Atypical pneumonia caused by Chlamydia psittaci during the COVID-19 pandemic.

OBJECTIVES: Here, we retrospectively described the diagnosis and treatment of 32 cases diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic. METHODS: Clinical information was collected from all the patients. Reverse transcription-PCR and ELISAs were conducted for the detection of COVID-19 using nasal swabs and bronchoalveolar lavage fluid (BALF) samples. Metagenomic next-generation sequencing (mNGS) was performed for the identification of causative pathogens using BALF, peripheral blood and sputum samples. End-point PCR was performed to confirm the mNGS results. RESULTS: All 32 patients showed atypical pneumonia and had infection-like symptoms that were similar to COVID-19. Results of reverse transcription-PCR and ELISAs ruled out COVID-19 infection. mNGS identified C. psittaci as the suspected pathogen in these patients within 48 hours, which was validated by PCR, except for three blood samples. The sequence reads that covered fragments of C. psittaci genome were detected more often in BALF than in sputum or blood samples. All patients received doxycycline-based treatment regimens and showed favorable outcomes. CONCLUSION: This retrospective study, with the highest number of C. psittaci pneumonia enrolled cases in China so far, suggests that human psittacosis may be underdiagnosed and misdiagnosed clinically, especially in the midst of the COVID-19 pandemic.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

Epidemiology of Drug- and Herb-Induced Liver Injury Assessed for Causality Using the Updated RUCAM in Two Hospitals from China.

Drug- and herb-induced liver injury (DILI and HILI) is an increasingly common and serious condition. Here, data for DILI and HILI patients from two large tertiary hospitals were retrospectively analyzed. Patient characteristics, causes and severity of DILI and HILI, the correlation between expression of p62 and the severity of DILI and HILI, treatment of DILI and HILI, and the prognostic factors of DILI and HILI were studied. A total of 82 patients with DILI and HILI were recruited for the study. Most patients presented with hepatocellular injury, followed by cholestatic injury and mixed injury. Our results indicate that traditional Chinese medicine or herbal and dietary supplements were the prevalent causal agents of HILI, which was characterized by higher frequencies of hepatocellular injury. Expression of p62 in the liver correlated with the severity of DILI and HILI. Improvements in the results of the liver enzymatic tests correlated with alanine transaminase (ALT) levels upon the first diagnosis of DILI and HILI and with the hepatocellular type of DILI and HILI. In conclusion, we provide an epidemiological assessment of DILI and HILI based on causality using the updated RUCAM on patients from two hospitals in China. ALT levels at first diagnosis and the hepatocellular type of injury may be prognostic factors of DILI and HILI.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China.

BACKGROUND: Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient's serum to establish a solid pathogen diagnosis. CASE PRESENTATION: We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient's abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient's serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure. CONCLUSION: The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.

Inhibitory effects of genistein in combination with gefitinib on the hepatocellular carcinoma Hep3B cell line.

Combination therapy is an important method for treating advanced hepatocellular carcinoma (HCC). Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor, which has profound effects on HCC. The purpose of the present study was to investigate the effects of genistein in combination with gefitinib on the proliferation and apoptosis of HCC cells and the associated mechanism. Cell counting kit-8 assay was performed to calculate the IC50 values and cytotoxicity, whilst flow cytometry was used to assess cell apoptosis. Protein expression was detected using western blot analysis. The IC50 of genistein and gefitinib on Hep3B cells were calculated to be 128.078 and 13.657 µM, respectively. Genistein in combination with gefitinib significantly inhibited cell viability, promoted apoptosis and reduced EGFR, vascular endothelial growth factor receptor and platelet-derived growth factor receptor phosphorylation. Genistein in combination with gefitinib promoted the expression of cleaved caspase-3 and cleaved poly ADP-ribose polymerase. In addition, combined treatment of genistein and gefitinib strongly inhibited the activation of the Akt/Erk/mTOR signaling pathway. In conclusion, findings from the present study suggest that genistein in combination with gefitinib inhibit HCC cell proliferation and promote apoptosis by inhibiting the Akt/Erk/mTOR pathway.

