Lateral Quadratus Lumborum Block Versus Acupuncture for Postcaesarean Analgesia: A Randomized Clinical Trial.

BACKGROUND: Improved pain control after caesarean section remains a challenging objective. Although both the lateral quadratus lumborum block and acupuncture have been reported to provide superior postoperative analgesia after caesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of lateral quadratus lumborum block and acupuncture following elective caesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton term pregnancies scheduled for caesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or lateral quadratus lumborum block group. Lateral quadratus lumborum block group received bilateral lateral quadratus lumborum block with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy and sham lateral quadratus lumborum block. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 h. Secondary endpoints included pain scores in the first 48 h postoperatively, patient-controlled intravenous analgesia demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (IQR [range]) pain scores at 24 h on movement was similar in patients receiving acupuncture or lateral quadratus lumborum block (3 (2-4) vs. 3 (2-4), respectively; P = 0.40). Patient-controlled intravenous analgesia consumption and pain scores within 48 h postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 h postoperatively (P<0.001), as well as shortened the time to first flatus (P=0.03) and first drinking (P<0.001) compared to lateral quadratus lumborum block. In addition, the median time to mobilization in the lateral quadratus lumborum block group was markedly prolonged compare with acupuncture group (17.0 (15.0-19.0) h vs. 15.3 (13.3-17.0) h, estimated median difference, 1.5; 95%CI, 1-2; P<0.001;). CONCLUSIONS: As a component of multimodal analgesia regimen after caesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to lateral quadratus lumborum block.

Giant cavernous aneurysms occluded by aneurysmal thrombosis, calcification, parent artery occlusion: A case report and review of literature.

BACKGROUND: Patients with giant intracranial aneurysms (GIAs) are at a high risk of rupture, morbidity, and mortality even after surgical or endovascular treatment. We described a case of a spontaneously occluded GIA secondary to gradual growth of the GIA, continuously progressed aneurysmal thrombosis, complete aneurysmal calcification and complete occlusion of the parent artery-the right internal carotid artery (RICA). CASE SUMMARY: A 72-year-old female patient complained of sudden pain in her right eye upon admission to our hospital. She had been diagnosed with a GIA [30 mm (axial) × 38 mm (coronal) × 28 mm (sagittal)] containing an aneurysmal thrombus located in the cavernous sinus segment of RICA diagnosed by magnetic resonance imaging (MRI), enhanced MRI, and magnetic resonance angiography more than 14 years ago. Later, with slow growth of the cavernous carotid GIA, aneurysmal thrombosis progressed continuously, spontaneous occlusion of the RICA, complete aneurysmal calcification, and occlusion of the GIA occurred gradually. She had no history of subarachnoid hemorrhage but missed the chance for endovascular therapy at an early stage. As a result, she was left with severe permanent sequelae from the injuries to the right cranial nerves II, III, IV, V1/V2, and VI. CONCLUSION: The risk of rupture of the cavernous carotid GIAs was relatively low and possibly further be reduced by the stasis flow and spontaneous occlusion of the parent artery internal carotid artery (ICA) induced by the mass effect of the cavernous carotid GIAs and the extremely rare aneurysmal calcification. However, nowadays, it is advisable to recommend early endovascular treatment for the cavernous carotid GIAs to prevent injuries to the surrounding intracranial nerves and occlusion of the ICA, mainly caused by the mass effect of the cavernous carotid GIAs.

Cage-rearranged and cage-intact syntheses of azido-functionalized larger T10 and T12 POSSs.

Herein, we investigate the product type and distribution during the synthesis of azido-functionalized larger polyhedral oligomeric silsesquioxanes (POSSs) using 3-chloropropyl- and chloromethyldimethylsilylethyl-functionalized T8, T10, and T12 POSSs as precursors. Our findings indicate that cage rearrangement occurs for the 3-chloropropyl-functionalized POSS cages with a stability order of T12 > T10 > T8, while the chloromethyldimethylsilylethyl-functionalized POSS cages remain structurally intact after the nucleophilic substitution.

Lifestyle-based subtypes of childhood obesity and their association with cardiometabolic factors: A cluster analysis.

