Ceruloplasmin regulating fibrosis in orbital fibroblasts provides a novel therapeutic target for Graves' orbitopathy.

PURPOSE: In diagnosing the pathogenesis of Graves' orbitopathy (GO), there is a growing interest in fibrosis generated by orbital fibroblasts (OFs); nevertheless, the involvement of ceruloplasmin (CP) in OFs remains unknown. METHODS: Differentially expressed genes (DEGs) were identified through bioinformatic analysis. OFs were isolated from orbital tissue and identified with immunofluorescent staining. The levels of DEGs were validated in GO tissue samples and TGF-ß-challenged OFs, and CP was selected for the following laboratory investigations. CP overexpression or knockdown was achieved, and cell viability and fibrosis-associated proteins were investigated to assess the cell phenotype and function. Signaling pathways were subsequently investigated to explore the mechanism of CP function in OFs. RESULTS: CP and cathepsin C (CTSC) are two overlapped DEGs in GSE58331 and GSE105149. OFs were isolated and identified through fibrotic biomarkers. CP and CTSC were downregulated in GO tissue samples and TGF-ß-challenged OFs. CP overexpression or knockdown was achieved in OFs by transducing a CP overexpression vector or small interfering RNA against CP (si1-CP or si2-CP) and verified using a qRT-PCR. CP overexpression inhibited cell viability and reduced the levels of α-SMA, vimentin, fibronectin, and collagen I, whereas CP knockdown exerted opposite effects on OFs. CP overexpression inhibited the phosphorylation of Smad3, Erk1/2, p38, JNK, and AKT; conversely, CP knockdown exerted opposite effects on the phosphorylation of factors mentioned above. CONCLUSION: CP was downregulated in GO and suppressed the expression of fibrosis-associated proteins in both GO and normal OFs. CP might serve as a promising therapeutic agent in the treatment regimens for GO.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[Clinical value of nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy].

Objective: To investigate the clinical value and efficacy of the nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy. Methods: The clinical data of 259 patients with cholangiocarcinoma who received interventional therapy at the First Affiliated Hospital of zhengzhou University from January 2014 to June 2021 were retrospectively analyzed, including 148 males and 111 females, aged from 26 to 91 (65±12) years. They were randomly divided into a training group (181 cases) and a validation group (78 cases) in a ratio of 7∶3. Cox regression analysis was performed in the training group, independent risk factors affecting the prognosis of patients were screened, and a nomogram for 6-month, 1-year, and 2-year survival was constructed. The performance of the nomogram was analyzed by calculating the area under the receiver operating characteristic curve (AUC) value, calibration curve, and decision curve, and the predictive efficacy of the model was evaluated in the validation group. Results: There was no significant difference in baseline data between the training group and the validation group, which was comparable. Regression analysis showed that T stage (T2: HR=0.147,95%CI: 0.077-0.281;T3: HR=0.207,95%CI: 0.122-0.351;T4: HR=0.864,95%CI: 0.537-1.393), tumor diameter (17-33 mm: HR=0.201,95%CI: 0.119-0.341;≥33 mm: HR=0.795,95%CI: 0.521-1.211) and differentiation degree(middle differentiation: HR=3.318,95%CI: 2.082-5.289;highly differentiation: HR=1.842,95%CI: 1.184-2.867) were risk factors affecting the prognosis of interventional therapy for cholangiocarcinoma. The AUC values of the survival curve prediction models were generally consistent between the training and validation groups, and the AUC values of the training group at 6 months, 1 year, and 2 years were 0.925 (95%CI: 0.888-0.963), 0.921 (95%CI: 0.877-0.964) and 0.974 (95%CI: 0.957-0.993), respectively. In the validation group, the 6-month, 1-year, and 2-year AUC values were 0.951 (95%CI: 0.911-0.991), 0.917 (95%CI: 0.857-0.977) and 0.848 (95%CI: 0.737-0.959), respectively, and the AUC values were all greater than 0.8, suggesting that the nomogram had better discrimination ability. The calibration curves of the prediction models of the two groups were basically consistent, and the shape of the calibration curves at 6 months and 1 year fitted the ideal curve, while the fitting degree of the calibration curves at 2 years was relatively poor. The decision curve showed the high clinical utility of this nomogram in predicting the 6-month, 1-year survival of patients with cholangiocarcinoma. Conclusions: T stage, tumor diameter, and differentiation are independent risk factors affecting the prognosis of patients with interventional cholangiocarcinoma, and the nomogram model proposed in this study has good distinguishing ability and exact clinical value for prognosis evaluation.

