Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.

Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.

Advances in injectable hydrogels for radiation-induced heart disease.

Radiological heart damage (RIHD) is damage caused by unavoidable irradiation of the heart during chest radiotherapy, with a long latency period and a progressively increasing proportion of delayed cardiac damage due to conventional doses of chest radiotherapy. There is a risk of inducing diseases such as acute/chronic pericarditis, myocarditis, delayed myocardial fibrosis and damage to the cardiac conduction system in humans, which can lead to myocardial infarction or even death in severe cases. This paper details the pathogenesis of RIHD and gives potential targets for treatment at the molecular and cellular level, avoiding the drawbacks of high invasiveness and immune rejection due to drug therapy, medical device implantation and heart transplantation. Injectable hydrogel therapy has emerged as a minimally invasive tissue engineering therapy to provide necessary mechanical support to the infarcted myocardium and to act as a carrier for various bioactive factors and cells to improve the cellular microenvironment in the infarcted area and induce myocardial tissue regeneration. Therefore, this paper combines bioactive factors and cellular therapeutic mechanisms with injectable hydrogels, presents recent advances in the treatment of cardiac injury after RIHD with different injectable gels, and summarizes the therapeutic potential of various types of injectable hydrogels as a potential solution.

Synthesis, Characterization, Cytotoxicity, Cellular Imaging, Molecular Docking, and ADMET Studies of Piperazine-Linked 1,8-Naphthalimide-Arylsulfonyl Derivatives.

To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.

Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway.

OBJECTIVE: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). METHODS: Tumor necrosis factor (TNF)- α -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 µ mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg·day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-α, interleukin-6 (IL-6), and IL-1 ß, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. RESULTS: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-α, IL-6, and IL-1 ß (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-α, IL-6, and IL-1 ß, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). CONCLUSION: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.

Sesquiterpenoids and bibenzyl derivative from Dendrobium hercoglossum.

Three new sesquiterpenoids, dendrohercoglin A - C (1-3), and one new bibenzyl derivative, dendronbiline D (4), together with nine known sesquiterpenoids (5-13) were isolated from Dendrobium hercoglossum. The structures of the new compounds were elucidated by extensive spectroscopic analysis as well as NMR and ECD calculations. All the compounds were evaluated for their neuroprotective and anti-inflammatory activities. Compounds 2 and 3 increased the H2O2-damaged SH-SY5Y cell viabilities from 43.3% to 58.6% and 68.4%, respectively. Compound 4 exhibited pronounced anti-inflammatory activity with IC50 value of 9.5 ± 0.45 µM which was superior to the reference compound quercetin (IC50: 15.7 ± 0.89 µM).

[Research progress on Rhododendron molle in treatment of rheumatoid arthritis].

Rheumatoid arthritis(RA), as a chronic autoimmune disease, has a high incidence and disability rate, causing significant suffering to patients. Due to its complex pathogenesis, it has not been fully elucidated to date, and its treatment remains a challenging problem in the medical field. Although western medicine treatment options have certain efficacy, they require prolonged use and are expensive. Additionally, they carry risks of multiple infections and adverse reactions like malignancies. The Chinese herbal medicine Rhododendron molle is commonly used in folk medicine for its properties of dispelling wind, removing dampness, calming nerves, and alleviating pain in the treatment of diseases like rheumatic bone diseases. In recent years, modern clinical and pharmacological studies have shown that the diterpenoids in R. molle are effective components, exhibiting immune-regulatory, anti-inflammatory, and analgesic effects. This makes it a promising candidate for treating RA with a broad range of potential applications. However, R. molle has certain toxic properties that hinder its clinical application and lead to the wastage of its resources. This study reviewed recent research progress on the mechanism of R. molle in preventing and treating RA, focusing on its chemical components, anti-inflammatory and analgesic properties and summarized the adverse reactions associated with R. molle, aiming to offer new ideas for finding natural remedies for RA and methods to reduce toxicity while enhancing the effectiveness of R. molle. The study seeks to clarify the safety and efficacy of R. molle and its extracts, providing a theoretical basis for its application prospects and further promoting the development and utilization of R. molle resources.

