Autoantibody panel on small extracellular vesicles for the early detection of lung cancer.

This study evaluated a different form of autoantibody, which is on small extracellular vesicles (sEVs), as a biomarker for early detection of lung cancer. The sEVs were isolated from plasma by ultracentrifugation and validated with morphology and typical markers. The autoantibody levels were quantified by enzyme-linked immunosorbent assay, and further analysis indicated that the autoantibody panel on sEVs was better than that from serum to distinguish benign lung disease (n = 32) from lung cancer (n = 90). In the prospective study, autoantibody on sEVs performed better in identification of patients with a higher risk of lung cancer. Furthermore, with immunogold labeling transmission electron microscopy, Nanoflow cytometry and binding tests, we illustrated that the autoantibodies could bind to the antigens on sEVs, which may explain the detected autoantibodies on sEVs. Besides, the binding resulted in the attenuation of complement-mediated cytotoxicity, which may contribute to the immune escape of lung cancer.

Serum macrophage inhibitory cytokine-1 serves as a novel diagnostic biomarker of early-stage colorectal cancer.

BACKGROUND: Patients with colorectal cancer usually have a poor prognosis because of the absence of suitable biomarkers for diagnosing asymptomatic patients. Here we determined the ability of MIC-1 to detect precancerous lesions and CRC in an asymptomatic cohort from CRC Screening Program. METHODS: We screened 2759 subjects with risk factors. Endoscopic and histopathological analyses revealed that 19 and 47 subjects had CRC or precancerous lesions. We randomly selected 24 subjects with normal colonoscopies as healthy controls. We used receiver operating characteristic curve analysis to evaluate the diagnostic efficacy of MIC-1 for CRC and precancerous lesions. RESULTS: The optimal thresholds of MIC-1 levels with precancerous lesions or CRC were 314.12 pg/mL (sensitivity, 91.50%; specificity, 54.20%) and 357.64 pg/mL (sensitivity, 82.40%; specificity, 70.80%). Moreover, MIC-1 levels distinguished precancerous lesions better than CEA, CA19-9, or CA24-2 (AUC: 0.760 vs. 0.529, 0.624, and 0.585) or CRC (AUCs: 0.821 vs. 0.743, 0.657, and 0.688) from the healthy controls. The combination of MIC-1, CEA, CA19-9, and CA24-2 showed the highest in sensitivity and specificity for CRC diagnosis (sensitivity, 94.10%; specificity, 87.50%). CONCLUSIONS: Serum MIC-1 levels increased the sensitivity of detection of precancerous colorectal lesions and CRC and can be used to improve screening.

Analysis and validation of a highly sensitive one-step nested quantitative real-time polymerase chain reaction assay for specific detection of severe acute respiratory syndrome coronavirus 2.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is posing a serious threat to global public health. Reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. Due to technical limitations, the reported positive rates of qRT-PCR assay of throat swab samples vary from 30 to 60%. Therefore, the evaluation of alternative strategies to overcome the limitations of qRT-PCR is required. A previous study reported that one-step nested (OSN)-qRT-PCR revealed better suitability for detecting SARS-CoV-2. However, information on the analytical performance of OSN-qRT-PCR is insufficient. METHOD: In this study, we aimed to analyze OSN-qRT-PCR by comparing it with droplet digital PCR (ddPCR) and qRT-PCR by using a dilution series of SARS-CoV-2 pseudoviral RNA and a quality assessment panel. The clinical performance of OSN-qRT-PCR was also validated and compared with ddPCR and qRT-PCR using specimens from COVID-19 patients. RESULT: The limit of detection (copies/ml) of qRT-PCR, ddPCR, and OSN-qRT-PCR were 520.1 (95% CI: 363.23-1145.69) for ORF1ab and 528.1 (95% CI: 347.7-1248.7) for N, 401.8 (95% CI: 284.8-938.3) for ORF1ab and 336.8 (95% CI: 244.6-792.5) for N, and 194.74 (95% CI: 139.7-430.9) for ORF1ab and 189.1 (95% CI: 130.9-433.9) for N, respectively. Of the 34 clinical samples from COVID-19 patients, the positive rates of OSN-qRT-PCR, ddPCR, and qRT-PCR were 82.35% (28/34), 67.65% (23/34), and 58.82% (20/34), respectively. CONCLUSION: In conclusion, the highly sensitive and specific OSN-qRT-PCR assay is superior to ddPCR and qRT-PCR assays, showing great potential as a technique for detection of SARS-CoV-2 in patients with low viral loads.

