Multi-omics data-based analysis characterizes molecular alterations of the vesicle genes in human colorectal cancer.

The role of vesicular genes in the development of colorectal cancer (CRC) is crucial. Analyzing alterations in these genes at multi-omics can aid in understanding the molecular pathways behind colorectal carcinogenesis and identifying potential treatment targets. However, studies on the overall alteration of vesicular genes in CRC are still lacking. In this study, we aimed to investigate the relationship between vesicle genetic alterations and CRC progression. To achieve this, we analyzed molecular alterations in CRC vesicle genes at eight levels, including mRNA, protein, and epigenetic levels. Additionally, we examined CRC overall survival-related genes that were obtained from a public database. Our analysis of chromatin structural variants, DNA methylation, chromatin accessibility, and proteins (including phosphorylation, ubiquitination, and malonylation), along with RNA-seq data from the TCGA database, revealed multiple levels of alterations in CRC vesicle genes in the collected tissue samples. We progressively examined the alterations of vesicle genes in mRNA and protein levels in CRC and discovered the hub genes. Further investigation identified the probable essential transcription factors. This study contributes to a thorough knowledge of the connection between vesicle gene alterations at multiple levels and the development of CRC and offers a theoretical framework for the identification of novel treatment targets.

Strategy To Assess Zoonotic Potential Reveals Low Risk Posed by SARS-Related Coronaviruses from Bat and Pangolin.

In the last 2 decades, pathogens originating in animals may have triggered three coronavirus pandemics, including the coronavirus disease 2019 pandemic. Thus, evaluation of the spillover risk of animal severe acute respiratory syndrome (SARS)-related coronavirus (SARSr-CoV) is important in the context of future disease preparedness. However, there is no analytical framework to assess the spillover risk of SARSr-CoVs, which cannot be determined by sequence analysis alone. Here, we established an integrity framework to evaluate the spillover risk of an animal SARSr-CoV by testing how viruses break through key human immune barriers, including viral cell tropism, replication dynamics, interferon signaling, inflammation, and adaptive immune barriers, using human ex vivo lung tissues, human airway and nasal organoids, and human lung cells. Using this framework, we showed that the two pre-emergent animal SARSr-CoVs, bat BtCoV-WIV1 and pangolin PCoV-GX, shared similar cell tropism but exhibited less replicative fitness in the human nasal cavity or airway than did SARS-CoV-2. Furthermore, these viruses triggered fewer proinflammatory responses and less cell death, yet showed interferon antagonist activity and the ability to partially escape adaptive immune barriers to SARS-CoV-2. Collectively, these animal viruses did not fully adapt to spread or cause severe diseases, thus causing successful zoonoses in humans. We believe that this experimental framework provides a path to identifying animal coronaviruses with the potential to cause future zoonoses. IMPORTANCE Evaluation of the zoonotic risk of animal SARSr-CoVs is important for future disease preparedness. However, there are misconceptions regarding the risk of animal viruses. For example, an animal SARSr-CoV could readily infect humans. Alternately, human receptor usage may result in spillover risk. Here, we established an analytical framework to assess the zoonotic risk of SARSr-CoV by testing a series of virus-host interaction profiles. Our data showed that the pre-emergent bat BtCoV-WIV1 and pangolin PCoV-GX were less adapted to humans than SARS-CoV-2 was, suggesting that it may be extremely rare for animal SARSr-CoVs to break all bottlenecks and cause successful zoonoses.

Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020 / 中华预防医学杂志

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).

ACE2-independent infection of T lymphocytes by SARS-CoV-2.

