Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/ß-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

Identification of Novel Cuproptosis-Related Genes Mediating the Prognosis and Immune Microenvironment in Cholangiocarcinoma.

BACKGROUND: Cuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown. METHODS: A systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line. RESULTS: First, a 10-cuproptosis-related gene signature (ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3, and TMPRSS6) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients' sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma. CONCLUSIONS: Collectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.

Hyperthermia improves gemcitabine sensitivity of pancreatic cancer cells by suppressing the EFNA4/ß-catenin axis and activating dCK.

Background: Previously, our investigations have underscored the potential of hyperthermia to improve the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC). Nonetheless, the precise underlying mechanisms remain elusive. Methods: We engineered two GEM-resistant PC cell lines (BxPC-3/GEM and PANC-1/GEM) and treated them with GEM alongside hyperthermia. The impact of hyperthermia on the therapeutic potency of GEM was ascertained through MTT assay, assessment of the concentration of its active metabolite dFdCTP, and evaluation of deoxycytidine kinase (dCK) activity. Lentivirus-mediated dCK silencing was further employed to validate its involvement in mediating the GEM-sensitizing effect of hyperthermia. The mechanism underlying hyperthermia-mediated dCK activation was explored using bioinformatics analyses. The interplay between hyperthermia and the ephrin A4 (EFNA4)/ß-catenin/dCK axis was investigated, and their roles in GEM resistance was further explored via the establishment of xenograft tumor models in nude mice. Results: Hyperthermia restored dCK expression in GEM-resistant cell lines, concurrently enhancing GEM sensitivity and fostering DNA damage and cell death. These observed effects were negated by dCK silencing. Regarding the mechanism, hyperthermia activated dCK by downregulating EFNA4 expression and mitigating ß-catenin activation. Overexpression of EFNA4 activated the ß-catenin while suppressing dCK, thus diminishing cellular GEM sensitivity-a phenomenon remediated by the ß-catenin antagonist MSAB. Consistently, in vivo, hyperthermia augmented the therapeutic efficacy of GEM on xenograft tumors through modulation of the ephrin A4/ß-catenin/dCK axis. Conclusion: This study delineates the role of hyperthermia in enhancing GEM sensitivity of PC cells, primarily mediated through the suppression of the EFNA4/ß-catenin axis and activation of dCK.

Cardamom consumption may improve cardiovascular metabolic biomarkers in adults: A systematic review and meta-analysis of randomized controlled trials.

The bioactive compounds in cardamom have been found to enhance cardiovascular health by improving blood lipids and inflammation. We hypothesized that cardamom consumption might ameliorate cardiovascular metabolic biomarkers in adults; however, there is still debate regarding its impact on cardiac metabolism. This research was therefore designed to determine if cardamom consumption had a favorable impact on lipid profiles, inflammatory markers, and oxidative stress indices as they related to cardiovascular diseases. A comprehensive search was conducted through PubMed, Scopus, Embase, Web of Science, and the Cochrane Library on July 4, 2023. Using a random-effects model pooled the weighted mean difference (WMD) and 95% confidence interval (CI). The final 12 trials containing 989 participants were included. The results illustrated that cardamom consumption could improve total cholesterol (WMD = -8.56 mg/dL; 95% CI, -14.90 to -2.22), triglycerides (WMD = -14.09 mg/dL; 95% CI, -24.01 to -4.17), high-sensitivity C-reactive protein (WMD = -1.01 ng/mL; 95% CI, -1.81 to -0.22), and interleukin-6 (WMD = -1.81 pg/mL; 95% CI, -3.06 to -0.56). However, it did not have significant influences on high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and some indicators of oxidative stress. In conclusion, cardamom consumption can improve specific cardiovascular metabolic biomarkers and potentially confer protective effects on cardiovascular health. However, more large-scale clinical research with better designs would further validate the findings, which will offer substantial evidence of cardamom as nutritional and functional products.

Association analysis between organophosphorus flame retardants exposure and the risk of depression: Data from NHANES 2017-2018.

