[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

[Inter-laboratory comparison analysis of noise measurement in 91 occupational hygiene technical service organizations].

Objective: To understand the comparability of noise measurement results of various occupational hygiene technical service organizations in Guangdong Province by conducting inter-laboratory comparison of measuring instruments and personnel operation. Methods: In October 2020, the instrument comparison and personnel comparison among 91 occupational hygiene technical service organizations engaged in noise measurement in Guangdong Province were carried out in the form of fixed-point measurement and simulated workplace measurement, and the results were analyzed and evaluated by using the robust z-ratio score. Results: In the instrument comparison, 6 organizations had 1 or 2 outliers in their z-ratio scores, 2 organizations had 2 problematic values in their z-ratio scores, and a total of 8 organizations (accounting for 8.8%) were judged as unqualified; A total of 83 organizations (accounting for 91.2%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. In the personnel comparison, there were 11 organizations with 1 or 2 outliers in the z-ratio score, and 1 organization with 2 problematic values in the z-ratio score. A total of 12 organizations (13.2%) were judged as unqualified and 79 organizations (accounting for 86.8%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. Through comprehensive judgment, 20 organizations (22.0%) were judged as unqualified, and 71 organizations (78.0%) were judged as qualified. There was no statistically significant difference in the qualified rates of instrument comparison results, personnel comparison results and comprehensive evaluation results of non-private organizations and private organizations (P>0.05). There was no significant difference in the qualified rates of instrument comparison results and comprehensive evaluation results of qualified organizations and unqualified organizations (P>0.05), there was significant difference in the qualified rate of personnel comparison results (P<0.05) . Conclusion: The noise measurement results of some occupational health technical service organizations in Guangdong Province are generally comparable. To carry out inter-laboratory comparison of noise instrument performance and personnel operation ability of occupational hygiene technical service organizations, can comprehensively evaluate the testing process of each organization and find out the problems existing in each organization.

Reconstructing historical exposure to asbestos: the validation of 'educated guesses'.

BACKGROUND: In both the epidemiological and legal context, the causal attribution of asbestos-related lung diseases requires retrospective exposure assessment (REA). AIMS: To assess the correlation between the retrospective assessment of occupational and anthropogenic environmental exposure to asbestos and its content in the lung tissue. METHODS: Based on the available exposure information, a team of occupational physicians retrospectively assessed cumulative exposure to asbestos in 24 subjects who died of asbestos-related diseases. The asbestos lung content was analysed using analytical scanning electron microscope (SEM-EDS). The Log10 asbestos fibre count in the autoptic samples was predicted as a function of the Log10 estimated cumulative exposure using univariate regression analysis. RESULTS: The median count of asbestos fibres by grams of dry weight (ff/gdw) in the lung tissue was 81 339 (range 0-2 135 849.06); it was 287 144 (range 0-2 135 849.06) among the occupationally exposed, and 29 671 (range 0-116 891) among the subjects who only had anthropogenic environmental and/or household exposure. Amphiboles, and particularly amosite (52%) and crocidolite (43%), were detected in all the study subjects. Chrysotile was not detected in any of the samples. Overall, the retrospective estimate of lifetime cumulative exposure to asbestos showed a moderate correlation with the total asbestos fibre count in the autoptic lung, with the regression model explaining 38-55% of the total variance. CONCLUSIONS: Detailed information on occupational, environmental and household exposure circumstances would be indispensable for experienced industrial hygienists and/or occupational physicians to reliably assess past exposure to amphiboles or mixed types of asbestos.

Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression.

BACKGROUND: Cytomegalovirus (CMV) infection is a well-recognised complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus infection, previously immunocompetent intensive care unit patients, and individuals on immunosuppressive medications for various underlying diseases. OBJECTIVES: This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression. SOURCES: Selected peer-reviewed publications on CMV infections published until December 2021. CONTENT: CMV infection affects various organ systems through direct cytolytic mechanisms but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations but also mitigate various immunopathological processes to reduce graft-vs.-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the intensive care unit. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation. IMPLICATIONS: A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with human immunodeficiency virus infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomised controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.

The Surgical Challenges of Intertrochanteric Hip Fracture in a Patient with Polio Dysplastic Hip and Previous Distal Femur Fracture: A Case Report.