LncRNA HOXA-AS3 Sponges miR-29c to Facilitate Cell Proliferation, Metastasis, and EMT Process and Activate the MEK/ERK Signaling Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high morbidity and mortality across the world. Recent findings have suggested that long noncoding (lnc)RNA HOXA-AS3 plays an important role in tumorigenesis and metastasis in a variety of cancers. However, the role of lncRNA HOXA-AS3 in the initiation and progression of HCC remains largely unclear. In the present study, HOXA-AS3 was highly expressed in HCC tumor tissues and cell lines. High HOXA-AS3 expression was correlated with low survival of HCC patients. Loss-of-function experiments showed that knockdown of HOXA-AS3 inhibited cell proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT) process, and the mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathway in HCC. Molecular mechanism exploration uncovered that HOXA-AS3 could directly interact with and negatively regulate miR-29c. BMP1 is a downstream target gene of miR-29c, and HOXA-AS3 could regulate BMP1 expression by targeting miR-29c. miR-29c negatively regulated and BMP1 promoted the progression of HCC. Rescue experiments revealed that miR-29c inhibitor could partially counteract the impact induced by HOXA-AS3 knockdown in HCC. Taken together, our study is the first to show the interaction of HOXA-AS3 with miR-29c in facilitating cell proliferation, metastasis, EMT process, and MEK/ERK signaling pathway in HCC.

Serum Proteomic Changes as Candidate Biomarkers of Intermediate Liver Fibrosis in Chronic Hepatitis B Infection.

Chronic hepatitis B (CHB) is a major global health burden. Liver fibrosis, an insidious process, is the main histopathological change in CHB that might lead to the end-stage liver disease if left untreated. The intermediate liver fibrosis (S2) is the optimal time to start antiviral therapy. The aim of the present study was to examine the proteomic changes in patients with CHB at different fibrotic stages, with a view to identify future serum biomarkers for S2. Ninety CHB patients were grouped into mild (S0-1), intermediate (S2), and severe liver fibrosis (S3-4) (61 men and 29 women; age 25-63 years). Isobaric tagging for relative and absolute quantitation was applied to screen proteins differentially expressed among the patient groups. Another 46 patients with CHB (age 25-59 years; 31 men and 15 women), and 16 healthy controls (age 26-61 years; 11 men and 5 women) were enrolled in a validation group. Enzyme-linked immunosorbent assay was used to verify the diagnostic value of the candidate biomarkers. We found 139 proteins that were differentially expressed between various fibrotic stage-paired comparisons. Five protein candidates were selected as potential biomarkers of S2 for further verification. Notably, ficolin-2 (FCN2) and carboxypeptidase B2 (CPB2) showed differential expression between patients and healthy controls. In conclusion, serum proteomic changes reported here offer new molecular leads for future research on biomarker candidates to identify liver fibrotic stages in CHB. In particular, FCN2 and CPB2 warrant further research on their possible mechanistic involvement in CHB pathogenesis.

Identification of potential metabolic biomarkers of cerebrospinal fluids that differentiate tuberculous meningitis from other types of meningitis by a metabolomics study.

Tuberculous meningitis (TBM) is caused by tuberculosis infection of of the meninges, which are the membrane systems that encircle the brain, with a high morbidity and mortality rate. It is challenging to diagnose TBM among other types of meningitis, such as viral meningitis, bacterial meningitis and cryptococcal meningitis. We aimed to identify metabolites that are differentially expressed between TBM and the other types of meningitis by a global metabolomics analysis. The cerebrospinal fluids (CSF) from 50 patients with TBM, 17 with viral meningitis, 17 with bacterial meningitis, and 16 with cryptococcal meningitis were analyzed using ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS). A total of 1161 and 512 features were determined in positive and negative electrospray ionization mode, respectively. A clear separation between TBM and viral, bacterial or cryptococcal meningitis was achieved by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) analysis. Potential metabolic markers and related pathways were identified, which were mainly involved in the metabolism of amino acid, lipids and nucleosides. In summary, differential metabolic profiles of the CSF exist between TBM and other types of meningitis, and potential metabolic biomarkers were identified to differentiate TBM from other types of meningitis.

Old age and hydrocephalus are associated with poor prognosis in patients with tuberculous meningitis: A retrospective study in a Chinese adult population.

Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis with a very poor prognosis. We aimed at assessing risk factors related to the prognosis of patients with TBM.Forty-five inpatients with TBM in our institution from January 2013 to December 2015 were enrolled retrospectively. The good or poor prognosis in the patients was defined, based on Glasgow Outcome Scale System at discharge. Patients with a GOS score less than 5 were defined as "poor prognosis." Univariate and multivariate logistic regression analyses were performed to assess the predictors for TBM outcome.Among 45 TBM patients, 35 (77.8%) and 10 (22.2%) were in good, poor prognoses, respectively. Old age, disturbance of consciousness, moderate to severe electroencephalogram abnormality, hydrocephalus, remarkable increase of protein (≥ 236 mg/dL) and white blood cell counts (≥ 243 /µL) in cerebral spinal fluid were associated with poor prognosis. Multivariate analysis indicated that old age (odds ratio (OR) = 18.395, P = .036) and hydrocephalus (OR = 32.995, P = .049) were independent factors for a poor outcome of TBM.In conclusion, old age and hydrocephalus are the predictors for poor prognosis of TBM. Patients with these risk factors should be treated promptly with a special care paid to improve their outcomes.

Clinical characteristics and prognostic factors of liver cirrhosis patients with systemic inflammatory response syndrome.

AIM: Our objective is to study the clinical characteristics of cirrhosis patients with SIRS and investigate its prognostic factors. METHODS: We analyzed 285 consecutive patients and their data were evaluated retrospectively. Data were compared in patients with/without SIRS during hospitalization. Univariate and multivariate Cox regression analyses were undertaken separately for cirrhotic patients with SIRS to assess predictive factors for 90-day mortality. RESULTS: The mortality was 38.24% (52/136) in patients with SIRS and 6.04% (9/149) in patients without SIRS for 90-day follow-up (P < 0.001). The univariate analysis showed gastrointestinal hemorrhage (P < 0.001), hepatic encephalopathy (P < 0.001), albumin <30 g/L (P < 0.037), creatinine (Cr) >175 µmol/L (P < 0.001), cholinesterase(ChE) activity <3000 U/L (P = 0.019), white blood cell count ≥10 000 (109/L) (P = 0.018), neutrophils ≥80% (P = 0.018), C-reactive protein (CRP) ≥25 mg/L (P < 0.001), procalcitonin ≥1.0 ng/mL (P = 0.007), Child-Pugh class C (P < 0.001), septicemia (P < 0.001), pulmonary infection (P < 0.001),multi-site infection (P = 0.001), acute-on-chronic liver failure (ACLF) (P < 0.001), and advanced hepatocellular carcinoma (HCC) (P < 0.001). In multivariate analysis, only Cr ≥175 µmol/L (hazard ratio [HR] = 2.768; confidence interval [CI], 1.53-5.04; P = 0.001), C-reactive protein ≥25 mg/L (HR = 3.179; CI, 1.772-7.03; P = 0.004), multi-site infection (HR = 19.427; CI, 7.484-50.431; P < 0.001), ACLF (HR = 7.308; CI, 3.048-17.521; P < 0.001), advanced HCC (HR = 2.523; CI, 1.019-6.248; P = 0.045) were independent predictors of 90-day mortality in cirrhotic patients with SIRS. CONCLUSION: Cr ≥ 175 µmol/L, CRP ≥ 25 mg/L, multi-site infection, ACLF, and advanced HCC independently predicted a higher rate of 90-day mortality in liver cirrhosis with SIRS.

Peliosis hepatis: 2 case reports of a rare liver disorder and its differential diagnosis.

RATIONALE: Peliosis hepatis (PH) is a rare tumor-like liver lesion composed of multiple blood-filled cavities within the liver parenchyma. It is hard to differentiate PH from other liver lesions by imaging, such as carcinoma, metastases, or abscess. PATIENT CONCERNS: Here, we reported 2 cases that presented with liver lesions under ultrasound and computed tomography (CT) scanning, without any history of liver diseases or drug usage traced back. DIAGNOSES: Liver biopsy and laparoscopy were processed, and the lesions were eventually diagnosed as PH by histopathology, which microscopically presented with multiple sinusoidal dilatations with blood-filled cystic spaces. INTERVENTIONS: After the liver biopsy or laparoscopy, the patients were discharged and followed up in the clinic. OUTCOMES: Both patients were followed up for at least 1 year with good recovery. LESSONS: PH should always be recognized in the differentiation of liver lesions, particularly indistinctive lesion(s) without any history of liver-related diseases.

Serum metabolomic signatures discriminate early liver inflammation and fibrosis stages in patients with chronic hepatitis B.