BACKGROUND: Organophosphorus flame retardants (OPFRs) can damage the brain and may cause abnormal behaviors. There was no population-based study to reveal the relationship between OPFRs and the occurrence of depression. This study utilized a publicly available database to investigate the correlation between OPFRs exposure and the risk of depression, and the mediation effect of inflammation on the correlation. METHODS: Data in this study was from the database of the National Health and Nutrition Examination Survey. Multifactorial logistic regression was used to estimate the relationship between OPFRs exposure and the risk of depression, and a mediation effect model was constructed to explore the impact of inflammation on the correlation. RESULTS: Data of 1273 participants was included in the study. It was found that individuals with high urinary concentration of bis-(2-chloroethyl) phosphate had an increased risk of developing depression (OR = 1.217, 95 % CI: 1.032-1.435). Combined exposure to OPFRs was significantly associated with the increased risk of depression than single OPFRs exposure. Subgroup analyses based on inflammatory levels in the body revealed that inflammation might exert the mediation effect on the association between OPFRs exposure and the risk of depression, with the contribution proportion of 8.23 %. LIMITATIONS: Cross-sectional data and rapid metabolism of OPFRs lead to uncertainty in revealing long-term exposure in the body. CONCLUSIONS: There was a correlation between OPFRs exposure and the risk of depression, which may be mediated by inflammation in the body to some extent.

Diversity-Oriented Synthesis of Indole-Fused Polycyclic Scaffolds via Rhodium-Catalyzed NH-Indole-Directed C-H Coupling of 2-Phenyl-1H-indoles with Propargylic Alcohol Derivatives.

Diversity-oriented synthesis strategy for the efficient assembly of indole-fused polycyclic scaffolds via rhodium-catalyzed NH-indole-directed C-H coupling with propargylic alcohol derivatives in a regioselective manner was developed. Five 2-phenyl-1H-indole-embedded core skeletons were synthesized. In particular, three different indole-fused exo-olefin-containing polycycles were realized, which may be manipulated for further chemistry.

NF-κB affected the serum levels of TNF-α and IL-1ß via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1ß (IL-1ß) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO-guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF-κB and serum TNF-α、IL-1ß levels were detected by enzyme-linked immunosorbent assay. Protein expression of the MAPK/NF-κB signaling pathway including p-IκBα, p-p38 MAPK, p-NF-κB p65, IκBα, p38 MAPK, and NF-κB p65 was determined using western blot analysis. Compared with control group, the expression of NF-κB in lung tissue and the levels of serum TNF-α and IL-1ß rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF-κB p65 were found in APMTE group rats. And UK administration reversed the APMTE-induced increase in TNF-α, IL-1ß, p-IκBα, p-MAPK, and p-NF-κB protein. Furthermore, the levels of NF-κB, TNF-α, and IL-1ß were positively correlated with mean pulmonary artery. And the levels of TNF-α and IL-1ß were positively correlated with NF-κB. These findings suggest that the activation of MAPK/NF-κB pathway as a critical driver of increasing TNF-α and IL-1ß level in APMTE rats and UK exerted protective effects against APMTE-induced PH may be related to the downregulation of the MAPK/NF-κB signaling pathway.

The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Cold EMR vs. Hot EMR for the removal of sessile serrated polyps larger than 10 mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.

2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives.

Quinoline is a privileged heterocyclic ring which can be found in many drug molecules and bioactive compounds. The development of synthetic methods for making quinoline derivatives continuously attracts the interest of organic and medicinal chemists. This paper highlights 2-azidobenzaldehyde-based [4+2] annulation for the synthesis of quinoline derivatives including fused and spiro-quinolines, quinoline-4-ols, 4-aminoquinolines, and related compounds.

Homochiral π-Rich Covalent Organic Frameworks Enabled Chirality Imprinting in Conjugated Polymers: Confined Polymerization and Chiral Memory from Scratch.