Poliomyelitis is on the verge of eradication since the introduction of the vaccine in 1950. In developed countries, those afflicted with the disease are primarily in their sixth decade and beyond, usually with disabling complications. Due to the diminished muscle power coupled with the abnormal bony anatomy and joint contractures, patients with polio present unique surgical challenges when they sustain fragility fractures. We report an uncommon case of intertrochanteric hip fracture in a limb affected with polio and hip dysplasia, on a background of ipsilateral distal femur fracture with previous surgical fixation. We aim to outline the challenges encountered during the surgery and the preoperative planning to overcome these shortcomings.

Aerosol delivery of star polymer-siRNA nanoparticles as a therapeutic strategy to inhibit lung tumor growth.

Lung cancer is a major contributor to cancer-related death worldwide. siRNA nanomedicines are powerful tools for cancer therapeutics. However, there are challenges to overcome to increase siRNA delivery to solid tumors, including penetration of nanoparticles into a complex microenvironment following systemic delivery while avoiding rapid clearance by the reticuloendothelial system, and limited siRNA release from endosomes once inside the cell. Here we characterized cell uptake, intracellular trafficking, and gene silencing activity of miktoarm star polymer (PDMAEMA-POEGMA) nanoparticles (star nanoparticles) complexed to siRNA in lung cancer cells. We investigated the potential of nebulized star-siRNA nanoparticles to accumulate into orthotopic mouse lung tumors to inhibit expression of two genes [ßIII-tubulin, Polo-Like Kinase 1 (PLK1)] which: 1) are upregulated in lung cancer cells; 2) promote tumor growth; and 3) are difficult to inhibit using chemical drugs. Star-siRNA nanoparticles internalized into lung cancer cells and escaped the endo-lysosomal pathway to inhibit target gene expression in lung cancer cells in vitro. Nebulized star-siRNA nanoparticles accumulated into lungs and silenced the expression of ßIII-tubulin and PLK1 in mouse lung tumors, delaying aggressive tumor growth. These results demonstrate a proof-of-concept for aerosol delivery of star-siRNA nanoparticles as a novel therapeutic strategy to inhibit lung tumor growth.

Dermoscopy of cutaneous adnexal tumours: a systematic review of the literature.

Cutaneous adnexal tumours (ATs) encompass a variegated group of hamartomas and benign or malignant tumours, originating from the hair follicle, sebaceous, eccrine or apocrine glands that may simulate other cutaneous neoplasms. This study aims to provide a comprehensive overview of the spectrum of clinical and dermoscopic features of ATs, to better define these lesions and assist in the differential diagnosis. We performed a two-step systematic search of the literature in PubMed, Embase and Cochrane Library databases from inception until 4 September 2020. In the first step, we aimed to define histological variants of ATs with descriptions of dermoscopic criteria. The second step included a search for the name of each previously identified AT variants in the same databases adding 'AND (epilum* or dermosc* or dermatosc*)'. All study types in English language reporting dermoscopic images of ATs were included. Collisions between ATs and other inflammatory or neoplastic skin lesions were excluded, with the exception of collisions with a sebaceous nevus. The protocol of this study was prospectively registered in PROSPERO (CRD42021244677). In total, 206 articles met our inclusion criteria, encompassing 372 ATs in 365 patients. Most ATs were apocrine-eccrine (n = 217, 58.3%, n = 173 benign) with a prevalence of poromas (n = 82), followed by follicular ATs (n = 88, 23.7%, n = 83 benign) and sebaceous ATs (n = 67, 18.0%, n = 49 benign). Most patients had a single AT lesion (320, 86.0%), while 42 (11.3%) had multiple ATs. A syndrome causing multiple ATs was identified in 15 patients. Histopathological analysis revealed 82% benign (n = 305) and 18.0% malignant (n = 67). ATs were classified according to their ability to mimic four groups of more common skin tumours: basal cell carcinoma, squamous cell carcinoma, melanocytic lesions and benign cutaneous lesions. Moreover, we have highlighted the ability of malignant variants of ATs to simulate benign skin lesions. This systematic review offers a comprehensive overview of the common clinical and dermoscopic features of follicular, sebaceous and apocrine-eccrine ATs and details possible differential dermoscopic features.

Lessons of the month 1: When what you see is not UC (ulcerative colitis): an unusual presentation of pancolitis in a developed country.

The misdiagnosis of intestinal schistosomiasis is not uncommon given its variety of clinical manifestations and often shares similarities with ulcerative colitis. While endoscopy aids in diagnosis, findings are often non-specific and correlation with histopathological features is crucial in arriving at an accurate diagnosis which is confirmed by the presence of schistosome ova within the lamina propria. In this case study, we report our experience with a 50-year-old woman, who had been residing in Singapore for more than a decade, presenting with recurrent episodes of bloody diarrhoea.