[Investigation and influencing factors on pelvic floor muscle strength of 929 adult females in gynecological outpatient department].

Objective: To investigate the present situation of pelvic floor muscle strength, and to analyze the factors affecting pelvic floor muscle strength. Methods: The data of patients who were admitted into the general outpatient department of gynecology, Peking University People's Hospital from October 2021 to April 2022 were collected, and the patients who met the exclusion criteria were included in this cross sectional study. The patient's age, height, weight, education level, defecation way and defecation time, birth history, maximum newborn birth weight, occupational physical activity, sedentary time, menopause, family history and disease history were recorded by questionnaire. Morphological indexes such as waist circumference, abdomen circumference and hip circumference were measured with tape measure. Handgrip strength level was measured with grip strength instrument. After performing routine gynecological examinations, the pelvic floor muscle strength was evaluated by palpation with modified Oxford grading scale (MOS). MOS grade>3 was taken as normal group and ≤3 as decreased group. Binary logistic regression was used to investigate the related factors of deceased pelvic floor muscle strength. Results: A total of 929 patients were included in the study, and the average MOS grade was 2.8±1.2. By univariate analysis, birth history, menopausal time, defecation time, handgrip strength level, waist circumference and abdominal circumference were related to the decrease of pelvic floor muscle strength (all P<0.05). By binary logistic regression analysis, the level of handgrip strength (OR=0.913, 95%CI: 0.883-0.945; P<0.001) was correlated with normal pelvic floor muscle strength; waist circumference (OR=1.025, 95%CI: 1.005-1.046; P=0.016), birth history (OR=2.224, 95%CI: 1.570-3.149; P<0.001), sedentary time> 8 hours (OR=2.073, 95%CI: 1.198-3.587; P=0.009) were associated with the decrease of pelvic floor muscle strength. Conclusions: The level of handgrip strength is related to the normal pelvic floor muscle strength of females, while the waist circumference, birth history and sedentary time>8 hours are related to the decrease of pelvic floor muscle strength of females. In order to prevent the decrease of pelvic floor muscle strength, it is necessary to carry out relevant health education, enhance exercise, improve the overall strength level, reduce daily sedentary time, maintain symmetry, and carry out comprehensive overall intervention to improve pelvic floor muscle function.

[Multiple pulmonary masses with diffuse cystic lesions].

A 50-year-old female patient, presenting with a past history of Reynaud's syndrome, xerostomia and xerophthalmia, was admitted to Fujian Provincial Hospital because of coughing for 10 days and left anterior chest pain for 1 day. Chest imaging showed multiple nodules and masses, and diffuse cystic lesions in both lungs. Based on the differential diagnosis of multiple pulmonary masses and diffuse cystic lesions respectively, autoantibodies, radionuclide dynamic imaging of the parotid, positron emission tomography-CT, CT-guided percutaneous transthoracic needle biopsy, and other examinations were performed. The diagnosis of diffuse large B-cell lymphoma stage ⅣA (lung, parotid gland) and Sjögren's syndrome was confirmed. By analyzing the imaging features and pathogenesis in detail, the diffuse cystic lesions of both lungs were considered to be related to lymphocytic interstitial pneumonia caused by Sjögren's syndrome. The pulmonary space-occupying lesions in the lungs were significantly absorbed after RCHOP regimen for lymphoma.

Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.

