Cytoplasmic expression of UTP23 promotes colorectal cancer progression.

UTP23 (UTP23 small subunit processome component) plays a pivotal role in the intricate processing and maturation of the small subunit of ribosomes within the nucleolus. In cases of nucleolar stress, such as those observed in certain tumor cells, the aberrant nucleolar organization and structure can lead to the translocation of nucleolar proteins into the nucleus or cytoplasm, consequently impacting the physiological processes of the tumor cells through non-ribosome-related functions. Our investigation revealed altered localization of UTP23 protein in colorectal cancer clinical tissue samples. Upon analyzing UTP23 expression and its correlation with patient prognosis in a cohort of 143 colorectal cancer patients, the result suggested that high cytoplasmic expression pattern of UTP23 was occured in early-stage metastasis-free colorectal cancer and was significantly associated with poor prognosis. Furthermore, we demonstrated that cytoplasmic expression of UTP23 significantly promoted the metastatic and invasive capabilities of colorectal cancer cells, which was not showed in the nucleollcalised UTP23. Intriguingly, mass spectrometry result suggested that KRT5 bind to UTP23 and showed a regulatory influence on UTP23 metastatic potential in colorectal cancer cells. Conclusively, our study demonstrated that the localization of UTP23 play a key role in colorectal cancer metastatic progression, which may serve as a novel prognostic indicator.

No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy / 中国结合医学杂志

OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Specific intracellular retention of circSKA3 promotes colorectal cancer metastasis by attenuating ubiquitination and degradation of SLUG.

Our previous study demonstrated that tumor-suppressor circular RNAs (circRNAs) can be specifically secreted outside of colorectal cancer (CRC) cells within exosomes to maintain tumor cell fitness. However, whether tumor-driving circRNAs can be specifically retained in cells to facilitate tumor progression remains unknown. In this study, circRNA-seq showed that circSKA3 was significantly upregulated in CRC tissues but downregulated in serum samples from CRC patients. In addition, circSKA3 promoted CRC progression in vitro and in vivo and was retained in CRC cells via a specific cellmotif element. Interestingly, the cellmotif element was also the site of interaction of circSKA3 with SLUG, which inhibited SLUG ubiquitination degradation and promoted CRC epithelial-mesenchymal transition (EMT). Moreover, FUS was identified as a key circularization regulator of circSKA3 that bound to the key element. Finally, we designed and synthesized specific antisense oligonucleotides (ASOs) targeting circularization and cellmotif elements, which repressed circSKA3 expression, abolished the SLUG-circSKA3 interaction, and further inhibited CRC EMT and metastasis in vitro and in vivo.

Introduction and Establishment of SARS-CoV-2 Gamma Variant in New York City in Early 2021

BackgroundMonitoring the emergence and spread of SARS-CoV-2 variants is an important public health objective. Travel restrictions, aimed to prevent viral spread, have major economic consequences and unclear effectiveness despite considerable research. We investigated the introduction and establishment of the Gamma variant in New York City (NYC) in 2021. MethodsWe performed phylogeographic analysis on 15,967 Gamma sequences available on GISAID and sampled between March 10th through May 1st, 2021, to identify geographic sources of Gamma lineages introduced into NYC. We identified locally circulating Gamma transmission clusters and inferred the timing of their establishment in NYC. FindingsWe identified 16 phylogenetically-distinct Gamma clusters established in NYC (cluster sizes ranged 2-108 genomes). Most of the NYC clusters were introduced from Florida and Illinois; only one was introduced from outside the United States (US). By the time the first Gamma case was reported by genomic surveillance in NYC on March 10th, the majority (57%) of circulating Gamma lineages had already been established in the city for at least two weeks. InterpretationDespite the expansion of SARS-CoV-2 genomic surveillance in NYC, there was a substantial gap between Gamma variant introduction and establishment in January/February 2021, and its identification by genomic surveillance in March 2021. Although travel from Brazil to the US was restricted from May 2020 through the end of the study period, this restriction did not prevent Gamma from becoming established in NYC as most introductions occurred from domestic locations.

