Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death.

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02).

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

[Clinical observation of sarcandra glabra combined chemoradiotherapy for treating patients with local advanced nasopharyngeal carcinoma].

OBJECTIVE: To observe the short-term efficacy and radiotherapy induced acute reactions of sarcandra glabra (SG) combined chemoradiotherapy for treating patients with local advanced nasopharyngeal carcinoma. METHODS: Totally 100 nasopharyngeal carcinoma phase III - IVa patients were randomly assigned to the control group and the observation group, 50 patients in each group. All patients received chemoradiotherapy. Patients in the observation group took SG decoction at the daily dose of 20 g. RESULTS: Totally 98 patients completed the treatment. There was no statistical difference in the complete remission rate, the partial remission rate, 1-year and 2-year total survival rates, or disease free progression rate between the two groups. The occurrence rate of II - III degree radioactive oral mucositis and dry mouth were obviously lower in the observation group than in the control group, showing statistical difference (P <0.05). CONCLUSION: SG combined chemoradiotherapy could attenuate radiotherapy induced acute adverse reactions in treating advanced nasopharyngeal carcinoma.

[Research on the quality changes in pre-and-post-processed pieces of Radix Polygalae].

OBJECTIVE: To study the quality changes in pre-and-post-processed pieces of Radix Polygalae. METHODS: The changes of the content of senegenin and polygalacic acid were studied. RESULTS: The content of polygalacic acid in post-processed piece was lower than that in pre-processed piece. The content of senegenin had no obvious difference. CONCLUSION: The processing can make the quality change.

[Clinical observation on treatment of 75 mid-late stage cancer patients with yanshu Injection].

OBJECTIVE: To study the effect of Yanshu Injection (YI) used in comprehensive treatment on mid-late stage cancer. METHODS: One hundred and fifty patients with malignant cancer were equally randomized into the comprehensive treatment group (group A) and the control group (group B), both groups were treated systematically according to the NCCN 2005 cancer practice guideline, but 20 ml of YI was given additionally to group A every day. RESULTS: After treatment, the level of plasma CD4 and CD4/CD8 ratio were significantly lower in group B than those in group A (P < 0.05); the response rate (RR) was 32.00% (24/75) and 38.67% (29/75) in group B and A respectively, showing insignificant difference (P>0.05), and the clinical benefit rate (CBR)was 58.67% (44/75) in group A, lower than that in group B (85.33% (64/75), P< 0.05); the quality of life (QOL) in group A was superior to that in group B (P<0.05); and the incidence of main adverse reaction to chemotherapeutic agents was significantly lower in group A as compared to that in group B (P<0.05). CONCLUSION: YI could regulate the function of T-lymphocyte subsets, raise the CBR and QOL and reduce adverse reaction of chemotherapy in patients with mid-late stage cancer.