Adverse Effects of Opioid Analgesics in Osteoarthritis Treatment: A Global Meta-Analysis, 2000-2022.

Osteoarthritis (OA) treatment commonly depends on nonsteroidal anti-inflammatory drugs and opioid medications. Nevertheless, the clinical use of opioids is controversial due to their adverse effects and addiction potential. This study, drawing on 24 randomized controlled trials (RCTs) with a total of 9,586 patients, thoroughly explored the various side effects associated with opioid use in OA treatment. The results provide additional insight into the non-addictive risks of opioids and may assist clinicians in their judicious use, potentially fostering the advancement of safer treatment options. By reducing the risks of misuse and addiction, public health and safety can be enhanced.

miR-200a-3p promotes the malignancy of endometrial carcinoma through negative regulation of epithelial-mesenchymal transition.

BACKGROUND: miR-200a-3p is involved in the progression of malignant behavior in various tumors, and its mechanism of action in endometrial cancer is speculated to be related to epithelial-mesenchymal transition (EMT). Therefore, this study explored the metastatic mechanism of miR-200a-3p and EMT in endometrial cancer, with the aim of identifying potential therapeutic targets. METHODS: qRT-PCR was used to analyze miR-200a-3p expression in HEC-1B and Ishikawa cell lines. The cell proliferation assay, transwell assay, and cell scratch test were used to assess changes in the malignant phenotypes of cells after regulating miR-200a-3p expression. Changes in EMT-related protein zinc finger E-box binding homeobox 1 (ZEB1) were detected after regulating miR-200a-3p expression. An endometrial carcinoma transplantation mouse tumor model was constructed, and multiple EMT-related proteins were examined. RESULTS: The expression of miR-200a-3p and ZEB1 in the endometrial cancer cell lines was higher than in normal endometrial epithelial cell lines (P < 0.05). After silencing miR-200a-3p, the expression of EMT-related protein ZEB1 increased, indicating a negative correlation. Simultaneously, the proliferation, invasion, and metastasis of endometrial cancer cells were significantly enhanced. After miR-200a-3p overexpression, the corresponding malignant phenotype was reversed (P < 0.05). In in vivo experiments, the degree of tumor malignancy and the expression level of EMT-related proteins were significantly reduced in the miR-200a-3p mimic group (P < 0.05). CONCLUSION: This study found that miR-200a-3p is a promising target, regulating the EMT process and promoting endometrial cancer progression.

Rapid Detection of the Monkeypox Virus Genome and Antigen Proteins Based on Surface-Enhanced Raman Spectroscopy.

The conventional detection methods cannot satisfy the need for early and rapid detection of monkeypox virus (MPXV) infection. This is due to complicated pretreatment, time consumption, and complex operation of the diagnostic tests. Based on surface-enhanced Raman spectroscopy (SERS), this study attempted to capture the characteristic fingerprints of the MPXV genome and multiple antigenic proteins without the need to design specific probes. The minimum detection limit of this method is 100 copies/mL, with good reproducibility and signal-to-noise ratio. Therefore, the relationship between characteristic peak intensity and the protein and nucleic acid concentration can be used to construct a concentration-dependent spectral line with a good linear relationship. Additionally, principal component analysis (PCA) could identify the SERS spectra of four different MPXV proteins in serum. Therefore, this rapid detection method in the current outbreak of monkeypox control and the future response to possible new outbreaks has broad application prospects.

A novel enhanced substrate for label-free detection of SARS-CoV-2 based on surface-enhanced Raman scattering.

Accurate and sensitive detection of SARS-CoV-2 is an effective strategy for preventing the COVID-19 pandemic in the current absence of specific drug therapy. This study presents a novel enhanced substrate for label-free detection of respiratory viruses using surface-enhanced Raman Scattering. Sodium borohydride reduces silver ions to clustered silver nanoparticles to eliminate the disorganized peak signal of the traditional citrate reducing agent. Meanwhile, the study obtained the fingerprints and concentration-dependent curves of many respiratory viruses, including SARS-CoV-2, human adenovirus type 7, and H1N1 virus, with good linear relationships. The three viruses were also identified in serum and saliva within two minutes, combined with linear discriminant diagnostic analysis. Therefore, establishing this enhanced substrate is greatly valuable for the global response to the COVID-19 pandemic.