SARS-CoV-2 induced marked lymphopenia in severe patients with COVID-19. However, whether lymphocytes are targets of viral infection is yet to be determined, although SARS-CoV-2 RNA or antigen has been identified in T cells from patients. Here, we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells (PBCs) or postmortem lung T cells, and the infectious virus could also be detected from viral antigen-positive PBCs. We next prove that SARS-CoV-2 infects T lymphocytes, preferably activated CD4 + T cells in vitro. Upon infection, viral RNA, subgenomic RNA, viral protein or viral particle can be detected in the T cells. Furthermore, we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking experiments. Next, we demonstrate that viral antigen-positive T cells from patient undergone pronounced apoptosis. In vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent pathways. Finally, we demonstrated that LFA-1, the protein exclusively expresses in multiple leukocytes, is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells, compared to a list of other known receptors. Collectively, this work confirmed a SARS-CoV-2 infection of T cells, in a spike-ACE2-independent manner, which shed novel insights into the underlying mechanisms of SARS-CoV-2-induced lymphopenia in COVID-19 patients.

SARS-CoV-2 Causes Acute Kidney Injury by Directly Infecting Renal Tubules.

Acute kidney injury (AKI) is one of the most prevalent complications among hospitalized coronavirus disease 2019 (COVID-19) patients. Here, we aim to investigate the causes, risk factors, and outcomes of AKI in COVID-19 patients. We found that angiotensin-converting enzyme II (ACE2) and transmembrane protease serine 2 (TMPRSS2) were mainly expressed by different cell types in the human kidney. However, in autopsy kidney samples, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein was detected in ACE2+ or TMPRSS2+ renal tubular cells, whereas the RNAscope® Assay targeting the SARS-CoV-2 Spike gene was positive mainly in the distal tubular cells and seldom in the proximal tubular cells. In addition, the TMPRSS2 and kidney injury marker protein levels were significantly higher in the SARS-CoV-2-infected renal distal tubular cells, indicating that SARS-CoV-2-mediated AKI mainly occurred in the renal distal tubular cells. Subsequently, a cohort analysis of 722 patients with COVID-19 demonstrated that AKI was significantly related to more serious disease stages and poor prognosis of COVID-19 patients. The progressive increase of blood urea nitrogen (BUN) level during the course of COVID-19 suggests that the patient's condition is aggravated. These results will greatly increase the current understanding of SARS-CoV-2 infection.

Biomarkers for detecting and improving AKI after liver transplantation: From diagnosis to treatment.

Orthotopic liver transplantation (OLT) is a well-established treatment for patients with liver failure. The shortage of donor organs and postoperative complications remain major obstacles for improving patient survival. Among these complications, acute kidney injury (AKI) is one of the most frequent types, contributing to graft loss. The timely detection and reversal of AKI can reduce its adverse influences on graft and patient outcomes. Traditional markers for detecting AKI are often limited with regard to their accuracy and specificity, and the discovery of better AKI markers and therapeutic targets assumes great importance. During past decades, studies directed toward early detection and treatment of AKI in OLT have been available. This review summarizes the evidence of these biomarkers for the prediction, diagnosis, treatment and prognosis stratification of AKI associated with OLT.

Epidemiological investigation of a COVID-19 family cluster outbreak transmitted by a 3-month-old infant.

OBJECTIVE: To investigate the clinical characteristics, epidemiological characteristics, and transmissibility of coronavirus disease 2019 (COVID-19) in a family cluster outbreak transmitted by a 3-month-old confirmed positive infant. METHODS: Field-based epidemiological methods were used to investigate cases and their close contacts. Real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) was used to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for all collected specimens. Serum SARS-CoV-2 IgM and IgG antibodies were detected by Chemiluminescence and Gold immnnochromatography (GICA). RESULTS: The outbreak was a family cluster with an attack rate of 80% (4/5). The first case in this family was a 3-month-old infant. The transmission chain was confirmed from infant to adults (her father, mother and grandmother). Fecal tests for SARS-CoV-2 RNA remained positive for 37 days after the infant was discharged. The infant's grandmother was confirmed to be positive 2 days after the infant was discharged from hospital. Patients A (3-month-old female), B (patient A's father), C (patient A's grandmother), and D (patient A's mother) had positive serum IgG and negative IgM, but patients A's grandfather serum IgG and IgM were negative. CONCLUSION: SARS-CoV-2 has strong transmissibility within family settings and presence of viral RNA in stool raises concern for possible fecal-oral transmission. Hospital follow-up and close contact tracing are necessary for those diagnosed with COVID-19.

