Improving cancer immunotherapy in prostate cancer by modulating T cell function through targeting the galectin-1.

Our study aimed to elucidate the role of Galectin-1 (Gal-1) role in the immunosuppressive tumor microenvironment (TME) of prostate cancer (PCa). Our previous findings demonstrated a correlation between elevated Gal-1 expression and advanced PCa stages. In this study, we also observed that Gal-1 is expressed around the tumor stroma and its expression level is associated with PCa progression. We identified that Gal-1 could be secreted by PCa cells, and secreted Gal-1 has the potential to induce T cell apoptosis. Gal-1 knockdown or inhibition of Gal-1 function by LLS30 suppresses T cell apoptosis resulting in increased intratumoral T cell infiltration. Importantly, LLS30 treatment significantly improved the antitumor efficacy of anti-PD-1 in vivo. Mechanistically, LLS30 binds to the carbohydrate recognition domain (CRD) of Gal-1, disrupting its binding to CD45 leading to the suppression of T cell apoptosis. In addition, RNA-seq analysis revealed a novel mechanism of action for LLS30, linking its tumor-intrinsic oncogenic effects to anti-tumor immunity. These findings suggested that tumor-derived Gal-1 contributes to the immunosuppressive TME in PCa by inducing apoptosis in effector T cells. Targeting Gal-1 with LLS30 may offer a strategy to enhance anti-tumor immunity and improve immunotherapy.

Stomach as the target organ of Rickettsia heilongjiangensis infection in C57BL/6 mice identified by click chemistry.

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

A real-world study of foreign body aspiration in children with 4227 cases in Western China.

The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P < 0.01). FBA most commonly occurs in January and February. More than 60% of FBAs occur between the ages of 1 and 2 years, and the incidence of FBA may be greater in children who are cared for by grandparents. A rigid bronchoscope can be used to remove most aspirated foreign bodies in a median of 16 min.

Alterations in coenzyme Q10 status in a cybrid line harboring the 3243A>G mutation of mitochondrial DNA is associated with abnormal mitochondrial bioenergetics and dysregulated mitochondrial biogenesis.

Mitochondrial DNA (mtDNA) mutations, including the m.3243A>G mutation that causes mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), are associated with secondary coenzyme Q10 (CoQ10) deficiency. We previously demonstrated that PPARGC1A knockdown repressed the expression of PDSS2 and several COQ genes. In the present study, we compared the mitochondrial function, CoQ10 status, and levels of PDSS and COQ proteins and genes between mutant cybrids harboring the m.3243A>G mutation and wild-type cybrids. Decreased mitochondrial energy production, defective respiratory function, and reduced CoQ10 levels were observed in the mutant cybrids. The ubiquinol-10:ubiquinone-10 ratio was lower in the mutant cybrids, indicating blockage of the electron transfer upstream of CoQ, as evident from the reduced ratio upon rotenone treatment and increased ratio upon antimycin A treatment in 143B cells. The mutant cybrids exhibited downregulation of PDSS2 and several COQ genes and upregulation of COQ8A. In these cybrids, the levels of PDSS2, COQ3-a isoform, COQ4, and COQ9 were reduced, whereas those of COQ3-b and COQ8A were elevated. The mutant cybrids had repressed PPARGC1A expression, elevated ATP5A levels, and reduced levels of mtDNA-encoded proteins, nuclear DNA-encoded subunits of respiratory enzyme complexes, MNRR1, cytochrome c, and DHODH, but no change in TFAM, TOM20, and VDAC1 levels. Alterations in the CoQ10 level in MELAS may be associated with mitochondrial energy deficiency and abnormal gene regulation. The finding of a reduction in the ubiquinol-10:ubiquinone-10 ratio in the MELAS mutant cybrids differs from our previous discovery that cybrids harboring the m.8344A>G mutation exhibit a high ubiquinol-10:ubiquinone-10 ratio.

Water- and heat-activated dynamic passivation for perovskite photovoltaics.

