A Novel Inhibitor of Poly(ADP-Ribose) Polymerase-1 Inhibits Proliferation of a BRCA-Deficient Breast Cancer Cell Line via the DNA Damage-Activated cGAS-STING Pathway.

Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)-N-(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1-/-) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS-STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS-STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Regiospecificity C(sp2)-C(sp3) Bond Construction between Purines and Alkenes to Synthesize C6-Alkylpurines and Purine Nucleosides Using O2 as the Oxidant.

A highly site-selective and Markovnikov-type radical C6-H alkylation of purines with alkenes is achieved, allowing fast construction of the C(sp2)-C(sp3) bond at the C-6-position of purines and purine nucleosides using O2 as a green oxidant and alkenes as cheap alkylation reagents. The route was also a radical route to synthesize C6-alkyl-N7-substituted purines with potential steric hindrance between C6-alkyl groups and N7-substituted groups. This reaction is easily scaled up and has excellent functional group compatibility and broad substrate scopes. Moreover, the unstable intermediate was also separated, which was the key evidence for the reaction mechanism.

Metal-free direct C-6-H alkylation of purines and purine nucleosides enabled by oxidative homolysis of 4-alkyl-1,4-dihydropyridines at room temperature.

Herein we report the application of 4-alkyl-1,4-dihydropyridines (DHPs), which are easily prepared from inexpensive aldehydes in one step, for the direct site-specific C-H alkylation of purines and purine nucleosides. Despite there being three active C(sp2)-H bonds (C-2-H, C-6-H, and C-8-H) in the structure, the reactions still show high regioselectivity at the purinyl C-6-H position. Importantly, the reactions successfully avoid the use of transition metal catalysts and additional acids. Meanwhile, the protocols are not sensitive to moisture and require only persulfate as an oxidant. Besides, this method displays broad functional group compatibility and is easy to scale up. Notably, pharmaceutical purines, e.g. the natural product 6-hydroxymethyl nebularine isolated from basidiomycetes, can be smoothly prepared using this protocol.

Integrative pan cancer analysis reveals the importance of CFTR in lung adenocarcinoma prognosis.

Cystic fibrosis (CF) and cystic fibrosis transmembrane conductance regulator (CFTR) mutations have been shown to be associated with the risk of a variety of cancers. However, the clinical significance of aberrant CFTR gene expression in human tumors remains unknown. The expression profiles and prognostic landscapes of CFTR in human cancers were identified from the PubMed, OVID, CNKI, TCGA, ONCOMINE, PrognoScan, and GEPIA databases. Over 11, 000 cancer samples from the literature, GEPIA database, and PrognoScan database were included in this study. In general, CFTR has various expression and prognostic profiles in cancers, but the results from cross-database and meta-analyses revealed that CFTR is a robust biomarker for LUAD prognosis. Collectively, this study suggests that CFTR is an important prognostic biomarker for LUAD survival, implying that it could be used as a prognostic biomarker and therapeutic target for LUAD.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

IRGS: an immune-related gene classifier for lung adenocarcinoma prognosis.

BACKGROUND: Tumour cells interfere with normal immune functions by affecting the expression of some immune-related genes, which play roles in the prognosis of cancer patients. In recent years, immunotherapy for tumours has been widely studied, but a practical prognostic model based on immune-related genes in lung adenocarcinoma comparable to existing model has not been established and reported. METHODS: We first obtained publicly accessible lung adenocarcinoma RNA expression data from The Cancer Genome Atlas (TCGA) for differential gene expression analysis and then filtered immune-related genes based on the ImmPort database. By using the lasso algorithm and multivariate Cox Proportional-Hazards (CoxPH) regression analysis, we identified candidate genes for model development and validation. The robustness of the model was further examined by comparing the model with three established gene models. RESULTS: Gene expression data from a total of 524 lung adenocarcinoma patients from TCGA were used for model development. We identified four biomarkers (MAP3K8, CCL20, VEGFC, and ANGPTL4) that could predict overall survival in lung adenocarcinoma (HR = 1.98, 95% CI 1.48 to 2.64, P = 4.19e-06) and this model could be used as a classifier for the evaluation of low-risk and high-risk groups. This model was validated with independent microarray data and was highly comparable with previously reported gene expression signatures for lung adenocarcinoma prognosis. CONCLUSIONS: In this study, we identified a practical and robust four-gene prognostic model based on an immune gene dataset with cross-platform compatibility. This model has potential value in improving TNM staging for survival predictions in patients with lung adenocarcinoma. IMPACT: The study provides a method of immune relevant gene prognosis model and the identification of immune gene classifier for the prediction of lung adenocarcinoma prognosis with RNA sequencing and microarray compatibility.

