Hub Genes Involved in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. With an increasing number of patients, NAFLD has been identified as a risk factor for Hepatocellular Carcinoma (HCC). The precise pathophysiology of NAFLD-related HCC has not been completely understood recently. OBJECTIVE: We analyzed the hub genes related to NAFLD and HCC to predict the risk of NAFLD progressing to HCC. METHODS: Two datasets of NAFLD were used to identify differentially expressed genes. Lasso-Cox regression analysis was performed to determine a gene model to predict the risk of the progression from NAFLD to HCC. Three validation datasets were analyzed to evaluate the performance of the gene model, including normal and NAFLD with fibrosis, NAFLD with fibrosis and NAFLD-related HCC, and normal and NASH-related HCC. RESULTS: Seven genes, including COL1A1, TIPM1, VCAN, FOS, CD79A, CXCL9, and VWF, were identified as the hub genes, and then a gene model was constructed. By calculating, the area under the receiver operating characteristic curves (AUCs) for risk prediction were 0.97, 0.886, and 0.751 in the three validation datasets, respectively. Gene set enrichment analysis indicated that the MAPK, TGFß, p53, PPAR, insulin signaling pathways, and fatty acid metabolism were significantly upregulated in the high-risk group. GTPase activity and intrinsic apoptotic signaling pathway had significant upregulation in the low-risk group. CONCLUSION: The seven hub genes may predict the risk of NAFLD developing into HCC by mediating the potential molecular mechanism, which could be used as biomarkers for predicting the progression, diagnosis, and treatment of NAFLD.

Clinical characteristics and pathogen analysis of bronchoalveolar lavage fluid in elderly patients with community-acquired pneumonia.

OBJECTIVE: To analyze the clinical characteristics and bronchoalveolar lavage fluid pathogens in elderly patients with community-acquired pneumonia (CAP). METHODS: This was a retrospective observational epidemiological study using that elderly cases diagnosed with community-acquired pneumonia receiving treatment at the Affiliated Hospital of North China University of Technology, Tangshan Hongci Hospital and Tangshan Fengnan District Hospital of Traditional Chinese Medicine. A total of 92 cases were divided into two groups according to age. There were 44 patients over 75-year-old and 48 patients between 65 and 74-year-old. RESULTS: Compared with the elderly 65 to 74-year-old, the elderly over 75-year-old with diabetes are more likely to suffer from CAP (35.42% vs. 63.64%, p = 0.007) and are more likely to have mixed infections (6.25% vs. 22.73%, p = 0.023) or larger lesions (45.83% vs. 68.18%, p = 0.031). Their hospital stays will also be extended (39.58% vs. 63.64%, p = 0.020), and the albumin level (37.51 ± 8.92 vs. 30.93 ± 6.58, p = 0.000), the neutrophils level (9.09(6.26-10.63) vs. 7.18(5.35-9.17),p = 0.026) is significantly lower and the d-dimer (505.42 ± 197.12 vs. 611.82 ± 195.85, p = 0.011), PCT (0.08 ± 0.04 vs. 0.12 ± 0.07, p = 0.001) levels are significantly higher. CONCLUSION: The clinical symptoms and signs of elderly CAP patients are not so typical, and the infection is more serious. Attention should therefore be paid to elderly patients. Hypoalbuminemia and high d-dimer can predict the prognosis of patients.

Characteristic gene expression in the liver monocyte-macrophage-DC system is associated with the progression of fibrosis in NASH.

Background: The monocyte-macrophage-dendritic cell (DC) (MMD) system exerts crucial functions that may modulate fibrogenesis in nonalcoholic steatohepatitis (NASH). In this study, we explored the cell characteristics, distribution and developmental trajectory of the liver MMD system in NASH mice with fibrosis and clarified characteristic genes of the MMD system involved in liver fibrosis progression in NASH mice and patients. Methods: Single cells in liver tissue samples from NASH and normal mice were quantified using single-cell RNA sequencing (scRNA-seq) analysis. Differentially expressed genes (DEGs) in the MMD system by pseudotime analysis were validated by tyramide signal amplification (TSA)-immunohistochemical staining (IHC) and analyzed by second harmonic generation (SHG)/two-photon excitation fluorescence (TPEF). Results: Compared with control mice, there were increased numbers of monocytes, Kupffer cells, and DCs in two NASH mouse models. From the transcriptional profiles of these single cells, we identified 8 monocyte subsets (Mono1-Mono8) with different molecular and functional properties. Furthermore, the pseudotime analysis showed that Mono5 and Mono6 were at the beginning of the trajectory path, whereas Mono2, Mono4, Kupffer cells and DCs were at a terminal state. Genes related to liver collagen production were at the late stage of this trajectory path. DEGs analysis revealed that the genes Fmnl1 and Myh9 in the MMD system were gradually upregulated during the trajectory. By TSA-IHC, the Fmnl1 and Myh9 expression levels were increased and associated with collagen production and fibrosis stage in NASH mice and patients. Conclusions: Our transcriptome data provide a novel landscape of the MMD system that is involved in advanced NASH disease status. Fmnl1 and Myh9 expression in the MMD system was associated with the progression of NASH fibrosis.

