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Xiao-Fan Xu,1– 3 Jian-Wei Fan,2 Jia-Qi Xin,4 Nan Wu,4 He Gao,2 Li-Fang Duan,2 Wen-Bin Zou,3 Hong Zhang,2,5 Zhao-Shen Li3 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2Basic Medical Academy, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of China; 3Department of Gastroenterology, Changhai Hospital, Shanghai, People’s Republic of China; 4Department of Gastroenterology, Internal Medicine II, Klinikum Rechts der Isar, Technical University of Munich (TUM), Munich, Germany; 5Shaanxi International Cooperation Base, Shaanxi University of Chinese Medicine, Xianyang, People’s Republic of ChinaCorrespondence: Zhao-Shen Li; Hong Zhang, Email zhaoshenli@smmu.edu.cn; zhangh1227@sntcm.edu.cnAim: Chronic pancreatitis (CP) is a complex and intractable disease mainly manifested as chronic inflammation and fibrosis. Aspirin(acetylsalicylic acid, ASA) has been reported to be used in the treatment of acute pancreatitis (AP), but its effectiveness on CP is unclear. This study aimed to investigate the therapeutic effects of ASA in CP mice.Methods: A murine model of CP was induced by intraperitoneal injection with 20% L-arginine. After one week of L-arginine administration, mice in the ASA treatment group were administered aspirin (100mg/kg/d) by intragastric gavage. At two, four, and six weeks after the first injection of L-arginine, mice were euthanized and the pancreas was collected for histological and molecular analysis. A second model of CP (caeruelin-induced) was used as a validation experiment to test the effect of ASA.Results: L-arginine-induced CP resulted in over-expression of the inflammatory enzyme cyclooxygenase (COX)-2. COX-2 expression decreased after ASA treatment. Pancreatic-injury inflammatory response (measured by changes in amylase, CK-19, F4/80, CD3, MCP-1, IL-6) and fibrosis degree (measured by expression of COL1A1, MMP-1 and TIMP-1) was reduce in ASA -treated mice model. The therapeutic effect of ASA was also observed in caeruelin-induced CP.Conclusion: ASA has an ameliorating effect in murine models of CP through inhibition of pancreatic inflammation and fibrosis, which may be a promising option for clinical treatment.Keywords: chronic pancreatitis, fibrosis, inflammation, aspirin, COX-2

Jingping Zhao,1,* Lehua Li,1,* Jianguo Shi,2 Yi Li,3 Xiufeng Xu,4 Keqing Li,5 Lili Zhang,6 Shangli Cai,6 Yu Feng,6 Jianmin Zhuo,6 Weihong Liu,6 Huafei Lu6 1Department of Psychiatry, The Mental Health Institute, The Second Xiangya Hospital of Central South University, 2Department of Psychiatry, Mental Health Center of Xi’an City, 3Department of Psychiatry, Mental Health Center of Wuhan City, 4Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, 5Department of Psychiatry, The Sixth People’s Hospital of Hebei Province, 6Department of Medical Affairs, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China *These authors contributed equally to this work Rationale: Long-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.Objective: The aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.Methods: In this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).Results: Of the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, -27.2 [18.30]; P

Objectives: To investigate the pharmacokinetics of talipexole hydrochloride tablets and the potential influence of Madopar (benserazide and levodopa combination; co-beneldopa) tablets on talipexole's pharmacokinetics when the two tablets are coadministered orally to healthy Chinese volunteers. Methods: A sensitive liquid chromatographytandem mass spectrometry (LC-MS/MS) method was developed to measure talipexole concentration in human plasma in an open-label, randomized, two-way crossover, single-dose study, with 1-week washout period. Healthy Chinese volunteers were randomized to receive talipexole tablets either alone or together with Madopar tablets by oral administration after an overnight fast. Serial blood samples were collected for a period of 36 h after the administration. Pharmacokinetic parameters Cmax, tmax, t1/2z, mean residence time (MRT), AUC0-tau, AUC0-infinity, CLz/F and Vz/F were determined under the non-compartmental model. Pharmacokinetic values of talipexole administered alone to the subjects were compared with those administered simultaneously with Madopar to determine whether or not the differences were statistically significant. Results: The subjects experienced mild gastrointestinal irritation when talipexole was administered alone as well as together with Madopar. For talipexole hydrochloride, there were no significant differences in the pharmacokinetic values between the two administrations. No pharmacokinetic differences based on gender were observed either. Conclusion: A single oral dose of Madopar co-administered with talipexole does not significantly change talipexole's pharmacokinetics in human. [ABSTRACT FROM AUTHOR]