BACKGROUND: Lifestyle factors play an important role in the development and management of childhood obesity and its related cardiometabolic complications. OBJECTIVE/METHODS: We aimed to explore childhood obesity subtypes based on lifestyle factors and examine their association with cardiometabolic health. We included 1550 children with obesity from the National Health and Nutrition Examination Survey. Cluster analysis identified obesity subtypes based on four lifestyle factors (physical activity, diet quality, sedentary time and smoking). Multiple linear regression assessed their association with cardiometabolic factors. RESULTS: Five subtypes of childhood obesity were identified: unhealthy subtype (n = 571; 36.8%), physically active subtype (n = 185; 21.1%), healthy diet subtype (n = 404; 26.1%), smoking subtype (n = 125; 8.1%) and non-sedentary subtype (n = 265; 17.1%). Compared with the unhealthy subtype, the physically active subtype had lower insulin and HOMA-IR levels, and smoking subtype was associated with lower HDL levels. When compared with children with normal weight, all obesity subtypes had worse cardiometabolic profile, except the physically active subtype who had similar DBP, HbA1c and TC levels; smoking subtype who had similar TC levels; and healthy diet and non-sedentary subtypes who had similar DBP levels. CONCLUSION: Children of different lifestyle-based obesity subtypes might have different cardiometabolic risks. Our new classification system might help personalize assessment of childhood obesity.

To analyze the relationship between gut microbiota, metabolites and migraine: a two-sample Mendelian randomization study.

Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related. Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium (n = 18,340) and the Dutch Microbiota Project (n = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found. Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium (nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis, respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified. Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.

HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study.

Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30-1.84, P = 6.87 × 10-7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

Risk Factors for Ocular Surface Irritation Symptoms in Inactive Mild and Moderate-to-Severe Graves' Orbitopathy.

INTRODUCTION: This study aims to analyze risk factors for ocular surface irritation symptoms in patients with non-corneal-damage inactive mild and moderate-to-severe Graves' orbitopathy (GO). METHODS: This retrospective study enrolled 307 patients with non-corneal-damage inactive GO admitted to Sun Yat-sen Memorial Hospital from April 2017 to September 2023. The activity and severity of GO were evaluated using the Clinical Activity Score (CAS) and the European Group on Graves' Orbitopathy (EUGOGO) classification, respectively. Multivariate logistic regression analysis was performed to analyze risk factors for ocular surface irritation symptoms. RESULTS: Among patients with inactive GO, for mild cases, CAS (P < 0.001), upper eyelid lag (P = 0.049), and extraocular muscle involvement (P = 0.019) in the symptomatic group were greater than those in the asymptomatic group, and multivariate logistic regression analysis demonstrated that upper eyelid lag (P = 0.048), CAS 1 (P < 0.001), CAS 2 (P = 0.005), and extraocular muscle involvement (P = 0.029) were risk factors for ocular surface irritation symptoms; for moderate-to-severe cases, CAS (P = 0.004), extraocular muscle involvement (P < 0.001), marginal reflex distance 1 (MRD1) (P = 0.030), and thyroid-stimulating hormone (TSH) (P = 0.034) in the symptomatic group were greater than those in the asymptomatic group, while multivariate logistic regression analysis indicated that extraocular muscle involvement (P = 0.018) and MRD1 (P = 0.012) were risk factors for ocular surface irritation symptoms. CONCLUSION: In non-corneal-damage inactive mild and moderate-to-severe GO, eyelid malposition and periocular muscle inflammation are risk factors for ocular surface irritation symptoms.

Graves' orbitopathy is the most common outward sign of Graves' disease. Patients with inactive Graves' orbitopathy often complain of ocular surface irritation symptoms. This study retrospectively collected clinical data from 307 patients with inactive Graves' orbitopathy and no concurrent corneal damage. The aim was to analyze risk factors for ocular surface irritation symptoms. Upper lid lag, eye movement disorder, and the Clinical Activity Score were found to be risk factors for mild cases. Eye movement disorder and the distance between the upper eyelid margin and corneal reflection point were risk factors for moderate-to-severe cases. To reduce symptoms, it may be helpful to treat inflammation around the eyes and address any eyelid abnormalities.

