Mouse promyelocytic leukemia zinc finger protein (PLZF) regulates hepatic lipid and glucose homeostasis dependent on SIRT1.

Previous studies have demonstrated that promyelocytic leukemia zinc finger protein (PLZF) promotes the expression of gluconeogenic genes and hepatic glucose output, which leads to hyperglycemia. However, the role played by PLZF in regulating lipid metabolism is not known. In this study, we aimed to examine the function of PLZF in regulating hepatic lipid and glucose homeostasis and the underlying mechanisms. The expression of PLZF was determined in different mouse models with regard to non-alcoholic fatty liver disease (NAFLD). In the next step, adenoviruses that express PLZF (Ad-PLZF) or PLZF-specific shRNA (Ad-shPLZF) were utilized to alter PLZF expression in mouse livers and in primary hepatocytes. For the phenotype of the fatty liver, histologic and biochemical analyses of hepatic triglyceride (TG), serum TG and cholesterol levels were carried out. The underlying molecular mechanism for the regulation of lipid metabolism by PLZF was further explored using luciferase reporter gene assay and ChIP analysis. The results demonstrated that PLZF expression was upregulated in livers derived from ob/ob, db/db and diet-induced obesity (DIO) mice. Liver PLZF-overexpressing C57BL/6J mice showed fatty liver phenotype, liver inflammation, impaired glucose tolerance and insulin sensitivity. On the other hand, hepatic PLZF knockdown in db/db and DIO mice alleviated hepatic steatosis. Of note, we found that PLZF activates SREBP-1c gene transcription through binding directly to the promoter fragment of this gene, which would induce a repressor-to-activator conversion depending on its interaction with SIRT1 in the role played by PLZF in the transcription process through deacetylation. Thus, PLZF is identified as an essential regulator of hepatic lipid and glucose metabolism, where the modulation of its liver expression could open up a therapeutic path for treating NAFLD.

Automatic system for high-throughput and high-sensitivity diagnosis of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had severe consequences for health and the global economy. To control the transmission, there is an urgent demand for early diagnosis and treatment in the general population. In the present study, an automatic system for SARS-CoV-2 diagnosis is designed and built to deliver high specification, high sensitivity, and high throughput with minimal workforce involvement. The system, set up with cross-priming amplification (CPA) rather than conventional reverse transcription-polymerase chain reaction (RT-PCR), was evaluated using more than 1000 real-world samples for direct comparison. This fully automated robotic system performed SARS-CoV-2 nucleic acid-based diagnosis with 192 samples in under 180 min at 100 copies per reaction in a "specimen in data out" manner. This throughput translates to a daily screening capacity of 800-1000 in an assembly-line manner with limited workforce involvement. The sensitivity of this device could be further improved using a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based assay, which opens the door to mixed samples, potentially include SARS-CoV-2 variants screening in extensively scaled testing for fighting COVID-19.

Prognostic significance of combined pretreatment body mass index (BMI) and BMI loss in patients with esophageal cancer.

Background: Body mass index (BMI) has been associated with a risk of esophageal cancer. However, the influence of BMI and BMI loss on people with esophageal cancer that were treated with different therapies has not been described in China. Methods: In total, 615 consecutive patients that underwent esophagectomy and/or chemotherapy/radiotherapy were classified according to the Asian-specific BMI (kg/m2) cutoff values. The impact of BMI and BMI loss on long-term overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results: Multivariate analysis showed that overweight and obese patients had a more favorable survival than normal weight and underweight patients (p=0.017). Patients with a low BMI and high BMI loss before therapy had worse OS than others (p=0.001). Subgroup analysis showed that patients with a high BMI were more likely to suffer hypertension (p<0.001) and receive only surgery (p<0.001), and they were less likely to be smokers (p=0.007) and anemic (p<0.001). Conversely, patients with high BMI loss were more likely to be anemic (p=0.001), to have advanced pathological stage (p=0.012), and to receive chemotherapy and radiotherapy (p=0.001). Moreover, the mortality rate was higher when patients had a high BMI loss. There is no survival benefit of higher BMI in the non-esophageal squamous cell carcinoma (ESCC) group. Conclusion: Pretreatment BMI was an independent prognostic factor for long-term survival in esophageal cancer patients treated with different treatments. The overall survival was increased in esophageal cancer patients with a high pretreatment BMI and no BMI loss. There is no survival benefit of higher BMI in the non-ESCC group.