Optically active π-conjugated polymers (OACPs) have garnered increasing research interest for their resemblance to biological helices and intriguing chirality-related functions. Traditional methods for synthesizing involve decorating achiral conjugated polymer architectures with enantiopure side substituents through complex organic synthesis. Here, we report a new approach: the templated synthesis of unsubstituted OACPs via supramolecularly confined polymerizations of achiral monomers within nanopores of 2D or 3D chiral covalent organic frameworks (CCOFs). We show that the chiral π-rich nanospaces facilitate the in situ enantiospecific polymerization and self-propagation, akin to nonenzymatic polymerase chain reaction (PCR) system, resulting in chiral imprinting. The stacked polymer chains are kinetically inert enough to memorize the chiral information after liberating from CCOFs, and even after treatment at temperature up to 200 °C. The isolated OACPs demonstrate robust enantiodiscrimination, achieving up to 85 % ee in separating racemic amino acids. This underscores the potential of utilizing CCOFs as templates for supramolecularly imprinting optical activity into CPs, paving the way for synthetic evolution and advanced functional exploration of OACPs.

Ag engineered NiFe-LDH/NiFe2O4 Mott-Schottky heterojunction electrocatalyst for highly efficient oxygen evolution and urea oxidation reactions.

Efficient and durable electrocatalysts with sufficient active sites and high intrinsic activity are essential for advancing energy-saving hydrogen production technology. In this study, a Mott-Schottky heterojunction electrocatalyst with Ag nanoparticles in-situ grown on NiFe layered double hydroxides (NiFe-LDH)/NiFe2O4 nanosheets (Ag@NiFe-LDH/NiFe2O4) were designed and successfully synthesized through a hydrothermal process and subsequent spontaneous redox reaction. The in-situ growth of metallic Ag on semiconducting NiFe-LDH/NiFe2O4 triggers a strong electron interaction across the Mott-Schottky interface, leading to a significant increase in both the intrinsic catalytic activity and the electrochemical active surface area of the heterojunction electrocatalyst. As a result, the Ag@NiFe-LDH/NiFe2O4 demonstrates impressive oxygen evolution reaction (OER) performance in alkaline KOH solution, achieving a low overpotential of 249 mV at 100 mA cm-2 and a Tafel slope of 42.79 mV dec-1. When the self-supported Ag@NiFe-LDH/NiFe2O4 is coupled with the Pt/C electrocatalyst, the alkaline electrolyzer reaches a current density of 10 mA cm-2 at a cell voltage of only 1.460 V. Furthermore, X-ray photoelectron spectroscopy and in-situ Raman analysis reveal that the Ni(Fe)OOH is the possible active phase for OER in the catalyst. In addition, when employed for UOR catalysis, the Ag@NiFe-LDH/NiFe2O4 also displays intriguing activity with an ultralow potential of 1.389 V at 50 mA cm-2. This work may shed light on the rational design of multiple-phase heterogeneous electrocatalysts and demonstrate the significance of interface engineering in enhancing catalytic performance.

Eco-friendly flame-retardant bamboo fiber/polypropylene composite based on the immobilization of halloysite nanotubes by tannic acid-Fe3+ complex.

Bamboo fibers (BF), as an important sustainable natural material, are becoming a hot alternative to synthetic fibers for the reinforcement of polypropylene (PP)-based composites. However, the weak interfacial compatibility between BF and PP as matrix and their inherent flammability limit the practical application of BF/PP composites (BPC). Here, a fire-safe BPC was fabricated by constructing flame-retardant interfacial layers containing tannic acid (TA)-Fe3+ complex and halloysite nanotubes (HNTs) on the fiber matrix followed by a hot-pressing process. The results showed that the interfacial chelating of TA with Fe3+ improved the dispersion of HNTs on the fibers and the interfacial interactions within the fiber matrix, resulting in the as-fabricated composite with significantly improved mechanical properties and water resistance. In addition, the flame-retardant composite exhibited higher thermal stability and enhanced residual char content. Moreover, the composite possessed significant flame-retardant performances with a reduction of 23.75 % in the total heat release and 32.44 % in the total smoke production, respectively, owing to the flame retarding in gaseous phase and condensed phase of TA-Fe3+@HNTs layers. This work offers a green and eco-friendly strategy to address the inherent problems of BPC material in terms of fire safety and interfacial compatibility, thus broadening their applications in the automotive interior and construction industries.