SFTSV Infection Induces BAK/BAX-Dependent Mitochondrial DNA Release to Trigger NLRP3 Inflammasome Activation.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus that carries a high fatality rate of 12%-50%. In-depth understanding of the SFTSV-induced pathogenesis mechanism is critical for developing effective anti-SFTS therapeutics. Here, we report transcriptomic analysis of blood samples from SFTS patients. We observe a strong correlation between inflammatory responses and disease progression and fatal outcome. Quantitative proteomic analysis of SFTSV infection confirms the induction of inflammation and further reveals virus-induced mitochondrial dysfunction. Mechanistically, SFTSV infection triggers BCL2 antagonist/killer 1 (BAK) upregulation and BAK/BCL2-associated X (BAX) activation, leading to mitochondrial DNA (mtDNA) oxidization and subsequent cytosolic release. The cytosolic mtDNA binds and triggers NLRP3 inflammasome activation. Notably, the BAK expression level correlates with SFTS disease progression and fatal outcome. These findings provide insights into the clinical features and molecular underpinnings of severe SFTS, which may aid in patient care and therapeutic design, and may also be conserved during infection by other highly pathogenic viruses.

Angiopoietin-Tie signaling in kidney diseases: an updated review.

Angiopoietins (Angs) are a family of vascular growth factors that share multiple cellular functions related to cell survival, proliferation, and migration. Angs play physiological and pathological roles through the Tie tyrosine kinase receptors. The Ang-Tie signaling pathway participates in the developmental and tumor-induced angiogenesis and is also involved in many disease settings, such as vascular diseases, systemic inflammation, and cancers. Since Angs are widely expressed in the kidney, an enormous amount of research focuses on their roles in the kidney. In this review, we describe the biological functions of the Ang-Tie signaling pathway and summarize their roles in kidney development and maturation, acute and chronic kidney diseases, diabetic nephropathy, lupus nephropathy, hemolytic uremic syndrome, end-stage renal diseases, and renal cell carcinoma. Understanding the molecular mechanisms of Ang-Tie signaling may reveal potential therapeutic targets for preventing or alleviating kidney diseases.

A New Pathogenesis of Albuminuria: Role of Transcytosis.

Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria.

Efficacy and safety of tacrolimus vs. cyclophosphamide for idiopathic membranous nephropathy: A meta-analysis of Chinese adults.

The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) in the treatment of idiopathic membranous nephropathy (IMN) were compared in Chinese adult patients using a meta- analysis of the available literatures. Randomized controlled clinical trials (RCTs) of the treatment of primary IMN with TAC or CTX combined with corticosteroids in the English databases PubMed, Embase and Cochrane, as well as Chinese databases, were searched. Qualified studies were subjected to quality assessment and meta-analysis. A total of 8 RCTs, including 359 Chinese patients, were included in the meta-analysis. The complete remission rate and overall remission rate in the TAC treatment group after 6 months of treatment were higher than those in the CTX treatment group. No significant difference in remission rate was found after 12 months of treatment. There was no significant difference in the adverse reaction between the two groups at the 6th or 12th months. TAC-based treatment was associated with a faster response than CTX at the 6th month, but there was no significant difference between the two groups at 12th month in Chinese adults. Further study is needed to evaluate the long-term efficacy and safety of this treatment regimen.

Clinicopathological features of renal amyloidosis: a single-center study on 47 cases.

The correlations between the clinicopathological features and the long-term outcomes of renal amyloidosis (RA) were analyzed with a view to develop strategies for improving diagnosis and prognosis of RA. We retrospectively reviewed the clinicopathological characteristics of 47 patients diagnosed with RA between 2004 and 2014 at the Wuhan Union Hospital. The data on the renal histology, clinical manifestations, and prognosis of RA patients were retrieved from the hospital records and characteristic patterns were identified. The histological changes in the kidneys were correlated with the clinical manifestations of RA. Additionally, most RA patients in this study had decreased serum levels of κ light chain and increased urine levels of κ and λ light chains as well as presence of M-protein in the urine and serum. Patients with early RA showed no specific pathognomonic symptoms. Bleeding associated with diagnostic renal biopsy was rare. We recommend that the routine work-up of patients aged over 40 years and presenting with non-diabetic nephropathy includes the non-invasive tests for the measurement of serum and urine levels of κ and λ light chains as well as protein electrophoresis tests for the presence of urinary and serum M-protein. Additionally, such patients should undergo renal biopsy screening with Cong-red staining to ensure early diagnosis of RA and improve their survival, since the risk of hemorrhage related to renal biopsy screening is low at early stages of RA.