Laboratory and Molecular Characterization of Dengue Viruses in a 2014 Outbreak in Guangfo Region, Southern China.

Non-specific symptoms and low viremia levels make early diagnosis of dengue virus (DENV) infection challenging. This study aimed to i) identify laboratory markers that can be used to predict a DENV-positive diagnosis and ii) perform a molecular characterization of DENVs from the 2014 Guangdong epidemic. This retrospective study analyzed 1,044 patients from the Guangdong epidemic who were clinically suspected cases of dengue. Viral RNA was detected by real-time RT-PCR, and viral-specific NS1 antigen was detected using enzyme-linked immuno sorbent assay. A molecular phylogenetic analysis was performed for the with the DENV C-prM gene junction. Patients with dengue infection had leukopenia (2.8 × 109/L), thrombocytopenia (109.0 × 109/L), elevated aspartate aminotransferase (56.0 IU/L) and alanine aminotransferase (43.5 IU/L), and prolonged activated partial thromboplastin time (APTT, 33.5 s) (all P ＜ 0.001) compared to patients without dengue. The positive predictive value of leukopenia and thrombocytopenia for DENV infection were 96.9% and 93.0%, respectively. Leukopenia, thrombocytopenia, elevated aminotransferases, and prolonged APTT were useful predictive markers for an early diagnosis of DENV infection. Phylogenetic analysis indicated that the DENVs from the 2014 epidemic were closely related to a 2010 New Delhi strain and a 2013 Guangzhou strain. The 2014 epidemic consisted of co-circulating DENV-1 genotypes I and V from multiple origins. Efficient dengue surveillance can facilitate rapid response to future outbreaks.

Molecular epidemiology and characteristic of virulence gene of community-acquired and hospital-acquired methicillin-resistant Staphylococcus aureus isolates in Sun Yat-sen Memorial hospital, Guangzhou, Southern China.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of both hospital and community infections globally. It's important to illuminate the differences between community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA), but there have been confusions on the definition, especially for the MRSA isolates identified within 48 h of admission. This study aimed to determine the molecular characteristics and virulence genes profile of CA and HA-MRSA isolates identified less than 48 h after hospital admission in our region. METHODS: A total 62 MRSA isolates identified within 48 h after admission and the clinical data were collected. Antimicrobial susceptibility test (AST) of collected isolates were performed according to the guidelines of Clinical and Laboratory Standards Institute (CLSI) 2015, and staphylococcal cassette chromosome mec (SCCmec) typing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and virulence gene profiling were performed to explore the molecular diversity. RESULTS: SCCmec III and sequence type (ST) 239 were the most prevalent SCCmec type and ST in both CA and HA-MRSA groups. HA-MRSA group had higher prevalence of SCCmec III (87.2 %) and ST239 (79.5 %) compared with CA-MRSA (60.9 and 43.4 %, both P < 0.001), while the frequency of SCCmec IV (26.0 %) and ST59 (21.7 %) were higher in CA-MRSA than its counterpart (P < 0.001 and P = 0.003). MRSA-ST239-III was the predominant type in this study (61.3 %, 38/62), especially in HA-MRSA group (76.9 %, 30/39). However, CA-MRSA strains exhibited more diversity in genotypes in this study. Meanwhile, CA-MRSA tended to have lower resistant percentage to non-ß-lactams antibiotics but more virulence genes carriage, especially the staphylococcal enterotoxins (SE) genes. Notably, seb gene was only detected in CA-MRSA isolates (52.2 %), likely a significant marker for CA-MRSA isolates. Panton-Valentine leukocidin gene (PVL) was highly detected in both groups, while appeared no significantly different between CA-MRSA (47.8 %) and HA-MRSA (43.6 %). CONCLUSIONS: Our findings support a difference in the molecular epidemiology and virulence genes profile of CA-MRSA and HA-MRSA. Furthermore, this study indicates a possible transmission from HA-MRSA to CA-MRSA, which may cause the overlap of the definition.