A human pluripotent stem cell-based model of SARS-CoV-2 infection reveals an ACE2-independent inflammatory activation of vascular endothelial cells through TLR4.

To date, the direct causative mechanism of SARS-CoV-2-induced endotheliitis remains unclear. Here, we report that human ECs barely express surface ACE2, and ECs express less intracellular ACE2 than non-ECs of the lungs. We ectopically expressed ACE2 in hESC-ECs to model SARS-CoV-2 infection. ACE2-deficient ECs are resistant to the infection but are more activated than ACE2-expressing ones. The virus directly induces endothelial activation by increasing monocyte adhesion, NO production, and enhanced phosphorylation of p38 mitogen-associated protein kinase (MAPK), NF-κB, and eNOS in ACE2-expressing and -deficient ECs. ACE2-deficient ECs respond to SARS-CoV-2 through TLR4 as treatment with its antagonist inhibits p38 MAPK/NF-κB/ interleukin-1ß (IL-1ß) activation after viral exposure. Genome-wide, single-cell RNA-seq analyses further confirm activation of the TLR4/MAPK14/RELA/IL-1ß axis in circulating ECs of mild and severe COVID-19 patients. Circulating ECs could serve as biomarkers for indicating patients with endotheliitis. Together, our findings support a direct role for SARS-CoV-2 in mediating endothelial inflammation in an ACE2-dependent or -independent manner.

First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

Electric Scooter Battery Detonation: A Case Series And Review Of Literature.

Since 2016 there has been a 20-fold increase in known burns injury from personal mobility device (PMD) related fires. The root cause is the failure of high-density lithium ion (Li-ion) battery packs powering the PMDs. This failure process, known as thermal runaway, is well documented in applied science journals. Importantly, the liberation of hydrogen fluoride from failing Li-ion batteries may contribute to unrecognized chemical burns. A clinical gap in knowledge exists in the understanding of the explosive nature of Li-ion batteries. We reviewed the electrochemical pathophysiology of a failing Li-ion cell as it impacts clinical management of burn injuries. This retrospective study was carried out in two major institutions in Singapore. All admitted PMD-related burns and follow up appointments were captured and reviewed from 2016 - 2020. Thirty patients were admitted to tertiary hospitals, 43% of patients were in the pediatric population and 57% were adult patients, aged from 0.3 to 77 years. TBSA of burns ranged from 0 to 80% with a mean 14.5%. 73% of cases presented with inhalation injury, 8 of whom did not suffer any cutaneous burns. 50% of patients sustained both cutaneous and inhalation burn injuries. 27% of patients sustained major burns of >20% TBSA, with 2 in the pediatric group. Mortali ty rate was 10% from PMD-related fires. This cause of burn injury has proven to be fa tal. Prevention of PMD-related fires by ensuring proper battery utilization, adherence to PMD sanctions for battery standards and public education is vital to reducing the morbidity and mortality of this unique type of thermal injury.

Depuis 2016, les rapports de brûlures après incendie de véhicules électriques personnels (VEP) ont été multipliés par 20. La cause essentielle en est le dysfonctionnement de la batterie lithium/ion (Li/ion) les motorisant. Ce dysfonctionnement est connu sous le terme d'emballement thermique, bien décrit dans les revues technologiques. La libération de fluorure d'hydrogène lors de cette réaction peut entraîner des brûlures chimiques ignorées et la physiopathologie exacte de ces brûlures reste largement méconnue des cliniciens. Nous avons revu les mécanismes physico- chimiques de l'emballement thermique des batteries Li/ion et leur conséquences sur la prise en charge des brûlures occasionnées. Cette étude rétrospective a été réalisée par 2 grosses structures singapouriennes. Tous les dossiers d'accidents de VEP survenus entre 2016 et 2020, comprenant le suivi à distance, ont été revus. Ils regroupaient 30 patients âgés de 3 mois à 77 ans, dont 43% d'enfants. La surface brûlée représentait 0 à 80% de SCT (moyenne 14,5%) et 27% des patients (dont 2 enfants) étaient brûlés sur plus de 20% SCT. Une inhalation était retrouvée dans 73% des cas (dont 8 sans brûlure cutanée). La moitié des patients avaient une brûlure et une inhalation. La mortalité s'élevait à 10%. La prévention de ces accidents par le contrôle- qualité des batteries (sanctions à l'appui) et l'éducation à l'utilisation correcte des VEP et de leur batterie est nécessaire pour éviter ces dysfonctionnements potentiellement létaux.