Primary hepatic sarcomas are rare tumors that are difficult to diagnose clinically. Different primary hepatic sarcomas may have different clinical, morphologic, and radiological features. In this pictorial review, we summarized computed tomography (CT) findings of some relatively common types of hepatic sarcomas, including angiosarcoma, epithelioid hemangioendothelioma (EHE), liposarcoma, undifferentiated embryonal sarcoma (UES), leiomyosarcoma, malignant fibrous histiocytoma (MFH), and carcinosarcoma (including cystadenocarcinosarcoma). To our knowledge, hepatic cystadenocarcinosarcoma has not been described in the English literature. The CT findings in our case are similar to that of cystadenocarcinoma, a huge, multilocular cystic mass with a large mural nodule and solid portion. The advent of CT has allowed earlier detection of primary hepatic sarcomas as well as more accurate diagnosis and characterization. In addition, we briefly discuss the MRI findings and diagnostic value of primary hepatic sarcomas. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic heavy metal with a high propensity to accumulate within the body, and Cd accumulation has been shown to cause organ damage. However, it is unclear whether Cd accumulation is a cause of impaired decidualization, which induces to spontaneous abortion (SA). In this study, we found that the decidual Cd concentration was increased in patients with SA and positively correlated with the occurrence of SA. The levels of two decidualization markers (prolactin, PRL and insulin-like growth factor binding protein 1, IGFBP1) were reduced in the decidua of all-cause SA patients. Using 8-week ICR female mice, we further established a uterus-specific Cd accumulation mouse model and verified that Cd-accumulating mice had increased numbers of absorbed fetuses and defective decidualization. Finally, using in vitro-cultured human ENdometrial stromal cells (hEnSCs), we found that Cd accumulation significantly inhibited decidualization; and moreover, Cd treatment downregulated the regulatory genes upstream of PRL and IGFBP1 such as PGR, ESR1, ESR2 and FOXO1. This study suggests that Cd accumulation could produce impaired decidualization by downregulating the upstream regulators of PRL and IGFBP1, thereby increasing the risk of SA. Our study offered new possibilities for the prevention and treatment of spontaneous abortion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

A novel lactam penicillactam (1), two rare mycophenolic acid (MPA) derivatives penimycophens A and B (2 and 3), together with two known biogenetically related MPA derivatives (4 and 5) and a known alkaloid (6) were isolated from the Penicillium sclerotiorum JBHL321. The structures of these compounds were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by electronic circular dichroism (ECD) calculations. Compound 1 represent the rare example of a oxygen bridge-linked lactam from natural products. Structurally, compounds 2 and 3 were rare MPA derivatives featuring a methoxy group at C-3. The inhibitory activity of compounds 1-6 against two phytopathogenic fungi, three phytopathogenic bacteria and four cancer cell lines were evaluated. Compounds 2-5 exhibited significant cytotoxic activity against HeLa, MCF-7, A549 and MGC-803 cells with IC 50 values in the low micromolar to nanomolar. Compound 3 exhibited especially cytotoxic activity against four different cell lines with IC 50 values ranging from 0.06-0.14 μM, compared to IC 50 values ranging from 0.62-2.51 μM for epirubicin., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Liver metastasis impacts survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); however, current guidelines lack consensus on post-resection surveillance and adjuvant therapy. A comprehensive risk stratification tool is needed to guide personalized management., Objective: We aimed to develop and validate a predictive model for liver metastasis risk after surgical resection of GEP-NETs that incorporates pathological factors and adjuvant therapy., Methods: Patients with GEP-NETs who underwent surgical resection with curative intent at three major Chinese hospitals (2010-2022) were identified. Univariable and multivariable Cox regression analysis identified independent risk factors of liver metastasis. The liver metastasis score (LMS) was developed using weighted risk factors and validated by tenfold cross-validation., Results: Among the 724 patients included in the analytic cohort, liver metastasis occurred in 66 patients (9.1%) at a median of 36 months; patients with liver metastasis had a worse 5-year overall survival (no liver metastasis 63.6% vs. liver metastasis 95.8%; p < 0.001). Independent predictors were Ki-67 index (hazard ratio [HR] 10.36 for Ki-67 3-20%, HR 18.30 for Ki-67 >20%, vs. <3%), vascular invasion (HR 5.03), lymph node metastases (HR 2.24), and lack of adjuvant therapy (HR 3.03). The LMS demonstrated excellent discrimination (C-index 0.888) and stratified patients into low, intermediate, and high-risk relative to 5-year risk of liver metastasis: 2.9%, 20.8%, and 49.7%, respectively (p < 0.001)., Conclusions: The novel LMS effectively predicted the risk of liver metastasis after surgical resection of GEP-NETs. This validated model can help guide personalized surveillance and adjuvant treatment strategies, potentially improving outcomes for high-risk patients., Competing Interests: Ethics approval: The study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Boards of all the participating hospitals, (© 2024. Society of Surgical Oncology.)

