Intestinal flora is closely associated with chronic hepatitis B (CHB). Recent studies have shown that the imbalance of intestinal flora is associated with the development, progression, and prognosis of CHB, and the environment of intestinal flora may also change with disease progression, suggesting that intestinal flora and CHB interact with each other. This article reviews the influence of intestinal flora on the progression of CHB and related liver diseases and the role of intestinal flora regulation in the diagnosis and treatment of CHB and related liver diseases, in order to provide new ideas for the clinical treatment of CHB.

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Objective: To preliminarily establish the reference interval for serum creatinine in healthy adults aged 20-79 years in city of Lianyungang. Methods: A total of 34 577 cases of reference individuals were selected from physical examination population by using the principle of complete randomization, and the concentration of serum creatinine was detected by AU5821 automatic biochemical analyzer with its matching reagents.According to the standards of CLSI C28-A3 and WS/T 402-2012 " Clinical Laboratory Test Project Reference Interval Formulation" , the reference interval of serum creatinine was established. Results: There was statistically significant difference of serum creatinine in gender and age between healthy adults in this area (male group: 78[72-84]μmol/L, female group: 61[56-66]μmol/L; aged 20-59 of male group: 78[72-84]μmol/L, aged 60-79 of male group: 77[70-85]μmol/L; aged 20-59 of female group: 60[56-65]μmol/L, aged 60-79 of female group: 63[58-69]μmol/L) (Z=120.93, Z=31.53, Z=28.45; all P<0.05). Therefore, the reference interval of serum creatinine was established based on gender and age, and its reference interval was 61-97μmol/L (aged 20-59 of male), 60-106μmol/L (aged 60-79 of male), 47-76μmol/L (aged 20-59 of female) and 49-86μmol/L (aged 60-79 of female), respectively. Conclusion Establishment of reference interval in serum creatinine plays an important role in the auxiliary diagnosis, progression and prognosis evaluation of various kidney diseases.

Objective To observe the changes of inflammatory factors after the hepatic cystic echinococcosis surgery and explore the intervention effect of ulinastatin on postoperative inflammatory factors. Methods Sixty patients with hepatic cystic echinococcosis were selected and randomly divided into a control group and ulinastatin intervention group according to whether or not use ulinastatin. The peripheral venous blood was extracted in all the patients and the levels of IL-6, IL-8, IL-9, and IL-10 were detected by the ELISA method on the day before operation, 1 day, 3 days, 5 days and 7 days after operation, respectively. The data was statistical analyzed to detect the relationships between/among the inflammatory factors mentioned above and ulina-statin and time. Results The variation of the levels of IL-6, IL-8, IL-9, and IL-10 were changed by the intervention of ulina-statin at different time. The differences of the levels of IL-6, IL-8, IL-9, and IL-10 between the ulinastatin intervention group and the control group were not significant on the day before operation, 1 day and 3 days after operation (t = -1.15 to 1.82, all P > 0.05), but the levels of IL-6, IL-8, IL-9, and IL-10 of the ulinastatin intervention group were significantly lower than those of the control group and there were statistically significant differences 5 days and 7 days after the operation (t = 3.22 and 23.51, both P<0.05) . Conclusion Ulinastatin has a good effect in inhibiting the inflammatory factors and can protect and repair the postoperative hepatic injury as well in patients with hepatic cystic echinococcosis.

Objective To screen the effective parts of loosening bowel and relieving constipation in mice from different extracted parts of Angelica and to investigate the utilization of fuzzy matter-element model in evaluating the effect of moisturizing intestine to relaxing the bowels of Angelica's different extracted parts.Methods Kunming mice were randomly divided into 11 groups,including normal group,model group (constipation),positive control group (Nongsuo Danggui Wan and Runchang Wan:20 μL · g-1),medicated group consisted by 7 different extracted parts of Angelica (3.4 g · kg-1 Angelica herbs).The constipation model was formed by the compound difenoxate solution 5.0 mg · kg-1 and finished after 30 min.We used the first defecation time as well as the dark stool points in 6 h,the weight of stools,the pushing rate of intestine and intestinal moisture as detection index and then using fuzzy matter-element model on variation coefficient weight to evaluate the comprehensive effect of different extract parts of Angelica.Results Time of first black stool discharge as well as the dark stool points in 6 h,the weight of stools,the pushing rate of intestine and intestinal moisture in model group were (241.90 ± 48.10) min,(9.00 ± 5.40) count,(149.10 ± 86.80) mg,(48.90 ± 16.50) ％,(1.45 ± 0.16) g,respectively.The 70％ ethanol impregnation part (part 2) on the factors were (172.60 ± 40.70) min,(17.30 ± 4.50) count,(223.70 ± 63.40) mg,(73.70 ± 13.10) ％,(1.71 ± 0.18) g,respectively.The difference between part 2 and model group was statistically significant in the factors (P ＜0.05 or P ＜0.01).Combining with the result of the value of Euclid approach degree,the maximum is 0.71 (part 2:70％ alcohol impregnation part).Conclusion The 70％ alcohol impregnation part is the effective part of loosening bowel to relieve constipation in mice.The method and model can be used to objectively evaluate the effect of moisturizing intestine to relaxing the bowels of Angelica' s different extracted parts.