Asari Radix et Rhizoma consumption lacks relevance for hepatocellular carcinoma in patients: A retrospective cohort study / 中草药·英文版

Objective: Although some studies have linked Asari Radix et Rhizoma (Asari Radix) administration to hepatocellular carcinoma (HCC), few studies have examined the association between the development of HCC and use of Asari Radix among patients in mainland China. This study aimed to evaluate the real-world association between Asari Radix and HCC in patients to strengthen the understanding of Asari Radix safety. Methods: A retrospective cohort study among hepatitis B virus (HBV)-monoinfected patients and non-HBV-monoinfected patients were performed. Patients over 18 years of age were eligible for inclusion. Prescription records of inpatients and outpatients were inquired to distinguish Asari Radix users and nonusers. The risk of developing HCC among Asari Radix users and nonusers in the HBV cohort and the non-HBV cohort was analyzed. Results: There were 49 500 HBV and 133 148 non-HBV patients involved in the two cohorts. Among HBV patients (2 901 users; 46 599 nonusers), the prevalence of HCC in Asari Radix users was lower than that in nonusers (145.70 vs. 265.43 per 10

CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a heterogeneous and multifactorial disorder. In recent years, there has been an increasing interest in research on the pathogenesis and treatment of POI, owing to the implementation of the second-child policy in China. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that can bind to specific RNA sequences. CPEB3 can bind to and affect the expression, cellular location, and stability of target RNAs. Cpeb3 is highly expressed in the ovary; however, its functions remain unknown. In this study, Cpeb3-mutant mice were used to characterize the physiological functions of CPEB3. Cpeb3-mutant female mice manifested signs of gradual loss of ovarian follicles, ovarian follicle development arrest, increased follicle atresia, and subfertility with a phenotype analogous to POI in women. Further analysis showed that granulosa cell proliferation was inhibited and apoptosis was markedly increased in Cpeb3-mutant ovaries. In addition, the expression of Gdf9, a potential target of CPEB3, was decreased in Cpeb3-mutant ovaries and oocytes. Altogether, these results reveal that CPEB3 is essential for ovarian follicle development and female fertility as it regulates the expression of Gdf9 in oocytes, disruption of which leads to impaired ovarian follicle development and POI.

SARS-CoV-2 lineage B.1.526 emerging in the New York region detected by software utility created to query the spike mutational landscape

Wide-scale SARS-CoV-2 genome sequencing is critical to tracking viral evolution during the ongoing pandemic. Variants first detected in the United Kingdom, South Africa, and Brazil have spread to multiple countries. We developed the software tool, Variant Database (VDB), for quickly examining the changing landscape of spike mutations. Using VDB, we detected an emerging lineage of SARS-CoV-2 in the New York region that shares mutations with previously reported variants. The most common sets of spike mutations in this lineage (now designated as B.1.526) are L5F, T95I, D253G, E484K or S477N, D614G, and A701V. This lineage was first sequenced in late November 2020 when it represented <1% of sequenced coronavirus genomes that were collected in New York City (NYC). By February 2021, genomes from this lineage accounted for ~32% of 3288 sequenced genomes from NYC specimens. Phylodynamic inference confirmed the rapid growth of the B.1.526 lineage in NYC, notably the sub-clade defined by the spike mutation E484K, which has outpaced the growth of other variants in NYC. Pseudovirus neutralization experiments demonstrated that B.1.526 spike mutations adversely affect the neutralization titer of convalescent and vaccinee plasma, indicating the public health importance of this lineage.

CPEB3-mediated MTDH mRNA translational suppression restrains hepatocellular carcinoma progression.

Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein. We had reported that CPEB3 is involved in hepatocellular carcinoma (HCC) progression. However, the underlying mechanisms of CPEB3 in HCC remain unclear. In this study, we firstly performed RNA immunoprecipitation to uncover the transcriptome-wide CPEB3-bound mRNAs (CPEB3 binder) in HCC. Bioinformatic analysis indicates that CPEB3 binders are closely related to cancer progression, especially HCC metastasis. Further studies confirmed that metadherin (MTDH) is a direct target of CPEB3. CPEB3 can suppress the translation of MTDH mRNA in vivo and in vitro. Besides, luciferase assay demonstrated that CPEB3 interacted with 3'-untranslated region of MTDH mRNA and inhibited its translation. Subsequently, CPEB3 inhibited the epithelial-mesenchymal transition and metastasis of HCC cells through post-transcriptional regulation of MTDH. In addition, cpeb3 knockout mice are more susceptible to carcinogen-induced hepatocarcinogenesis and subsequent lung metastasis. Our results also indicated that CPEB3 was a good prognosis marker, which is downregulated in HCC tissue. In conclusion, our results demonstrated that CPEB3 played an important role in HCC progression and targeting CPEB3-mediated mRNA translation might be a favorable therapeutic approach.

