Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans ; Aged ; Sarcopenia/diagnostic imaging* ; Carcinoma, Hepatocellular/diagnostic imaging* ; Muscle, Skeletal/diagnostic imaging* ; Deep Learning ; Prognosis ; Radiomics ; Liver Neoplasms/diagnostic imaging* ; Retrospective Studies

OBJECTIVE: The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker. METHODS: A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL). RESULTS: The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m ³. The OELs for COEs exposure using the BBMD were 0.00170 mg/m ³ for the total population, 0.00158 mg/m ³ for males, and 0.00174 mg/m ³ for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m ³, respectively. CONCLUSION Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m ³. This value will provide a benchmark for determining possible OELs.
Male ; Female ; Animals ; Coke ; Polycyclic Aromatic Hydrocarbons ; DNA Copy Number Variations ; Benchmarking ; Occupational Exposure/analysis* ; DNA, Mitochondrial/genetics* ; DNA Damage

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism. Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection. More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern. Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type I interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.

Background::The study aimed to describe the aortic valve morphology in Chinese patients underwent transcatheter aortic valve replacement (TAVR) for symptomatic severe aortic stenosis (AS), and the impact of sizing strategies and related procedural outcomes.Methods::Patients with severe AS who underwent TAVR were consecutively enrolled from 2012 to 2019. The anatomy and morphology of the aortic root were assessed. "Downsize" strategy was preformed when patients had complex morphology. The clinical outcomes of patients who performed downsize strategy were compared with those received annular sizing strategy. The primary outcome was device success rate, and secondary outcomes included Valve Academic Research Consortium-3 clinical outcomes variables based on 1-year follow-up.Results::A total of 293 patients were enrolled. Among them, 95 patients (32.4%) had bicuspid aortic valve. The calcium volume (Hounsfield Unit-850) of aortic root was 449.90 (243.15-782.15) mm 3. Calcium is distributed mostly on the leaflet level. Downsize strategy was performed in 204 patients (69.6%). Compared with the patients who performed annular sizing strategy, those received downsize strategy achieved a similar device success rate (82.0% [73] vs. 83.3% [170], P= 0.79). Aortic valve gradients (downsize strategy group vs. annular sizing group, 11.28 mmHg vs. 11.88 mmHg, P = 0.64) and percentages of patients with moderate or severe paravalvular regurgitation 2.0% (4/204) vs. 4.5% (4/89), P = 0.21) were similar in the two groups at 30 days after TAVR. These echocardiographic results were sustainable for one year. Conclusions::Chinese TAVR patients have more prevalent bicuspid morphology and large calcium volume of aortic root. Calcium is distributed mostly on the leaflet level. Compare with annular sizing strategy, downsize strategy provided a non-inferior device success rate and transcatheter heart valve hemodynamic performance in self-expanding TAVR procedure.

Objective:To study serum procalcitonin (PCT), C-reactive protein (CRP) and platelet count (PLT) in evaluation of severity of acute cholangitis (AC).Methods:Ninety patients with AC who were treated at the General Surgery Department, Guangming Hospital, Liaocheng, Shandong Province from January 2016 to December 2018 entered into the observation group, while 60 patients with bile duct stones but without infection treated at the hospital during the study period entered into the control group. Using the " Guidelines for the Diagnosis and Treatment of Acute Biliary Tract Infections" , the study group of patient was further divided into the mild infection, moderate infection, and severe infection groups. The PCT, CRP and PLT levels of all the subjects were checked. Spearman correlation was used to analyze the relationship between PCT, CRP, PLT indexes with severity of infection. The receiver operating characteristic curve was used to analyze the sensitivity and specificity of PCT, CRP and PLT in the diagnosis of patients with different degrees of infection.Results:In the observation group, there were 46 males and 44 females with a Mean±SD age of (45.6±21.1) years. In the control group, there were 30 males and 30 females, with a Mean±SD age of (45.0±19.3) years. The levels of PLT in the observation group and the control group were (8.2±1.1) ng/ml and (0.4±0.1) ng/ml, respectively. The corresponding CRP were (92.7±21.1) mg/L and (6.1±1.0) mg/L, respectively. The observation group had higher levels than the control group. The PLT counts were (62.6±17.6)×10 9/L and (156.3±35.3)×10 9/L for the two groups, with the observation group having lower platelet count than the control group (both P<0.05). The severity of infection was positively correlated with blood PCT levels and CRP indicators ( r=0.427, r=0.584, all P<0.05), and negatively correlated with the PLT ( r=-0.429, P<0.05). The sensitivity and specificity of PCT using a cut-off value of 9.4 μg/L were 84.0% and 65.0%, respectively, which were higher than the CRP using a cut-off value of 145.7 mg/L. The sensitivity and specificity were 67.0% and 48.0%, respectively. When PLT using a cut-off value of 52.8×10 9/L, the sensitivity and specificity were 71.0% and 52.0%, respectively. Conclusions:Changes in serum PCT, CRP and PLT reflected the severity of infection in patients with AC; PCT had a higher sensitivity and specificity, and it can be used to guide treatment.