Competing Interests: Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Boards of all participating hospitals.

Acute-stress-induced anxiety helps animals avoid danger, but the neural and molecular mechanisms controlling this behavior remain largely elusive. Here, we find that acute physical stress activates many neurons in the primary somatosensory cortex, trunk region (S1Tr). Single-cell sequencing reveals that the S1Tr c-fos-positive neurons activated by acute stress are largely GABAergic somatostatin (Sst) neurons. These S1Tr Sst neurons desensitize during subsequent anxiety-like behavior tests. Inhibiting or inducing apoptosis of S1Tr Sst neurons mimics acute-stress effects and induces anxiety, while activating these neurons reduces acute-stress-induced anxiety. S1Tr Sst cells receive inputs from secondary auditory cortex, dorsal area (AUD) GABAergic neurons to modulate this anxiety. Spatial transcriptome sequencing and targeted Pde4b protein knockdown show that acute stress reduces Pde4b-regulated cAMP signaling in AUD GABA -S1Tr Sst projections, leading to decreased S1Tr Sst neuron activity in subsequent behavioral tests. Our study reports a neural and molecular mechanism for acute-stress-induced anxiety, providing a basis for treating anxiety disorders., Competing Interests: Declaration of interests None of the authors has a conflict of interest to declare in relation to the present research., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Ulinastatin is a protease-inhibiting drug with anti-inflammatory and other pharmacological properties. Little is known regarding its role following acute type A aortic dissection (ATAAD) surgery. We perform a randomized controlled trial to investigate the protective effect of ulinastatin against negative inflammatory response and organ dysfunction in ATAAD surgery (PANDA). The primary outcome of mean daily Sequential Organ Failure Assessment (SOFA) score from baseline to 7 days of surgery is 8.80 (SD, 4.11) in the ulinastatin group and 8.61 (SD, 4.47) in the control group (mean difference between groups was 0.04; 95% confidence interval [CI], -0.24 to 0.33; p = 0.765). Systemic inflammatory response syndrome (SIRS) within 7 days of surgery is lower in the ulinastatin group than in the control group (p < 0.001). Additional ulinastatin to standard treatment is likely to reduce SIRS rates instead of preventing organ dysfunction, highlighting the potential importance of the benefits of anti-inflammatory pharmacotherapeutics. The trial is registered on clinicaltrials.org (NCT04711889)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pigeons and certain other avian species produce a milk-like secretion in their crop sacs to nourish offspring, yet the detailed processes involved are not fully elucidated. This study investigated the crop sacs of 225-day-old unpaired non-lactating male pigeons (MN) and males initiating lactation on the first day after incubation (ML). Using RNA sequencing, ribosome profiling, and single-cell transcriptome sequencing (scRNA-seq), we identified a significant up-regulation of genes associated with ribosome assembly and protein synthesis in ML compared to MN. Results from scRNA-seq analysis identified 12 distinct cell types and 22 clusters, with secretory epithelial cells (SECs) exhibiting marked expression of plasma cell markers, including IGLL1 and MZB1 . RNA fluorescence in situ hybridization (RNA FISH) and IgY quantification confirmed the critical role of SECs in producing endogenous IgY during lactation. We propose that fibroblast-derived BAFF signals activate SECs, mimicking B cell transformation and enhancing protein production through the unfolded protein response (UPR). These findings shed light on the cellular dynamics of pigeon milk production and contribute to a broader understanding of avian biology.

