mean level of estradiol was maintained at 124.82-221.04 pmol/L and levels of FSH and LH did not change significantly during the treatment. The major side effect was irregular bleeding (75%, 36/48). Conclusions: DNG could effectively relieve REAP and is a well-tolerated therapy. It may supply an alternative option for patients with REAP.

Silk-elastinlike copolymers enhance bioaccumulation of semisynthetic glycosaminoglycan ethers for prevention of radiation induced proctitis.

Radiation-induced proctitis (RIP) is a debilitating adverse event that occurs commonly during lower abdominal radiotherapy. The lack of prophylactic treatment strategies leads to diminished patient quality of life, disruption of radiotherapy schedules, and limitation of radiotherapy efficacy due to dose-limiting toxicities. Semisynthetic glycosaminoglycan ethers (SAGE) demonstrate protective effects from RIP. However, low residence time in the rectal tissue limits their utility. We investigated controlled delivery of GM-0111, a SAGE analogue with demonstrated efficacy against RIP, using a series of temperature-responsive polymers to compare how distinct phase change behaviors, mechanical properties and release kinetics influence rectal bioaccumulation. Poly(lactic acid)-co-(glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid)-co-(glycolic acid) copolymers underwent macroscopic phase separation, expelling >50% of drug during gelation. Poloxamer compositions released GM-0111 cargo within 1 h, while silk-elastinlike copolymers (SELPs) enabled controlled release over a period of 12 h. Bioaccumulation was evaluated using fluorescence imaging and confocal microscopy. SELP-415K, a SELP analogue with 4 silk units, 15 elastin units, and one elastin unit with lysine residues in the monomer repeats, resulted in the highest rectal bioaccumulation. SELP-415K GM-0111 compositions were then used to provide localized protection from radiation induced tissue damage in a murine model of RIP. Rectal delivery of SAGE using SELP-415K significantly reduced behavioral pain responses, and reduced animal mass loss compared to irradiated controls or treatment with traditional delivery approaches. Histological scoring showed RIP injury was ameliorated for animals treated with GM-0111 delivered by SELP-415K. The enhanced bioaccumulation provided by thermoresponsive SELPs via a liquid to semisolid transition improved rectal delivery of GM-0111 to mice and radioprotection in a RIP model.

[Distribution characteristics of blood lipid profile in Hainan centenarians].

Objective: To explore the prevalence of lipid profile and the influencing factors of dyslipidemia in centenarians in Hainan province, and provide basic data for the study of the lipid profile in centenarians. Methods: The data of this study were from the baseline data of China Hainan Centenarian Cohort Study from June 2014 to December 2016. A total of 1 002 centenarians were recruited. According to the guidelines for the prevention and treatment of dyslipidemia in Chinese adults in 2016, the prevalence of lipid profile were described and the prevalence of dyslipidemia with different clinical classifications were compared, and the main influencing factors were analyzed. Results: The median levels of TC, TG, LDL-C and HDL-C were 4.60 mmol/L, 1.05 mmol/L, 2.77 mmol/L and 1.41 mmol/L, respectively, in centenarians in Hainan. Blood lipid profile level was higher in females than in males. With the increase of BMI, TC, TG and LDL-C increased significantly, while HDL-C decreased significantly. The total prevalence of dyslipidemia was 19.1%. Smoking, BMI and area distribution were the main influencing factors of dyslipidemia. Conclusion: The prevalence of dyslipidemia in centenarians in Hainan was at a low level compared with other countries, and the blood lipid profile level was higher in females than in males.

[Relationship between obesity related anthropometric indicators and depression risk in Hainan centenarians].

