Percutaneous ultrasound-guided coaxial core needle biopsy for the diagnosis of multiple splenic lesions: A case report.

BACKGROUND: The overlap of imaging manifestations among distinct splenic lesions gives rise to a diagnostic dilemma. Consequently, a definitive diagnosis primarily relies on histological results. The ultrasound (US)-guided coaxial core needle biopsy (CNB) not only procures sufficient tissue to help clarify the diagnosis, but reduces the incidence of puncture-related complications. CASE SUMMARY: A 41-year-old female, with a history of pulmonary tuberculosis, was admitted to our hospital with multiple indeterminate splenic lesions. Gray-scale ultrasonography demonstrated splenomegaly with numerous well-defined hypoechoic masses. Abdominal contrast-enhanced computed tomography (CT) showed an enlarged spleen with multiple irregular-shaped, peripherally enhancing, hypodense lesions. Positron emission CT revealed numerous abnormal hyperglycemia foci. These imaging findings strongly indicated the possibility of infectious disease as the primary concern, with neoplastic lesions requiring exclusion. To obtain the precise pathological diagnosis, the US-guided coaxial CNB of the spleen was carried out. The patient did not express any discomfort during the procedure. CONCLUSION: Percutaneous US-guided coaxial CNB is an excellent and safe option for obtaining precise splenic tissue samples, as it significantly enhances sample yield for exact pathological analysis with minimum trauma to the spleen parenchyma and surrounding tissue.

Comparison contrast-enhanced CT with contrast-enhanced US in diagnosing combined hepatocellular-cholangiocarcinoma: a propensity score-matched study.

OBJECTIVES: To develop and compare noninvasive models for differentiating between combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and HCC based on serum tumor markers, contrast-enhanced ultrasound (CEUS), and computed tomography (CECT). METHODS: From January 2010 to December 2021, patients with pathologically confirmed cHCC-CCA or HCC who underwent both preoperative CEUS and CECT were retrospectively enrolled. Propensity scores were calculated to match cHCC-CCA and HCC patients with a near-neighbor ratio of 1:2. Two predicted models, a CEUS-predominant (CEUS features plus tumor markers) and a CECT-predominant model (CECT features plus tumor markers), were constructed using logistic regression analyses. Model performance was evaluated by the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: A total of 135 patients (mean age, 51.3 years ± 10.9; 122 men) with 135 tumors (45 cHCC-CCA and 90 HCC) were included. By logistic regression analysis, unclear boundary in the intratumoral nonenhanced area, partial washout on CEUS, CA 19-9 > 100 U/mL, lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT were independent factors for a diagnosis of cHCC-CCA. The CECT-predominant model showed almost perfect sensitivity for cHCC-CCA, unlike the CEUS-predominant model (93.3% vs. 55.6%, p < 0.001). The CEUS-predominant model showed higher diagnostic specificity than the CECT-predominant model (80.0% vs. 63.3%; p = 0.020), especially in the ≤ 5 cm subgroup (92.0% vs. 70.0%; p = 0.013). CONCLUSIONS: The CECT-predominant model provides higher diagnostic sensitivity than the CEUS-predominant model for CHCC-CCA. Combining CECT features with serum CA 19-9 > 100 U/mL shows excellent sensitivity. CRITICAL RELEVANCE STATEMENT: Combining lack of cirrhosis, incomplete tumor capsule, and nonrim arterial phase hyperenhancement (APHE) volume < 50% on CECT with serum CA 19-9 > 100 U/mL shows excellent sensitivity in differentiating cHCC-CCA from HCC. KEY POINTS: 1. Accurate differentiation between cHCC-CCA and HCC is essential for treatment decisions. 2. The CECT-predominant model provides higher accuracy than the CEUS-predominant model for CHCC-CCA. 3. Combining CECT features and CA 19-9 levels shows a sensitivity of 93.3% in diagnosing cHCC-CCA.

Global burden of burns and its association with socio-economic development status, 1990-2019.