Risk Factors for Asymptomatic Intracranial Small Aneurysm Rupture Determined by Electrocardiographic-Gated 4D Computed Tomographic (CT) Angiography.

BACKGROUND To study the risk predictors of intracranial asymptomatic small aneurysm rupture by electrocardiographic (ECG)-gated 4D-CT angiography (4D-CTA). MATERIAL AND METHODS A total of 168 patients with intracranial aneurysms <7 mm who underwent 4D-CTA examinations were retrospectively analyzed and divided into a ruptured group and an unruptured group. The original scanning data of all cases were reconstructed to obtain 20 groups of data in 5% time intervals in the cardiac cycle. After processing with 3D workstation software, 20 sets of images and dynamic images were achieved. The morphological characteristics and clinical features of the 2 groups of aneurysms were analyzed through univariate analysis, then logistic regression analysis was performed for the meaningful indicators. Finally, the optimum diagnostic cut-off point was calculated by ROC curve analysis. RESULTS Univariate analysis showed that sex, smoking history, vascular bifurcation point, pulsation point appearance, aneurysm height, aspect ratio (AR), and size ratio (SR) were significantly different (P<0.05) between the ruptured group and unruptured group. Multivariate regression analysis indicated that the pulsation points (OR=8.188, 95% CI: 3.984-17.198) and high SR values (OR=5.325, 95% CI: 1.503-18.867) were independent predictors of asymptomatic small aneurysm rupture. When the SR value was higher than 1.65, the area below the ROC curve was 0.723, the diagnostic sensitivity was 75%, and the specificity was 80%. CONCLUSIONS The occurrence of pulsation points and SR values >1.65 were independent predictors for the rupture of asymptomatic small intracranial aneurysms <7 mm in diameter.

Upregulated circular RNA circ_0070934 facilitates cutaneous squamous cell carcinoma cell growth and invasion by sponging miR-1238 and miR-1247-5p.

Accumulating studies have appreciated circular RNAs (circRNAs) as novel prognostic biomarkers and therapeutic targets in malignant carcinomas. Here, we aim to investigate the expression of a novel circRNA, circ_0070934. The biological roles and mechanisms of circ_0070934 in cutaneous squamous cell carcinoma (CSCC) were explored. The expression of circ_0070934 in CSCC tissues and cell lines was evaluated by qRT-PCR. Loss-of-function and gain-of-function assays were performed to detect cell proliferation, apoptosis, migration and invasion in vitro. Moreover, the underlying molecular mechanism of circ_0070934 was predicted by online database and luciferase reporter assay. Abnormally overexpression of circ_0070934 was detected in CSCC samples and cell lines. Inhibition of cell proliferation, invasion, migration, and increased apoptosis were observed upon circ_0070934 knockdown. The opposite effect was observed in the circ_0070934 overexpression cells. Circ_0070934 expression was negatively correlated with miR-1238 and miR-1247-5p expression in CSCC and luciferase reporter experiment verified the binding ability between circ_0070934 and miR-1238/miR-1247-5p. Rescue experiments further identified that the oncogenic role of circ_0070934 is attributed to its suppression of miR-1238 and miR-1247-5p. Taken together, our results implicate that circ_0070934 is correlated with tumor aggressiveness by serving as an oncogenic circRNA in CSCC.

TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by upregulating claudin-1 in non-small-cell lung cancer cells.

Lung cancer is the most frequent cause of cancer-related deaths worldwide, but its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3 (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a cancer suppressor. However, our research has demonstrated that TUSC3 expression is significantly upregulated in non-small-cell lung cancer compared to benign controls. In this study, we analyzed the consequences of TUSC3 knockdown or overexpression on the biological functions of non-small-cell lung cancer cell lines. To identify the molecules and signaling pathways with which TUSC3 might interact, we completed immunoblotting, quantitative polymerase chain reaction, microarray, co-immunoprecipitation, and immunofluorescence assays. We demonstrated that TUSC3 knockdown leads to decreased proliferation, migration, and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer cell lines, whereas opposite results were observed with overexpression of TUSC3. In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by downregulating the expression of claudin-1, which plays an indispensable role in EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT progress by upregulating claudin-1 expression. Overall, our observations suggest that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal transition in non-small-cell lung cancer cells; we also identified claudin-1 as a target of TUSC3.