Bacteremia Caused by Turicella otitidis in a Patient with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Invasive Gram-positive bacilli infections are commonly encountered in immunocompromised patients. In this paper, we report a bacteremia caused by Turicella otitidis in a patient with diffuse large B-cell lymphoma. METHODS: Bacteria was identified by VITEK MALDI-TOF MS. Drug sensitivity was analyzed by disk diffusion method. RESULTS: MALDI-TOF MS data demonstrated that the infection bacteria was Turicella otitidis. Drug susceptibility data showed that Turicella otitidis was possibly sensitive to vancomycin, polymyxin B, and chloramphenicol. Body temperature of the patient dropped after administration of vancomycin. The data indicated that vancomycin could be used to treat the infections caused by Turicella otitidis. CONCLUSIONS: MALDI-TOF MS can be used for the rapid and accurate identification of Turicella otitidis. Vancomycin can be used to treat the infection caused by Turicella otitidis. This study may provide a reference for the diagnosis and treatment of Turicella otitidis.

Fungal Infection Caused by Geotrichum capitatum in a Severe Aplastic Anemia Patient: a Case Report and Review of the Literature.

BACKGROUND: Invasive fungal infections often occur in immunocompromised patients. Here, we report an infection case caused by Geotrichum capitatum in a severe aplastic anemia patient. METHODS: Identification of the pathogenic bacteria was done by sequencing and mass spectrometric analysis. RESULTS: The fungal infection was isolated from blood cultures. The pathogenic bacteria were identified as Geotrichum capitatum. The infection was primarily cured by voriconazole and caspofungin monotherapy. However, the effect was not obvious. Then a combination of liposomal amphotericin B and caspofungin was used. Body temperature of the patient decreased, and clinical symptoms improved. CONCLUSIONS: Sequencing and mass spectrometric analysis could have a role for Geotrichum capitatum diagnosis. Curative effect of using a single antifungal drug was unsatisfactory. Using liposome amphotericin B combined with caspofungin might obtain certain curative effect. Early diagnosis and appropriate combined therapy were necessary to improve the outcome of patients with Geotrichum capitatum infection.

LukS-PV-Regulated MicroRNA-125a-3p Promotes THP-1 Macrophages Differentiation and Apoptosis by Down-Regulating NF1 and Bcl-2.

BACKGROUND/AIMS: LukS-PV is a component of Panton-Valentine leukocidin (PVL). We have previously demonstrated that LukS-PV potently promoted differentiation and induced apoptosis in THP-1 cells. However, the precise mechanisms of these actions remain unknown. MicroRNAs (miRs) play important roles in cellular differentiation and apoptosis. This study aimed to investigate the role of miR-125a-3p in LukS-PV-regulated differentiation and apoptosis and its underlying mechanism in THP-1 cells. METHODS: MicroRNA profiling analyses were conducted to determine differential miRNA expression levels in THP-1 cells treated with LukS-PV. Cell differentiation and apoptosis were measured in THP-1 cells by gain-of-function and loss-of-function experiments. Bioinformatics analysis and luciferase reporter assays were used to confirm the targets of miR-125a-3p. The effects of the miR-125a-3p targets on cellular differentiation were determined by knocking them down. RESULTS: MiR-125a-3p was up-regulated after treating the human monocytic leukaemia cell line THP-1 with LukS-PV. In addition, miR-125a-3p positively regulated apoptosis and differentiation in THP-1 cells treated with LukS-PV. Concordantly, luciferase reporter assays confirmed that neurofibromatosis type 1 (NF1) and B-cell lymphoma 2 (Bcl-2) were direct target genes of miR-125a-3p. Moreover, NF1 knockdown in THP-1 cells significantly promoted differentiation in vitro. Finally, the extracellular signal-regulated kinase (ERK) pathway, a downstream target of NF1, was activated after NF1 knockdown. CONCLUSIONS: These findings confirm that miR-125a-3p is involved in LukS-PV-mediated cell differentiation and apoptosis in THP-1 cells.

Water-promoted ortho-selective monohydroxymethylation of phenols in the NaBO2 system.

Water-promoted ortho-selective monohydroxymethylation of phenols in the NaBO2 system generates salicyl alcohols in 65-97% yields. A remarkable rate-enhancement by water was observed, and NaBO2 appeared to serve the dual role of a suitable base and an efficient chelating reagent. This protocol possesses many advantages such as short reaction times, expanded substrate scope, and high mono- and regio-selectivities. The experimental results were explained by the calculations based on local ionisation energy minima, leading to a possible reaction mechanism.

ACY1 Downregulation Enhances the Radiosensitivity of Cetuximab-Resistant Colorectal Cancer by Inactivating the Wnt/ß-Catenin Signaling Pathway.