Basic leucine zipper (bZIP) transcription factors serve as crucial regulators in plants' response to abiotic stress; however, its function in grapevine heat tolerance is still largely unknown. Here, we undertook a comprehensive investigation of grape genome, leading to the identification of 65 VvbZIP genes, among which 16 VvbZIPs were significantly induced under heat stress. Overexpression of VvbZIP36 enhanced heat tolerance in grape calli, while virus-induced gene silencing (VIGS) of VvbZIP36 reflected thermal sensitivity. Additionally, we examined the metabolomic and transcriptomic profiles of grape seedlings, which showed that grapes exhibited increased accumulation of flavonoids, coinciding with the significantly induced expression of the VvFLS (Flavanol synthase) gene under heat stress. Overexpression of VvFLS also improved the heat tolerance in grape calli by scavenging reactive oxygen species (ROS). A yeast one-hybrid assay (Y1H) demonstrated that VvbZIP36 was capable of specifically activating the promoter of VvFLS, which was subsequently confirmed through a luciferase reporter assay. Furthermore, the overexpression of VvbZIP36 resulted in enhanced quercetin content, while the exogenous application of quercetin improved heat tolerance of grape. Collectively, our findings suggest that VvbZIP36 binds to the VvFLS promoter, thereby enhancing heat stress tolerance by increasing quercetin production and mitigating oxidative damage in grapes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Non-suicidal self-injury (NSSI) is common among adolescents and frequently co-occurs with depression. Understanding the distinct patterns of NSSI behaviors, along with their associated risk and protective factors, is crucial for developing effective interventions., Aim: To classify NSSI behaviors and examine interactions between risk and resilience factors in Chinese adolescents., Methods: A cross-sectional study involving 3967 Chinese students (51.7% female, mean age 13.58 ± 2.24 years) who completed questionnaires on parenting styles, bullying, childhood maltreatment, depression, resilience, and NSSI. Latent profile analysis (LPA) was used to identify NSSI subtypes, and network analysis explored interactions between risk and resilience factors., Results: Three NSSI subtypes were identified: NSSI with depression (18.8%), NSSI without depression (12.3%), and neither (68.9%). Bullying was the central risk factor across subtypes, while emotional control and family support were key protective factors. Statistical analyses showed significant differences between groups ( P < 0.001)., Conclusion: This study identified three NSSI subtypes among Chinese adolescents. Bullying emerged as a central risk factor, while emotional control and family support were key protective factors. Targeting these areas may help reduce NSSI behaviors in this population., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.