Low Frequency of Peripheral Lymphocyte in Chronic Hepatitis B Patients Predicts Poor Progression to Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and the second leading cause of cancer-related deaths worldwide. The poor prognosis of HCC is mainly because of its discovery at advanced stages. Because chronic hepatitis B (CHB) accounts for 50-80% HCC occurrence worldwide, and immunity is regarded as an emerging hallmark of cancer, we investigated the predictive role of peripheral immune cells in HCC incidence in CHB patients. METHODS: This investigation collected and analyzed data from 89 CHB patients, 94 primary HCC patients with hepatitis B virus (HBV), 81 primary HCC patients without HBV, 69 normal healthy patients, and 257 CHB patients with at least 3-year regular followup. RESULTS: The results demonstrated that CHB and primary HCC patients had different concentrations of lymphocytes, neutrophils, and monocytes in their peripheral circulation. Further study showed that the peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients during the 3 years of followup. Finally, a predictive HCC incidence model with an AUROC (area under the receiver operating characteristic) of 0.832 was constructed based on the peripheral lymphocyte concentration, serum alpha-fetoprotein (AFP) concentration, and cirrhosis status of CHB patients. CONCLUSIONS: The peripheral lymphocyte concentration was an independent prognostic factor for HCC incidence in CHB patients, and a more accurate predictive model based on peripheral lymphocytes, serum AFP, and cirrhosis status was constructed.

Differences in Staphylococcus aureus nasal carriage and molecular characteristics among community residents and healthcare workers at Sun Yat-Sen University, Guangzhou, Southern China.

BACKGROUND: The pathogenic potential and commensal nature of Staphylococcus aureus allows for easy transmission both within and outside of the hospital environment, and nasal carriage may be responsible for some serious infections. This study aimed to determine the molecular and epidemiological characteristics of nasal colonization by S. aureus in community residents (CR) and healthcare workers (HW) at Sun Yat-Sen University, Guangzhou, China. METHODS: A total of 589 volunteers, both CR (n = 297) and HW (n = 292), were recruited. Each subject completed a questionnaire, and specimens were obtained from the anterior nares for S. aureus screening. Genotypic analysis included pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and virulence gene detection. RESULTS: A total of 138 S. aureus isolates were recovered from separate subjects (23.4%, 138/589), with four isolates showing methicillin resistance (0.7%, 4/589). The prevalence of S. aureus carriage was 25.3% (75/297) in CR and 21.6% (63/292) in HW. Methicillin-resistant S. aureus (MRSA) were isolated from one CR (0.3%, 1/297) and three HW (1.0%, 3/292). The most common risk factors for S. aureus carriage in CR were being male, age ≤ 30 years, and nasal cavity cleaning habits. Having a household member in the healthcare profession was associated with increased risk among HW. Sequence type (ST)188 and ST59 were the most prevalent among the 20 observed STs, accounting for 14.6% and 12.2% of all isolates, respectively. The four MRSA isolates presented four different STs, with one isolate carrying a type IVa SCCmec element and the other three isolates containing type III SCCmec. PFGE analysis grouped the 129 isolates into 23 pulsotypes, with profiles A, N, E, L, and O the most prevalent. The Panton-Valentine leucocidin gene (pvl) was identified in two of the 138 isolates, while 57.5% of isolates carried both the Staphylococcus aureus enterotoxin A (sea) and enterotoxin B (seb) genes. CONCLUSIONS: These data indicate a low prevalence of nasal MRSA carriage but evidence of molecular heterogeneity among S. aureus isolates from CR and HW at Sun Yat-Sen University, Guangzhou. Differences in epidemiological and molecular characteristics of S. aureus between CR and HW populations may be useful for the understanding and prevention of S. aureus infection.

Neutrophil-to-Lymphocyte Ratio Positively Correlates to Age in Healthy Population.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) was reported to be an independent easy-to-measure marker for many diseases, while the distribution of NLR in healthy population was not formally studied. So we investigated NLR in healthy people in this study. METHODS: Data include NLR, systolic pressure, diastolic pressure, and body mass index (BMI), which were collected from 3,262 healthy population. Correlations of NLR with variables were analyzed with SPSS16.0. RESULTS: Results demonstrated that NLR was positively associated with age (P < 0.001). The eldest age group possessed the highest NLR and the youngest age group had the lowest NLR. NLR was also slightly positively associated with systolic pressure, diastolic pressure, and BMI (P < 0.001). CONCLUSION: Older people possessed relatively high NLR in healthy population.