Objective: To analyze the association of waist circumference, BMI, waist-hip ratio, waist-height ratio, calf circumference and waist-calf circumference ratio (WCR) with depression risk in centenarians in Hainan province. Methods: A total of 1 002 centenarians in Hainan were selected by cluster sampling. GDS-15 was used to investigate the depression. Multivariate linear regression and logistic regression analyses were conducted to evaluate the correlation between anthropometric indicators and depression risk. Restricted cubic spline was used to analyze and visualize the linear relationship. Results: After adjusting demographic characteristics (gender, age, ethnic group, marital status, educational level and type of residence) and lifestyle (smoking and drinking), the standard ß of BMI, WC, WHR, WHtR, calf circumference and WCR associated with GDS-15 were -0.069, -0.032,0.009, -0.009, -0.099 and 0.060, respectively, and the P values of BMI and calf circumference were <0.05. With the increase of calf circumference, the risk of depression decreased, OR value was 0.94 (95% CI:0.90-0.98), and after adjustment, the results were still significant. Classified variable analysis indicated with the decrease of calf circumference and the increase of WCR, the risk of depression increased gradually, the trend P values were 0.038 and 0.042, respectively. Conclusion: Central obesity (waist circumference and WCR) and periphery obesity (calf circumference) have differed effects on depression in centenarians, and increased calf circumference is a protective factor for depression in female centenarians, attention should be paid to the mental health of the elderly women with lower calf circumference.

[Research progress of radiomics with artificial intelligence in precise diagnosis and treatment of hepatocellular carcinoma].

With the advent of the era of artificial intelligence, radiomics is an emerging field in which high-throughput imaging data are extracted from different types of images to model and predict clinical prognosis in a non-invasive manner. Currently, this field is in its initial stage of development and lacks standardized assessment criteria, but still remains a promising tool for the future research direction. Radiomics analysis of hepatocellular carcinoma will aid in the early diagnosis, prognostic evaluation and treatment plan, thereby promoting the continuous improvement of clinical treatment strategies, and providing precise treatment methods to improve the survival rate and cure rate of patients. This article introduces the radiomics research process of hepatocellular carcinoma, and discusses its application progress, challenges and future development directions in the precise diagnosis and treatment of hepatocellular carcinoma.

Management of immune checkpoint inhibitor-related acute hypoxic neuromuscular respiratory failure using high-flow nasal cannula.

Immune-related adverse events are increasingly associated with the use of immune checkpoint inhibitors for treatment of cancers. While neurological immune-related adverse events are rare, immune-related myasthenia gravis and immune-related myositis can lead to myasthenic crisis and acute respiratory failure. High-flow nasal cannula is an emerging alternative in critically ill patients for early treatment in neuromuscular acute hypoxic respiratory failure as well as for those who cannot endure noninvasive positive pressure ventilation with face mask. We describe use of high-flow nasal cannula in a patient with acute hypoxic respiratory failure and psychological distress due to the immune-related adverse event of myasthenic crisis.

[Efficacy of three-dimensional visualization technology in the precision diagnosis and treatment for primary liver cancer: a retrospective multicenter study of 1 665 cases in China].

Objective: To evaluate the efficacy of three-dimensional(3D) visualization technology in the precision diagnosis and treatment for primary liver cancer. Methods: A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males(75.4%) and 410 females(24.6%), with age of (52.9±11.9) years (range: 18 to 86 years). The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data. Kaplan-Meier curve was used to calculate overall survival and disease-free survival rate. Results: (1)In the sample of 1 265 patients, 3D reconstructed models clearly displayed as follows. tumor size: ≤2 cm in 155 cases (9.31%), >2 cm to 5 cm in 551 cases (33.09%), >5 cm to 10 cm in 636 cases (38.20%), >10 cm in 323 cases (19.40%). (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ(normal type) in 1 494 cases(89.73%),variant hepatic artery in 171 cases (10.27%), including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%),variant hepatic veins in 470 cases(28.23%), including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein:normal type in 1 315 cases (78.98%), variant portal veins in 350 cases (21.02%), including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%). Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%). Three types of vascular variation in 4 cases (0.24%), including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation:1 499.3 (514.4)ml (range:641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4)ml (range:306.1 to 5 638.0 ml) for residual function. (4)Operative methods: anatomical hepatectomy in 1 458 cases (87.57%); non-anatomic hepatectomy in 207 cases (12.43%). (5)the median operation time was 285(165)minutes (range: 40 to720 minutes). (6)The median intraoperative blood loss was 200(250)ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7)Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%), cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%). Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8)Postoperative complications in 207 cases (12.43%), including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively. Conclusion: 3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

[Effect of silent information regulator 1 on the LPS induced lncRNA expression of macrophages in mice].