The burden of hepatitis C virus in the world, China, India, and the United States from 1990 to 2019.

Background and aim: Hepatitis C virus infection can lead to an enormous health burden worldwide. Investigating the changes in HCV-related burden between different countries could provide inferences for disease management. Hence, we aim to explore the temporal tendency of the disease burden associated with HCV infection in China, India, the United States, and the world. Methods: Detailed data on the total burden of disease related to HCV infection were collected from the Global Burden of Disease (GBD) 2019 database. Joinpoint regression models were used to simulate the optimal joinpoints of annual percent changes (APCs). Further analysis of the age composition of each index over time and the relationship between ASRs and the socio-demographic Index (SDI) were explored. Finally, three factors (population growth, population aging, and age-specific changes) were deconstructed for the changes in the number of incidences, deaths, and DALYs. Results: It was estimated that 6.2 million new HCV infections, 0.54 million HCV-related deaths, and 15.3 million DALYs worldwide in 2019, with an increase of 25.4, 59.1, and 43.6%, respectively, from 1990, are mainly due to population growth and aging. China experienced a sharp drop in age-standardized rates in 2019, the United States showed an upward trend, and India exhibited a fluctuating tendency in the burden of disease. The incidence was increasing in all locations recently. Conclusion: HCV remains a global health concern despite tremendous progress being made. The disease burden in China improved significantly, while the burden in the United States was deteriorating, with new infections increasing recently, suggesting more targeted interventions to be established to realize the 2030 elimination goals.

Role of Clinical Features, Pathogenic and Etiological Characteristics of Community-acquired Pneumonia with Type 2 Diabetes Mellitus in Early Diagnosis.

OBJECTIVE: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease. METHODS: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups. RESULTS: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups. CONCLUSION: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D.

Appendicular Skeletal Muscle Index and HbA1c Evaluate Liver Steatosis in Patients With Metabolic Associated Fatty Liver Disease.

Background and Aims: Liver steatosis, as the main feature of metabolic associated fatty liver disease (MAFLD), was associated with the progression of liver fibrosis and metabolic syndrome, which needed to be estimated accurately. In this study, we explored the significance of appendicular skeletal muscle index (ASMI) in evaluating liver steatosis of MAFLD patients. Methods: Eight hundred and ninety-nine cases with MAFLD from 2017 to 2018 National Health and Nutrition Examination Surveys (NHANES) database were included. All the analyzed data were obtained from NHANES database. The association between ASMI and liver steatosis were evaluated using R and EmpowerStats. Results: MAFLD individuals were randomly divided into a training (n = 450) and validation cohort (n = 449). In univariate analysis, HbA1c, arms fat, arms lean mass, legs lean mass, trunk lean mass, total fat, total lean mass and ASMI were significantly associated with liver steatosis (p < 0.05). Multivariate analysis showed that HbA1c (OR: 1.6732; 95% CI: 1.2753-2.1929, p = 0.0002) and ASMI (OR: 1.6723; 95% CI: 1.1760-2.5204, p = 0.0052) were independently associated with severe liver steatosis. ASMI accurately evaluated severe liver steatosis with an AUROC of 0.73 and 0.81 in training and validation cohort, respectively. Compared with ASMI only, ASMI combined with HbA1c improved the AUROC to 0.85 and 0.88. Furthermore, the AUROC of our model was superior to FLI in the evaluation of liver steatosis. Conclusion: ASMI combined with HbA1c has good evaluation value for liver steatosis in MAFLD patients, which might be beneficial for the management of MAFLD clinically.

Clinical characteristics, risk factors and antiviral treatments of influenza in immunosuppressed inpatients in Beijing during the 2015-2020 influenza seasons.