Analysis of Risk Factors of SkinAdverse Reactions by Intravenous Injection of Iodine ContrastAgent / 中国药房

OBJECTIVE：To investiga te main risk factors for adverse drug reactions （ADR）of skin by intravenous injection of iodine contrast agent. METHODS ：From Jan. 2009 to Apr. 2020，the patients suffering from skin ADR after enhanced CT with iodine contrast agent were collected from our hospital. The basic information ，laboratory test results before using iodine contrast agent and ADR related information were collected through hospital information system （HIS）. The use of iodine contrast agent ，main manifestations of skin ADR and drug combination were analyzed statistically. Taking the sex ，age，body mass index （BMI），the dosage of iodine contrast agent ，length of stay ，laboratory examination ，tumor history ，basic disease ，allergy history ，drinking history as independent variables ，the incidence of skin ADR related to iodine contrast agent was analyzed by single factor analysis ，and the variables with statistically significant were selected for multivariate Logistic stepwise regression analysis. RESULTS ：There were 157 cases of skin ADR ，involving 79 males（50.3％）and 78 females（49.7％）. The age ranged from 19 to 86 years old ，being（52.68± 18.73）years old in average. BMI was 14.6-40.7 kg/m2，being（22.5±3.7） kg/m2. 67 cases（42.68％）were treated with iprodione ，34 cases（21.66％）with iodixanol ，31 cases（19.74％）with iohexol and 25 cases（15.92％）with iopamidol ；the dose of iodine contrast agent were 50-100 mL，being（73.06±13.29）mL in average. There was no significant difference among different dosage of 4 kinds of iodine contrast agents （P≤0.05）. Among 4 kinds of iodine contrast agents ，the incidence of skin ADR induced by iopromide was the highest（0.197％）. The skin ADR related to iodine contrast agent was mainly acute （89.2％），the severity was mild （75.2％），and urticaria（38.9％）was the most common. After symptomatic treatment ，135 cases were cured ，13 cases were improved and 9 cases were not improved. Among the patients with iodine contrast agent related skin ADR ，the incidence of ADR induced by combined use of anti infective drugs was the highest （33.1％）；however，the combined use of anti-tumor drugs was the main cause of severe skin ADR. The length of stay ｛11～20 d[OR＝1.21，95％CI（1.07，1.20），P＝0.042]、21～30 d[OR＝1.39，95％CI（1.12，1.52），P＝0.035]、31～40 d[OR＝1.15，95％CI（1.03，1.37），P＝0.008]、＞40 d[OR＝1.33，95％CI（1.28，1.53），P＝0.003]｝，respitatory and circulatory system tumor history[OR ＝1.51，95％CI（1.35，1.61），P＝0.037]，injection allergy history[OR ＝1.50，95％CI（1.37，1.59），P＝0.005] can significantly increase the incidence of iodine contrast agent related skin ADR. CONCLUSIONS ：The main manifestation of skin ADR related to iodine contrast agent was urticaria. The main risk factors of skin ADR related to iodine contrast agent were length of stay （＞ 10 d），respiratory and circulatory system tumor history and injection allergy history.

Juglone eliminates MDSCs accumulation and enhances antitumor immunity.

Myeloid-derived suppressor cells (MDSCs) contribute to immune activity suppression and promote the tumor progression. Elimination of MDSCs is a promising cancer therapeutic strategy, and some chemotherapeutic agents have been reported to hamper tumor progression by suppressing MDSCs. Juglone has been showed to exert a direct cytotoxic effect on tumor cells. However, the effect of juglone on MDSCs and anti-tumor immune statue has remained unexplored. In our study, we observed that juglone suppressed tumor growth and metastasis markedly, and the tumor growth suppression in immunocompetent mice was more drastic than that in immunodeficient mice. Juglone reduced the accumulation of MDSCs and increased IFN-γ production by CD8+ T cells. Consistently, juglone affected myeloid cells differentiation and maturation, impairing the immunosuppressive functions of MDSCs. Moreover, juglone down-regulated the level of IL-1ß which was mediating accumulation of MDSCs. In addition, juglone inhibited 5FU-induced liver injury in a colorectal carcinoma-bearing mice model. Thus, our work suggests that the anti-tumor effect of juglone is mediated, at least in part, by eliminating accumulation of MDSCs.

Heme Oxygenase-1 Inhibits Tumor Metastasis Mediated by Notch1 Pathway in Murine Mammary Carcinoma.

Heme oxygenase-1 (HO-1) plays an important role in the progression of several malignancies including breast cancer. However, its role in breast cancer metastasis is still ambiguous. In this study, we observed the effect of HO-1 on mouse mammary carcinoma metastasis using the in vivo tumor metastasis model. Our results revealed that overexpression of HO-1 strongly inhibits the lung metastasis of 4T1 cells. In in vitro analysis, associated indices for epithelial-mesenchymal transition (EMT), migration, and proliferation of 4T1 cells were evaluated. The results show that HO-1 inhibits EMT, migration, and proliferation of 4T1 cells. In addition, the Notch1/Slug pathway is found to mediate an antimetastasis role of HO-1 in mouse mammary carcinoma. In conclusion, since HO-1/Notch1/Slug axis plays an important role in breast cancer metastasis, induction of HO-1 could be used as a potential therapeutic strategy for breast cancer treatment.