Immunological Study of Reconstructed Common Ancestral Sequence of Adenovirus Hexon Protein.

Aim: To reconstruct the ancestral sequence of human adenoviral hexon protein by combining sequence variations and structural information. And to provide a candidate hexon protein for developing new adenoviral vector capable of escaping the pre-existing immunity in healthy populations. Methods: The sequences of 74 adenovirus-type strains were used to predict the ancestral sequence of human adenovirus hexon protein using FastML and MEGA software. The three-dimensional structure model was built using homology modeling methods. The immunological features of ancestral loop 1 and loop 2 regions of sequences were tested using protein segments expressed in a prokaryotic expression system and polypeptides synthesized with human serum samples. Results: The tower region of the hexon protein had the highest sequence variability, while the neck and base regions remained constant among different types. The modern strains successfully predicted the common ancestral sequence of the human adenovirus hexon. The positive sera against neutralizing epitopes on the common ancestor of adenoviral hexon were relatively rare among healthy adults. Conclusion: The existing strains inferred the common ancestor of human adenoviruses, with epitopes never observed in the current human strains. The predicted common ancestor hexon is a good prospect in the improvement of adenovirus vectors.

Epidemiological and genetic characteristics of influenza virus and the effects of air pollution on laboratory-confirmed influenza cases in Hulunbuir, China, from 2010 to 2019.

OBJECTIVE: A continuous survey on influenza was conducted in Hulunbuir, China from January 2010 to May 2019 to reveal epidemiological, microbiological and air pollutants associated with laboratory-confirmed influenza cases. METHODS: Influenza-like illness and severe acute respiratory infection subjects were enrolled from a sentinel hospital in Hulunbuir during the study period for epidemiological and virological investigation. The association between air pollutants and influenza-positivity rate was assessed by a generalised additive model. RESULTS: Of 4667 specimens, 550 (11.8%) were tested positive for influenza. The influenza-positivity was highest in the age groups of 5-14 years, 50-69 years and ⩾70 years. We found that the effect of particulate matter ⩽2.5 µm (PM2.5) concentrations on the influenza-positivity rate was statistically significant, particularly on day lag-4 and lag-5. Genetic characterisations showed that (H1N1) pdm09 strains belonged to subclade 6B.1 and that influenza B isolates belonged to subclade 1A-3Del, with significant substitutions in the haemagglutinin and neuraminidase proteins compared with those in the WHO-recommended vaccine strains. CONCLUSIONS: Elderly individuals and school-age children were at high risk for influenza infection. PM2.5 concentrations showed significant effects on influenza-positivity rate in Hulunbuir, which could be considered in local influenza prevention strategies.

Prevalence of Common Respiratory Viral Infections and Identification of Adenovirus in Hospitalized Adults in Harbin, China 2014 to 2017.