Chronic HBV (CHB) infected patients with intermediate necroinflammation and fibrosis are recommended to receive antiviral treatment. However, other than liver biopsy, there is a lack of sensitive and specific objective method to determine the necroinflammation and fibrosis stages in CHB patients. This study aims to identify unique serum metabolomic profile associated with histological progression in CHB patients and to develop novel metabolite biomarker panels for early CHB detection and stratification. A comprehensive metabolomic profiling method was established to compare serum samples collected from health donor (n = 67), patients with mild (G < 2 and S < 2, CHB1, n = 52) or intermediate (G ≥ 2 or S ≥ 2, CHB2, n = 36) necroinflammation and fibrosis. Multivariate models were developed to differentiate CHB1 and CHB2 from controls. A set of CHB-associated biomarkers was identified, including lysophosphatidylcholines, phosphatidylcholines, phosphatidylinositol, phosphatidylserine, and bile acid metabolism products. Stratification of CHB1 and CHB2 patients by a simple logistic index, the PIPSindex, based on phosphatidylinositol (PI) and phosphatidylserine (PS), was achieved with an AUC of 0.961, which outperformed all currently available markers. A panel of serum metabolites that differentiate health control, CHB1 and CHB2 patients has been identified. The proposed metabolomic biosignature has the potential to be used as indicator for antiviral treatment for CHB management.

Inhibition of MEK/ERK activation attenuates autophagy and potentiates pemetrexed-induced activity against HepG2 hepatocellular carcinoma cells.

Identification of efficient chemo-therapeutic/chemo-preventive agents for treatment of hepatocellular carcinoma (HCC) is important. In this study, we examined the activity of pemetrexed, an anti-folate chemotherapy drug, against HepG2 human HCC cells. Pemetrexed treatment in vitro exerted weak but significant cytotoxic activity against HepG2 cells. When analyzing the possible pemetrexed-resistance factors, we indentified that pemetrexed treatment in HepG2 cells induced cyto-protective autophagy activation, evidenced by GFP-light chain 3B (LC3B) puncta formation, p62 downregulation and Beclin-1/LC3B-II upregulation. Correspondingly, autophagy inhibitors, including bafliomycin A1, 3-methyladenine and chloroquine, enhanced pemetrexed-induced cytotoxicity against HepG2 cells. Further, RNAi-mediated knockdown of Beclin-1 in HepG2 cells also increased pemetrexed sensitivity. Pemetrexed activated MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular-signal-regulated kinase) signaling in HepG2 cells, which was required for autophagy induction. Pharmacological inhibition of MEK/ERK activation attenuated pemetrexed-induced autophagy, enhanced HepG2 cell death and apoptosis. In summary, pemetrexed activates MEK/ERK-dependent cyto-protective autophagy, and inhibition of this pathway potentiates pemetrexed's activity in HepG2 cells.

[Clinical significance of serum differential protein examination in chronic hepatitis B related liver fibrosis].

OBJECTIVE: To investigate the clinical significance of the expression of serum differential protein in patients with chronic hepatitis B (CHB) related liver fibrosis. METHODS: One hundred and ten CHB patients confirmed by liver biopsies were enrolled, 83 for modeling and 27 for verification. According to Ishak staging, 55 patients in the modeling group were with significant liver fibrosis ( F is more than or equal to 3 ) and 28 patients with normal/mild liver fibrosis ( F0-F2 ). While that in the verification group were 15 ( F is more than or equal to 3 ) and 12 ( F0-F2 ), respectively. MALDI-TOF-MS/MS was used to detect serum proteins and the spectrum for each sample was analyzed in FlexAnalysis3.0 to produce the spectrum of differential proteins. The results were compared with clinicopathologic diagnosis and the diagnosis model based on genetic algorithm was established and evaluated. RESULTS: There were 15 proteins differentially expressed in significant liver fibrosis group and normal/mild fibrosis group ( P value is less than 0.01), in which the differences on proteins 2081.73 m/z and 1944.41 m/z were the most significant. Based on these two proteins, the coordinate system was set up and the diagnosis model based on genetic algorithm was established by six characteristic peaks. After detecting 12 cases of normal/mild liver fibrosis and 15 cases of significant liver fibrosis, the results showed that the diagnostic model could identify significant fibrosis ( F is more than or equal to 3 ) and normal/mild liver fibrosis ( F0-F2 ) at 100% recognition, 94.14% prediction and 100% accuracy. CONCLUSION: Serum differential proteins examination can be used for early prediction of CHB related fibrosis. The study provides the basis for non-invasive diagnosis of hepatic fibrosis according to identifying the potential differences of the serum samples from patients with HBV related fibrosis.