BACKGROUND: Burns represent important global health problems. Whereas many studies are limited by the difficulties in estimating the burden of burns and instead focus on the causes of burns, such as fire, heat, and hot substances. Therefore, a complete assessment of the burden of all injuries leading to burns is essential to developing reasonable global intervention strategies. METHODS: Data on three classes of burns, including "< 20 % total burned surface area without lower airway burns" (Moderate injury), "> =20 % total burned surface area or > = 10 % burned surface area if head/neck or hands/wrist involved w/o lower airway burns" (Major injury), "Lower airway burns" (Inhalation injury) were collected from the Global Burden of Disease 2019 database. Age-standardized incidence rates (ASR-I) and Years Lived with Disability (ASR-YLDs) for burns has been standardized by removing the influence of population size and age structure. They were extracted and stratified by cause, year, sex, age, socio-demographic index, country, and territory. RESULTS: In terms of ASR-I and ASR-YLDs, burns showed a significant decrease from 1990 to 2019, especially for moderate and major injury. In 2019, the burden of moderate injury was positively correlated with socio-demographic index while major injury was negatively correlated (P < 0.05). We found no correlation between socio-demographic index and the burden for inhalation injury (P > 0.05). Fire, heat, and hot substances were the most important cause of burns except for inhalation injury. The most common association with inhalation injury was falls, which were also a major cause of moderate and major injury. CONCLUSIONS: The Global Burden of Disease 2019 database data can be used to guide the allocation of resources to reduce ASR-I and ASR-YLDs of different burn classes.

Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis.

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

Neoadjuvant immune checkpoint inhibitor therapy and chemotherapy improve pulmonary ventilation and diffusion function in patients with lung cancer. / å ç–«æ£€æŸ¥ç‚¹æŠ‘åˆ¶å‰‚è”åˆåŒ–ç–—æ”¹å–„ä¸­æ™šæœŸè‚ºç™Œæ‚£è€ è‚ºé€šæ°”åŠŸèƒ½å’Œå¼¥æ•£åŠŸèƒ½.

OBJECTIVES: To investigate changes of pulmonary ventilation function and diffusion function in lung cancer patients after neoadjuvant immune checkpoint inhibitors (ICIs) therapy combined with chemotherapy treatment. METHODS: Patients with newly diagnosed lung cancer (Ⅱa-Ⅲb) admitted to Zhejiang Cancer Hospital from October 2021 to July 2022, who received ICIs combined with chemotherapy for more than two courses were enrolled. Patients underwent pulmonary ventilation function and diffusion function assessments before and after treatment. The demographic information, sizes and locations of cancer lesions, doses and duration of ICIs used, pulmonary function results before and after treatment, and the tumor regression were documented. The changes of pulmonary function parameters before and after the treatment were analyzed with paired t test and Wilcoxon rank-sum test. The factors influencing the pulmonary function changes were analyzed by multiple linear Lasso regression and ridge regression. RESULTS: Among the 52 patients, 50 cases were males (96.15%) and 43 cases were squamous carcinoma (82.69%). The medium age of the patients was 67 years. After neoadjuvant therapy, 36 patients (69.23%) showed remission of tumor lesions. After treatment, the parameters of pulmonary ventilation inspiratory vital capacity (IVC) and the area under the expiratory flow-volume curve (AREAex), and the parameter of pulmonary diffusion total lung capacity increased compared with the baseline (all P<0.05). Forced vital capacity (FVC) and forced expiratory volume in first second (FEV1) also showed an increasing trend. Multivariate linear Lasso regression and ridge regression showed that baseline IVC had a significant negative effect on IVC improvement (Beta=－0.435, t=－2.968, P<0.01), baseline TLC had a significant negative effect on the improvement of TLC (Beta=－0.266, t=－2.474, P<0.05), and the remission of obstructive pneumonia favored the improvement of TLC (Beta=0.308, t=2.443, P<0.05). CONCLUSIONS: After ICIs neoadjuvant treatment combined with chemotherapy, the lung ventilation and diffusion function can be improved in lung cancer patients, particularly for those with reduced baseline ventilation and diffusion function.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.