Background: Respiratory infections pose a great challenge in global health, and the prevalence of viral infection in adult patients has been poorly understood in northeast China. Harbin is one of the major cities in northeast China, and more than half of any given year in Harbin is occupied by winter. To reveal the viral etiology and seasonality in adult patients from Harbin, a 4-year consecutive survey was conducted in Harbin, China. Methods: From January 2014 to December 2017, specimens were obtained from adult patients admitted to the Second Affiliated Hospital of Harbin Medical University with lower respiratory tract infections. Sputum samples were examined by direct immunofluorescence assays to detect seven common respiratory viruses, including influenza virus (type A and B), parainfluenza virus (type 1 to 3), respiratory syncytial virus and adenovirus. Adenovirus positive samples were seeded onto A549 cells to isolate viral strains. Phylogenetic analysis was conducted on the highly variable region of adenoviral hexon gene. Results: A total of 1,300 hospitalized adult patients with lower respiratory tract infections were enrolled, in which 189 patients (14.5%) were detected as having at least one viral infection. The co-infection rate in this study was 25.9% (49/189). The dominant viral pathogen from 2014 to 2017 was parainfluenza virus, with a detection rate of 7.2%, followed by influenza virus, respiratory syncytial virus and adenovirus. Based on the climate seasons determined by daily average temperature, the highest overall viral detection rate was detected in spring (22.0%, 52/236), followed by winter (13.4%, 109/813), autumn (11.4%, 13/114) and summer (10.9%, 15/137). Adenovirus type 3 strains with slight variations were isolated from positive cases, which were closely related to the GB strain from the United States, as well as the Harbin04B strain isolated locally. Conclusion: This study demonstrated that common respiratory viruses were partially responsible for hospitalized lower respiratory tract infections in adult patients from Harbin, China, with parainfluenza virus as the dominant viral pathogen. Climate seasons could be rational indicators for the seasonality analysis of airborne viral infections. Future surveillance on viral mutations would be necessary to reveal the evolutionary history of respiratory viruses.

Toxicity of Radiosurgery for Brainstem Metastases.

BACKGROUND: Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a review of all available studies reporting SRS treatment for BSM was performed. METHODS: Twenty-nine retrospective studies investigating SRS for BSM were reviewed. RESULTS: The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events, varied from 0 to 9.5% (mean 3.4 ± 2.9%). Overall, the median time to toxicity after SRS was 3 months, with 90% of toxicities occurring before 9 months. A total of 1243 cases had toxicity and location data available. Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811). CONCLUSIONS: Current data suggest that brainstem substructure location does not predict for toxicity and lesion volume within this cohort with median tumor volumes 0.04-2.8 cc does not predict for toxicity.

Brainstem metastases treated with Gamma Knife stereotactic radiosurgery: the Indiana University Health experience.

Brainstem metastases offer a unique challenge in cancer treatment, yet stereotactic radiosurgery (SRS) has proven to be an effective modality in treating these tumors. This report discusses the clinical outcomes of patients with brainstem metastases treated at Indiana University with Gamma Knife (GK) radiosurgery from 2008 to 2016. 19 brainstem metastases from 14 patients who had follow-up brain imaging were identified. Median tumor volume was 0.04 cc (range: 0.01-2.0 cc). Median prescribed dose was 17.5 Gy to the 50% isodose line (range: 14-22 Gy). Median survival after GK SRS treatment to brainstem lesion was 17.2 months (range: 2.8-45.6 months). The experience at Indiana University confirms the safety and efficacy of range of GK SRS prescription doses (14-22 Gy) to brainstem metastases.

MARCKS Signaling Differentially Regulates Vascular Smooth Muscle and Endothelial Cell Proliferation through a KIS-, p27kip1- Dependent Mechanism.

BACKGROUND: Overexpression of the myristolated alanine-rich C kinase substrate (MARCKS) occurs in vascular proliferative diseases such as restenosis after bypass surgery. MARCKS knockdown results in arrest of vascular smooth muscle cell (VSMC) proliferation with little effect on endothelial cell (EC) proliferation. We sought to identify the mechanism of differential regulation by MARCKS of VSMC and EC proliferation in vitro and in vivo. METHODS AND RESULTS: siRNA-mediated MARCKS knockdown in VSMCs inhibited proliferation and prevented progression from phase G0/G1 to S. Protein expression of the cyclin-dependent kinase inhibitor p27kip1, but not p21cip1 was increased by MARCKS knockdown. MARCKS knockdown did not affect proliferation in VSMCs derived from p27kip1-/- mice indicating that the effect of MARCKS is p27kip1-dependent. MARCKS knockdown resulted in decreased phosphorylation of p27kip1 at threonine 187 and serine 10 as well as, kinase interacting with stathmin (KIS), cyclin D1, and Skp2 expression. Phosphorylation of p27kip1 at serine 10 by KIS is required for nuclear export and degradation of p27kip1. MARCKS knockdown caused nuclear trapping of p27kip1. Both p27kip1 nuclear trapping and cell cycle arrest were released by overexpression of KIS, but not catalytically inactive KIS. In ECs, MARCKS knockdown paradoxically increased KIS expression and cell proliferation. MARCKS knockdown in a murine aortic injury model resulted in decreased VSMC proliferation determined by bromodeoxyuridine (BrdU) integration assay, and inhibition of vascular wall thickening. MARCKS knockdown increased the rate of re-endothelialization. CONCLUSIONS: MARCKS knockdown arrested VSMC cell cycle by decreasing KIS expression. Decreased KIS expression resulted in nuclear trapping of p27kip1 in VSMCs. MARCKS knockdown paradoxically increased KIS expression in ECs resulting in increased EC proliferation. MARCKS knockdown significantly attenuated the VSMC proliferative response to vascular injury, but accelerated reestablishment of an intact endothelium. MARCKS is a novel translational target with beneficial cell type-specific effects on both ECs and VSMCs.