OBJECTIVETo investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.

METHODSThe dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.

RESULTSMatrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).

CONCLUSIONCYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.

Alkaloids ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; pathology ; Pyrimidines ; pharmacology ; Quinolizines ; pharmacology ; Thiazoles ; pharmacology

OBJECTIVETo investigate the effects of cycle-dependent kinase (CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia (AML) HL-60 cells and its molecular mechanisms.

METHODSCultured AML HL-60 cells were treated with various concentrations of SNS-032. Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK2/STAT3 pathway were detected by Western blotting.

RESULTSApoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9±1.7)%, (12.1±3.1)% and (59.4±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032. MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378c were down-regulated by SNS-032,whereas the levels of miR-320a and miR-H7* were up-regulated. Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT3 and protein expression of JAK2,C-MYC and MCL-1.

CONCLUSIONCDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family.

Apoptosis ; Cell Survival ; Down-Regulation ; Flow Cytometry ; HL-60 Cells ; Humans ; Janus Kinase 2 ; metabolism ; MicroRNAs ; metabolism ; Oxazoles ; pharmacology ; Phosphorylation ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Thiazoles ; pharmacology

Objective: To investigate the effects of cycle-dependent kinase ( CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia ( AML) HL-60 cells and its molecular mechanisms .Methods:Cultured AML HL-60 cells were treated with various concentrations of SNS-032 .Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK 2/STAT3 pathway were detected by Western blotting .Results:Apoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9 ±1.7)%, (12.1 ± 3.1)% and (59.4 ±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032.MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378 c were down-regulated by SNS-032 , whereas the levels of miR-320a and miR-H7* were up-regulated.Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT 3 and protein expression of JAK 2, C-MYC and MCL-1.Conclusion:CDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family .

OBJECTIVETo explore diagnosis and treatments of invasive pulmonary aspergillosis (IPA) in children with non-hematologic diseases.

METHODTwenty one patients without hematological malignancy were diagnosed with proven or possible IPA from July 2002 to June 2008. The risk factors, clinical manifestations, chest radiographic findings, microbiological and histopathological evidence, diagnostic procedures, treatment and prognosis were retrospectively reviewed.

RESULTFive children had proven IPA, and 16 patients had possible IPA. Thirteen children were classified as having acute invasive pulmonary aspergillosis (AIPA), eight children as having chronic necrotizing pulmonary aspergillosis (CNPA). Definitive diagnosis of primary immunodeficiency (PID) was made in 6 children (4 with chronic granulomatous disease, 2 with cellular immunodeficiency); three children were suspected of having PID. Corticosteroids and multiple broad-spectrum antibiotics had been administered in 5 patients (3 of these 5 patients also had invasive mechanical ventilation). Two children had underlying pulmonary disease. Three patients had unknown risk factors. Among these three patients, two had history of environmental exposure. Fever and cough were present in all the children. Fine rales were found in nineteen children. Six children had hepatosplenomegaly. The common roentgenographic feature of AIPA in 13 patients was nodular or mass-like consolidation with multiple cavity. "air-crescent" was seen in 10 of patients with AIPA. Lobar consolidation with cavity and adjacent pleural thickening was found in all children with CNPA. The positive rate of sputum and/or BALF culture in AIPA and CNPA were 72.1% and 22.4%, respectively. A large number of septate hyphae on wet smear were found in all of the children whose sputum and/or BALF culture were positive. Lung biopsy was performed in 3 children with CNPA, and necrosis, granulomatous inflammation, as well as septate, branching hyphae were observed on histopathologic examination. Fifteen children were treated with anti-fungal therapy (amphotericin B, voriconazole, itraconazole and caspofungin used alone or in combination), symptoms and lung lesions resolved in 12 children. Three children died. Six children did not receive anti-fungal therapy and died. The side effects of amphotericin B include chill, fever, hypokalemia and transient increase in BUN, none of which needed discontinuation of the antifungal therapy. Children had a good tolerance to fluconazole and caspofungin, there were no apparent side effects.

CONCLUSIONMost of the children without hematologic diseases who suffered from invasive pulmonary aspergillosis had risk factors or exposure history. Roentgenographic findings were relatively characteristic for invasive pulmonary aspergillosis. Risk factors and roentgenographic findings were clues to consider clinically invasive pulmonary aspergillosis. Sputum culture was the key point to clinical diagnosis. The patients in whom the antifungal therapy was initiated early had a good outcome.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Invasive Pulmonary Aspergillosis ; diagnosis ; etiology ; therapy ; Male ; Retrospective Studies