INTRODUCTION: We propose that MuSC-derived myoblasts in PAD have transcriptomic differences that can highlight underlying causes of ischemia-induced myopathy. METHODS: Differentiation capacity among perfused and ischemic human myoblasts was compared. Following next generation sequencing of mRNA, Ingenuity Pathway Analysis (IPA) was performed for canonical pathway enrichment. Live cell imaging and immunofluorescence were performed to determine myocyte fusion index and protein expression based on insights from IPA, specifically concerning cell cycle regulators including cell-division cycle protein 2 (CDC2) and polo-like kinase 1 (PLK1). RESULTS: Ischemic myoblasts formed attenuated myotubes indicative of reduced fusion. Additionally, myoblasts from ischemic segments showed significant differences in canonical pathways associated with PLK1 (upregulated) and G2/M DNA damage checkpoint regulation (downregulated). PLK1 inhibition with BI2536 did not affect cell viability in any group over 24 h but deterred fusion more significantly in PAD myoblasts. Furthermore, PLK1 inhibition reduced the expression of checkpoint protein CDC2 in perfused but not ischemic cells. CONCLUSION: Differentiating myoblasts derived from ischemic muscle have significant differences in gene expression including those essential to DNA-damage checkpoint regulation and cell cycle progress. DNA-damage checkpoint dysregulation may contribute to myopathy in PAD.

LINC00839 Promotes the Progression of Gastric Cancer by Sponging miR-1236-3p.

In this paper, LINC00839 expression in gastric cancer (GC) was confirmed by real-time quantitative PCR. The function of LINC00839 in GC was detected by loss of function assays. Luciferase assays was performed to confirm the interaction between LINC00839 and miR-1236-3p. Then we investigated the regulatory effect of LINC00839 on miR-1236-3p. The results confirmed that the expression level of LINC00839 in GC was significantly up-regulated. LINC00839 could promote GC cell proliferation, mobility, and invasion. The detection of luciferase reporter gene confirmed that LINC000839 could bind to the binding site of miR-1236-3p. Our findings suggest that LINC00839 promotes GC progression through sponging miR-1236-3p.

[Clinicopathological features of low-grade oncocytic renal tumor (CD117-negative, cytokeratin 7-positive): report of seven cases].

Objective: To explore clinicopathological features of low-grade oncocytic tumor (LOT) of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor (HOCT) of the kidney, renal oncocytoma (RO), and chromophobe renal cell carcinoma (chRCC). Methods: Seven LOTs were identified from the pathologic archives of two hospitals, including Xiangya Hospital (5 cases) and the Second Xiangya Hospital (2 cases) of Central South University between 2012 and 2019. Clinical data of the LOTs were collected. The tumor morphology was analyzed and immunohistochemistry was performed. Results: All LOTs occurred in adults, aged from 49 to 72 years (median 56.0 years, mean 60.7 years). The tumor size ranged from 2.5 to 6.0 cm (median 4.3 cm, mean 4.3 cm). There were three male and four female patients. Three cases occurred in the left kidney and four in the right. All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé (BHD) syndrome or oncocytosis. Five patients had available follow-up data (follow-up period 23-95 months, median 69.0 months, mean 64.6 months) and all were alive without disease. Microscopically, all LOTs were well-circumscribed (7/7). Three LOTs were partly encapsulated. The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels, imparting an organoid architecture (7/7), but variable numbers of glandular or gland-like structures were often seen among the small nests (7/7). There were frequently areas with loose, edematous stroma, and the tumor cells exhibited reticular, trabecular, or single cell arrangements (6/7). Focal hemorrhage was also commonly present in both compact and loose areas (5/7). In addition, focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case. The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC, including abundantly eosinophilic granular cytoplasm, ovoid to round nuclei with mostly smooth contours, discernable small nucleoli (RO features), frequently delicate perinuclear halos, and occasional binucleation (chRCC features). The tumors were typically CK7-positive and CD117-negative (7/7), and variable staining for PAX8 (5/7), P504s (2/7), and vimentin (1/7). They were negative for CK20, CD10 and FOXI1. All tumors retained SDHB immunostaining. Conclusions: LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC. There are some clinicopathologic overlaps between LOT and sporadic HOCT. The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.

[Application of three risk assessment methods to noise risk assessment in an automobile foundry enterprise].