CADM2, as a new target of miR-10b, promotes tumor metastasis through FAK/AKT pathway in hepatocellular carcinoma.

BACKGROUND: Cell adhesion molecules (CADMs) comprise of a protein family whose functions include maintenance of cell polarity and tumor suppression. Hypo-expression of CADM2 gene expression has been observed in several cancers including hepatocellular carcinoma (HCC). However, the role and mechanisms of CADM2 in HCC remain unclear. METHODS: The expression of CADM2 and miRNA-10b (miR-10b) in HCC tissues and cell lines were detected using real-time PCR and Western blotting. Immunofluorescence was used to detect Epithelial-mesenchymal transition (EMT) progression in HCC cell lines. Dual-luciferase reporter assay was used to determine miR-10b binding to CADM2 3'UTR. Wound healing assay and Transwell assay were performed to examine the migration and invasion of HCC cells. RESULTS: We report the effect of CADM2 as a tumor suppressor in HCC. Firstly, we confirmed that CADM2 expression was significantly down regulated in HCC tissues compared to normal tissues according to TCGA data analysis and fresh HCC sample detection. Secondly, overexpression of CADM2 could inhibit EMT process, migratory and invasion ability of HCC cells. Furthermore, the results indicated that CADM2 is a direct target of miR-10b in HCC cells and miR-10b/CADM2 modulates EMT process and migration ability via focal adhesion kinase (FAK) /AKT signaling pathway in HCC. CONCLUSIONS: Our study demonstrates that miR-10b-CADM2-FAK/AKT axis plays an important role in HCC metastasis, which might be a novel potential therapeutic option for HCC treatment.

Case Analysis of Participation of Clinical Pharmacists in Anti-infective Treatment for a Case of Septic Shock Induced by Intrauterine Infection / 中国药房

OBJECTIVE: To explore the role of clinical pharmacists in anti-infective treatment for the patient with septic shock induced by intrauterine infection. METHODS: Clinical pharmacists participated in anti-infective treatment for a patient with septic shock induced by intrauterine infection, and assisted physicians to formulate empirical anti-infective treatment, determine that Escherichia coli was pathogenic bacteria and analyze the causes of fluctuations in body temperature. According to the patient's disease condition and results of assistant examination, clinical pharmacists suggested using Imipenem and cilastatin sodium for injection 1. 0 g, ivgtt, q6 h, stopping Teicoplanin for injection, de-escalation using Cefoxitin sodium for injection 2. 0 g, ivgtt, q8 h for anti-infective treatment, with oral sequential therapy. RESULTS: Physicians adopted most advice of pharmacists. After 30 d anti-infective and symptomatic treatment, the patients symptoms were better than before, and discharged from the hospital. CONCLUSIONS: Clinical pharmacists participate in formulating individual anti-infective treatment regimen, so as to promote the rational use of antibiotics and improve the response rate and success rate of treatment.

Antimicrobiai bioceramic combined with chitosan and ceftriaxone sodium:Preparation and its in vitro and in vivo study / 中华显微外科杂志

Objective To synthesize antimicrobial bioceramic using chitosan and calcium phosphate cements mixed with ceftriaxone sodium. Methods The bioceramic was synthesized through the hardening of chitosan liquid combined with calcium phosphate cements and cefiriaxone sodium.The released ceftriaxone sodium was studied according to the linear equation between UV-VIS absorbance to concentration.The in vitro bactefiostatic effect of the chosen bioceramic was investigated via the microbiological method.The model of rats'contaminated bone defect were deployed to study the antimicrobial performance of the bioceramic. Results The best synthesis condition was chosen at:0.1g calcium phosphate cements and 10.4 mg ceftriaxone sodium combined with 2.4 ml hardening liquid C.then keeping the mixture at 60℃ and 100%humidity for 24 h.In vitro release of the resulting antimicrobial bioceramic remained stable,while that of ceftriaxone sodium lasted for a week,higher than the minimal inhibitory concentration(MIC) of Staphylococcus aureus.As proved by the WBC number and tissue sectioning,a lighter inflammatory response of treatment group was observed as compared with the control group. Conclusion The antimicrobial bioceramic combined with chitosan and ceftriaxone sodium shows promising antimicrobial performance.