Treatment of cetuximab-resistant colorectal cancer (CRC) is a global healthcare problem. This study aimed to assess the effects of radiotherapy on cetuximab-resistant CRC and explore the underlying mechanism. We established a cetuximab-resistant HCT116 cell line (HCT116-R) by extracorporeal shock. Differentially expressed mRNAs were screened from cells treated with different radiation doses using second-generation high-throughput sequencing. Sequence data showed that ACY1 was significantly downregulated in HCT116-R cells after irradiation. Analysis of the GEO and TCGA datasets revealed that high ACY1 expression was associated with lymph node metastasis and a poor prognosis in CRC patients. In addition, immunohistochemistry results from CRC patients revealed that ACY1 protein expression was related to cetuximab resistance and lymph node metastasis. These findings suggested that ACY1 may function as an oncogene to promote CRC progression and regulate the radiosensitivity of cetuximab-resistant CRC. As expected, ACY1 silencing weakened the proliferation, migration, and invasion abilities of HCT116-R cells after radiotherapy. Mechanistically, TCGA data demonstrated that ACY1 expression was closely related to the Wnt/ß-catenin pathway in CRC. We validated that radiotherapy first reduced ß-catenin levels, followed by decreased expression of the metastasis-related protein E-cadherin. Silencing ACY1 dramatically enhanced these changes in ß-catenin and E-cadherin after radiotherapy. In conclusion, ACY1 downregulation could enhance the radiosensitivity of cetuximab-resistant CRC by inactivating Wnt/ß-catenin signaling, implying that ACY1 may serve as a radiotherapy target for cetuximab-resistant CRC.

Impaired Self-Referential Cognitive Processing in Bipolar Disorder: A Functional Connectivity Analysis.

Patients with bipolar disorder have deficits in self-referenced information. The brain functional connectivity during social cognitive processing in bipolar disorder is unclear. Electroencephalogram (EEG) was recorded in 23 patients with bipolar disorder and 19 healthy comparison subjects. We analyzed the time-frequency distribution of EEG power for each electrode associated with self, other, and font reflection conditions and used the phase lag index to characterize the functional connectivity between electrode pairs for 4 frequency bands. Then, the network properties were assessed by graph theoretic analysis. The results showed that bipolar disorder induced a weaker response power and phase lag index values over the whole brain in both self and other reflection conditions. Moreover, the characteristic path length was increased in patients during self-reflection processing, whereas the global efficiency and the node degree were decreased. In addition, when discriminating patients from normal controls, we found that the classification accuracy was high. These results suggest that patients have impeded integration of attention, memory, and other resources of the whole brain, resulting in a deficit of efficiency and ability in self-referential processing.

Decline in serum progastrin-releasing peptide predicts the response of patients with small cell lung cancer to chemotherapy.

The utility of serum progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) as biomarkers for treatment monitoring and as prognostic factors was investigated in small cell lung cancer (SCLC) patients. Patients were first diagnosed pathologically at the First Affiliated Hospital of the University of Science and Technology of China and had their serum ProGRP and NSE levels measured using an electrochemiluminescence immunoassay. A total of 120 SCLC patients were enrolled. In responsive patients, ProGRP levels decreased significantly following two cycles of chemotherapy and continued to decline over the course of treatment. However, this decrease in ProGRP levels was not observed in non-responsive patients. Changes in ProGRP levels were more accurate than changes in NSE levels for monitoring the effects of chemotherapy in patients with SCLC. Following two treatment cycles or after the occurrence of drug resistance, changes in ProGRP levels in patients with low ProGRP levels at the time of diagnosis were not notably, regardless of whether or not patients were responders. The area under the receiver operating characteristic curve of the decline in ProGRP levels as a therapeutic biomarker of SCLC was 0.9643, and the cut-off value was 55.02%. A decline in ProGRP levels maybe a good predictor of objective response to chemotherapy in patients with SCLC with higher ProGRP levels at diagnosis. This model is expected to replace or be combined with imaging to predict chemotherapeutic treatment effects in patients with SCLC.

Serum 25 hydroxyvitamin D levels in alopecia areata, female pattern hair loss, and male androgenetic alopecia in a Chinese population.