PURPOSE: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown. METHODS AND MATERIALS: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response. Genomic and transcriptomic profiles before and after nCRT were analyzed. RESULTS: Codeficiency of the DNA damage repair and HIPPO pathways synergistically sensitized ESCC to nCRT. nCRT induced small INDELs and focal chromosomal loss concurrently. Acquired INDEL% exhibited a decreasing trend with the increase of tumor regression grade (P = .06, Jonckheere's test). Multivariable Cox analysis indicated that higher acquired INDEL% was associated with better survival (adjusted hazard ratio [aHR], 0.93; 95% CI, 0.86-1.01; P = .067 for recurrence-free survival [RFS]; aHR, 0.86; 95% CI, 0.76-0.98; P = .028 for overall survival [OS], with 1% of acquired INDEL% as unit). The prognostic value of acquired INDEL% was confirmed by the Glioma Longitudinal AnalySiS data set (aHR, 0.95; 95% CI, 0.902-0.997; P = .037 for RFS; aHR, 0.96; 95% CI, 0.917-1.004; P = .076 for OS). Additionally, clonal expansion degree was negatively associated with patient survival (aHR, 5.87; 95% CI, 1.10-31.39; P = .038 for RFS; aHR, 9.09; 95% CI, 1.10-75.36; P = .041 for OS, with low clonal expression group as reference) and also negatively correlated with acquired INDEL% (Spearman ρ = -0.45; P = .02). The expression profile was changed after nCRT. The DNA replication gene set was downregulated, while the cell adhesion gene set was upregulated after nCRT. Acquired INDEL% was negatively correlated with the enrichment of the DNA replication gene set (Spearman ρ = -0.56; P = .003) but was positively correlated with the enrichment of the cell adhesion gene set (Spearman ρ = 0.40; P = .05) in posttreatment samples. CONCLUSIONS: nCRT remodels the genome and transcriptome of ESCC. Acquired INDEL% is a potential biomarker to indicate the effectiveness of nCRT and radiation sensitivity.

Non-invasive evaluation of liver steatosis with imaging modalities: New techniques and applications.

In the world, nonalcoholic fatty liver disease (NAFLD) accounts for majority of diffuse hepatic diseases. Notably, substantial liver fat accumulation can trigger and accelerate hepatic fibrosis, thus contributing to disease progression. Moreover, the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases. Therefore, early detection and quantified measurement of hepatic fat content are of great importance. Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis. However, liver biopsy has several limitations, namely, its invasiveness, sampling error, high cost and moderate intraobserver and interobserver reproducibility. Recently, various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content, including ultrasound- or magnetic resonance-based methods. These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content, which is useful for longitudinal follow-up. In this review, we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Transcriptomic analysis of mRNA expression in giant congenital melanocytic nevi.

BACKGROUND AND OBJECTIVE: GCMN is a sporadic disease with an incidence ranging from 1/20,000 to 1/500000. So far, several studies have found that GCMN is related to somatic mutations, but most of them have focused on known pathogenic genes, and transcriptome sequencing based on large datasets is relatively uncommon. At present, the use of next-generation sequencing technologies and bioinformatics platforms makes genomic information study more comprehensive and efficient. In this study, the transcriptome differences between GCMN lesions and surrounding normal skin tissues were investigated using high-throughput transcriptome sequencing, and hub genes and pathways related to pathogenesis were identified, providing a theoretical foundation for further research into the pathogenesis of GCMN. METHODS: Pathological skin tissue and surrounding normal skin tissue from GCMN patients, namely the pathological group (PG) and the control group (CG), were obtained. 1. All specimens were stained with HE to ensure that the samples met the experimental requirements. 2. Ten pairs of specimens were selected for high-throughput transcriptome sequencing, and the differentially expressed genes (DEGs) between the PG and the CG were obtained. The DEGs were analyzed by clusterProfiler R software for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The function of the subnetwork was analyzed and the hub genes were identified by the STRING database and Cytoscape software. 3. The expression differences of hub genes PTGS2, EGF, and SOX10 in pathological skin tissues and normal skin tissues were verified by qRT-PCR and immunofluorescence staining. RESULTS: 1. HE staining revealed a lot of melanocytes in the dermis and subcutaneous tissues. They were found around the hair follicles, sweat glands, sebaceous glands, and blood vessel walls, or in a specific pattern. 2. The screening threshold was set at p < 0.01 and |log2fc|<1, and a total of 1163 DEGs were discovered between the PG and CG, with 519 genes up-regulated and 644 genes down-regulated in the pathological tissues. According to the GO functional analysis, 29 biological processes, 18 cell compositions, and 17 molecular functions were significantly enriched, with the majority of them being related to keratinocytes and the extracellular matrix. There were 779 nodes and 2359 interactions in the protein interaction network. Using the MCODE plug-in, the network was divided into 25 functional clusters. According to ClueGO results, Cluster5 was involved in melanin biosynthesis and melanocyte proliferation. Using 11 operation methods in the Cytohubba plug-in, PTGS2, EGF, and SOX10 in Cluster5 were chosen as hub genes. 3. qRT-PCR and immunofluorescent staining revealed that compared to normal skin tissue, the expression of SOX10 was significantly up-regulated, and the expression of PTGS2 and EGF was significantly down-regulated in pathological skin tissue(P < 0.001). CONCLUSIONS: In GCMN, keratinocytes and extracellular matrix may directly and indirectly affect melanocyte activity. PTGS2, EGF, and SOX10 are important genes and significantly differentially expressed in pathological and normal skin tissues. These findings may serve as a springboard for future research.