Objective: To explore the applicability of three different kinds of noise occupational health risk assessment methods to the occupational health risk assessment of noise exposed positions in an automobile foundry enterprise. Methods: In July 2020, the occupational-health risk assessment of noise-exposed positions was conducted by using the Guidelines for risk management of occupational noise hazard (guideline method) , the International Commission on Mining and Metals Guidelines for Occupational Health Risk Assessment (ICMM) method and the Occupational-health risk index method (index method) respectively, and the results were analyzed and compared. Results: Through the occupational health field investigation, the noise exposure level of the enterprise's main workstations was between 80.3 and 94.8 dB (A) , among which the noise of the posts of shaking-sand, cleaning and modeling was greater than 85 dB (A) ; The noise risk of each position was evaluated by the three methods, and the adjustment risk level was between 2 and 5 assessed using the guideline method, between 2 and 3 assessed using the index method, and 5 evaluated using the ICMM model. Conclusion: Each of the three risk assessment methods has its own advantages and disadvantages. The ICMM model has a large difference in value assignment, and values in the results are larger than expected. The evaluation results of the guideline method and the index method are consistent in some positions, there is certain subjectivity in the evaluation using the index method, and the guideline method is more objective.

MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3.

Down-regulated miR-223-3p was found in rheumatoid arthritis. This study aimed to further explore the level and role of miR-223-3p in gout arthritis (GA). After monosodium urate (MSU)-induced GA rat and fibroblast-like synoviocytes (FLSs) models were established, the rat paw volume and gait score were documented and the FLSs were transfected with miR-223-3p mimic/inhibitor or NLR family pyrin domain containing 3 (NLRP3) over-expression plasmids. The MiR-223-3p target was found through bioinformatics and the dual-luciferase reporter. The rat joint pathological damage was observed by hematoxylin and eosin staining. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and articular elastase in rats were detected by enzyme-linked immunosorbent assay (ELISA). The viability and pyroptosis of FLSs were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry. The expressions of miR-223-3p, NLRP3, cleaved caspase-1, IL-1ß, apoptosis-associated speck-like protein (AS) and cleaved N-terminal gasdermin D (GSDMD) in FLSs or rat synovial tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Western blot or immunohistochemistry analysis. MSU increased the paw volume, gait score, inflammation in synovial tissues and increased the levels of IL-1ß, TNF-α and articular elastase in rats. MSU decreased the viability and increased the pyroptosis of FLSs, up-regulated the expression of NLRP3, ASC, cleaved caspase-1, cleaved N-terminal GSDM, and IL-1ß, and down-regulated miR-223-3p expression in synovial tissues of rat joints and FLSs. MiR-223-3p mimic reversed the effect of MSU on lowering cell viability, increasing pyroptosis in FLSs, while miR-223-3p inhibitor further enhanced the effect of MSU on FLSs. NLRP3 was a target of miR-223-3p. Also, NLRP3 over-expression reversed the effects of miR-223-3p on MSU-induced FLSs. MiR-223-3p inhibited pyroptosis in MSU-induced rats and FLSs by targeting NLRP3.

Psychosocial adjustment mediates impacts of playmate positive support on body mass index and overweight risk in adolescents.

OBJECTIVES: We examined the mediation effects of psychosocial adjustment on the impact of playmate positive support throughout childhood and early adolescence (from age 54 months to 11 years) on later body mass index (BMI) and overweight risk in middle adolescence (age 15 years). STUDY DESIGN: This was a prospective cohort study. METHODS: Among 844 children and their families, positive support between child-playmate dyads was repeatedly assessed from child's age 54 months to Grade 5. Long-term positive support between child-playmate dyads throughout childhood and early adolescence was prospectively linked to child's BMI and overweight/obesity status at age 15 years. The average scores of repeated assessments of internalizing and externalizing behavior problems from Grades 3 to 6 were used as mediators. RESULTS: Significant mediations of internalizing and externalizing behavior problems were observed on pathways from positive support between child-playmate dyads to later BMI and overweight/obesity status at age 15 years. The observed mediations were mainly sustained with pronounced magnitudes in girls, but not in boys. CONCLUSIONS: Our findings demonstrated a significant mediating role of psychosocial adjustment. Future research efforts are highly encouraged to replicate our findings and further explore this underlying mediation mechanism.