Dynamic Volume Change Rate and Aspect Ratio Are Correlated to the Formation of an Irregular Morphology of Unruptured Intracranial Aneurysm.

OBJECTIVE: The aim of this research was to study the factors influencing the formation of intracranial aneurysms with irregular morphology by observing the dynamic volume change rate of intracranial unruptured aneurysms and other aneurysm characteristics. METHOD: Sixty-five unruptured intracranial aneurysms of 51 consecutive patients from 1 center were included in this study. All patients underwent a dual-source computed tomography electrocardiogram-gated 4-dimensional computed tomography angiography examination. The original data at the end of the scan were reconstructed, and 20 sets of data packages through a cardiac cycle with 5% interval were obtained. Data packages were processed by a 3-dimensional software workstation to obtain 20 sets of images and dynamic diagrams. The volume of each aneurysm in the 20 sets of images was measured, and the volume change was calculated by a specific formula. The other data features of the aneurysm such as aneurysm neck, aneurysm height, aspect ratio (AR), location at bifurcation, and clinical features such as age, sex, hypertension history, type 2 diabetes history, smoking history, family history, multiple aneurysm history, and subarachnoid hemorrhage history, were documented in detail. After single factor analysis data, logistic regression analysis of the meaningful indicator was conducted to study the predictive factors of irregular aneurysms. RESULTS: Of the 65 aneurysms, 25 possessed an irregular shape and 40 were of regular shape; 51 were anterior circulatory aneurysms and 14 were posterior circulatory aneurysms. Single factor analysis showed that AR (P = 0.001), volume change rate (P = 0.002), and location of aneurysm at the bifurcation (P = 0.038) of the vessel were significantly correlated with irregular aneurysms, but not correlated with age, sex, hypertension history, type 2 diabetes history, smoking history, family history, multiple aneurysm history, and subarachnoid hemorrhage history. Multifactor analysis showed that volume change rate greater than 30% (P = 0.008; odds ratio, 6.934) and AR greater than 1.4 (P = 0.004; odds ratio, 8.258) were independent correlative factors of the formation of intracranial aneurysm with irregular shape. CONCLUSION: The volume change rate and AR are independent correlative factors of the formation of intracranial aneurysm with irregular shape.

Association of Glasgow Coma Scale with Total Homocysteine Levels in Patients with Hemorrhagic Stroke.

OBJECTIVES: We aimed to evaluate the association between Glasgow Coma Scale (GCS) and total homocysteine (tHcy) levels and examine the possible effect modifiers in patients with hemorrhagic stroke. METHODS: A total of 1,516 participants with hemorrhagic stroke and having the complete data on baseline GCS and tHcy measurements were included in the final analysis. RESULTS: The mean (SD) of age, tHcy, and GCS levels were 61.5 (11.3) years, 17.0 (10.3) µmol/L, and 13.9 (2.2), respectively. Compared with participants with severe damage (GCS <9), those with mild damage (GCS ≥13) had significantly lower transformed tHcy levels (ß = -2.46; 95% CI -4.80 to -0.12). Consistently, a significantly lower transformed tHcy levels were found in participants with mild damage (GCS ≥13; ß = -1.37; 95% CI -2.66 to -0.08) compared with those with moderate to severe damage (GCS <13). In the stratified analysis, a stronger inverse association between GCS categories (≥13 vs. <13) and tHcy concentrations was observed in ever smokers (vs. never; p for interaction = 0.045), and in participants with systolic blood pressure (SBP) ≥160 mm Hg (vs. <160 mm Hg; p for interaction = 0.031), or total cholesterol (TC) ≥5.2 mmol/L (vs. <5.2 mmol/L; p for interaction = 0.025). CONCLUSION: There was an inverse association between GCS level and tHcy concentration among patients with hemorrhagic stroke, especially in ever smokers or in participants with higher SBP or TC levels.

Monitoring Dynamic Morphological Changes With Electrocardiography-Gated Dynamic 4-Dimensional Computed Tomography Angiography to Predict Intraoperative Rupture of Intracranial Aneurysms.