Identification of multiple risk factors for colorectal cancer relapse after laparoscopic radical resection.

BACKGROUND: Colorectal cancer (CRC) is a common life-threatening disease that often requires surgical intervention, such as laparoscopic radical resection. However, despite successful surgeries, some patients experience disease relapse. Identifying the risk factors for CRC relapse can help guide clinical interventions and improve patient outcomes. AIM: To determine the risk factors that may lead to CRC relapse after laparoscopic radical resection. METHODS: We performed a retrospective analysis using the baseline data of 140 patients with CRC admitted to our hospital between January 2018 and January 2020. All included participants were followed up until death or for 3 years. The baseline data and laboratory indicators were compared between the patients who experienced relapse and those who did not experienced relapse. RESULTS: Among the 140 patients with CRC, 30 experienced relapse within 3 years after laparoscopic radical resection and 110 did not experience relapse. The relapse group had a higher frequency of rectal tumors with low differentiation and lymphatic vessel invasion than that of the non-relapse group. The expression of serum markers and the prognostic nutritional index were lower, whereas the neutrophil-to-lymphocyte ratio, expression of cytokeratin 19 fragment antigen 21-1, vascular endothelial growth factor, and Chitinase-3-like protein 1 were significantly higher in the relapse group than those in the non-relapse group. The groups did not differ significantly based on other parameters. Logistic regression analysis revealed that all the above significantly altered factors were independent risk factors for CRC relapse. CONCLUSION: We identified multiple risk factors for CRC relapse following surgery, which can be considered for the clinical monitoring of patients to reduce disease recurrence and improve patient survival.

Evaluating the Antioxidant Properties of the Leaves and Stems of Alpinia oxyphylla In Vitro and Its Growth-Promoting, Muscle Composition Change, and Antioxidative Stress Function on Juvenile Litopenaeus vannamei.

Alpinia oxyphylla is a homology of medicine and food. This study aims to investigate the dominant chemical composition and explore the antioxidant properties of the ethanol extract of the leaves and stems of A. oxyphylla (AOE) on juvenile shrimp, Litopenaeus vannamei. An in vitro test showed that AOE and its dominant chemical composition procyanidin B-2 (1) and epicatechin (2) presented DPPH and ABTS radical scavenging activities. A shrimp feeding supplement experiment revealed that shrimp growth parameters and muscle composition were improved significantly when fed with a 200 mg/Kg AOE additive. Meanwhile, the activities of antioxidant enzymes (CAT, GSH-Px, SOD, and T-AOC) in serum and the liver and the expression of related genes (LvMn-SOD, LvCAT, LvproPo, and LvGSH-Px) were enhanced with various degrees in different AOE additive groups while the content of MDA was significantly decreased. Moreover, the antioxidative effect of AOE additive groups on shrimp was also observed in an acute ammonia nitrogen stress test.

[Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model].

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Cytotoxic steroids from the stems of Strophanthus divaricatus.

Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C21 pregnane, together with eleven known steroids. Their structures were elucidated by a comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 16 was determined by comparison of the experimental and computed ECD spectra. Compounds 1-13 and 15 displayed potent to significant cytotoxicity against human cancer cell lines K562, SGC-7901, A549 and HeLa with IC50 values of 0.02-16.08, 0.04-23.13, 0.06-22.31 and 0.06-15.13 µM, respectively.

Pharmacological effects of the Cassia Seed on atherosclerosis: A meta-analysis based on network pharmacology.