Further improvements in perovskite solar cells (PSCs) require better control of ionic defects in the perovskite photoactive layer during the manufacturing stage and their usage1-5. Here, we report a living passivation strategy using a hindered urea/thiocarbamate bond6-8 Lewis acid-base material (HUBLA), where dynamic covalent bonds with water and heat-activated characteristics can dynamically heal the perovskite to ensure device performance and stability. Upon exposure to moisture or heat, HUBLA generates new agents and further passivates defects in the perovskite. This passivation strategy achieved high-performance devices with a power conversion efficiency (PCE) of 25.1%. HUBLA devices retained 94% of their initial PCE for approximately 1500 hours of aging at 85 °C in N2 and maintained 88% of their initial PCE after 1000 hours of aging at 85 °C and 30% relative humidity (RH) in air.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

Clinical presentation and treatment of four children with pulmonary mucoepidermoid carcinoma.

Primary lung cancer in childhood is extremely rare, with an incidence rate of less than 2/100,0000, and pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. Their symptoms are usually not specific, and there are no guidelines for their management, which makes their clinical management a challenge for pediatricians. The purpose of this report is to discuss the clinical presentation, positive signs, examinations, pathological characteristics, surgical modalities, chemotherapy regimens, and prognosis in children. The clinical data of four patients diagnosed with PMEC at the Children's Hospital of Chongqing Medical University from June 2021 to November 2022 were retrospectively analyzed, and their clinical features, treatment, and prognosis were summarized. Among them, two were male and two were female; their ages ranged from 3 years and 10 months to 10 years and 11 months, and all were staged according to tumor node metastasis classification (TNM). Immunohistochemical tests were performed in all children, among which four cases were positive for cytokeratin (CK), two cases were positive for CK7, four cases were positive for p63, about 5-10% of tumor cells were positive for Ki67. Among the four children, three had surgery alone and one had surgery + chemotherapy. All four children are presently living, with no evidence of tumor recurrence or metastasis. PMEC in children is very rare, and its age of onset and symptoms are not specific, and there is no obvious correlation with gender. Its diagnosis mainly relies on pathomorphological diagnosis, and immunohistochemical detection has no specific performance. The prognosis of children with PMEC is related to the clinical stage and whether surgery is performed. Whether further chemotherapy or radiotherapy is needed for patients who cannot undergo surgical resection and for those who have a combination of distant metastases requires further clinical studies.

Clinical presentation and treatment of 4 children with pulmonary mucoepidermoid carcinomaLung cancer in childhood is extremely rare, occurring at a rate of less than 2/1000000, and a type of lung cancer called pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. The symptoms are usually not specific, and there are no guidelines for its management, which is a challenge for doctors. The purpose of this report is to discuss the signs and symptoms medical examinations, disease characteristics, surgical procedures, chemotherapy regimens and prognosis in children with pulmonary mucoepidermoid carcinoma. The clinical data of four patients diagnosed with pulmonary mucoepidermoid carcinoma at the Children's Hospital of Chongqing Medical University from June 2021 to November 2022 were analyzed, and their clinical features, treatment and prognosis were summarized. All four children are currently alive, and there is no recurrence or spread of the tumor after treatment. We have discussed various aspects of the disease, such as the rate of occurrence, causes, signs and symptoms, the way in which it might be diagnosed and treated, and the survival rate after operation, hoping to provide some insights for future work.

A Statovirus-like virus from respiratory tracts of patients, China.

The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.

Assessment of left ventricular ejection fraction in artificial intelligence based on left ventricular opacification.

