Locally advanced rectal cancer with dMMR/MSI-H may be excused from surgery after neoadjuvant anti-PD-1 monotherapy: a multiple-center, cohort study

ObjectiveExamine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR).MethodsLARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded.ResultsTwenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs.ConclusionNeoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT

Prevalence and clinical management of cytomegalovirus retinitis in AIDS patients in shanghai, china

<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus retinitis is a common AIDS-associated illness, leading to blindness in up to 30% of patients. This study was to investigate the prevalence and clinical management of the cytomegalovirus retinitis associated with AIDS in a large municipality of China.</p> <p>Methods</p> <p>Clinical and laboratory data from 23 cytomegalovirus retinitis patients (35 eyes) out of 303 hospitalized AIDS individuals in a single medical center were analyzed retrospectively. Two of 23 patients were diagnosed cytomegalovirus retinitis just before hospitalization without anti-CMV therapy. Ganciclovir combined with the high active anti-retroviral therapy was installed for treatment of cytomegalovirus retinitis after diagnosis was confirmed. The data were analyzed by specialists and statistics was also applied.</p> <p>Results</p> <p>The prevalence of cytomegalovirus retinitis in hospitalized AIDS patients was 7.6% in this study. The level of CD₄⁺T lymphocytes was correlated well with the occurrence of cytomegalovirus retinitis, showing 16.8% (19/113) (95% confidence interval: 10.4,25.0), 5.4% (3/56) (95% confidence interval: 1.1,14.9), and 1.4% (1/69) (95% confidence interval: 0.0,7.8) occurrence in the patients with CD₄⁺T lymphocyte counts < 50, 50~99, and 100~199 cells/μl, respectively. The mean CD₄⁺T lymphocyte counts was 31.7 ± 38.6 cells/μl in 23 AIDS patients with cytomegalovirus retinitis. Median CD₄⁺T lymphocyte count is 20 cells/μl with inter-quartile range as (5, 36). Seven patients died (11 eyes) and 16 patients (24 eyes) survived. The proportion of blindness and low vision in eyes infected with cytomegalovirus retinitis respectively was 20.8% (5/24) and 29.2% (7/24) when they were diagnosed in survivors. The ganciclovir therapy was effective in 16 patients (24 eyes). Clinical recovery of cytomegalovirus retinitis was 41.7% (10/24) and clinical improvement 58.3% (14/24). After anti-CMV treatment, the proportion of blindness or low vision was 16.7% (4/24).</p> <p>Conclusions</p> <p>The AIDS patients with CD₄⁺T lymphocyte < 50 cells/μl had increased susceptibility to cytomegalovirus associated retinitis. Cytomegalovirus retinitis is a serious disease causing blindness. The cytomegalovirus retinitis in the AIDS patients was response well to ganciclovir therapy. We should check their eyes routinely such as dilated fundus examination with an indirect ophthalmoscope in the AIDS patients with CD₄⁺T lymphocyte counts < 50 cells/μl.</p

USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase

Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow–derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I

Clinical features and prognosis of AIDS complicated by drug-induced liver injury: an analysis of 119 cases