A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors / 医学前沿

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

An improved explants culture method: Sustainable isolation of keloid fibroblasts with primary characteristics.

BACKGROUND: Keloid (KD) is a complex fibroproliferative disease, but the exact mechanisms underlying keloid pathogenesis remain to be elucidated. The primary keloid fibroblasts (KFs) culture in vitro has always been a fundamental measure to study the pathogenesis of keloid. However, the traditional primary culture methods have some limitations, such as a long culture cycle, low specimen utilization rate and so on. AIMS: Improve the keloid explants culture method sts. MATERIALS & METHODS: We proposed an improved new "explants multiple culture method"-reusing keloid explants for primary culture and harvesting the primary KFs in specific culture times. Meanwhile, the purity, proliferation, apoptosis, migration, invasion, extracellular matrix synthesis, and some fibrosis and inflammation-related proteins of KFs obtained from the first, fifth, and tenth explants cultures were detected. RESULTS: The results showed that the culture cycle of this new method (Cell Isolation: 2.67 ± 0.86 days, Explants removal: 8.83 ± 0.79 days, Cell Passage: 15.17 ± 1.39 days) was significantly shorter than that of the traditional method (Cell Isolation: 8.67 ± 1.84 days, Explants removal: 17.67 ± 2.17 days, Cell Passage: 22.67 ± 1.84 days). No significant difference was observed between the phenotypes of the fibroblasts obtained from the first explants culture and cultures less than 10 times (p > 0.05). DISSCUSSION: Taken together, this study provides an effective method for the primary culture of KFs with a higher specimen utilization rate and shorter culture cycle. CONCLUSION: This method breaks through the limitation of traditional explants culture requiring a large number of keloid specimens and provides a rich source of KFs for the study of keloid.

Baicalin Ameliorates Radiation-Induced Lung Injury by Inhibiting the CysLTs/CysLT1 Signaling Pathway.

Objective: Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumors. This study investigated the alleviating effect of baicalin (BA) on RILI and its possible mechanism. Methods: RILI model was established by chest irradiation (IR) of C57BL/6 mice for 16 weeks. Different concentrations of BA were administered, and dexamethasone (DXM) was used as a positive control. Then, the lung pathological changes were observed by HE and Masson staining. The levels of TGF-ß, TNF-α, IL-1ß, IL-6, CysLT, LTC4, and LTE4 were measured by ELISA. The CysLT1 expression was detected by qPCR, immunohistochemistry, and western blot. Type II AEC cells were pretreated with LTD-4 to establish the RILI cell model and intervened with different concentrations of BA. Then, the collagen I protein level was measured by ELISA. The CysLT1 and α-SMA expression were detected by qPCR, immunofluorescence, and western blot. Results: BA could effectively improve lung histopathological changes and pulmonary fibrosis. In vivo, BA could inhibit the levels of TGF-ß, TNF-α, IL-1ß, and IL-6 and reduce the levels of CysLT, LTC4, and LTE4. In vitro, different concentrations of LTD4 could reduce the viability of type II AEC cells, which could be reversed by the administration of different concentrations of BA. In addition, BA could reduce CysLT1 mRNA, as well as CysLT1 and α-SMA protein levels in vitro and in vivo. Conclusion: BA attenuated lung inflammation and pulmonary fibrosis by inhibiting the CysLTs/CysLT1 pathway, thereby protecting against RILI.

Comparison of three different surgical approaches for the treatment of large/giant congenital melanocytic nevus.