Case report: The utilization of crizotinib and brentuximab vedotin as a bridge to autologous stem cell transplantation and followed by CD30-directed CAR-T cell therapy in relapsed/refractory ALK+ ALCL.

Background: Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ ALCL) is a rare, mature T-cell non-Hodgkin lymphoma. The prognosis of patients with relapsed or refractory ALCL following first-line chemotherapy is extremely poor. NCCN guidelines recommend intensified chemotherapy with or without ASCT consolidation for r/r ALCL, however, this is not an effective treatment for all ALK+ALCL. Case report: Herein, we report a patient with relapsed/refractory ALK+ ALCL who received crizotinib and brentuximab vedotin as bridging therapy, followed by autologous stem cell transplantation and sequential anti-CD30 CAR T cell therapy. Conclusion: The patient achieved complete remission and long-term disease-free survival of months and continues to be followed up. The combination therapy model in this case may provide guidance for the management of relapsed/refractory ALK+ ALCL, and further prospective trials are needed to confirm its effectiveness.

DNA Methylation and Chromatin Accessibility Impact Subgenome Expression Dominance in the Common Carp (Cyprinus carpio).

DNA methylation and chromatin accessibility play important roles in gene expression, but their function in subgenome expression dominance remains largely unknown. We conducted comprehensive analyses of the transcriptome, DNA methylation, and chromatin accessibility in liver and muscle tissues of allotetraploid common carp, aiming to reveal the function of epigenetic modifications in subgenome expression dominance. A noteworthy overlap in differential expressed genes (DEGs) as well as their functions was observed across the two subgenomes. In the promoter and gene body, the DNA methylation level of the B subgenome was significantly different than that of the A subgenome. Nevertheless, differences in DNA methylation did not align with changes in homoeologous biased expression across liver and muscle tissues. Moreover, the B subgenome exhibited a higher prevalence of open chromatin regions and greater chromatin accessibility, in comparison to the A subgenome. The expression levels of genes located proximally to open chromatin regions were significantly higher than others. Genes with higher chromatin accessibility in the B subgenome exhibited significantly elevated expression levels compared to the A subgenome. Contrastingly, genes without accessibility exhibited similar expression levels in both subgenomes. This study contributes to understanding the regulation of subgenome expression dominance in allotetraploid common carp.

Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Baiheqingjin formula reduces inflammation in mice with asthma by inhibiting the PI3K/AKT/NF-κb signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baiheqingjin Decoction (BHQJ), which consists of 7 traditional Chinese herbs including Baibu (Stemona tuberosa Lour.), Hezi (Terminalia chebula Retz.), Mahuang (Ephedra sinica Stapf.), Ziwan (Aster tataricus L. f.), Dilong (Pheretima), Sangbaipi (Morus alba L.), and Xianhecao (Agrimonia pilosa Ledeb.). BHQJ is commonly used for treating cough asthma, and variant cough-variant asthma as it, is effective in improving asthma symptoms and reducing airway inflammation. AIM OF THE STUDY: To investigate the mechanisms of BHQJ in treating allergic asthma. MATERIALS AND METHODS: We collected information about the components and targets of 6 Chinese medicines (excluding Pheretima) from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Additionally, we obtained genes associated with asthma from six disease databases. To create a protein-protein interaction network, we conducted an intersection analysis using differentially expressed genes derived from RNA transcriptome data. Subsequently, we carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To validate the findings from network pharmacology and transcriptomics, we established an allergic asthma mouse model induced by ovalbumin and conducted in vivo experiments. RESULTS: Using network pharmacology and transcriptomics analyses, we identified the pathways including the PI3K/AKT signaling pathway, and NF-κB signaling pathway. Among these, the involvement of the PI3K/AKT/NF-κB signaling pathway in various pathological processes of asthma, such as airway inflammation, smooth muscle contraction, and excessive mucus production, are well-documented. Histopathological examinations indicated that BHQJ had the potential to mitigate inflammatory cell infiltration and the excessive growth of goblet cells in the airways of asthmatic mice, consequently reducing mucus secretion. Results from Western blot demonstrated that BHQJ could inhibit the activation of the PI3K/AKT/NF-κB pathway at the protein levels. Enzyme-linked immunosorbent assay findings revealed that BHQJ could reduce the production of typical "type 2 asthma" cytokines and immunoglobulin (Ig) E in the blood. These discoveries imply that BHQJ has the potential to reduce the release of inflammatory cytokines and suppress the overactivation of the PI3K/AKT/NF-κB signaling pathway, thus offering a therapeutic approach for asthma. CONCLUSION: Our research offers initial insights into the fundamental mechanisms through which BHQJ treats asthma. This study reveals the potential mechanism of BHQJ in treating asthma, particularly its role in reducing inflammatory cytokines, mucus production, and cell infiltration, as well as inhibiting the expression of PI3K/AKT/P65 phosphorylated protein. These findings indicate the potential of BHQJ in treating asthma. In summary, our study provides preliminary insights into the asthma treatment mechanism of BHQJ and provides guidance for future research.

