101 women; median age was 47•5 years (range 7-90). The most common symptoms at onset of illness were fever (193 [84%] patients), cough (159 [69%] patients), and sputum production (98 [43%] patients). Diarrhoea was observed in 49 (21%) patients. Patients with diarrhoea were older and were more likely to have comorbidities than patients without diarrhoea (table). A greater proportion of patients admitted to hospital had diarrhoea as the outbreak progressed: nine (43%) of 21 patients admitted between Feb 12 and March 6, 2020, had diarrhoea versus 40 (19%) of 209 patients admitted between Jan 19 and Feb 11, 2020.More patients with diarrhoea showed severe symptoms of pneumonia hospitals in Guangdong province, two in Hubei province, and ten in Jiangxi province) between Jan 19, 2020, and March 6, 2020. Most patients were admitted because of fever, cough, dyspnoea, and chest CT findings consistent with COVID-19 pneumonia. Diagnosis of COVID-19 was based on positive SARS-CoV-2 RNA tests. Two patients with pre-existing digestive diseases were excluded from our analysis. The analysis was approved by the institutional review boards of Sun Yat-sen University and the participating hospitals. Full details of the methods used are in the appendix (p 1).The clinical and demographic characteristics of the 230 patients analysed are shown in the appendix (p 2). There were 129 men and

Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2β and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment.

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MicroRNAs (miRNAs) are stably expressed in serum, which could serve as great potential prognostic biomarkers in a variety of diseases, including various cancers. We analyzed the miRNA expression profiles to investigate the role of serum miRNA in predicting response to rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone (R-CHOP) treatment in diffuse large B cell lymphoma (DLBCL) patients. The present study proceeded through three phases. In the discovery phase, real-time polymerase chain reaction (PCR)-based miRNA profiling was used to test the difference in levels of serum miRNAs between 20 patients with complete remission after 6 cycles of R-CHOP treatment and 20 patients with primary refractory disease matched by age, sex, and stage. After the marker selection phase, the selected serum miRNAs were validated in 133 patients using the quantitative reverse transcriptase-PCR assays during the validation phases. Fifteen serum miRNAs were found to be altered more than 10-fold by real-time PCR-based miRNA profiling between the complete remission and primary refractory groups. The levels of five miRNAs (miR-224, miR-455-3p, miR-1236, miR-33a, and miR-520d-3p) were significantly associated with response to R-CHOP treatment in DLBCL patients. The five-miRNA signature was also a significant predictor of response independent from the International Prognostic Index score. The expression levels of these five serum miRNAs may serve as novel prognostic biomarkers to predict the clinical outcome of DLBCL patients treated with R-CHOP regimen.

Bromodomain PHD finger transcription factor (BPTF), a core subunit of nucleosome-remodeling factor (NURF) complex, plays an important role in chromatin remodeling. However, its precise function and molecular mechanism involved in hepatocellular carcinoma (HCC) growth are still poorly defined. Here, we demonstrated the tumor-promoting role of BPTF in HCC progression. BPTF was highly expressed in HCC cells and tumor tissues of HCC patients compared with normal liver cells and tissues. Knockdown of BPTF inhibited cell proliferation, colony formation and stem cell-like traits in HCC cells. In addition, BPTF knockdown effectively sensitized the anti-tumor effect of chemotherapeutic drugs and induced more apoptosis in HCC cells. Consistently, knockdown of BPTF in a xenograft mouse model also suppressed tumor growth and metastasis accompanied by the suppression of cancer stem cells (CSC)-related protein markers. Moreover, the mechanism study showed that the tumor-promoting role of BPTF in HCC was realized by transcriptionally regulating the expression of human telomerase reverse transcriptase (hTERT). Furthermore, we found that HCC patients with high BPTF expression displayed high hTERT expression, and high BPTF or hTERT expression level was positively correlated with advanced malignancy and poor prognosis in HCC patients. Collectively, our results demonstrate that BPTF promotes HCC growth by targeting hTERT and suggest that the BPTF-hTERT axis maybe a novel and potential therapeutic target in HCC.