Synergistic amelioration between Ligusticum striatum DC and borneol against cerebral ischemia by promoting astrocytes-mediated neurogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

Mechanistic study on the alleviation of postmenopausal osteoporosis by Lactobacillus acidophilus through butyrate-mediated inhibition of osteoclast activity.

In China, traditional medications for osteoporosis have significant side effects, low compliance, and high costs, making it urgent to explore new treatment options. Probiotics have demonstrated superiority in the treatment of various chronic diseases, and the reduction of bone mass in postmenopausal osteoporosis (PMOP) is closely related to the degradation and metabolism of intestinal probiotics. It is crucial to explore the role and molecular mechanisms of probiotics in alleviating PMOP through their metabolites, as well as their therapeutic effects. We aim to identify key probiotics and their metabolites that affect bone loss in PMOP through 16srDNA sequencing combined with non-targeted metabolomics sequencing, and explore the impact and possible mechanisms of key probiotics and their metabolites on the progression of PMOP in the context of osteoporosis caused by estrogen deficiency. The sequencing results showed a significant decrease in Lactobacillus acidophilus and butyrate in PMOP patients. In vivo experiments confirmed that the intervention of L. acidophilus and butyrate significantly inhibited osteoclast formation and bone resorption activity, improved intestinal barrier permeability, suppressed B cells, and the production of RANKL on B cells, effectively reduced systemic bone loss induced by oophorectomy, with butyric acid levels regulated by L. acidophilus. Consistently, in vitro experiments have confirmed that butyrate can directly inhibit the formation of osteoclasts and bone resorption activity. The above research results indicate that there are various pathways through which L. acidophilus inhibits osteoclast formation and bone resorption activity through butyrate. Intervention with L. acidophilus may be a safe and promising treatment strategy for osteoclast related bone diseases, such as PMOP.

Endoscopic treatment for early duodenal papillary carcinoma: long-term outcomes.

BACKGROUND AND AIM: This study aims to determine whether endoscopic papillectomy (EP) is a safe and effective treatment for early duodenal papillary carcinoma with long-term follow-up. METHODS: From June 2012 to September 2022, 48 patients with early duodenal papilloma carcinoma who received endoscopic treatment were included. The histological types, percentage of complete resections, postoperative residuals, adverse events, and recurrences were evaluated. RESULTS: EP was successful in all patients; 46 were lumped, and two were fragmented, with a 95.8% intact removal rate (46/48). The preoperative biopsy pathological positive rate was 70.8% (34/48). The incidence of early postoperative adverse events (within 1 month after EP) were 16.7% (8/48), including four cases of acute pancreatitis, three cases of delayed bleeding, and one case of acute cholangitis. In addition, 4.2% (2/48) of the late adverse events were bile duct stenosis. After 6 months, the postoperative residual rate was 0%. The median time to recurrence was 17.5 months, and the postoperative recurrence rate was 16.7% (8/48) in patients treated with radiofrequency ablation. The median progression-free survival was 18.6 months (95% CI, 12.1-25.1), and the median overall survival was 121.5 months (95% CI, 105.6-120.9). CONCLUSIONS: EP is a safe and efficient alternative therapy for early duodenal papillary carcinoma. Endoscopic follow-up and treatment are essential because of the potential for recurrence.

Risk prediction and analysis of gallbladder polyps with deep neural network.