Objective: To investigate the effect of Silent information regulator 1 (Sirt1) on the expression profile of long non-coding RNA (lncRNA) in macrophages upon lipopolysaccharide (LPS) treatment. Methods: Peritoneal macrophages (PM) were isolated from nine wild-type C57BL/6 male mice (wild-type group) and nine myeloid-specific Sirt1 knock-out mice (knock-out group). RNA samples were extracted from macrophages stimulated with 1 µg/ml LPS. Sequencing and the differentially expressed lncRNA were screened after the RNA was quantified. The threshold set for up-and down-regulated genes was a fold change (wild-type group/knock-out group) ≥2 and P≤0.05. Afterwards, gene ontology (GO) and pathway enrichment analysis were conducted and co-expression network map was constructed. Results: Four hundred and forty five lncRNA genes were differentially expressed (185 lncRNA genes were up-regulated and 260 lncRNA genes were down-regulated). Two hundred mRNA genes were differentially expressed (113 mRNA genes were up-regulated and 87 mRNA genes were down-regulated). It was found that the differentially expressed lncRNA genes and the predicted corresponding target genes were mainly distributed in the regions of biological processes of macrophage inflammatory response, macrophage chemotaxis and cell metabolism by GO and pathway enrichment analysis. Conclusion: lncRNA expression profile changes significantly in LPS induced macrophages isolated from Sirt1 knock out mice, which is closely related to the function of macrophages.

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia.

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.

[Comparison between minimally invasive surgery and traditional laminectomy in the resection of schwannoma of lumbar vertebra].

Objective: To explore the application, advantages and disadvantages of minimally invasive surgery for lumbar schwannoma. Methods: this study was a prospective, non-randomized controlled study with a trial group (minimally invasive surgery group) and a control group (traditional laminectomy group).For the patients with lumbar schwannoma hospitalized in the neurosurgical spinal ward of Beijing Tian Tan hospital, the surgeon communicated with them one-on-one to inform the patients of the advantages and disadvantages of minimally invasive surgery through channels and traditional laminectomy. After the surgical risks and their respective advantages and disadvantages were identified, patients who underwent minimally invasive surgery to remove tumors through the channel were admitted to the channel surgery group according to the wishes of the patients; otherwise, patients who underwent traditional laminectomy were included in the control group. From December 2017 to March 2019, a total of 15 patients (experimental group) were treated with minimally invasive surgery. A total of 15 patients with tumors similar in size and location to those in the experimental group were selected from the control group who were hospitalized during the same period for traditional laminectomy. Relevant clinical data of the two groups of patients were collected and analyzed, including preoperative lesion imaging characteristics, intraoperative blood loss, operation time, postoperative hospital stay, postoperative complications, symptom improvement, etc. Results: the operating time of the experimental group and the control group was (157±27) min and (158±29) min, respectively (P=0.897). Intraoperative blood loss was (66±27) ml and (110±43) ml, respectively (P=0.020). The mean hospital stay was (7.60±1.29) days and (11.67±1.23) days, respectively (P=0.000). Postoperative JOA scores were 26.73±2.84 and 26.60±2.41, respectively (P=0.891). Postoperative VAS scores were 0.40±1.12 and 0.27±0.71, respectively (P=0.699).The mean blood loss and hospital stay in the experimental group were significantly lower than those in the control group, the difference in operation time between the two groups was not significant, and there was no difference in neurological function results. Conclusion: In certain types of lumbar schwannoma tumors (non-giant tumors), minimally invasive resection through channels has the advantages of less surgical trauma, less bleeding, faster recovery and definite curative effect, which is a safe and effective surgical treatment.