[Medication rules of Chinese herbal compound prescriptions for treating angina in national patent database based on multiple data mining].

This study explored the medication rules of Chinese herbal compound prescriptions for the treatment of angina based on the Chinese herbal compound patents in the patent database of the China National Intellectual Property Administration. The data of eligible Chinese herbal compound patents for the treatment of angina were collected from the patent database of the China National Intellectual Property Administration from database inception to November 10, 2022, and subjected to data modeling, analysis of main syndromes, medication frequency analysis, cluster analysis, association rule analysis, and data visualization by using Excel 2021, IBM SPSS Statistics 26.0, IBM SPSS Modeler 18.0, Cytoscape 3.9.1, and Rstudio R 4.2.2.2 to explore the medication rules for angina. The study included 636 pieces of patent data for angina that met the inclusion criteria, involving 815 drugs, with a total frequency of 6 586. The most common main syndromes were blood stasis obstructing the heart syndrome(222, 34.91%) and Qi deficiency and blood stasis syndrome(112, 17.61%). The top 10 most frequently used drugs were Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notoginseng Radix et Rhizoma, Astragali Radix, Angelicae Sinensis Radix, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Borneolum Syntheticum, and Corydalis Rhizoma. High-frequency drugs included blood-activating and stasis-resolving drugs(1 197, 18.17%) and deficiency-tonifying drugs(809, 12.28%). Cluster analysis identified eight drug combinations, including five new prescriptions suitable for clinical use and new drug development, and three drug pairs. The core drug combination of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Carthami Flos was identified through the complex co-occurrence network analysis of Chinese medicines. Association rule analysis yielded a total of 17 rules, including 13 drug pairs and 4 tripartite combinations. Common drug pairs included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma(support degree 25.79%, confidence coefficient 69.49%, lift 1.30) and Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma(support degree 22.01%, confidence coefficient 61.95%, lift 1.16). Common tripartite combinations included Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix(support degree 10.85%, confidence coefficient 73.40%, lift 1.37) and Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Notoginseng Radix et Rhizoma(support degree 10.69%, confidence coefficient 79.07%, lift 1.48). The results showed that the underlying pathogenesis of angina involved blood stasis obstructing the heart and Qi deficiency and blood stasis. The overall nature of the disease was characterized as asthenia in origin and sthenia in superficiality. In the prescription formulation, blood-activating and stasis-resolving drugs, such as Salviae Miltiorrhizae Radix et Rhizoma, Chuanxiong Rhizoma, and Carthami Flos were often used to resolve the excess manifestation, which were combined with tonifying drugs such as Astragali Radix, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, and Ginseng Radix et Rhizoma to reinforce the deficiency. The syndrome, pathogenesis, disease nature, and medication were consistent with clinical practice. Additionally, the new compound prescriptions and drug combinations derived from the multiple data mining in this study could provide references and insights for the clinical diagnosis and treatment of angina and the development of new drugs.

Nerve trunk healing and neuroma formation after nerve transection injury.