Background: Social isolation not only increases the risk of mortality in later life but also causes depressive symptoms, cognitive and physical disabilities. Although RNA m6A modifications are suggested to play key roles in brain development, neuronal signaling and neurological disorders, both the roles of m6A and the enzymes that regulate RNA m6A modification in social isolation induced abnormal behavior is unknown. The present study aims to explore the possible epitranscriptomic role of RNA m6A modifications and its enzymes in social isolation induced impaired behavior., Methods: 3-4 weeks mice experiencing 8 weeks social isolation stress (SI) were used in the present study. We quantified m6A levels in brain regions related to mood and cognitive behavior. And the expression of hippocampal m6A enzymes was also determined. The role of hippocampal m6A and its enzymes in SI induced abnormal behavior was further verified by the virus tool., Results: SI led to not only depressive and anxiety-like behaviors but also cognitive impairment, with corresponding decreases in hippocampal m6A and METTL14. Hippocampal over-expression METTL14 with lentivirus not only rescued these behaviors but also enhanced the hippocampal m6A level. Hippocampal over-expression METTL14 resulted in increased synaptic related genes., Conclusions: We provide the first evidence that post-weaning social isolation reduces hippocampal m6A level and causes altered expression of m6A enzyme in mice. Importantly, hippocampal METTL14 over-expression alleviated the SI-induced depression/anxiety-like and impaired cognitive behaviors and enhanced m6A level and synaptic related genes expression., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest or any known competing financial interests or personal relationships that may bias the performance or interpretation of the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: The ASAP score, which incorporates age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence-II, has demonstrated promise for early detection of hepatocellular carcinoma (HCC). However, its prognostic value after HCC treatment remains unknown. The current study sought to evaluate the prognostic value of the ASAP score to predict recurrence and survival following curative hepatic resection for HCC., Methods: This study using prospectively collected data included HCC patients who underwent curative-intent hepatic resection. The ASAP score was calculated preoperatively, and X-tile analysis was used to determine the optimal cutoff value. Univariate and multivariate analyses were performed to identify independent risk factors associated with recurrence and overall survival (OS)., Results: Among 1239 patients in the analytic cohort, the optimal ASAP score cutoff was 4.8; patients were divided into low (n = 749) and high (n = 490) ASAP score subgroups. Patients with high ASAP scores had a higher incidence of 5-year recurrence (73.9% vs 51.0%, P < 0.001) and worse OS (31.7% vs 60.1%, P < 0.001) versus individuals with low scores. Multivariate analysis identified ASAP score ≥4.8 as an independent risk factor of both recurrence (hazard ratio [HR] 1.976, 95% confidence interval [CI]: 1.633-2.390, P < 0.001) and OS (HR 1.407, 95% CI 1.170-1.691, P < 0.001) after controlling for established clinicopathological factors., Conclusion: Preoperative ASAP score was independently associated with recurrence and survival after HCC resection. The clinical utility of the ASAP score may be applicable to both diagnosis and prognosis, potentially improving postoperative surveillance and management strategies for HCC patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Endoscopic submucosal dissection (ESD) is widely utilized for the treatment of large adenomas, submucosal lesions, and early gastric cancer. A significant artificial ulcer typically forms after ESD. Delayed or incomplete healing of these ulcers can result in complications such as delayed bleeding and perforation. However, a comprehensive review of the outcomes and risk factors related to ulcer healing following ESD is currently lacking., Aim: To assess ulcer healing outcomes and identify risk factors associated with delayed ulcer healing., Methods: Databases retrieved by computer include PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, and VIP. The study collects reports on ESD post-surgical ulcer healing outcomes and risk factors, using Stata 16.0 and RevMan 5.0 software for meta-analysis., Results: Our analysis included 12 studies, involving a total of 3430 patients. The meta-analysis revealed an overall healing rate of 65.55% for ulcers following ESD [odds ratio (OR) = 2.71; 95% confidence interval (CI): 2.45-3.00]. The healing rate within eight weeks was 48.32% (OR = 0.76; 95%CI: 0.35-1.66), while the rate beyond eight weeks was 88.32% (OR = 6.73; 95%CI: 3.82-11.87). Risk factors included Helicobacter pylori ( H. pylori ) infection (OR: = 5.32; 95%CI: 1.90-14.87; P = 0.001), ulcer size (OR = 2.08; 95%CI: 1.19-3.61; P = 0.01), lesion site (OR = 2.08; 95%CI: 1.19-3.11), and pathological type (OR = 1.64; 95%CI: 1.06-2.52). Diabetes (OR = 0.56; 95%CI: 0.05-5.80; P = 0.63) and duration of operation (OR = 1.00; 95%CI: 0.99-1.01; P = 0.96) were not significant factors., Conclusion: The healing rate of ulcers following ESD is high after eight weeks. Risk factors affecting the healing process include H. pylori infection, ulcer size, lesion site, and pathological type., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The combination of chemotherapy and photodynamic therapy holds immense potential for achieving synergistic anti-tumor efficacy. However, challenges such as poor stability and premature drug release prior to reaching tumor sites impede the widespread application of this synergistic therapeutic approach. In this study, a novel ATP-responsive NIR fluorescence nanosystem (CDZ) for imaging-guided chemotherapy and PDT has been developed. This nanosystem, based on ZIF-90, encapsulates the chemotherapy drug doxorubicin (DOX) and the photosensitizer asymmetrical cyanine dye Cy through self-assembly. The obtained nanosystem CDZ could efficiently avoid premature drug leakage in the blood circulation due to its high stability in the physiological environment and accumulates at the tumor sites via the enhanced permeability and retention (EPR) effect. Upon uptake by tumor cells, the skeleton structure of CDZ is disrupted by overexpressed ATP levels, leading to the release of DOX, which inhibits cancer cell proliferation and induces cell death. Additionally, the released photosensitizer Cy emits strong NIR fluorescence signals, enabling real-time imaging of ATP levels in tumors. Moreover, under NIR light irradiation, this nanosystem generates high levels of ROS, achieving effective phototherapy even in deeper tumor regions. In tumor model mice, CDZ demonstrated a high rate of tumor inhibition without causing damage to major organs. This ZIF-based NIR fluorescence nanosystem, combining chemotherapy and photodynamic therapy, holds promise as a solution for treating and monitoring cancer without the associated risks of resistance and systemic toxicity.