ObjectiveTo investigate the clinical features and prognosis of AIDS patients complicated by drug-induced liver injury (DILI). MethodsA total of 119 patients who were diagnosed with AIDS in First Department of Infectious Diseases in Shanghai Public Health Clinical Center from January 2014 to December 2015 and met the diagnostic criteria for DILI were enrolled. The clinical data including medications, CD4+ T lymphocyte count, clinical manifestations, liver biochemical parameters, therapies, duration of liver injury, and prognosis were analyzed, and DILI type and classification were determined for all patients. The influence of DILI caused by different drugs on liver biochemical parameters was analyzed. The Wilcoxon rank sum test was used for comparison of continuous data between two groups and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. ResultsThe 58 patients who received highly active antiretroviral treatment (HAART) had significantly higher grade of liver injury (χ2=15.756, P＜0.001) and levels of total bilirubin (TBil) (Z=-3.466, P=0.010) and albumin (Alb) (Z=-1.968, P=0.049) than the 61 patients who did not. Among the patients who had a clear cause of DILI, 8 had DILI caused by antifungal drugs, 41 had DILI caused by antibacterial drugs, 18 had DILI caused by antitubercular agents, and 24 had DILI caused by antiviral drugs; the patients with DILI caused by antitubercular agents had a significantly higher level of TBil than those with DILI caused by other three types of drugs (H=12.804, P＜0.05), the patients with DILI caused by antibacterial drugs and antitubercular agents had a significantly lower level of Alb than those with DILI caused by the other two types of drugs (H=14.236, P＜0.05), and the patients with DILI caused by antitubercular agents and antiviral drugs had a significantly higher grade of liver injury than those with DILI caused by the other two types of drugs (χ2=16.373, P＜0.05). The hepatocellular injury-type patients had a shorter length of hospital stay (χ2=8.046, P=0.045). A high level of alkaline phosphatase and a low level of alanine aminotransferase indicated a longer length of hospital stay (Z=-2.943 and -2.592, both P＜0.05). ConclusionAIDS patients are given various drugs and have a high incidence rate of DILI. HARRT can aggravate liver injury, but it does not significantly affect patients' prognosis. Liver function examination should be performed regularly during clinical medication to know the state of liver inflammation and reduce the incidence rate of DILI in AIDS patients

Identification of the proto-inkstone by organic residue analysis: a case study from the Changle Cemetery in China

Abstract The inkstone is a specific writing implement in China that was popularized since the Han Dynasty (202 BC–AD 220). A rectangular/round grinding plate accompanied with a grinding stone is considered as a kind of proto-inkstone. However, little scientific investigation has been performed to support this hypothesis. In this paper, a micro-destructive approach, including Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and gas chromatography coupled with mass spectrometry (GC–MS), were employed to analyse the black residues on a grinding plate and a grinding stone excavated from the Changle Cemetery (202 BC–AD 8) in northwestern China. The FTIR and Raman analyses indicated that the residues were ancient ink. GC–MS analysis further identified that the residues were pine-soot ink, based on the relative abundances of the main polycyclic aromatic hydrocarbons, as well as the detection of conifer biomarkers. The trace of animal glue was not detected in the residues; thus, the ink was possibly formed as small pellets and the small grinding stone was necessary to assist during the ink-grinding process. This study confirms that this set of stone implements is indeed an early type of inkstone, and offers some insight into the co-evolution relationship between ink production and inkstone shapes

MOESM1 of Identification of the proto-inkstone by organic residue analysis: a case study from the Changle Cemetery in China

Additional file 1: Figure S1. Chinese inkstones from different periods: (a, b) a round/rectangular stone plate with a small grinding stone in the Western Han Dynasty (202 BC–AD 8)[1][2]; (c) a concave inkstone in the Wei-Jin Dynasties (AD 220–420)[3]; (d) an inkstone in the contemporary age (collected in National Museum of China). [1] HPICR (Hubei Provincial Institute of Cultural Relics) (1993) Fenghuangshan M168 of the Han Dynasty in Jiangling County (in Chinese), Acta Archaeologica Sinica, 4: 455-513. [2] Yun J (2015) Inkstones (in Chinese). Hangzhou City. Zhejiang Ancient Book Publishing House. [3] IA CASS (Institute of Archaeology, Chinese Academy of Social Sciences), MAT (Museum of Ancient Tombs in Luoyang) (1994) Excavation of Jing tomb of Xuanwu Emperor in the Northern Wei Dynasty (in Chinese), Archaeology, 9, 801-814

MOESM2 of Identification of the proto-inkstone by organic residue analysis: a case study from the Changle Cemetery in China

Additional file 2: Figure S2. The extraction solvent of chloroform/methanol (2:1 V/V) (a) and acetone (b) after centrifugation

MOESM3 of Identification of the proto-inkstone by organic residue analysis: a case study from the Changle Cemetery in China

Additional file 3: Figure S3. Total ion current (TIC) chromatograms of the modern pine soot samples with different sampling methods: (a) TIC chromatogram of PS 1, (b) TIC chromatogram of PS 2. Chromatographic peak assignments are shown in Additional file 6: Table S1