Background: Left ventricular opacification (LVO) improves the accuracy of left ventricular ejection fraction (LVEF) by enhancing the visualization of the endocardium. Manual delineation of the endocardium by sonographers has observer variability. Artificial intelligence (AI) has the potential to improve the reproducibility of LVO to assess LVEF. Objectives: The aim was to develop an AI model and evaluate the feasibility and reproducibility of LVO in the assessment of LVEF. Methods: This retrospective study included 1305 echocardiography of 797 patients who had LVO at the Department of Ultrasound Medicine, Union Hospital, Huazhong University of Science and Technology from 2013 to 2021. The AI model was developed by 5-fold cross validation. The validation datasets included 50 patients prospectively collected in our center and 42 patients retrospectively collected in the external institution. To evaluate the differences between LV function determined by AI and sonographers, the median absolute error (MAE), spearman correlation coefficient, and intraclass correlation coefficient (ICC) were calculated. Results: In LVO, the MAE of LVEF between AI and manual measurements was 2.6% in the development cohort, 2.5% in the internal validation cohort, and 2.7% in the external validation cohort. Compared with two-dimensional echocardiography (2DE), the left ventricular (LV) volumes and LVEF of LVO measured by AI correlated significantly with manual measurements. AI model provided excellent reliability for the LV parameters of LVO (ICC > 0.95). Conclusions: AI-assisted LVO enables more accurate identification of the LV endocardium and reduces observer variability, providing a more reliable way for assessing LV function.

Identifying therapeutic targets for breast cancer: insights from systematic Mendelian randomization analysis.

Background: Breast cancer (BC) exhibits a high incidence rate, imposing a substantial burden on healthcare systems. Novel drug targets are urgently needed for BC. Mendelian randomization (MR) has gained widespread application for identifying fresh therapeutic targets. Our endeavor was to pinpoint circulatory proteins causally linked to BC risk and proffer potential treatment targets for BC. Methods: Through amalgamating protein quantitative trait loci from 2,004 circulating proteins and comprehensive genome-wide association study data from the Breast Cancer Association Consortium, we conducted MR analyses. Employing Steiger filtering, bidirectional MR, Bayesian colocalization, phenotype scanning, and replication analyses, we further solidified MR study outcomes. Additionally, protein-protein interaction (PPI) network was harnessed to unveil latent associations between proteins and prevailing breast cancer medications. The phenome-wide MR (Phe-MR) was employed to assess potential side effects and indications for the druggable proteins of BC. Finally, we further affirmed the drugability of potential drug targets through mRNA expression analysis and molecular docking. Results: Through comprehensive analysis, we identified five potential drug targets, comprising four (TLR1, A4GALT, SNUPN, and CTSF) for BC and one (TLR1) for BC_estrogen receptor positive. None of these five potential drug targets displayed reverse causation. Bayesian colocalization suggested that these five latent drug targets shared variability with breast cancer. All drug targets were replicated within the deCODE cohort. TLR1 exhibited PPI with current breast cancer therapeutic targets. Furthermore, Phe-MR unveiled certain adverse effects solely for TLR1 and SNUPN. Conclusion: Our study uncovers five prospective drug targets for BC and its subtypes, warranting further clinical exploration.

N-Benzylhydroxylamine as a novel synthetic block in "C1N1" embedding reaction via α-C(sp3)-H activation strategy.

A novel process using N-benzylhydroxylamine hydrochloride as a "C1N1 synthon" in [2+2+1] cyclization for the construction of 1,2,5-trisubstituted imidazoles has been described for the first time. The key to realizing this process lies in capturing arylamines by in situ generated novel acyl ketonitrone intermediates. Subsequent tautomerization activates the α-C(sp3)-H of N-benzylhydroxylamines, and thus breaks through its inherent reaction mode and achieves N, α-C site-selective cyclization. Furthermore, this method enables scale-up synthesis and late-stage modification of complex molecules.

Honokiol Exhibits Anti-NLRP3 Inflammasome and Antimicrobial Properties in Neisseria gonorrhoeae-Infected Macrophages.

Purpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1ß, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages. Methods: Honokiol's impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay. Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1ß, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae. Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.

Cinnamaldehyde inhibits the NLRP3 inflammasome by preserving mitochondrial integrity and augmenting autophagy in Shigella sonnei-infected macrophages.

BACKGROUND: Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1ß and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. METHODS: Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. RESULTS: CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1ß and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. CONCLUSION: CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.

Validity of the I­FEED classification in assessing postoperative gastrointestinal impairment in patients undergoing elective lumbar spinal surgery with general anesthesia: a prospective observational study.