[Clinical diagnosis and treatment of 27 cases of metanephric adenoma].

The clinical features, imaging features, treatment methods and pathological features of 27 patients with metanephric adenoma were analyzed. It was found that the clinical features and imaging features of metanephric adenoma were difficult to differentiate from renal malignantology. Pathology can be clearly diagnosed and some can be combined with malignant components. Nephron sparing surgery is the first choice, and the prognosis is good, but still need regular follow-up.

[A prospective multi-center clinical investigation of HIV-negative pulmonary cryptococcosis in China].

Objective: To investigate the current status of the diagnosis and treatment of pulmonary cryptococcosis in respiratory medicine and improve the understanding of the clinical characteristics of HIV-negative pulmonary cryptococcosis in China. Methods: A prospective multi-center open cohort study was designed to screen for pulmonary cryptococcosis in the general wards and intensive care units of the Department of Respiratory Diseases in 22 hospitals. The HIV-negative patients with positive cryptococcal etiological diagnosis based on smear culture, antigen detection and histopathology were enrolled in the study. The clinical data of enrolled patients were collected and analyzed. Results: A total of 457 cases of pulmonary cryptococcosis were enrolled, among which 3.28% (15/457) were disseminated infections. The case fatality rate was 0.88% (4/457). The majority of the cases were diagnosed by histopathological examinations (74.40%, 340/457) and cryptococcus antigen detection (37.64%, 172/457). Patients with pulmonary cryptococcosis accounted for 2.04‰ (457/223 748) of the total hospitalized patients in the Department of Respiratory Diseases during the same period, and the ratio was the highest in south and east China. Meanwhile, 70.24% (321/457) of the patients had no underlying diseases, while 87.75% (401/457) were found to have immunocompetent status. Cough and expectoration were the most common clinical symptoms in patients with pulmonary cryptococcosis. However, 25.16% (115/457) of the patients had no clinical symptom or physical signs. In terms of imaging features on pulmonary CT, multiple pulmonary lesions were more common than isolated lesions, and there were more subpleural lesions than perihilar or medial lesions. Morphologically, most of the lesions were middle-sized nodules (1-5 cm) or small-sized nodules (3 mm to 1 cm). The sensitivity of serum cryptococcus antigen test was 71.99% (203/282). Moreover, antigen-positive patients differed from antigen-negative patients in terms of basic immune status, clinical symptoms, imaging features and infection types. Meanwhile, immunocompromised patients differed from immunocompetent patients in terms of clinical symptoms, physical signs, infection-related inflammation indicator levels, imaging features, serum cryptococcus antigen positive rate and prognosis. Conclusions: The majority of cases of HIV-negative pulmonary cryptococcosis in China had no underlying disease or immunocompromised status, and the overrall prognosis was favorable. However, early diagnosis of HIV-negative pulmonary cryptococcosis remains challenging due to the complicated manifestations of the disease.

Metabolomics Changes of Serum and Tissues in Mice Died of Acute Tetracaine Poisoning.

ABSTRACT: Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.

Risk factors for death from hand-foot-mouth disease: a meta-analysis.

In recent years, outbreaks of hand-foot-mouth disease (HFMD) in China, Singapore and other Western Pacific Region, involving millions of children, have become a big threat to public health. This study aimed to quantitatively assess all qualified studies and identify the risk factors for HFMD death. A systematic search of the databases PubMed, Medline, Embase and the Cochrane Library was performed. Study heterogeneity and publication bias were estimated. Seven case-control studies involving 1641 participants (634 died and 1007 survived) were included in the meta-analysis. Human enterovirus 71 infection, male, age ⩽3 years, vomiting, cyanosis, convulsion, duration of fever ⩾3 days, atypical rashes and abdominal distention were not significantly related to HFMD death (P ⩽ 0.05). Lethargy (odds ratio (OR) = 6.62; 95% CI 3.61-12.14; I2 = 0%; P < 0.0001), pneumonoedema/pneumorrhagia (OR = 4.09; 95% CI 2.44-6.87; I2 = 0%; P < 0.0001), seizures (OR = 6.85; 95% CI 2.37-19.74; I2 = 0%; P = 0.0004), dyspnoea (OR = 8.24; 95% CI 2.05-33.19; I2 = 83%; P = 0.003) and coma (OR = 3.76; 95% CI 1.85-7.67; I2 = 0%; P = 0.0003) were significantly associated with HFMD death, which were risk factors for HFMD death.