Fetal programming of atherosclerosis: may the barker hypothesis explain the susceptibility of a subset of patients to develop stroke or cardiac infarct?

The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life.

Painful and swollen tongue: mucosal leishmaniasis due to Leishmania infantum.

BACKGROUND: Leishmaniasis is a parasitic disease caused by different Leishmania species. L. infantum is found in the Mediterranean area. It usually causes visceral or cutaneous leishmaniasis, but rarely mucosal leishmaniasis (ML). METHODS: A 62-year-old man with metastatic non-small-cell lung carcinoma visited the outpatient clinic because of a painful and swollen tongue. Initially, oral candidiasis was suspected and patient was unsuccessfully treated accordingly. Subsequently, a biopsy from the tongue was taken. RESULTS: Histology of the tongue biopsy showed an inflammation with histiocytes and Leishmania amastigotes. Molecular analysis determined these parasites as L. donovani complex. Based on the patient's travel history, ML caused by L. infantum was diagnosed. CONCLUSION: ML is an unusual presentation of L. infantum. ML is not only caused by Leishmania species endemic in Latin America, but also should be considered in the differential diagnosis for European patients. A biopsy of the affected location is needed to confirm the diagnosis.

High incidence of Plasmodium knowlesi malaria compared to other human malaria species in several hospitals in Malaysia.

Through the regional control programme, Malaysia has been successfully reducing the incidence of Plasmodium falciparum and Plasmodium vivax infections. However, the incidence of zoonotic malaria Plasmodium knowlesi infection is increasing and now has been the major cause of malaria in Malaysia especially Malaysian Borneo. The emergence of knowlesi infection has threatened the malaria elimination programme which the government aims to reduce the overall malaria infections by 2020. Unlike other benign human Plasmodium spp., P. knowlesi can cause fatal infections. The aim of this study was to determine the incidence and distribution of five human malaria parasites including P. knowlesi in Peninsular Malaysia and Malaysian Borneo. A total of 112 blood samples were collected from seven states and district hospitals in Peninsular Malaysia and Malaysian Borneo from year 2015 to 2016. The samples were examined by microscopy and further confirmed by nested PCR assay targeting 18S rRNA gene of Plasmodium spp. Following the nested PCR assays, a total of 54 (48.2%) samples were positive for P. knowlesi infections, 12 (10.7%) cases were positive for P. vivax infections, followed by 7 (6.3%) cases of P. falciparum and 4 (3.5%) cases of P. malariae. There were 3 cases (2.7%) of mixed infections (P. knowlesi/P. vivax). However, no cases were identified as P. ovale. A total of 32 (28.6%) cases were found as negative infections. LoopMediated Isothermal Amplification Assay (LAMP) was performed to confirm inconclusive results produced by microscopy and nested PCR. P. knowlesi showed the highest prevalence in Sarawak (n= 30), Sabah (n=13), Pulau Pinang (n=5) and Pahang (n=6). PCR and LAMP was not able to detect a large number of microscopy positive samples due to DNA degradation during storage and shipping. Among all the states involved in this study, the highest prevalence of P. knowlesi infection was found in Sabah and Sarawak.

Experimental Study on Plasmodium knowlesi Normocyte Binding Protein Xa Region II (PkNBPXaII) for Erythrocyte Binding.

Normocyte binding protein Xa (NBPXa) has been implied to play a significant role in parasite invasion of human erythrocytes. Previous phylogenetic studies have reported the existence of three types of NBPXa for Plasmodium knowlesi (PkNBPXa). PkNBPXa region II (PkNBPXaII) of type 1, type 2 and type 3 were expressed on mammalian cell surface and interacted with human and macaque (Macaca fascicularis) erythrocytes. The binding activities of PkNBPXaII towards human and macaque erythrocytes were evaluated using erythrocyte-binding assay (EBA). Three parameters were evaluated to achieve the optimal protein expression of PkNBPXaII and erythrocyte binding activity in EBA: types of mammalian cells, post transfection time and erythrocyte incubation time. COS-7, HEK-293, and CHO-K1 cells showed successful expression of PkNBPXaII, despite the protein expression is weak compared to the positive control. COS-7 was used in EBA. All three types of PkNBPXaII showed rosette formation with macaque erythrocytes but not with human erythrocytes. Future studies to enhance the PkNBPXaII expression on surface of mammalian cells is indeed needed in order to elucidate the specific role of PkNBPXaII in erythrocytes invasion.