OBJECTIVE: This study aims to evaluate dynamic morphological changes of intracranial aneurysms to predict intraoperative aneurysm rupture (IAR) during clipping. METHODS: Included in this study were 153 patients, who had ruptured and microsurgical-clipped aneurysms. All patients underwent dual-source computed tomography examination of electrocardiography-gated dynamic 4-dimensional computed tomography angiography before clipping. Original scanning data were reconstructed to produce 20 data sets of cardiac cycles with 5% time intervals. The aneurysm neck, transverse and longitudinal diameters, and volume from the 20 groups of images were measured to calculate their respective change rates. In addition, other data and clinical characteristics were recorded. Data were analyzed by logistic regression to identify factors associated with IAR. RESULTS: Of the 153 patients, 24 patients experienced IAR. Multivariable analysis revealed that the aneurysm neck change rate (P = 0.0001; odds ratio, 1.276) and aspect ratio (height/neck ratio, P = 0.025; odds ratio, 2.387) are predictors for IAR. When the change rate was greater than or equal to 60%, and the sensitivity and specificity were 91.7% and 76.7%, respectively. CONCLUSIONS: Aneurysm neck change rate is independent predictor of IAR.

Hg(II) adsorption using amidoximated porous acrylonitrile/itaconic copolymers prepared by suspended emulsion polymerization.

Initially, porous acrylonitrile/itaconic acid copolymers (AN/IA) were prepared by suspended emulsion polymerization. Successively, the cyano groups in AN/IA copolymers were converted to amidoxime (AO) groups by the reaction with hydroxylamine hydrochloride. The structures of the AN/IA and amidoximated AN/IA (AO AN/IA) were characterized by infrared spectroscopy, scanning electron microscopy, and porous structural analysis. The adsorption properties of AO AN/IA for Hg(II) were investigated. The results show that AO AN/IA has mesopores and macropores, and surface area of 11.71 m(2) g(-1). It was found that AO AN/IA has higher affinity for Hg(II), with the maximum adsorption capacity of 84.25 mg g(-1). The AO AN/IA also can effectively remove Hg(II) from different binary metal ion mixture systems. Furthermore, the adsorption kinetics and thermodynamics were studied in detail. The adsorption equilibrium can quickly be achieved in 4 h determined by an adsorption kinetics study. The adsorption process is found to belong to the second-order model, and can be described by the Freundlich model.

Scientific publications in critical care medicine journals from East Asia: A 10-year survey of the literature.

OBJECTIVE: The quantity and quality of publications in critical care medicine from East Asia haven't been reported. This study aimed to investigate the contribution of publications from East Asia. METHODS: Articles from China, Japan and South Korea in 2005 to 2014 were retrieved from Web of Science and Pubmed. The number of publications, impact factor, citation, and article types were analyzed. RESULTS: There were 3076 publications from East Asia (1720 from China, 913 from Japan, and 443 from South Korea). There were a significant decrease in publications from Japan (p = 0.024) and significant increases from China (p = 0.000) and South Korea (p = 0.009). From 2006, the number of articles from China exceed Japan. China had the highest total impact factor (6618.48) and citation (18416), followed by Japan (4566.03; 15440) and South Korea (1998.19; 5599). Japan had the highest mean impact factor (5.00) and citations (16.91), followed by South Korea (4.51; 12.64) and China (3.85; 10.71). CONCLUSIONS: China and South Korea`s contributions to critical care medicine had significant increases during the past 10 years, while Japan had a significant decrease. China was the most productive region in East Asia since 2006. Japan had the highest quality research output.

The correlation of expression of VEGF and EGFR with SUV of (18)FDG-PET-CT in non-small cell lung cancer.

AIM OF THE STUDY: To explore the correlation of the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) with maximum standardised uptake value (SUVmax) of (18)FDG-PET-CT in non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: Thirty patients received PET-CT imaging protocol first, and then all the patients underwent needle biopsy though CT guidance. The tumour tissue of each patient was taken from two biopsy areas: one area was SUVmax = 2.5-5, and the other was SUVmax > 5. Expression of VEGF and EGFR were detected and analysed by immunohistochemical staining. RESULTS: The expressions of both VEGF and EGFR had no statistically significant correlation with SUVmax in age, gender, pathology, or differentiation (p > 0.05). The expressions of both VEGF and EGFR had statistically significant correllation with SUVmax in tumour size and clinical stage (p < 0.05). SUVmax correlated positively with VEGF and EGFR expressions (r = 0.879, p < 0.05). CONCLUSIONS: SUVmax correlated positively with expressions of VEGF and EGFR (r = 0.879, p = 0.000; r = 0.839, and p = 0.000, respectively). This study may provide guidance for radiotherapy of NSCLC.

Hematoporphyrin injection mediated photodynamic therapy for secondary squamous cell carcinoma of arsenical keratosis: A case report.