Locally advanced cervical carcinoma (LACC) remains a significant global health challenge owing to its high recurrence rates and poor outcomes, despite current treatments. This study aimed to develop a comprehensive risk stratification model for LACC by integrating Cox regression and competing risk analyses. This was done to improve clinical decision making. We analyzed data from 3428 patients with LACC registered in the Surveillance, Epidemiology, and End Results program and diagnosed them between 2010 and 2015. Cox regression and competing risk analyses were used to identify the prognostic factors. We constructed and validated nomograms for overall survival (OS) and disease-specific survival (DSS). Multivariate Cox regression identified key prognostic factors for OS, including advanced International Federation of Gynecology and Obstetrics stage, age, marital status, ethnicity, and tumor size. Notably, International Federation of Gynecology and Obstetrics stages IIIA, IIIB, and IVA had hazard ratios of 2.227, 2.451, and 4.852, respectively, significantly increasing the mortality risk compared to stage IB2. Ethnic disparities were evident, with African Americans facing a 39.8% higher risk than Caucasians did. Competing risk analyses confirmed the significance of these factors in DSS, particularly tumor size. Our nomogram demonstrated high predictive accuracy, with area under the curve values ranging from 0.706 to 0.784 for DSS and 0.717 to 0.781 for OS. Calibration plots and decision curve analyses further validated the clinical utility of this nomogram. We present effective nomograms for LACC risk stratification that incorporate multiple prognostic factors. These models provide a refined approach for individualized patient management and have the potential to significantly enhance therapeutic strategies for LACC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chromatographic techniques were employed to separate and purify the active components with antioxidant activity from the aboveground part of Lythrum salicaria. The data of 1D/2D NMR, optical rotation, and high-resolution mass spectrometry were used to identify the purified compounds. Six phenolic glucosides were identified, including 6'-(p-methoxyphenyl)gallate-7-O-β-D-glucopyranoside(1), 6'-ethyl-p-hydroxyphenylethanol-β-D-glucopyranoside(2), 3,4,5-trimethoxyphenol-β-D-glucopyranoside(3), 3,4,5-trimethoxyphenyl 1-O-β-apiofuranosyl(1″→6')-β-glucopyranoside(4), benzylalcohol O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(5), and 6'-acetylethanol-β-D-glucopyranoside(6). Compounds 1 and 2 were novel phenolic glucosides, and compounds 3-6 were isolated from Lythrum for the first time. Furthermore, the antioxidant activities of compounds 1-6 were evaluated. Compound 1 showed potent antioxidant activity, with the half maximal inhibitory concentration(IC&#95;(50)) of 0.16 mmol·L~(-1), which was stronger than that of the positive control trolox with the IC&#95;(50) of 0.24 mmol·L~(-1).