The nerve trunk healing process of a transected peripheral nerve trunk is composed of angiogenesis, nerve fiber regeneration, and scarring. Nerve trunk healing and neuroma formation probably share identical molecular mediators and similar regulations. At the nerve transection site, angiogenesis is sufficient and necessary for nerve fiber regeneration. Angiogenesis and nerve fiber regeneration reveal a positive correlation in the early time. Scarring and nerve fiber regeneration show a negative correlation in the late phase. We hypothesize that anti-angiogenesis suppresses neuromas. Subsequently, we provide potential protocols to test our hypothesis. Finally, we recommend employing anti-angiogenic small-molecule protein kinase inhibitors to investigate nerve transection injuries.

Insight into the mechanism of DNA methylation and miRNA-mRNA regulatory network in ischemic stroke.

BACKGROUND: Epigenetic changes, such as DNA methylation and miRNA-target gene mechanisms, have recently emerged as key provokers in Ischemic stroke (IS) onset. However, cellular and molecular events harboring these epigenetic alterations are poorly understood. Therefore, the present study aimed to explore the potential biomarkers and therapeutic targets for IS. METHODS: miRNAs, mRNAs and DNA methylation datasets of IS were derived from the GEO database and normalized by PCA sample analysis. Differentially expressed genes (DEGs) were identified, and GO and KEGG enrichment analyses were performed. The overlapped genes were utilized to construct a protein-protein interaction network (PPI). Meanwhile, differentially expressed mRNAs and miRNAs interaction pairs were obtained from the miRDB, TargetScan, miRanda, miRMap and miTarBase databases. We constructed differential miRNA-target gene regulatory networks based on mRNA-miRNA interactions. RESULTS: A total of 27 up-regulated and 15 down-regulated differential miRNAs were identified. Dataset analysis identified 1053 and 132 up-regulated and 1294 and 9068 down-regulated differentially expressed genes in the GSE16561 and GSE140275 datasets, respectively. Moreover, 9301 hypermethylated and 3356 hypomethylated differentially methylated sites were also identified. Moreover, DEGs were enriched in terms related to translation, peptide biosynthesis, gene expression, autophagy, Th1 and Th2 cell differentiation, primary immunodeficiency, oxidative phosphorylation and T cell receptor signaling pathway. MRPS9, MRPL22, MRPL32 and RPS15 were identified as hub genes. Finally, a differential miRNA-target gene regulatory network was constructed. CONCLUSIONS: RPS15, along with hsa-miR-363-3p and hsa-miR-320e have been identified in the differential DNA methylation protein interaction network and miRNA-target gene regulatory network, respectively. These findings strongly posit the differentially expressed miRNAs as potential biomarkers to improve ischemic stroke diagnosis and prognosis.

The Tian-Men-Dong decoction suppresses the tumour-infiltrating G-MDSCs via IL-1ß-mediated signalling in lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Tian-Men-Dong decoction (TD) has been able to effectively treat lung cancer in China for thousands of years. TD improves the quality of life in lung cancer patients by promoting nourishment of yin and reducing dryness, clearing the lung and removing toxins. Pharmacological studies show that TD contains active antitumour ingredients, but its underlying mechanism remains unknown. AIM OF THE STUDY: This study aims at exploring potential mechanisms of TD in the treatment of lung cancer by regulating granulocytic-myeloid-derived suppressor cells (G-MDSCs). MATERIALS AND METHODS: An orthotopic lung cancer mouse model was generated by intrapulmonary injection with LLC-luciferase cells in immunocompetent C57BL/6 mice or immunodeficient nude mice. TD/saline was orally administered once to the model mice daily for 4 weeks. Live imaging was conducted to monitor tumour growth. Immune profiles were detected by flow cytometry. H&E and ELISA were applied to test the cytotoxicity of the TD treatment. RT-qPCR and western blotting were performed to detect apoptosis-related proteins in G-MDSCs. A neutralizing antibody (anti-Ly6G) was utilized to exhaust the G-MDSCs via intraperitoneal injection. G-MDSCs were adoptively transferred from wild-type tumour-bearing mice. Immunofluorescence, TUNEL and Annexin V/PI staining were conducted to analyse apoptosis-related markers. A coculture assay of purified MDSCs and T cells labelled with CFSE was performed to test the immunosuppressive activity of MDSCs. The presence of TD/IL-1ß/TD + IL-1ß in purified G-MDSCs cocultured with the LLC system was used for ex vivo experiments to detect IL-1ß-mediated apoptosis of G-MDSCs. RESULTS: TD prolonged the survival of immune competent C57BL/6 mice in an orthotopic lung cancer model, but did not have the same effect in immunodeficient nude mice, indicating that its antitumour properties of TD are exerted by regulating immunity. TD induced G-MDSC apoptosis via the IL-1ß-mediated NF-κB signalling cascade leading to effectively weaken the immunosuppressive activity of G-MDSCs and promote CD8+ T-cell infiltration, which was supported by both the depletion and adoptive transfer of G-MDSCs assays. In addition, TD also showed minimal cytotoxicity both in vivo and in vitro. CONCLUSION: This study reveals for the first time that TD, a classic TCM prescription, is able to regulate G-MDSC activity and trigger its apoptosis via the IL-1ß-mediated NF-κB signalling pathway, reshaping the tumour microenvironment and demonstrating antitumour effects. These findings provide a scientific foundation the clinical treatment of lung cancer with TD.