Hematoporphyrin injection (HpD) mediated photodynamic therapy (PDT) has demonstrated efficacy in treating various types of Bowen's disease, including basal-cell carcinoma, squamous cell carcinoma, extramammary Paget's disease, and actinic keratosis. We present a case of a male patient who developed squamous cell carcinoma as a result of repeated instances of arsenic-induced keratosis on both his hands and feet. Due to the involvement of the joint in both hands, the patient declined the conventional surgical resection treatment since it could potentially impact normal physiological function. Instead, the patient chose to undergo hemoporphyrin photodynamic therapy. After the treatment, the rash was entirely eliminated and there were no restrictions in the movement of the joint. Nevertheless, a local recurrence was detected throughout the two-year monitoring period. Arsenical keratosis carries a substantial likelihood of recurring. However, we believe that hemoporphyrin photodynamic therapy is effective in treating this condition.

Dietary additive ferulic acid alleviated oxidative stress, inflammation, and apoptosis induced by chronic exposure to avermectin in the liver of common carp (Cyprinus carpio).

Avermectin (AVM) has been utilized extensively in agricultural production since it is a low-toxicity pesticide. However, the pollution caused by its residues to fisheries aquaculture has been neglected. As an abundant polyphenolic substance in plants, ferulic acid (FA) possesses anti-inflammatory and antioxidant effects. The goal of the study is to assess the FA's ability to reduce liver damage in carp brought on by AVM exposure. Four groups of carp were created at random: the control group; the AVM group; the FA group; and the FA + AVM group. On day 30, and the liver tissues of carp were collected and examined for the detection of four items of blood lipid as well as the activity of the antioxidant enzymes catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in carp liver tissues by biochemical kits, and the transcript levels of indicators of oxidative stress, inflammation and apoptosis by qPCR. The results showed that liver injury, inflammation, oxidative stress, and apoptosis were attenuated in the FA + AVM group compared to the AVM group. In summary, dietary addition of FA could ameliorate the hepatotoxicity caused by AVM in carp by alleviating oxidative stress, inflammation, apoptosis in liver tissues.

Intentional use of both opioids and cocaine in the United States.

The combination of opioids and cocaine has been increasingly implicated in overdose fatalities, but it is unknown how much is intentional vs. fentanyl-adulterated drug supply. 2017-2019 data from the nationally representative National Survey on Drug Use and Health (NSDUH) was used. Variables included sociodemographics, health, and 30-day drug use. Opioid use captured heroin, and prescription pain reliever use not according to own doctor. Modified Poisson regressions were used to estimate prevalence ratios (PRs) for variables associated with opioid and cocaine use. Among the 167,444 responders, 817(0.49%) reported use of opioids on a regular or daily basis. Of these, 28% used cocaine ≥1 of prior 30 days, 11% >1 day. Of 332(0.20%) who used cocaine on a regular/daily basis, 48% used opioids ≥1 of prior 30 days, 25% >1 day. People with serious psychological distress were >6 times as likely to use both opioids and cocaine regularly/daily (PR = 6.48; 95% CI = [2.82-14.90]) and people who have never been married were 4 times as likely (PR = 4.17; 95% CI = [1.18-14.75]). Compared to those living in a small metropolitan region, people living in a large metropolitan region were >3 times as likely (PR = 3.29; 95% CI = [1.43-7.58]) and the unemployed were twice as likely (PR = 1.96; 95% CI = [1.03-3.73]). People with post-high school education were 53% less likely to use opioids and cocaine at least occasionally (PR = 0.47; 95% CI = [0.26-0.86]). People who use opioids or cocaine commonly choose to use the other. Knowing the characteristics of those most likely to use both should guide interventions for prevention and harm reduction.

Case report: Hematoporphyrin injection (HpD) photodynamic therapy for the treatment of groin extramammary Paget's disease in an elderly male patient.

Hematoporphyrin Derivative-Photodynamic Therapy (HpD-PDT) is a modality for cancer treatment, particularly suitable for challenging sites or elderly patients who can benefit from its minimally invasive and selective nature. We report a case of groin extramammary Paget's disease (EMPD) in a male patient with a lesion located in the right mons pubis. The patient was deemed unsuitable for surgical treatment due to his advanced age, underlying health conditions, extensive rash area, and the specific location of the groin lesion. He opted for hematoporphyrin photodynamic therapy instead of traditional wide local excision. The tumors were successfully treated, with no recurrence observed during the follow-up period. We suggest that hematoporphyrin photodynamic therapy may be an effective alternative to conventional surgery for the treatment of extramammary Paget's disease.