BACKGROUND: Compared with immunocompetent patients, immunosuppressed patients have higher morbidity and mortality, a longer duration of viral shedding, more frequent complications, and more antiviral resistance during influenza infections. However, few data on this population in China have been reported. We analysed the clinical characteristics, effects of antiviral therapy, and risk factors for admission to the intensive care unit (ICU) and death in this population after influenza infections and explored the influenza vaccination situation for this population. METHODS: We analysed 111 immunosuppressed inpatients who were infected with influenza virus during the 2015-2020 influenza seasons. Medical data were collected through the electronic medical record system and analysed. Univariate analysis and multivariate logistics analysis were used to identify risk factors. RESULTS: The most common cause of immunosuppression was malignancies being treated with chemotherapy (64.0%, 71/111), followed by haematopoietic stem cell transplantation (HSCT) (23.4%, 26/111). The most common presenting symptoms were fever and cough. Dyspnoea, gastrointestinal symptoms and altered mental status were more common in HSCT patients than in patients with immunosuppression due to other causes. Approximately 14.4% (16/111) of patients were admitted to the ICU, and 9.9% (11/111) of patients died. Combined and double doses of neuraminidase inhibitors did not significantly reduce the risk of admission to the ICU or death. Risk factors for admission to the ICU were dyspnoea, coinfection with other pathogens and no antiviral treatment within 48 h. The presence of dyspnoea and altered mental status were independently associated with death. Only 2.7% (3/111) of patients less than 12 months old had received a seasonal influenza vaccine. CONCLUSION: Fever and other classic symptoms of influenza may be absent in immunosuppressed recipients, especially in HSCT patients. Conducting influenza virus detection at the first presentation seems to be a good choice for early diagnosis. Clinicians should pay extra attention to immunosuppressed patients with dyspnoea, altered mental status, coinfection with other pathogens and no antiviral treatment within 48 h because these patients have a high risk of severe illness. Inactivated influenza vaccines are recommended for immunosuppressed patients.

Outcomes in Thoracolumbar and Lumbar Traumatic Fractures: Does Restoration of Unfused Segmental Mobility Correlated to Implant Removal Time?

BACKGROUND: Posterior fixation without fusion can treat thoracolumbar and lumbar traumatic fractures effectively in certain cases. However, whether patients benefit from implant removal and the correlation between the range of motion (ROM) of the involved segments and the removal time have not been determined. METHODS: From 2018 to 2020, we retrospectively reviewed data of patients with AO spine type A or B thoracolumbar or lumbar traumatic fractures who underwent implant removal. A total of 17 patients (group A), 21 patients (group B), and 12 patients (group C) underwent implant removal after the index surgery within 12 months, between 12 and 24 months, and over 24 months, respectively. Clinical and radiological outcomes, including visual analog scale for back pain, patient satisfaction, Oswestry disability index, and EuroQol 5 dimensions questionnaire, for quality of life and segmental ROM were analyzed. RESULTS: The average follow-up time was 9.1 ± 5.7 months after implant removal. There were no significant differences in visual analog scale and patient satisfaction among the 3 groups at the same observation time point. Among the 3 groups, patients in group A gained the lowest Oswestry disability index and highest EuroQol 5 dimensions questionnaire scores after removal and at the final follow-up. The best ROM was obtained in group A followed by groups B and C (11.5° ± 6.2°, 5.5° ± 1.6°, and 2.4° ± 0.6°, respectively). CONCLUSIONS: Immobilization of the involved segments over 24 months may lead to loss of ROM. Regained segmental ROM is correlated negatively with implant removal time, and removal within 12 months promises a better ROM and quality of life.

Molecular evolution and characterization of hemagglutinin and neuraminidase of influenza A(H1N1)pdm09 viruses isolated in Beijing, China, during the 2017-2018 and 2018-2019 influenza seasons.

We investigated and analysed the molecular evolution of hemagglutinin (HA) and neuraminidase (NA) of influenza A(H1N1)pdm09 virus during the 2017-2018 and 2018-2019 influenza seasons in Beijing, China. We collected and extracted RNA from influenza A(H1N1)pdm09 strains from Peking University People's Hospital and analyzed their HA and NA genes by RT-PCR and sequencing. Phylogenetic analysis of HA and NA sequences was used to compare the amino acid sequences of 51 strains with those of reference strains. All strains belonged to subclade 6B.1, with S162N and I216T substitutions (H1 numbering). Our strains differed from strain A/Michigan/45/2015, with the substitutions S91R, S181T and I312V in the HA antigenic epitope. An E189G mutation was detected in the 190 helix of the receptor binding region of HA. A new potential glycosylation site, 179 (NQT), which was not detected before the 2015 influenza season, was identified. Two strains were mutated at I223, the NA inhibitor resistance site. During 2012-2019, amino acids of HA and NA mutated over time. Co-occurrence mutations N146D, S200P, S202I and A273T in HA appeared along with Q51K, F74S and D416N in NA in six strains during two influenza seasons. Our work reveals the molecular changes and phylogenetic characteristics of influenza A(H1N1)pdm09 virus and suggests that a vaccine probably provides suboptimal protection. The biological characteristics of the new glycosylation and drug-resistance sites detected in this work need to be studied further. The co-occurrence of mutations in HA and NA might affect the characteristics of the virus and need to be given more attention.

Phylogenetic analysis and clinical characteristics of the co-occurring mutations in HA and NA genes of influenza A(H1N1)pdm09 viruses during 2015-2017 in Beijing, China.