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with concurrent acute myeloid leukemia (AML) and active pulmonary tuberculosis (TB) exhibit certain characteristics; cough, phlegm, fever, hemoptysis, weight loss and dyspnea are common symptoms of both diseases. These patients often cannot tolerate traditional intensive chemotherapy regimens, and finding the optimal timing in the treatment of both AML and active pulmonary TB is complex. Neglecting timely treatment can lead to serious complications and even fatal outcomes. The present paper reports two cases of patients with AML who were diagnosed with active pulmonary TB. The patients received intensive anti-TB treatment with isoniazid, rifampicin, pyrazinamide and ethambutol for 10-15 days. After three consecutive negative sputum smears, the patients in cases 1 and 2 were treated with a venetoclax, homoharringtonine and cytarabine regimen; and a venetoclax and azacitidine regimen for anti-AML therapy, respectively, as well as individualized anti-TB regimens of isoniazid, pyrazinamide, ethambutol and quinolone. Subsequently, both patients achieved complete remission of AML and their active TB was well controlled., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Ji et al.)

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Parkinson's disease (PD) is a prevalent disorder of the central nervous system, marked by the degeneration of dopamine (DA) neurons in the ventral midbrain. In the pathogenesis of PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators of peripheral inflammation in PD patients and to explore the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), and lymphocyte-to-monocyte ratio (LMR) in assessing PD risk., Methods: This study included 186 patients with PD and 201 matched healthy controls (HC) with baseline data. Firstly, the differences of hematological indicators between PD group and healthy participants were compared and analyzed. Univariate and multivariate regression analyses were then conducted. Smooth curve fitting was applied to further validate the relationships between NLR, LMR, AFR, and PD. Subsequently, subgroup analysis was conducted in PD group according to different duration of disease and Hoehn and Yahr (H&Y) stage, comparing differences in clinical indicators. Finally, the receiver operating characteristic (ROC) curve was employed to assess the diagnostic value of NLR, LMR, and AFR in PD., Results: Compared to the HC group, the PD group showed significantly higher levels of hypertension, diabetes, neutrophil count, monocyte count, CRP, homocysteine, fibrinogen, and NLR. Conversely, levels of LMR, AFR, lymphocyte count, HDL, LDL, TG, TC, uric acid, and albumin were significantly lower. The multivariate regression model indicated that NLR (OR = 1.79, 95% CI: 1.39-2.31, p  < 0.001), LMR (OR = 0.75, 95% CI: 0.66-0.85, p  < 0.001), and AFR (OR = 0.79, 95% CI: 0.73-0.85, p  < 0.001) were significant factors associated with PD. Smooth curve fitting revealed that NLR was positively linked to PD risk, whereas AFR and LMR were inversely associated with it. In ROC curve analysis, the AUC of AFR was 0.7290, the sensitivity was 63.98%, and the specificity was 76.00%. The AUC of NLR was 0.6200, the sensitivity was 50.54%, and the specificity was 71.50%. The AUC of LMR was 0.6253, the sensitivity was 48.39%, and the specificity was 73.00%. The AUC of the combination was 0.7498, the sensitivity was 74.19%, and the specificity was 64.00%., Conclusion: Our findings indicate that NLR, LMR, and AFR are significantly associated with Parkinson's disease and may serve as diagnostic markers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xu, Ren, Xu, Dai, Yang and Jin.)

Cluster headache (CH) is a common primary headache that severely impacts patients' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Li, Ren, Xu, Dai, Jin and Yang.)

Background: Identification of the unknown pathogenic factor driving atherosclerosis not only enhances the development of disease biomarkers but also facilitates the discovery of new therapeutic targets, thus contributing to the improved management of coronary artery disease (CAD). We aimed to identify causative protein biomarkers in CAD etiology based on proteomics and 2-sample Mendelian randomization (MR) design. Methods: Serum samples from 33 first-onset CAD patients and 31 non-CAD controls were collected and detected using protein array. Differentially expressed analyses were used to identify candidate proteins for causal inference. We used 2-sample MR to detect the causal associations between the candidate proteins and CAD. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified protein. Vascular expression of candidate protein in situ was also detected. Results: Among the differentially expressed proteins identified utilizing proteomics, we found that circulating Golgi protein 73 (GP73) was causally associated with incident CAD and other atherosclerotic events sharing similar etiology. Network MR approach showed low-density lipoprotein cholesterol and glycated hemoglobin serve as mediators in the causal pathway, transmitting 42.1% and 8.7% effects from GP73 to CAD, respectively. Apart from the circulating form of GP73, both mouse model and human specimens imply that vascular GP73 expression was also upregulated in atherosclerotic lesions and concomitant with markers of macrophage and phenotypic switching of vascular smooth muscle cells (VSMCs). Conclusions: Our study supported GP73 as a biomarker and causative for CAD. GP73 may involve in CAD pathogenesis mainly via dyslipidemia and hyperglycemia, which may enrich the etiological information and suggest future research direction on CAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD., (© 2024. The Author(s).)