Porous nitrogen-doped reduced graphene oxide-supported CuO@Cu2O hybrid electrodes for highly sensitive enzyme-free glucose biosensor.

Constructing high-performance enzyme-free biosensors for detecting glucose is essential to preliminary diabetes diagnosis. Here, copper oxide nanoparticles (CuO@Cu2O NPs) were anchored in porous nitrogen-doped reduced graphene oxide (PNrGO) to construct CuO@Cu2O/PNrGO/GCE hybrid electrode for sensitive detection of glucose. Benefiting from the remarkable synergistic effects between the multiple high activation sites of CuO@Cu2O NPs and the dramatic properties of PNrGO with excellent conductivity and large surface area with many accessible pores, the hybrid electrode possesses outstanding glucose sensing performance that is far superior to those of pristine CuO@Cu2O electrode. The as-fabricated enzyme-free glucose biosensor displays prominent glucose sensitivity of 2,906.07 µA mM-1 cm-2, extremely low limit of detection of 0.13 µM, and wide linear detection of 3 µM-6.772 mM. In addition, excellent reproducibility, favorable long-term stability, and distinguished selectivity are obtained in the glucose detection. Importantly, this study provides promising results for continuous improvement of non-enzyme sensing applications.

Alloying Matters for Ordering: Synthesis of Highly Ordered PtCo Intermetallic Catalysts for Fuel Cells.

Porous carbon-supported atomically ordered intermetallic compounds (IMCs) are promising electrocatalysts in boosting oxygen reduction reaction (ORR) for fuel cell applications. However, the formation mechanism of IMC structures under high temperatures is poorly understood, which hampers the synthesis of highly ordered IMC catalysts with promoted ORR performance. Here, we employ high-temperature X-ray diffraction and energy-dispersive spectroscopic elemental mapping techniques to study the formation process of IMCs, by taking PtCo for example, in an industry-relevant impregnation synthesis. We find that high-temperature annealing is crucial in promoting the formation of alloy particles with a stoichiometric Co/Pt ratio, which in turn is the precondition for transforming the disordered alloys to ordered intermetallic structures at a relatively low temperature. Based on the findings, we accordingly synthesize highly ordered L10-type PtCo catalysts with a remarkable ORR performance in fuel cells.

China's adaptive response to climate change through air-conditioning.

Studies have shown that the soaring demand for air conditioners in recent years is closely related to the worsening global warming; however, little evidence has been provided for China. This study uses weekly data of 343 Chinese cities to investigate how air conditioner sales respond to climate variability. We detected a U-shaped relationship between air-conditioning and temperature. An additional day with average temperature above 30°C increases weekly sales by 16.2%. Heterogeneity analysis shows that the adoption of air-conditioning is different for south and north China. By combining our estimates with shared socioeconomic pathway scenarios, we project China's mid-century air conditioner sales and the resulting electricity demand. Under the fossil-fueled development scenario, air conditioner sales in the Pearl River Delta would rise by 71% (65.7%-87.6%) in summer. On average, the per capita electricity demand for air-conditioning will surge by 28% (23.2%-35.4%) in China by mid-century.