Smart identification of psoriasis by images using convolutional neural networks: a case study in China.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, which holds a high incidence in China. However, professional dermatologists who can diagnose psoriasis early and correctly are insufficient in China, especially in the rural areas. A smart approach to identify psoriasis by pictures would be highly adaptable countrywide and could play a useful role in early diagnosis and regular treatment of psoriasis. OBJECTIVES: Design and evaluation of a smart psoriasis identification system based on clinical images (without relying on a dermatoscope) that works effectively similar to a dermatologist. METHODS: A set of deep learning models using convolutional neural networks (CNNs) was explored and compared in the system for automatic identification of psoriasis. The work was carried out on a standardized dermatological dataset with 8021 clinical images of 9 common disorders including psoriasis along with full electronic medical records of patients built over the last 9 years in China. A two-stage deep neural network was designed and developed to identify psoriasis. In the first stage, a multilabel classifier was trained to learn the visual patterns for each individual skin disease. In the second stage, the output of the first stage was utilized to distinguish psoriasis from other skin diseases. RESULTS: The area under the curve (AUC) of the two-stage model reached 0.981 ± 0.015, which outperforms a single-stage model. And, the classifier showed superior performance (missed diagnosis rate: 0.03, misdiagnosis rate: 0.04) than 25 Chinese dermatologists (missed diagnosis rate: 0.19, misdiagnosis rate: 0.10) in the diagnosis of psoriasis on 100 clinical images. CONCLUSIONS: Using clinical images to identify psoriasis is feasible and effective based on CNNs, which also builds a solid technical base for smart care of skin diseases especially psoriasis using mobile/tablet applications for teledermatology in China.

[Clinical features and high resolution CT imaging evolution of coronavirus disease 2019].

Objective: To investigate the clinical manifestations of the clinical characteristics of 141 patients with coronavirus disease 2019 (COVID-19) and the imaging evolution characteristics of High Resolution CT (HRCT) in the chest. Methods: From January 20, 2020 to February 8, 141 COVID-19 patients in Renmin Hospital of Wuhan University, 77 males and 64 females, with a median age of 49 (9,87) , were retrospectively analyzed. The clinical features, laboratory examination indexes and HRCT evolution findings of 141 COVID-19 patients were analyzed. Results: Laboratory examinations of 141 COVID-19 patients showed a decrease in white blood cell count and lymphocyte ratio. Among the 141 patients with COVID-19, fever (>37.5 â„ƒ) was the most common clinical manifestation in 139 cases (98.58%) , and occasionally non-respiratory symptoms such as diarrhea in 4 cases (2.84%) . 141 patients with COVID-19 had abnormal HRCT. 52 (36.88%) chest HRCT images showed ground-glass opacity (GGO) , mainly under pleural; 23 (16.31%) GGO with focal consolidation; 27 (19.15%) small flaky shadows; 20 cases (14.18%) large flaky consolidation shadows; 48 cases (34.04%) bronchovascular bundle thickening and vascular penetrating signs; 5 cases (3.55%) had air bronchial signs; 7 cases (4.96%) of small nodule shadows; 5 cases (3.55%) of fibrosis, grid shadows or strand shadows.135 cases (95.74%) were positive for the first time nucleic acid test, 6 cases (4.26%) were negative, and 71 cases (50.35%) of common type, 47 cases (33.33%) of severe type and 23 cases (16.31%) of critical type were found during the same period. The average time from onset of each type to the first CT examination was: (2.51±1.32) , (5.02±2.01) , and (5.91±1.76) days; 19 (19/47, 40.43%) of which were severe for the first time CT classification worsened at the second examination and lessened at the third examination. 141 cases (100%) were positive for the second nucleic acid test, and the HRCT results for the same period were 44 cases (31.21%) of common type, 53 cases (37.59%) of severe type, and 44 cases (31.21%) of critical type; the average interval time was (3.32±1.61) , (3.93±1.84) , (4.15±1.57) days;the third nucleic acid test were positive among 113 cases and 28 cases were negative, HRCT results of the same period were 79 cases (56.03%) of common type, 46 cases (32.62%) of severe type, and 16 cases (11.35%) of critical type;the average interval from the first CT examination were: (5.59±1.83) , (7.32±1.37) , (7.55±1.78) days. The differences in CT typing at different time were statistically significant (P<0.05) . Conclusion: The clinical features of COVID-19 and HRCT images are diverse, extensive GGO and infiltrates in both lungs are typical. Viral nucleic acid tests usually occur earlier or at the same time as the CT examination positive, and there are false negatives in nucleic acid tests. In some epidemiological backgrounds, CT imaging manifestations and evolutionary characteristics are of great significance for early warning of lung injury, assessment of disease severity, and assistance in clinical typing and post-treatment follow-up.