Objective: To explore the distribution characteristics of MTHFR gene polymorphism of Chinese Han population in Beijing, and analyze the differences of distribution of MTHFR gene polymorphism between Beijing area and the other parts of northern China. Methods: MTHFR C677T gene was detected by PCR-gold magnetic particles chromatography. The distribution characteristics of MTHFR gene polymorphism of 3 945 healthy subjects from September 2014 to May 2018 detected in Peking Union Medical College Hospital were analyzed retrospectively. The distribution of MTHFR gene polymorphism in Chinese Han population in Beijing area was compared with the Han population of the other area from northern China by reviewing domestic and foreign literature databases. Results: The frequencies of CC, CT and TT genotype of MTHFR C677T gene in the male population undergoing physical examination in Beijing were 23.3%, 50.5% and 26.2%, respectively, and the frequencies of C and T allele frequencies were 48.6% and 51.4%, respectively. The frequencies of CC, CT and TT genotype of MTHFR C677T gene in the female population were 22.7%, 49.4% and 27.9%, respectively, and the C and T allele frequencies were 47.4% and 52.6%, respectively. There was no difference in genotype frequency and allele freaaency between male and femal (P＞0.05). The frequencies of CC, CT and TT genotypes and allele frequencies of MTHFR C677T gene in the population of Beijing area were significantly different from those of Heilongjiang, Jilin, Hebei, Shandong and Henan provinces (P＜0.01). Conclusion There was no significant difference of polymorphism distribution of MTHFR C677T gene between male and female populations in Beijing. The distinct distribution characteristics of MTHFR gene in Beijing area should be presented.

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
Adalimumab ; Asia ; Asian Continental Ancestry Group ; Biological Factors ; Biosimilar Pharmaceuticals ; Colitis ; Colitis, Ulcerative ; Consensus ; Cooperative Behavior ; Crohn Disease ; Gastroenterology ; Hepatitis B ; Humans ; Immunologic Factors ; Inflammatory Bowel Diseases ; Infliximab ; Pharmacogenetics ; Philippines ; Practice Guidelines as Topic ; Tuberculosis ; Ulcer

Objective To investigate the effect of before and after combination therapy of thalidomide and methotrexate (T+M) on regulatory T cells and IL-6 expression profile,and to reveal the mechanism of therapeutic effect of T+M on rheumatoid arthritis.Methods A total of 58 patients with rheumatoid arthritis from August 2014 to August 2016 in the Third Affiliated Hospital of Wenzhou Medical University.The flow cytometry assay and enzyme-linked immunosorbent assay (ELISA) were used to estimate the ratio of peripheral blood regulatory T cells and expression profile of IL-6 in peripheral blood lymphocyte before and after combination therapy of thalidomide and methotrexate .Results After combination therapy of T+M,the ratio of peripheral blood CD25 +Foxp3/CD4 +T cells had a marked increase compared with before combination of therapy of T +M;but the expression of IL-6 had a significant decrease in the group of after combination therapy of T +M compared with before combination therapy.Conclusion The effect of combination therapy of T+M on rheumatoid arthritis is associated with increasing the ratio of regulatory T cells and decreasing the secretion of IL-6 that could regulate T cells to homeostasis.

Objective To investigate the genotype distribution of thalassemia intermedia , major and compound thalassemia in Peking Union Medical College Hospital from 2012 to 2015. Methods Retrospectively 1 084 suspected thalassemia cases were analyzed in recent four years .Three common deletions of αglobin chain were detected by GAP-PCR.Three common point mutations of αglobin chain and seventeen common mutations of βglobin chain were identified by PCR reverse dot blot hybridization . Hemoglobin electrophoresis was carried out by Capillary Electrophoresis System .RBC associated parameters and morphology were analyzed by hematology analyzer and blood smear .Results 702 cases were confirmed to be thalassemia, and the positive rate was 64.76% (702 /1084).19 types of gene defects were detected. There were 4 types of gene defects in 23 case with α-thalassemia intermeida, including -α3.7 /--SEA , -α4.2 /--SEA , αCSα/--SEA and αQSα/--SEA , -α3.7 /--SEA to be the most common genotype (18 cases) .3 cases with β-thalassemia intermeida were confirmed and the genotypes were βCD 17(A→T) /β-29(A→G) , β-28(A→G) /β-28(A→G) andβIVS-Ⅱ-654(C→T) /βCD17(A→T) , respectively.There were also 1 βCD 41 -42(-TTCT) /βCD17(A→T) thalassemia major case. The genotypes of 2 HbE/β-thalassemia cases were βCD41 -42(-TTCT) /βE and βCD17(A→T) /βE.5 αβ-thalassemia including 2 βCD 41 -42(-TTCT) /βA compounded with αα/-α3.7 , 1βIVS-Ⅱ-654(C→T) /βA compounded with --SEA /αCSα, 1βCD17(A→T) /βA compounded with -α4.2 /ααand 1βCD 41 -42(-TTCT) /βA compounded with αCS α/αα.Rare and untypical haematological results were found , such as normal level HbA 2 and undetectable HbH, in compound heterozygosity with --SEA /αCS α and βIVS-Ⅱ-654(C→T) /βA. Conclusions The genotypes of thalassemia intermedia, major and compound thalassemia in Peking Union Medical College were highly variable .

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (s). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated signif-icantly across the patient population with s. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.