BACKGROUND: The I-FEED classification, scored 0-8, was reported to accurately describe the clinical manifestations of gastrointestinal impairment after colorectal surgery. Therefore, it is interesting to determine whether the I-FEED scoring system is also applicable to patients undergoing lumbar spine surgery. METHODS: Adult patients undergoing elective lumbar spine surgery were enrolled, and the I-FEED score was measured for 4 days after surgery. The I-FEED scoring system incorporates five elements: intake (score: 0, 1, 3), feeling nauseated (score: 0, 1, 3), emesis (score: 0, 1, 3), results of physical exam (score: 0, 1, 3), and duration of symptoms (score: 0, 1, 2). Daily I-FEED scores were summed, and the highest overall score is used to categorize patients into one of three categories: normal (0-2 points), postoperative gastrointestinal intolerance (POGI; 3-5 points), and postoperative gastrointestinal dysfunction (POGD; 6 + points). The construct validity hypothesis testing determines whether the I-FEED category is consistent with objective clinical findings relevant to gastrointestinal impairment, namely, the longer length of hospital stay (LOS), higher inhospital medical cost, more postoperative gastrointestinal medical treatment, and more postoperative non-gastrointestinal complications. RESULTS: A total of 156 patients were enrolled, and 25.0% of patients were categorized as normal, 49.4% POGI, and 25.6% POGD. Patients with higher I-FEED scores agreed with the four validity hypotheses. Patients with POGD had a significantly longer length of hospital stay (1 day longer median stay; p = 0.049) and more inhospital medical costs (approximately 500 Taiwanese dollars; p = 0.037), and more patients with POGD required rectal laxatives (10.3% vs. 32.5% vs. 32.5%; p = 0.026). In addition, more patients with POGD had non-gastrointestinal complications (5.1% vs. 11.7% vs. 30.0%; p = 0.034). CONCLUSION: This study contributes preliminary validity evidence for the I-FEED score as a measure for postoperative gastrointestinal impairment after elective lumbar spine surgery.

Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease.

OBJECTIVE: To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. ANIMALS: 4 healthy horses without evidence of forelimb lameness. METHODS: A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 µg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points. RESULTS: Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point. CLINICAL RELEVANCE: Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.

Effects of electroacupuncture combined with paliperidone palmitate long-acting injection on withdrawal symptoms and neurotransmitters in methamphetamine addicts.

OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts. MATERIALS AND METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups. RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05). CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.

Cinnamaldehyde, A Bioactive Compound from the Leaves of Cinnamomum osmophloeum Kaneh, Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the NLRP3 Inflammasome.

Inflammatory bowel disease (IBD) comprises a group of idiopathic intestinal disorders, including ulcerative colitis and Crohn's disease, significantly impacting the quality of life for affected individuals. The effective management of these conditions remains a persistent challenge. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a complex molecular structure, regulates the production of pro-inflammatory cytokines such as interleukin-1ß. Abnormal activation of the NLRP3 inflammasome plays a pivotal role in the development of IBD, making it a compelling target for therapeutic intervention. Our research revealed that cinnamaldehyde (CA), a major bioactive compound found in the leaves of Cinnamomum osmophloeum kaneh, demonstrated a remarkable ability to alleviate colitis induced by dextran sulfate sodium (DSS) in a mouse model. This effect was attributed to CA's ability to downregulate the activation of the NLRP3 inflammasome and reduce the expression of pro-inflammatory mediators in the colon. In the mechanism study, we observed that CA inhibited the NLRP3 inflammasome in macrophages, at least partially, by enhancing the autophagic response, without reducing mitochondrial damage. These findings collectively suggest that CA holds significant potential as a therapeutic agent for enhancing the management of IBD, offering a promising avenue for further research and development.

Effect of scutellarin on BV-2 microglial-mediated apoptosis in PC12 cells via JAK2/STAT3 signalling pathway.

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study.

BACKGROUND: Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. OBJECTIVE: To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. METHODS: This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. RESULTS: The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P < .001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. LIMITATIONS: Observational study. CONCLUSION: Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.