OBJECTIVE: Treating large/giant congenital melanocytic nevus (L/GCMN) is challenging for surgeons. Operative approaches commonly used to remove L/GCMN include serial excision, tissue expansion, and skin grafting. Thus, we retrospectively compared these three operations' applications and therapeutic effects. METHODS: The clinical data of 97 L/GCMN patients from June 1, 2015, to June 1, 2019, were collected and divided into three groups according to the operations used: serial excision group (SE group, n = 18), tissue expansion group (TE group, n = 23), and skin grafting group (SG group, n = 56). The location and size of the lesion, the number of operations, duration of each operation, preoperative preparation time, postoperative hospital stay, complications, and clinical outcomes of all patients were collected and assessed. RESULTS: The SE group had the most times of operation (3.9 and 6.0 for LCMN and GCMN, respectively), the shortest surgery length (56.3 min), and the shortest postoperative hospital stay (10.0d). The SE and SG groups required much less time to prepare for surgery and had a lower rate of complications than the TE group. During the 11.9-month median follow-up period, the SE and TE groups had better postoperative outcomes than the SG group. CONCLUSION: Each of the three operations has different advantages and disadvantages, and the specific surgical strategy should be decided based on the patient's unique circumstances.

Global Burden of Bacterial Skin Diseases: A Systematic Analysis Combined With Sociodemographic Index, 1990-2019.

Background: The latest incidence and disability-adjusted life-years (DALYs) of major bacterial skin diseases (BSD) and their relationship with socioeconomic are not readily available. Objective: Describe the global age-standardized incidence and DALYs rates of BSD and analyze their relationship with socioeconomic. Methods: All data were obtained from Global Burden of Disease (GBD) 2019 database. The correlation between BSD and socioeconomic development status was analyzed. Results: The age-standardized incidence and age-standardized DALYs rate of BSD are: 169.72 million [165.28-175.44] and 0.41 million [0.33-0.48]. Of the two main BSD, pyoderma cause significantly much heavier burden than cellulitis. The change of age-standardized incidence (7.38% [7.06-7.67]) and DALYs (-10.27% [-25.65 to 25.45]) rate of BSD presented an upward or downward trend from 1990 to 2019. The highest burden was in the low-middle sociodemographic index (SDI) area while the area with the lowest burden was recorded in the high-middle SDI area in 2019. Limitations: GBD 2019 data of BSD are derived from estimation and mathematical modeling. Conclusion: The burden of BSD is related to socioeconomic development status. The results based on GBD2019 data may benefit policymakers in guiding priority-setting decisions for the global burden of BSD.

Global Burden, Incidence and Disability-Adjusted Life-Years for Dermatitis: A Systematic Analysis Combined With Socioeconomic Development Status, 1990-2019.

Background: Dermatitis is an important global health problem that not only affects social interaction and physical and mental health but also causes economic burden. Health problems or distress caused by dermatitis may be easily overlooked, and relevant epidemiological data are limited. Therefore, a better understanding of the burden of dermatitis is necessary for developing global intervention strategies. Methods: All data on dermatitis, including atopic dermatitis (AD), contact dermatitis (CD) and seborrhoeic dermatitis (SD), were obtained from the Global Burden of Disease 2019 (GBD2019) database. The extracted age-standardized incidence rates (ASIR) and disability-adjusted life-years (DALYs) rates (ASDR) data were analysed by stratification, including by sex, country or region, and sociodemographic index (SDI) indicators. Finally, we analysed the correlation between the global burden of dermatitis and socioeconomic development status. Results: According to the GBD 2019 estimate, the ASIR and ASDR for the three major types of dermatitis in 2019 were 5244.3988 (95% CI 4551.7244-5979.3176) per 100,000 person-years and 131.6711 (95% CI 77.5876-206.8796) per 100,000 person-years. The ASIR and ASDR of atopic dermatitis, contact dermatitis and seborrhoeic dermatitis are: Incidence (95%CI,per 100,000 person-years), 327.91 (312.76-343.67), 3066.04 (2405.38-3755.38), 1850.44 (1706.25- 1993.74); DALYs (95%CI, per 100,000 person-years), 99.69 (53.09-167.43), 28.06 (17.62-41.78), 3.93 (2.24-6.25). In addition, among the three dermatitis types, the greatest burden was associated with AD. According to the ASDR from 1990 to 2019, the burden of dermatitis has exhibited a slow downward trend in recent years. In 2019, the ASIR showed that the USA had the greatest burden, while the ASDR showed that Asian countries (such as Japan, Mongolia, Kazakhstan, and Uzbekistan) and some European countries (France, Estonia) had the greatest burden. According to SDI stratification and the three major dermatitis types, high ASIR and ASDR corresponded to high SDI areas (especially for AD). Conclusion: The burden of dermatitis is related to socioeconomic development status, especially for AD, which is positively correlated with the SDI. The results based on GBD2019 data are valuable for formulating policy, preventing and treating dermatitis and reducing the global burden of dermatitis.