[Influence of Halogenated Hydroxyl-Alkanes Inhalation Anesthetic on the Determination of Ethanol Content in Blood].

ABSTRACT: Objective To study the influence of halogenated hydroxyl-alkanes inhalation anesthetic on the determination of ethanol content in blood. Methods Halogenated hydroxyl-alkanes were analyzed by headspace gas chromatography with double column confirmatory detection method. The influence of halogenated hydroxyl-alkanes on determination of ethanol content in blood sample by headspace gas chromatography was explored under the different detection conditions of KB-BAC1/ KB-BAC2 and J&W DB-ALC1/DB-ALC2 gas chromatographic column. Results The retention time of sevoflurane and enflurane was similar to that of ethanol and tert butanol respectively when using the J&W DB-ALC1/DB-ALC2 gas chromatographic column, and interfered with the detection of ethanol content in blood; only J&W DB-ALC1 gas chromatographic column can separate the sevoflurane and ethanol components, so as to eliminate their influence on the detection of ethanol content in blood. When using KB-BAC1/KB-BAC2 gas chromatographic column, the retention time of sevoflurane, isoflurane and ethanol is similar, especially that of sevoflurane and ethanol, and sevoflurane obviously interferes with the determination of ethanol content in blood. Conclusion Halogenated hydroxy-alkanes interfere with determination of ethanol content in blood by headspace gas chromatography. The interference can be discriminated effectively by choosing the suitable chromatographic column and double column confirmatory detection.

Low frequency, weak MCP-1 secretion and exhausted immune status of peripheral monocytes were associated with progression of severe enterovirus A71-infected hand, foot and mouth disease.

A minority of hand, foot and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) results in severe neural complications. However, whether monocyte-mediated immunity is involved in the disease progression of HFMD remains unknown. One hundred and twenty mild and 103 severe HFMD patients were recruited and enzyme-linked immunosorbent assay (ELISA), flow cytometry and Transwell culture were performed in the study. Peripheral monocyte counts were lower in both absolute counts and frequencies in severe cases compared to mild cases. After screening 10 monocyte-related cytokines by ELISA, only monocyte chemoattractant protein-1 (MCP-1) was found at higher levels in sera of mild cases compared to those with severe symptoms. Monocytes purified from mild cases produced more MCP-1 than the cells from severe patients when stimulated in vitro. We observed that immune exhaustion markers programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) were highly regulated on the surface of monocytes from severe cases compared to mild cases. PD-L1 blockade induced a higher production of MCP-1 in the supernatant of a Transwell system. The production of MCP-1 also increased following PD-L1 blockade of purified monocytes activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with R848 or EV-A71 virus. Our results indicate that absolute count, frequency and levels of MCP-1 secretion of peripheral monocytes, together with their immune status, probably contribute to differential disease prognosis in EV-A71-associated HFMD.