BACKGROUND: Influenza A(H1N1)pdm09 viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; however, the effects of co-occurring mutations in HA and NA on the patients' clinical characteristics are still poorly understood. In this study, we analyzed molecular epidemiology and evolution of A(H1N1) pdm09, explored co-occurring mutations of HA and NA, and investigated effect of co-occurring mutations on patients' clinical features. METHODS: A(H1N1)pdm09 was confirmed by reverse transcription-polymerase chain reaction. HA and NA genes were sequenced and phylogenetically analyzed. Clinical characteristics of the co-occurring mutations were analyzed statistically. RESULTS: By analyzing the HA and NA gene sequences of 33 A(H1N1)pdm09 viruses during the 2015-2017 influenza season, we found that all the viruses shared high similarities to each other and the HA genes of these viruses exclusively belonged to subclade 6B.1A. Several unreported substitutions in HA and NA proteins were observed, furthermore, co-occurring mutations of HA-V169T, A278S, E508G, D518E and NA-V67I were detected in 30.3% (10/33) A(H1N1)pdm09 virus strains when comparing with vaccine strains A/California/07/2009 and A/Michigan/45/2015 (H1N1). Sore throat was significantly associated with co-occurring mutations in HA and NA of A(H1N1)pdm09 (χ2, P < 0.05). CONCLUSIONS: Co-occurring mutations in HA and NA were detected in A(H1N1)pdm09 isolated during 2015-2017 in Beijing. Symptomatically, sore throat was associated with co-occurring mutations in HA and NA of A(H1N1)pdm09. Therefore, studying the effect and mechanism of co-occurring mutations in HA and NA on patients' clinical features is of note needed.

LRRFIP1 expression triggers platelet agglutination by enhancing αIIbß3 expression.

Platelets primarily participate in hemostasis and antimicrobial host defense. The present study aimed to investigate the effects of leucine-rich repeat flightless-interacting protein-1 (LRRFIP1) on platelet agglutination. The bacterial strain of LRRFIP1 was used to synthesize the recombinant protein and a mouse model of LRRFIP1 gene knockout was established. Platelets were isolated from the mice and divided into the different trial groups according to their treatment with collagen, thrombin receptor SFLLRN, anti-wild-type (w)LRRFIP1monoclonal antibodies and the model of LRRFIP1 gene knockout. The platelets were prepared and platelet agglutination was examined using platelet aggregation apparatus. The active αIIbß3 integrin was examined by flow cytometry. The results revealed that the combined wLRRFIP1 protein was successfully expressed. wLRRFIP1 treatment significantly triggered platelet agglutination of collagen, thrombin and monoclonal antibody treated platelets. wLRRFIP1 knockout significantly decreased αIIbß3 levels compared with the wild-type. Platelet agglutination was also significantly inhibited in the LRRFIP1-/-mouse model compared with the wild-type. LRRFIP1 knockout significantly decreased the αIIbß3 levels in platelets undergoing convulxin treatment. In conclusion, LRRFIP1 treatment triggered platelet agglutination and LRRFIP1 gene knockout inhibited platelet agglutination. In addition, LRRFIP1 gene knockout significantly decreased the levels of αIIbß3. This suggests that LRRFIP1 my be applied to patients in a clinical setting to trigger platelet agglutination in inflammatory diseases and atherothrombotic diseases.

Utilization of ring-shaped bone allograft for surgical treatment of adolescent post-tubercular kyphosis: A retrospective study.

This study aimed to investigate the mid-term outcome of ring-shaped bone allografts in the surgical treatment of adolescent post-tubercular kyphosis secondary to spinal tuberculosis.The records of adolescent patients diagnosed with spinal tuberculosis who received treatment in our department between 2009 and 2013 were retrospectively reviewed. The anterior approach was used in cases of cervical kyphosis and the posterior approach was used in cases of thoracic and lumbar kyphosis. During the surgery, the ring-shaped bone was used as a structural bone graft associated with the cancellous bone filing in the center portion of the ring shape. Cobb's angle, signs of spinal infusion on computed tomography, and complications were followed up.A total of 25 patients were included in our study. Among them, 3 involved the cervical region, 5 involved the thoracic region, 8 involved the thoracolumbar region, and 9 involved the lumbar region. The preoperative kyphosis deformity was a mean 65° Cobb's angle (40°-97°) compared to the postoperative 14° Cobb's angle (10°-21°) for an average correction of 51°. All wounds healed well without graft rejection. All patients achieved bone fusion 3 months postoperative for a 100% fusion rate.Our results show that the ring-shaped allograft bone is an effective option for the treatment of adolescent kyphosis. The ring-shaped allograft bone demonstrated satisfactory mechanical strength and vertebral fusion without mid-term metallic toxicity.