A study of clinical anatomy of the safe zone for the volar approach for wrist arthroscopy.

OBJECTIVE: The current study was to perform an anatomical observation of the volar approach for wrist arthroscopy and to establish the safe zone for this approach. METHODS: Eight preserved specimens and 2 fresh specimens were used to simulate the medial-to-lateral operation and to mark the volar approach. Based on anatomical measurements of the volar approach, the closest distances from the 1/2, 6R, 6U, VR, VR' and VU approaches to the adjacent important structures were established. RESULTS: The closest distance from the 1/2 approach to the superficial branch of the radial nerve was 2.4±1.5mm. The closest distances from the 6U and 6R approaches to the dorsal carpal branch of the ulnar nerve were 16.2±1.3mm and 9.0±2.4mm, respectively. The closest distances from the VR and VR' approaches to the palmar cutaneous branch of the median nerve were 6.7±1.1mm and 2.8±0.9mm, respectively; the closest distances to the radial artery were 6.3±4.0mm and 10.0±3.4mm, respectively. Moreover, both of the two approaches passed through the base of the flexor carpi radialis tendon. The closest distance from the VU approach to the ulnar artery and flexor digitorum profundus tendon were 3.3±1.4mm and 0.3±2.5mm, respectively. CONCLUSIONS: In conclusion, a safe zone could be located for the establishment of the volar approach for wrist arthroscopy. LEVEL OF EVIDENCE: III; retrospective study with no control group.

Lipopolysaccharide and lipoteichoic acid regulate the PI3K/AKT pathway through osteopontin/integrin ß3 to promote malignant progression of non-small cell lung cancer.

Background: Lung cancer (LC) is a malignancy with one of the highest mortality rates. Respiratory microbiota is considered to play a key role in the development of LC, but the molecular mechanisms are rarely studied. Methods: We used lipopolysaccharide (LPS) and lipoteichoic acid (LTA) to study human lung cancer cell lines PC9 and H1299. The gene expression of CXC chemokine ligand (CXCL)1/6, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell-Counting Kit 8 (CCK-8) was used to analyze cell proliferation. Transwell assays were performed to analyze cell migration ability. Flow cytometry was used to observe cell apoptosis. Western blot and qRT-PCR were used to analyze the expression of secreted phosphoprotein 1 (SPP1), toll-like receptor (TLR)-2/4, and NLR family pyrin domain containing 3 (NLRP3) to determine the mechanism of LPS + LTA. We evaluated the effect of LPS + LTA on cisplatin sensibility by analyzing cell proliferation, apoptosis, and caspase-3/9 expression levels. We observed the proliferation activity, apoptosis, and migration ability of cells in which SPP1 had been transfected small interfering (si) negative control (NC) and integrin ß3 siRNA. Then the mRNA expression level and protein expression of PI3K, AKT, and ERK were analyzed. Finally, the nude mouse tumor transplantation model was conducted to verify. Results: We studied that in two cell lines, the expression level of inflammatory factors in LPS+LTA group was significantly higher than that in single treatment group (P<0.001). We explored LPS + LTA combined treatment group significantly increased the expression of NLRP3 and genes and proteins. LPS + LTA + Cisplatin group could significantly reduce the inhibitory effect of LPS on cell proliferation (P<0.001), reduce the apoptosis rate (P<0.001) and significantly reduce the expression levels of caspase-3/9 (P<0.001) compared with Cisplatin group. Finally, we verified that LPS and LTA could increase osteopontin (OPN)/integrin ß3 expression and activate the PI3K/AKT pathway to promote malignant progression of LC in vitro studies. Conclusions: This study provides a theoretical basis for further exploration of the influence of lung microbiota on NSCLC and the optimization of LC treatment in the future.