BACKGROUND: The aim of this study was to shed light on the active ingredients and potential targets of Cassia Seed about anti-atherosclerosis based on network pharmacology. METHODS: The active ingredients and potential targets of Cassia Seed were obtained from traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction database. Then, atherosclerosis-related targets were screened via GeneCards, online mendelian inheritance in man, therapeutic target database and DrugBank database. The common targets and protein-protein interaction (PPI) network was later identified and built. Furthermore, we used the database for annotation, visualization and integrated discovery (DAVID) database server to accomplish the enrichment analysis. The compounds-targets-pathways network was ultimately constructed by Cytoscape. RESULTS: A total of 14 active ingredients and 475 related targets were sifted from Cassia Seed. Among 574 potential atherosclerotic targets, there were 99 targets overlapped with those of Cassia Seed. Topological analysis with Cytoscape revealed that proto-oncogene tyrosine-protein kinase proto-oncogene tyrosine-protein kinase Src, transcription factor AP-1 (JUN), mitogen-activated protein kinase 8 (MAPK8), mitogen-activated protein kinase 14 (MAPK14) and catenin beta-1 were considered as the hub gene. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis suggested that the Cassia Seed had the potential to influence varieties of biological processes and pathways, including positive regulation of smooth muscle cell proliferation, inflammatory response, tumor necrosis factor (TNF) signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway and arachidonic acid (ARA) metabolism. CONCLUSION: Taken together, our findings support that anti-atherosclerosis effects of Cassia Seed are characterized by multi-component, multi-target and multi-path mechanism of action.

Suspicious symptom monitoring for leprosy: an optimal practice for early detection under a low endemic situation in Zhejiang Province, China.

BACKGROUND: Leprosy is a chronic infectious disease that causes disabilities and deformities. Early detection is a major strategy for leprosy control. This study reported a new practice of suspicious symptom monitoring for early detection of leprosy. METHODS: A descriptive and comparative analysis between a non-strategy group of pre-implementation of suspicious symptom monitoring in 2005-2011 and a strategy group of strategy implementation in 2012-2018 was conducted through indicators of the number of times of misdiagnoses, delayed period, proportion of early detected cases, and proportion of disabilities. RESULT: Compared with the non-strategy group in 2005-2011, the median number of times of misdiagnoses was decreased from two times to zero times (z = 4.387, P < 0.001), and the median delayed period of newly detected cases were shortened from 24 months to 13 months (z = 2.381, P < 0.001), the proportion of early detected cases was increased from 43.7% to 75.2% (χ2 = 29.464, P < 0.001), the proportion of grade 2 disabilities was decreased from 28.6% in the highest year of 2005 to 4.0% in the lowest year of 2014, and the average proportion of disabilities was decreased from 33.5% to 17.6% (χ2 = 9.421, P = 0.002) in the strategy group in 2012-2018, respectively. CONCLUSION: Suspicious symptom monitoring promoted early detection of cases by reducing the number of times misdiagnosis of leprosy patients, shortening the delayed period, increasing the proportion of early detection, and decreasing the proportion of disabilities. It is an important and recommendable public health strategy for leprosy prevention and control in a low epidemic condition.

Combination of radiofrequency ablation and percutaneous ethanol injection versus radiofrequency ablation alone for hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Radiofrequency ablation and percutaneous ethanol injection are important treatment modalities for hepatocellular carcinoma patients; Whether a combination treatment yields, additional benefit still remains controversial. METHODS: A systematic review and meta-analysis was concluded. Randomized controlled trials published before January 1, 2022, from PubMed, EMBASE, Scopus, and CNKI were searched. Studies were excluded when patients received different ablative treatment or had serious liver dysfunction. The risk of bias assessment was evaluated using the Cochrane Collaboration's tool. RESULTS: Ten studies, encompassing 854 patients, with histologically proven HCC were finally analyzed. The results demonstrated that patients who received RFA-PEI had slightly improvements in 1-year overall survival (OS) [risk ratio (RR): 1.11; 95% confidence interval (CI): 1.03, 1.19, I2 = 10%], 2-year OS (RR: 1.25; 95% CI: 1.12, 1.40, I2 = 0%), 3-year OS (RR: 1.42; 95% CI: 1.11, 1.83, I2 = 38%), 1-year local recurrence-free (LRF) proportion (RR: 1.2; 95% CI: 1.01, 1.42, I2 = 61%), and complete tumor necrosis (CTN) (RR: 1.32; 95% CI: 1.14, 1.53, I2 = 45%). Nevertheless, common complications, such as fever, were found to be significant (RR: 1.78, 95% CI: 1.13, 2.80). CONCLUSION: Despite RFA-PEI appearing to be superior for HCC patients with a compensated liver in terms of OS, current evidence contained moderate to significant heterogeneity, and it was difficult to draw a definite conclusion regarding the therapeutic management in terms of LRF and CTN.