Ossification of the Posterior Longitudinal Ligament: Imaging Findings in the Era of Cross-Sectional Imaging.

Imaging appearance and classification systems of ossification of the posterior longitudinal ligament (OPLL) on computed tomography and magnetic resonance imaging will be reviewed. Computed tomography evaluation most accurately demonstrates OPLL length and thickness, whereas magnetic resonance imaging has the advantage of demonstrating abnormal signal in the cord. Neurologic symptoms are most common in the cervical spine and are related to the degree of spinal stenosis and presence of cord edema. Surgical treatment usually involves cases of cervical OPLL and includes anterior or posterior decompression.

Are the Conclusions of Z11 Relevant to Community Practice?

BACKGROUND: Findings of the American College of Surgeons Oncology Group (ACOSOG) Z11 trial have proven controversial, leaving physicians divided over which patients with positive sentinel lymph nodes (+SLNs) benefit from axillary lymph node dissection (ALND). We reviewed our experience at our institution with Z11-eligible patients who did not undergo ALND and explored factors that predicted for positive lymph nodes (+LNs) on ALND after 1 to 2 +SLNs to determine which patients benefit from adjuvant therapy. MATERIALS AND METHODS: All breast cancer pathology reports from our institution containing the word "sentinel" between July 1998 and December 2001 were reviewed. We obtained follow-up information on patients meeting Z11 eligibility criteria who did not undergo ALND. We also compared pathological characteristics between patients with 1 to 2 +SLNs and +LNs on ALND to those with no further +LNs. RESULTS: Of the 432 pathology reports reviewed, 38 were from patients meeting Z11 criteria who did not undergo ALND. At a median follow-up of 11.9 years, these patients had 5-year overall survival (OS) of 93.3% and 10-year OS of 79.3%. No patient had recurrent disease in the axilla. Of the 80 patients with 1 to 2 +SLNs who underwent ALND, tumors with +LNs on ALND were generally larger, nonductal histology, more likely to be estrogen receptor positive (ER(+)) and progesterone receptor positive (PR(+)), and less likely to be HER2(+). CONCLUSION: Our institution's 5-year OS (93.3%) for Z11-eligible patients closely resembled those from the Z11 trial (92.5%) and our 10-year data provide evidence of what to expect for Z11-enrolled patients with continued follow-up. Larger tumor, nonductal, ER(+), PR(+), and HER2- were predictive for further +LNs on ALND, which might reflect surgical bias.

Dramatic Response of a Large, 10 Cm Hepatocellular Carcinoma to Monotherapy with Yttrium-90 Based Selective Internal Radiation Therapy.