BACKGROUND: It has been suggested that low vitamin D levels may affect the development of hair loss. AIMS: Our aim was to evaluate the serum 25-hydroxy vitamin D [25(OH)D] status in Chinese patients with alopecia areata (AA), female pattern hair loss (FPHL), and male androgenetic alopecia (MAGA) compared with healthy individuals. METHODS: We performed a case-control study including 443 AA patients, 657 FPHL patients, 777 MAGA patients, and 2070 normal controls (1064 male and 1006 female healthy individuals) from 2015 to 2017 to analyze the correlation of serum 25(OH)D levels and hair loss in a Chinese population. RESULTS: Serum 25(OH)D levels stratified by age, sex, and season were compared between patients and healthy individuals. AA patients' serum 25(OH)D levels were statistically lower than that of controls (P < .0001, α = .05). Serum 25(OH)D levels of FPHL patients (P < .0001, α = .05) and MAGA patients (P = .0005, α = .05) were also significantly lower than counterpart control subjects. CONCLUSION: Our findings suggest an association between serum 25(OH)D levels and alopecia areata, female pattern hair loss, or male androgenetic alopecia in a Chinese population.

LukS-PV induces differentiation by activating the ERK signaling pathway and c-JUN/c-FOS in human acute myeloid leukemia cells.

LukS-PV, a component of Panton-Valentine leukocidin, is a pore-forming cytotoxin secreted by Staphylococcus aureus. Here we examined the potential effect of LukS-PV in differentiation of human leukemia cells and the underlying mechanism. We found that LukS-PV could induce differentiation of human acute myeloid leukemia (AML) cells, including AML cell lines and primary AML blasts, as determined by morphological changes, phagocytosis assay and expression of CD14 and CD11b surface antigens. In addition, LukS-PV activated the extracellular signal-regulated kinase (ERK) pathway and significantly upregulated the phosphorylation of c-JUN and c-FOS transcriptional factors in the process of differentiation. Inhibiting ERK pathway activation with U0126 (a MEK1/2 inhibitor) markedly blocked LukS-PV-induced differentiation and decreased the phosphorylation of c-JUN and c-FOS. These findings demonstrate an essential role for the ERK pathway together with c-JUN and c-FOS in the differentiation activity of LukS-PV. Taken together, our data suggest that LukS-PV could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of AML.

Real-time measurements of airborne biologic particles using fluorescent particle counter to evaluate microbial contamination: results of a comparative study in an operating theater.

BACKGROUND: Airborne bacterial contamination poses a risk for surgical site infection, and routine surveillance of airborne bacteria is important. Traditional methods for detecting airborne bacteria are time consuming and strenuous. Measurement of biologic particle concentrations using a fluorescent particle counter is a novel method for evaluating air quality. The current study was to determine whether the number of biologic particles detected by the fluorescent particle counter can be used to indicate airborne bacterial counts in operating rooms. METHODS: The study was performed in an operating theater at a university hospital in Hefei, China. The number of airborne biologic particles every minute was quantified using a fluorescent particle counter. Microbiologic air sampling was performed every 30 minutes using an Andersen air sampler (Pusong Electronic Instruments, Changzhou, China). Correlations between the 2 different methods were analyzed by Pearson correlation coefficients. RESULTS: A significant correlation was observed between biologic particle and bacterial counts (Pearson correlation coefficient = 0.76), and the counting results from 2 methods both increased substantially between operations, corresponding with human movements in the operating room. CONCLUSION: Fluorescent particle counters show potential as important tools for monitoring bacterial contamination in operating theatres.

[Influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy].

OBJECTIVE: To observe the influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy, and provide evidence for clinical application of auricular point sticking. METHODS: One hundred and twenty cases of selective gynecological laparoscopy under general anesthesia were randomly divided into an auricular point sticking group and a placebo group, 60 cases in each group. In the auricular point sticking group, the auricular point sticking with vaccaria seeds was applied at Shenmen (TF 4), Wei (CO 4) and Jiaogan (AH 6a) before the operation and 1, 5, 9, 23 h after the operation, which were pressed 5 min each point each time. The two ears were proceeded at the same time. In the placebo group, the same point selection, sticking paste was used as the auricular point sticking group, but no sticking or pressing with vaccaria seeds was adopted. The incidence of nausea and vomiting, the usage rate of tropisetron and morphine within 24 hours of the operation, as well as the score of visual analogue scale (VAS) and other adverse reactions at 2, 6, 10, 24 h after the operation were observed respectively. RESULTS: Compared with the placebo group, the incidence of nausea and vomiting [31.7% (19/60), 16.7% (10/60) vs 58.3% (35/60), 35.0% (21/60)], the usage rate of tropisetron [21.7% (13/60) vs 48.3% (29/60)] and morphine [18.3% (11/60) vs 38.3% (23/60)], the VAS scores at all different time points in the auricular point sticking group were all decreased (all P < 0.05), and no adverse reaction was observed. CONCLUSION: The auricular point sticking could significantly decrease the incidence of nausea and vomiting in patients of gynecological laparoscopy and has positive analgesic effect.