New progress in understanding roles of nitric oxide during hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is a major clinical cause of morbidity and mortality in liver surgery and transplantation. Many studies have found that nitric oxide (NO) plays an important role in the HIRI and its increase or decrease can affect the progression and outcome of HIRI. However, the role of NO in HIRI is controversial and complicated. NO derived by endothelial NO synthase (eNOS) shows a protective role in HIRI, while excessive NO derived by inducible NO synthase (iNOS) accelerates inflammation and increases oxidative stress, further aggravating HIRI. Nevertheless, the overexpression of eNOS may exacerbate HIRI and iNOS-derived NO in some cases reduces HIRI. Here we review the new progress in the understanding of the roles of NO during HIRI: (1) NO possesses different roles in HIRI by increasing NO bioavailability, down-regulating leukotriene C4 synthase, inhibiting the activation of the nuclear factorκB (NFκB) pathway, enhancing cell autophagy, and reducing inflammatory cytokines and reactive oxygen species (ROS). And NO has both protective and deleterious effects by regulating apoptotic factors; (2) eNOS promotes NO production and suppresses its own overexpression, exerting a hepatoprotective effect reversely. Its activation is regulated by the PI3K/Akt and KLF2/AMPK pathways; and (3) iNOS derived NO mainly has deteriorating effects on HIRI, while it may have a protective function under some conditions. Their expression should reach a balance to reduce the adverse side and make NO protective in the treatment of HIRI. Thus, it can be inferred that NO modulating drugs may be a new direction in the treatment of HIRI or may be used as an adjunct to mitigate HIRI for the purpose of protecting the liver.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis.

Although the pan-genotypic direct-acting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. We evaluated the real-world safety and efficacy of two pan-genotypic regimens (Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir) for HCV-infected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua Christian Care System that commenced treatment between August 2018 and December 2020. This retrospective study evaluated the efficacy and safety of pan-genotypic direct-acting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment. Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow-up during treatment and one more patient after treatment. A total of four patients died. However, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%). Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotype-undetermined HCV infection real-world settings.

LC-MS-guided isolation of 2-(2-phenylethyl)chromone dimers from red soil agarwood of Aquilaria crassna.

Six new 2-(2-phenylethyl)chromone dimers (1-6) were isolated from ethyl ether extract of red soil agarwood of Aquilaria crassna from Vietnam by LC-MS-guided fractionation procedure. Their structures were unambiguously elucidated based on HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 2-(2-phenylethyl)chromone dimers was determined by comparison of the experimental and computed ECD spectra. Compound 6 displayed cytotoxicity against the human myeloid leukemia cell line (K562) with an IC50 value of 39.49 µM.

Phenolic compounds from the sclerotia of Inonotus obliquus.

Three phenolic compounds (±1 and 2) including a pair of new enantiomers were isolated from the sclerotia of Inonotus obliquus. Their structures were assigned by extensive spectroscopic analyses. All the compounds were evaluated for the neuroprotective activity against oxidative damage on human neuroblastoma SH-SY5Y cells induced by H2O2. Compound 2 showed remarkable neuroprotective effect and significantly improved the cell viability of SH-SY5Y cells treated by H2O2.

Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage.

Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of four fluorinated imidazole[4,5f][1,10]phenanthroline derivatives were synthesized and investigated as potential inhibitors to fight against the growth of liver cancer cells. The in vitro antitumor activity of targeted compounds have been evaluated by using MTT assay, and results showed that compound 4 (2-(2,3-difluorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC50 value of approximately 0.29 µM. This result has been further confirmed by colony formation assay, showing that compound 4 suppressed the proliferation of HepG2 cells. Moreover, cell apoptosis (AO/PI dual staining and flow cytometry) analyses as well as comet assay showed that compound 4 may induce apoptosis of HepG2 cells through triggering DNA damage. Furthermore, the in vivo anti-tumor activity were evaluated on zebrafish bearing HepG2 cells showed that compound 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly compound 4, may be developed as a potential agent to treat liver cancer in the future.