3,3'-Diindolylmethane attenuates inflammation and fibrosis in radiation-induced lung injury by regulating NF-κB/TGF-ß/Smad signaling pathways.

OBJECTIVE: This study aims to investigate the protective effect of 3,3'-diindolylmethane (DIM) on the radiation-induced lung injury (RILI) model and to explore its possible mechanism. Methods: A mouse model of RILI was established by thoracic irradiation, and dexamethasone was used as a positive drug to investigate the effect of DIM on RILI mice. Lung histopathology was analyzed by HE staining and Masson staining. Then the levels of inflammatory cytokines (TGF-ß, TNF-α, IL-1ß, and IL-6), inflammatory cell counts, and activity of MPO were detected. The expression of TGFß1/Smad signaling pathway-related proteins was determined by immunohistochemistry. qPCR was used to analyze the mRNA expression levels of inflammatory factors, α­SMA and COL1A1. The expression of COX-2, NF-κB, IκBα, PI3K, and Akt proteins was assessed by Western blot. Results: Histopathological staining of lung tissues showed that DIM administration alleviated the pulmonary inflammation and fibrosis caused by RILI. Moreover, the content of inflammatory factors such as IL-1ß and IL-6, the expression of NF-κB pathway-related proteins, and the counts of inflammatory cells were inhibited in lung tissue, indicating that DIM can inhibit the NF-κB pathway to reduce inflammation. In addition, DIM could down-regulate the mRNA levels of α-SMA, COL1A1, and downregulate TGFß1, Smad3, and p-Smad2/3 in lung tissues. Conclusion: Our study confirms that DIM has the potential to treat RILI in vivo by inhibiting fibrotic and inflammatory responses in lung tissue through the TGFß/Smad and NF-κB dual pathways, respectively.

Mongolian Medicine Areca Thirteen Pill (GY-13) Improved Depressive Syndrome via upregulating cAMP/PKA/CREB/BDNF signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca Thirteen Pill, also called Gao You-13 (GY-13), is a traditional Mongolian herbal formula and has been extensively used to treat depression in Mongolian areas, which belongs to Heyi disease in Mongolian medicine. Major depressive disorder is a serious psychiatric disease, only one-third of individuals with depression are responsive to current antidepressants in clinic. Growing attention has been attracted by traditional herbal medicines in fighting depression because they are considered safer alternatives to pharmacotherapy. AIM OF THE STUDY: To reveal the mechanism of GY-13 in the treatment of depression. MATERIALS AND METHODS: The rat depression model was established by chronic unpredictable mild stress (CUMS), and primary hippocampal neurons were used to construct a glutamate-induced excitotoxicity model. The antidepressant effect of GY-13 was then assessed by performing sucrose preference tests, open field tests, and body weight measurements on rats. The expression of cAMP and PKA, mRNA levels of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), and hippocampal neuronal apoptosis were measured. RESULTS: The results indicate that GY-13 significantly improves depression-like behavior, rescues decreased cAMP， PKA, recovers the mRNA levels of CREB and BDNF, and increases the proliferative activity of hippocampus. In addition, blockade of PKA reverses the effects of GY-13 treatment on CREB mRNA, BDNF mRNA levels. In vitro, GY-13 treatment increased hippocampal proliferative activity and attenuated Glu-induced apoptosis of hippocampal neurons as well as reduced CREB mRNA and BDNF mRNA expression levels. CONCLUSIONS: Our research demonstrated that GY-13 treatment exerted a potent antidepressant action via activation of cAMP/CREB/BDNF signaling pathway, promoting proliferation, and suppressing apoptosis. This research provides molecular biological ground for developing GY-13 into a potent alternative for the intervention of depression.

Foamy macrophages potentially inhibit tuberculous wound healing by inhibiting the TLRs/NF-κB signalling pathway.