Clinicopathological features of renal amyloidosis: A single-center study on 47 cases / 华中科技大学学报（医学）（英德文版）

The correlations between the clinicopathological features and the long-term outcomes of renal amyloidosis (RA) were analyzed with a view to develop strategies for improving diagnosis and prognosis of RA. We retrospectively reviewed the clinicopathological characteristics of 47 patients diagnosed with RA between 2004 and 2014 at the Wuhan Union Hospital. The data on the renal histology, clinical manifestations, and prognosis of RA patients were retrieved from the hospital records and characteristic patterns were identified. The histological changes in the kidneys were correlated with the clinical manifestations of RA. Additionally, most RA patients in this study had decreased serum levels of κ light chain and increased urine levels of κ and λ light chains as well as presence of M-protein in the urine and serum. Patients with early RA showed no specific pathognomonic symptoms. Bleeding associated with diagnostic renal biopsy was rare. We recommend that the routine work-up of patients aged over 40 years and presenting with non-diabetic nephropathy includes the non-invasive tests for the measurement of serum and urine levels of κ and λ light chains as well as protein electrophoresis tests for the presence of urinary and serum M-protein. Additionally, such patients should undergo renal biopsy screening with Cong-red staining to ensure early diagnosis of RA and improve their survival, since the risk of hemorrhage related to renal biopsy screening is low at early stages of RA.

Efficacy and safety of tacrolimus vs. cyclophosphamide for idiopathic membranous nephropathy: A meta-analysis of Chinese adults / 华中科技大学学报（医学）（英德文版）

The efficacy and safety of tacrolimus (TAC) and cyclophosphamide (CTX) in the treatment of idiopathic membranous nephropathy (IMN) were compared in Chinese adult patients using a meta- analysis of the available literatures. Randomized controlled clinical trials (RCTs) of the treatment of primary IMN with TAC or CTX combined with corticosteroids in the English databases PubMed, Embase and Cochrane, as well as Chinese databases, were searched. Qualified studies were subjected to quality assessment and meta-analysis. A total of 8 RCTs, including 359 Chinese patients, were included in the meta-analysis. The complete remission rate and overall remission rate in the TAC treatment group after 6 months of treatment were higher than those in the CTX treatment group. No significant difference in remission rate was found after 12 months of treatment. There was no significant difference in the adverse reaction between the two groups at the 6th or 12th months. TAC-based treatment was associated with a faster response than CTX at the 6th month, but there was no significant difference between the two groups at 12th month in Chinese adults. Further study is needed to evaluate the long-term efficacy and safety of this treatment regimen.

Clinicopathological features of renal amyloidosis: a single-center study on 47 cases / 华中科技大学学报（医学）（英德文版）

The correlations between the clinicopathological features and the long-term outcomes of renal amyloidosis (RA) were analyzed with a view to develop strategies for improving diagnosis and prognosis of RA. We retrospectively reviewed the clinicopathological characteristics of 47 patients diagnosed with RA between 2004 and 2014 at the Wuhan Union Hospital. The data on the renal histology, clinical manifestations, and prognosis of RA patients were retrieved from the hospital records and characteristic patterns were identified. The histological changes in the kidneys were correlated with the clinical manifestations of RA. Additionally, most RA patients in this study had decreased serum levels of κ light chain and increased urine levels of κ and λ light chains as well as presence of M-protein in the urine and serum. Patients with early RA showed no specific pathognomonic symptoms. Bleeding associated with diagnostic renal biopsy was rare. We recommend that the routine work-up of patients aged over 40 years and presenting with non-diabetic nephropathy includes the non-invasive tests for the measurement of serum and urine levels of κ and λ light chains as well as protein electrophoresis tests for the presence of urinary and serum M-protein. Additionally, such patients should undergo renal biopsy screening with Cong-red staining to ensure early diagnosis of RA and improve their survival, since the risk of hemorrhage related to renal biopsy screening is low at early stages of RA.