Hepatocellular carcinoma (HCC) is predominantly diagnosed in advanced stages and not amenable to surgical resection and transplantation. Systemic therapies have had a limited efficacy in treating HCC. Although HCC is a radiosensitive tumor, treatments with external-beam radiation are limited by radiosensitivity of normal liver tissue and surrounding organs-at-risk, i.e. bowel, stomach, and kidney. Several large retrospective series have demonstrated a modest effect of selective internal radiation therapy (SIRT) with Yttrium-90 ((90)Y) microspheres in unresectable HCC, both in terms of tumor response and survival. The authors present a patient with an extremely large, multifocal, unresectable HCC who achieved a dramatic response with SIRT treatment.

Detection of A. phagocytophilum and E. chaffeensis in patient and mouse blood and ticks by a duplex real-time PCR assay.

Human granulocytic anaplasmosis (HGA) and human monocytic ehrlichiosis (HME) are emerging, tick-borne, zoonotic infectious diseases caused by Anaplasma phagocytophilum and Ehrlichia chaffeensis, respectively. Early diagnosis is essential for rapid clinical treatment to avoid misdiagnosis and severe patient outcomes. Simple, sensitive and reliable diagnostic methods are urgently needed. In this study, we developed a duplex real-time PCR assay targeting the A. phagocytophilum ankA gene and the E. chaffeensis TRP120 gene, respectively. The lowest limit of detection of the duplex real-time PCR assay was 100 copies of the targeted A. phagocytophilum ankA gene and the E. chaffeensis TRP120 gene per reaction, and the specificity was 100%. Detection in blood DNA samples from the acute stage of illness for 22 HGA cases and 8 HME cases indicated that the duplex real-time PCR assay was more sensitive than the nested PCR assay. The infection of Citellusundulatus Pallas with A. phagocytophilum and E. chaffeensis was first confirmed in Xinjiang Province and the positive rate was 3.1% for A. phagocytophilum, 6.3% for E. chaffeensis and 3.1% for co-infection with both pathogens. The rates of A. phagocytophilum and E. chaffeensis infection of D. silvarum ticks collected from Shanxi Province were 8.2% and 14.8%, respectively, and the co-infection rate was 3.3%. The rates of A. phagocytophilum and E. chaffeensis infection in H. longicornis ticks collected from Shandong Province were 1.6% and 6.3%, respectively, and the co-infection rate was 1.6%.

Molecular analysis of Anaplasma phagocytophilum isolated from patients with febrile diseases of unknown etiology in China.

Although anaplasmosis cases have been nationally identified in China, no human isolates of A. phagocytophilum have been obtained, which limits the analysis of any molecular and genetic contributions to patients' severe clinical manifestations and the study of the bacteria's pathogeneses in China. Given this situation, a joint project was conducted in 2009-2010. A total of 421 febrile cases of unknown etiology were collected and the patients' blood samples were collected for laboratory diagnoses including serologic diagnosis based on the four-fold rise in the anti- A. phagocytophilum IgG titer by indirect micro-immunofluorescence assay (IFA), positive PCR assay and confirmation of A. phagocytophilum DNA and positive culture of A. phagocytophilum and confirmed by amplification and sequencing of the 16S rRNA and ank A genes of the A. phagocytophilum isolates. A total of 570 ticks were collected from the patients' domestic animals (456) and from wild fields (114) for culturing and amplifying and sequencing the 16S rRNA gene of A. phagocytophilum. Phylogenetic analyses were performed on the 16S rRNA and ank A gene sequences of the isolates and the ticks tested in the study. A total of 46 (10.9%) confirmed and 16 (3.8%) probable cases were diagnosed and severe clinical features and higher mortality rates were observed in these Chinese patients. Five isolates were obtained and the 16S rRNA genes of the 5 isolates were conserved but variety for ank A genes. Two human isolates and 1 tick isolate from Shandong Peninsula, where all patients exhibited severe clinical manifestations, were grouped as one clan based on the phylogenetic analyses, while 2 other human isolates were clustered in a second clan. 43.5% of H. longicornis were infected with A. phagocytophilum.The present study is the first to obtain clinical isolates of A. phagocytophilum in China. The diversity of the ank A genes of Chinese isolates will help us to further discern the relationship between the variations in the ank A genes and the severity of the disease's clinical manifestations in China.