To characterise the distribution, classification, and quantity of foamy macrophages (FMs) in tuberculous wound tissue and the relationship between FM and delayed healing of tuberculous wounds. Morphological studies were performed to explore the distribution of FM and Mycobacterium tuberculosis (Mtb) in tuberculous wounds, with acute and chronic wounds included for comparison. Phorbol-12-myristate-13-acetate stimulation-differentiated THP-1 cells were treated with Mtb to induce their differentiation into FM with oxidised low-density lipoprotein treatment serving as a control. Relative cytokine levels were determined by quantitative PCR and Western blotting. Varied co-culture combinations of Mtb, THP-1, FM, and fibroblasts were performed, and proliferation, migration, ability to contract collagen gel, and protein levels of the chemokines in the supernatants of the fibroblasts were assessed. The differentially expressed genes in human skin fibroblasts (HSFs) after co-culture with or without FM were identified using microarray. Many FM were found in the tissues of tuberculous wounds. The FM that did not engulf Mtb (NM-FM) were mainly distributed in tissues surrounding tuberculous wounds, whereas the FM that engulfed Mtb (M-FM) were dominantly located within granulomatous tissues. Co-culture experiments showed that, with the Mtb co-culture, the portions of NM-FM in the total FM grew over time. The migration, proliferation, chemokine secretion, and the ability of fibroblasts to contract collagen gel were inhibited when co-cultured with Mtb, FM, or a combination of the two. Further investigation showed that the TLRs/NF-κB signalling pathway is involved in fibroblast function under the stimulation of FM. TLRs and NF-κB agonists could reverse the phenotypic changes in HSFs after co-culture with FM. The tuberculous wound microenvironment composed of Mtb and FM may affect wound healing by inhibiting the functions of fibroblasts. FM potentially inhibit fibroblasts' function by inhibiting the TLRs/NF-κB signalling pathway in tuberculous wounds.

A study on the marine ecological security assessment of Guangdong-Hong Kong-Macao Great Bay Area.

The construction of world-class Bay makes the marine ecology in Guangdong-Hong Kong-Macao Great Bay Area in risk. Based on the DPSIR index framework, Lotka-Volterra symbiosis model is applied to calculate symbiosis degree between coastal socio-economic system and marine ecosystem in 9 coastal cities. It is found that the marine ecological pressure in this area have not been reversed in recent 20 years. Most cities are in the stage that socio-economic development and marine ecological damage coexist. In Shenzhen, Guangzhou, Dongguan and Zhongshan, the damaged marine ecology has begun to restrain the further expansion of economy and society. The massive population agglomeration in Hong Kong, Macao and other places has caused serious marine ecological stress. It is urgent to improve the marine ecological security by cultivating ecological industrial system and industrial clusters, establishing a land-sea ecological restoration, promoting joint-protection and co-governance across different administrative regions.

Gout-associated uric acid crystals induce tophi ulcerations and impair wound healing in a novel gouty ulcer model.

This study aimed to establish a novel gouty ulcer rat model induced by monosodium urate (MSU) deposition and preliminarily explored how MSU crystals affected wound healing. MSU crystals were subcutaneously injected into the back of rats to simulate tophi formation and ulceration. Ultrasound was used to detect the formation of gouty tophi. MSU crystal deposition and histopathological changes were analysed by haematoxylin-eosin staining. After the skin over the tophi became broken in the model group, a full-thickness tissue defect of the same area was made on the backs of the phosphate buffered saline (PBS) controls. On Days 3, 7, and 14 after wounding, the infiltration of neutrophils and macrophages and the expression of inflammatory markers, including interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), and Nod-like receptor protein 3 (NLRP3), were examined by immunohistochemical staining and Western blotting, respectively. After the first subcutaneous injection in rats, local tissues showed redness and swelling, indicating inflammation on approximately Day 14. Tophi-like manifestations appeared on approximately Day 18. Tophi appeared heterogeneously hyperechoic by ultrasound. Swelling and redness in injured tissue areas increased on approximately Day 22, skin tissue necrosis was seen in a small area on approximately Day 26, and skin necrosis was enlarged and the tophi were ulcerated on approximately Day 32, accompanied by yellowish-white, chalky secretions. Haematoxylin and eosin staining showed dermal deposition of needle-like crystals with surrounding granulomatous inflammation. On Days 3, 7, and 14 after wounding, immunohistochemical staining showed the infiltration of neutrophils and macrophages, and the expression of inflammation-related proteins (IL-1ß, TNF-α, and NLRP3) were upregulated in gouty ulcers compared with those of PBS controls. The gouty ulcers were not completely healed by Day 14 compared with those in the PBS controls. In this study, a novel gouty ulcer rat model was constructed, which also revealed the existence of persistent chronic inflammation.