Telomerase Expression in Peripheral Blood Mononuclear Cells in Children with Acute Kawasaki Disease / 实用儿科临床杂志

Objective To study the telomerase expression in peripheral blood mononuclear cells(PBMCs) in children with acute Kawasaki disease(KD) and its clinical significance.Methods The PBMCs of 64 children with acute KD [25 cases of them with coronary artery lesions(CAL),while the rest without] from 2 months to 6 years old admitted into Jiangxi Children's Hospital from Mar.2005 to Dec.2008 and those of 52 sex-age-matched healthy children (healthy control group) from 5 months to 7 years old were all assayed by Roche telomerase polymerase chain reaction enzymelinked immunosorbent assay(PCR ELISA).WBC,ESR and CRP were also detected.SPSS 11.0 software was used to analyze the data.Results The telomerase expression frequency of PBMCs in children with KD was 32.8%(21/64 cases),while that in healthy control group was only 15.4%(8/52 cases),the difference between the 2 groups was significant (?2= 4.65,P0.05).There were no significant difference of WBC,ESR and CRP between the telomerase of PBMCs positive group and negative group.Conclusions The higher frequency of telomerase expression in peripheral blood lymphocytes might be related to the development and progression of KD.

Therapeutic Effect of Aminophylline on Bronchiolitis in Children / 实用儿科临床杂志

Objective To explore the clinical effects of aminophylline on bronchiolitis in children.Methods One hundred and twen-ty-eight children with bronchiolitis in our hospital were randomly divided into the experiment and treated control group,in the meantime,and divided into the severe and mild group according to their condition.The children in control group were treated with traditional methods,in experiment group were treated with aminophylline(2 mg/kg,every day one time),as well as used traditional methods.All patients in 2 groups were checked by volume (VT), inhale time and exhale time ratio (Ti/tE),time to peak expiratory flow and expiratory time ratio(tPTEF/Te),time to peak expiratory flow to total expiratory time and volume ratio(vPTEF/vE) respectively. Meanwhile pulmonary function,alkyla-denine glycosylase in trachea secretion,IL-8,cytotaxonomy in trachea secretion on time,after the third day and the 7th day.Their curative effects were evaluated.All parameters were analyzed by statistical methods.Results Cytotaxonomy of the patients in the experiment were more improved than that of control group(P

Nuclear Factor-?B Activation in Peripheral Blood Mononuclear Cells during Acute Kawasaki Disease / 实用儿科临床杂志

Objective To explore the significance of nuclear factor-?B(NF-?B)activation in peripheral blood mononuclear cells(PBMC)during acute Kawasaki disease(KD).Methods Peripheral blood was collected from children with acute KD(n=30)and healthy age-matched children(n=20).PBMC were cultured in vitro and divided into 3 groups:naturally cultured blank control group,protein kinase C(PKC)activator stimulated phorbol 12-myristate 13-acetate(PMA)group and PMA plus NF-?B inhibitor treated PMA plus pyrrolidine dithiocarbamate(PDTC)group.Percentages of NF-?B activation were detected by immunohistochemistry.Results Under natural culturing,the percentage of cells with activated NF-?B was significantly higher in acute KD blank control group than that in healthy blank control group.The percentage of cells with activated NF-?B was significantly higher in acute KD PMA group than that in acute KD blank group and that in normal control PMA group,respectively(Pa0.05).Conclusions NF-?B activation in PBMC during acute KD is markedly increased,which suggests that NF-?B activation plays an important role in the formation of vasulitis and CAL in this disease.NF-?B activation in PBMCs in children with KD is regulated by the PKC signaling pathway and PDTC obviously inhibits the activation of NF-?B.J Appl Clin Pediatr,2009,24(1):35-37