Comparison of safety, efficacy, and long-term follow-up between "one-step" and "step-up" approaches for infected pancreatic necrosis.

BACKGROUND: Although the "Step-up" strategy is the primary surgical treatment for infected pancreatic necrosis, it is not suitable for all such patients. The "One-step" strategy represents a novel treatment, but the safety, efficacy, and long-term follow-up have not yet been compared between these two approaches. AIM: To compare the safety, efficacy, and long-term follow-up of two surgical approaches to provide a reference for infected pancreatic necrosis treatment. METHODS: This was a retrospective analysis of infectious pancreatic necrosis patients who underwent "One-step" or "Step-up" necrosectomy at Xuan Wu Hospital, Capital Medical University, from May 2014 to December 2020. The primary outcome was the composite endpoint of severe complications or death. Patients were followed up every 6 mo after discharge until death or June 30, 2021. Statistical analysis was performed using SPSS 21.0 and GraphPad Prism 8.0, and statistical significance was set at P < 0.05. RESULTS: One-hundred-and-fifty-eight patients were enrolled, of whom 61 patients underwent "One-step" necrosectomy and 97 patients underwent "Step-up" necrosectomy. During the long-term follow-up period, 40 patients in the "One-step" group and 63 patients in the "Step-up" group survived. The time from disease onset to hospital admission (53.69 ± 38.14 vs 32.20 ± 20.75, P < 0.001) and to initial surgical treatment was longer in the "Step-up" than in the "One-step" group (54.38 ± 10.46 vs 76.58 ± 17.03, P < 0.001). Patients who underwent "Step-up" necrosectomy had a longer hospitalization duration (65.41 ± 28.14 vs 52.76 ± 24.71, P = 0.02), and more interventions (4.26 ± 1.71 vs 3.18 ± 1.39, P < 0.001). Postoperative inflammatory indicator levels were significantly lower than preoperative levels in each group. Although the incisional hernia incidence was higher in the "One-step" group, no significant difference was found in the composite outcomes of severe complications or death, new-onset organ failure, postoperative complications, inflammatory indicators, long-term complications, quality of life, and medical costs between the groups (P > 0.05). CONCLUSION: Compared with the "Step-up" approach, the "One-step" approach is a safe and effective treatment method with better long-term quality of life and prognosis. It also provides an alternative surgical treatment strategy for patients with infected pancreatic necrosis.

A Nomogram for Predicting Laparoscopic and Endoscopic Cooperative Surgery during the Endoscopic Resection of Subepithelial Tumors of the Upper Gastrointestinal Tract.

BACKGROUND: Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper gastrointestinal (GI) subepithelial tumors (SET) increases. For relatively safer removal of upper GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery. This study aimed to analyze the outcome of endoscopic resection for SETs and develop a prediction model for the need for laparoscopic and endoscopic cooperative surgery (LECS) during the procedure. METHOD: We retrospectively analyzed 123 patients who underwent endoscopic resection for upper GI SETs between January 2012 and December 2020 at our institution. Intraoperatively, they underwent ESD or submucosal tunneling endoscopic resection (STER). RESULTS: ESD and STER were performed in 107 and 16 patients, respectively. The median age was 55 years, and the average tumor size was 1.5 cm. En bloc resection was achieved in 114 patients (92.7%). The median follow-up duration was 242 days without recurrence. Perforation occurred in 47 patients (38.2%), and 30 patients (24.4%) underwent LECS. Most perforations occurred in the fundus. Through multivariable analysis, we built a nomogram that can predict LECS requirement according to tumor location, size, patient age, and sex. The prediction model exhibited good discrimination ability, with an area under the curve (AUC) of 0.893. CONCLUSIONS: Endoscopic resection is a noninvasive procedure for small upper-GI SETs. Most perforations can be successfully managed endoscopically. The prediction model for LECS requirement is useful in treatment planning.