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs.  1-5 ), yet the experimental realization is hard to achieve 6,7 . The recently discovered vanadium-based kagome materials 8 , which exhibit both superconductivity 9-11 and charge-density-wave orders 12-14 , are nonmagnetic 8,9 and weakly correlated 15,16 . Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr 3 Sb 5 , which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a 0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, T c max  = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors 17,18 . Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Capturing and separating the greenhouse gas SF 6 from nitrogen N 2 have significant greenhouse mitigation potential and economic benefits. We used a pore engineering strategy to manipulate the pore environment of the metal-organic framework (MOF) by incorporating organic functional groups (-NH 2 ). This resulted in an enhanced adsorption of SF 6 and separation of the SF 6 /N 2 mixture in the MOF. The introduction of amino (-NH 2 ) groups into YTU-29 resulted in a reduction of the Brunauer-Emmett-Teller surface but an increase in interactions with SF 6 within the confined pores. Water-stable YTU-29-NH 2 showed a significantly higher SF 6 uptake (95.5 cm 3 /g) than YTU-29 (77.4 cm 3 /g). The results of the breakthrough experiments show that YTU-29-NH 2 has a significantly improved separation performance for SF 6 /N 2 mixtures, with a high SF 6 capture of 0.88 mmol/g compared to 0.56 mmol/g by YTU-29. This improvement is due to the suitable pore confinement and accessible -NH 2 groups on pore surfaces. Considering its excellent regeneration ability and cycling performance, ultrastable YTU-29-NH 2 demonstrates great potential for SF 6 capturing and SF 6 /N 2 separation.

Studies investigating the relationship between dietary vitamin B1 intake and risk of Hyperuricemia (HU) are scarce, the present study aimed to examine the association of dietary vitamin B1 intake and HU among adults. This cross-sectional study included 5750 adults whose data derived from National Health and Nutrition Examination Survey (NHANES) from March 2017 to March 2020. The dietary intake of vitamin B1 was assessed using 24-h dietary recall interviews. The characteristics of study participants were grouped into five levels according to the levels of vitamin B1 quintile. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of HU, according to the vitamin B1 intake quintile for male and female separately. The dose-response relationship was determined by the restricted cubic spline (RCS). Smoothed curve fitting was used to assess serum uric acid concentration versus dietary vitamin B1 intake in the study population. The prevalence of hyperuricemia was 18.90% (20.15% and 17.79% for males and females, respectively) in the United States from March 2017 to March 2020. Multiple logistic regression analyses showed that in the male population, the HU ratio (OR) of vitamin B1 intake in Q2 to Q5 compared with the lowest quintile (Q1) was 0.75 (95% CI 0.52, 1.09), 0.70 (95% CI 0.48, 1.02), 0.66 (95% CI 0.44, 0.99) and 0.55 (95% CI 0.34, 0.90). The P for trend was 0.028. In women, the ORs for vitamin B1 intake Q2 to Q5 were 0.87 (95% CI 0.64, 1.19), 0.97 (0.68-1.38), 1.05 (0.69-1.60) and 0.75 (0.42-1.34), respectively. The P for trend was 0.876. The RCS curve revealed a linear relationship between vitamin B1 intake and the risk of hyperuricemia in men (P nonlinear = 0.401). Smoothed curve fitting demonstrated a negative association between vitamin B1 intake and serum uric acid concentration in men, whereas there was no significant association between dietary vitamin B1 intake and the risk of hyperuricemia in women. In the US adult population, dietary vitamin B1 intake was negatively associated with hyperuricemia in males., (© 2024. The Author(s).)