The aim of this study is to analyze the risk factors associated with the development of adenomatous and malignant polyps in the gallbladder. Adenomatous polyps of the gallbladder are considered precancerous and have a high likelihood of progressing into malignancy. Preoperatively, distinguishing between benign gallbladder polyps, adenomatous polyps, and malignant polyps is challenging. Therefore, the objective is to develop a neural network model that utilizes these risk factors to accurately predict the nature of polyps. This predictive model can be employed to differentiate the nature of polyps before surgery, enhancing diagnostic accuracy. A retrospective study was done on patients who had cholecystectomy surgeries at the Department of Hepatobiliary Surgery of the Second People's Hospital of Shenzhen between January 2017 and December 2022. The patients' clinical characteristics, lab results, and ultrasonographic indices were examined. Using risk variables for the growth of adenomatous and malignant polyps in the gallbladder, a neural network model for predicting the kind of polyps will be created. A normalized confusion matrix, PR, and ROC curve were used to evaluate the performance of the model. In this comprehensive study, we meticulously analyzed a total of 287 cases of benign gallbladder polyps, 15 cases of adenomatous polyps, and 27 cases of malignant polyps. The data analysis revealed several significant findings. Specifically, hepatitis B core antibody (95% CI -0.237 to 0.061, p < 0.001), number of polyps (95% CI -0.214 to -0.052, p = 0.001), polyp size (95% CI 0.038 to 0.051, p < 0.001), wall thickness (95% CI 0.042 to 0.081, p < 0.001), and gallbladder size (95% CI 0.185 to 0.367, p < 0.001) emerged as independent predictors for gallbladder adenomatous polyps and malignant polyps. Based on these significant findings, we developed a predictive classification model for gallbladder polyps, represented as follows, Predictive classification model for GBPs = -0.149 * core antibody - 0.033 * number of polyps + 0.045 * polyp size + 0.061 * wall thickness + 0.276 * gallbladder size - 4.313. To assess the predictive efficiency of the model, we employed precision-recall (PR) and receiver operating characteristic (ROC) curves. The area under the curve (AUC) for the prediction model was 0.945 and 0.930, respectively, indicating excellent predictive capability. We determined that a polyp size of 10 mm served as the optimal cutoff value for diagnosing gallbladder adenoma, with a sensitivity of 81.5% and specificity of 60.0%. For the diagnosis of gallbladder cancer, the sensitivity and specificity were 81.5% and 92.5%, respectively. These findings highlight the potential of our predictive model and provide valuable insights into accurate diagnosis and risk assessment for gallbladder polyps. We identified several risk factors associated with the development of adenomatous and malignant polyps in the gallbladder, including hepatitis B core antibodies, polyp number, polyp size, wall thickness, and gallbladder size. To address the need for accurate prediction, we introduced a novel neural network learning algorithm. This algorithm utilizes the aforementioned risk factors to predict the nature of gallbladder polyps. By accurately identifying the nature of these polyps, our model can assist patients in making informed decisions regarding their treatment and management strategies. This innovative approach aims to improve patient outcomes and enhance the overall effectiveness of care.

Intestinal adipocytes transdifferentiate into myofibroblast-like cells and contribute to fibrosis in Crohn's disease.

BACKGROUND AND AIMS: Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD. METHODS: The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-ß signalling was also studied to explore the underlying mechanism. RESULTS: Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. LPS-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-ß signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue. CONCLUSIONS: Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-ß signalling.

Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin.

Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2SPD, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections.

Exploring the effect of different typical plant community on human stress reduction: a field experiment.

Research has demonstrated the positive effect of natural environment on human restoration and well-being. Time spent in nature can often alleviate both physiological and psychological stress. However, few studies have discussed the environmental health effects of the nature's components and characteristics. Sixty volunteers were recruited and one manufactured environment and five different natural environments were randomly assigned to them, including coniferous forests (pure coniferous forest-PC and mixed coniferous forest-MC), broad-leaved forests (pure broad-leaved forest-PB and mixed broad-leaved forest-MB), and mixed forest (mixed coniferous and broad-leaved forest-MCB). Each volunteer sat in a built or natural environment and looked around the environment for 15 min. Physiological (HR, HRV, BP, pulse rate and salivary cortisol) and psychological indicators (POMS and STAI) were used to evaluate the changes in their stress level. Results indicated a strong difference in HR, HRV, POMS and STAI between the built and natural environment, which showed that natural environment can lower the stress level. MC had the best effect on relieving physiological stress, whereas MCB is most successful in improving emotional state and reducing anxiety. Broad-leaved forest and mixed forest significantly affected the DBP and vigor level of the subjects, respectively. While coniferous forest did significantly increase the concentration of salivary cortisol in subjects. The study confirmed that compared to the built environment, the natural environment can relieve the human body's physical and psychological stress and negative emotions, while significantly increasing vitality. And different plant communities also have different effects on the physiological and psychological indicators of the subjects. These results will provide scientific basis for the construction and improvement of urban green space environment.