[A prospective comparative study on effectiveness of single versus continuous adductor canal block combined with local infiltration anesthesia in unicompartmental knee arthroplasty].

Objective: To compare the early analgesic effects and the impact on knee joint function recovery after unicompartmental knee arthroplasty (UKA) between single adductor canal block (SACB) and continuous adductor canal block (CACB) combined with local infiltration anesthesia (LIA) using a prospective study. Methods: The patients with knee osteoarthritis admitted between April 2022 and December 2023 were enrolled as a subject. Among them, 60 patients met the selection criteria and were enrolled in the study. They were randomly assigned to the SACB group or CACB group in a ratio of 1:1 using a random number table method. There was no significant difference between the two groups ( P>0.05) in terms of age, gender, height, body mass, body mass index, affected side, and preoperative resting visual analogue scale (VAS) score and active VAS score, Oxford knee score (OKS), and American Hospital of Special Surgery (HSS) score. All patients received multimodal analgesia management using LIA combined with SACB or CACB. The operation time, pain related indicators (resting and activity VAS scores, number and timing of breakthrough pain, opioid consumption), joint function related indicators (quadriceps muscle strength, knee range of motion, OKS score, and HSS score), as well as postoperative block complications and adverse events were recorded and compared between the two groups. Results: There was no significant difference in the operation time between the two groups ( P<0.05). All patients in the two groups were followed up with a follow-up time of (9.70±4.93) months in the SACB group and (12.23±5.05) months in the CACB group, and the difference was not significant ( P>0.05). The CACB group had a significant lower resting VAS score at 24 hours after operation compared to the SACB group ( P<0.05). There was no significant difference in resting and active VAS scores between the two groups at other time points ( P>0.05). The CACB group had a significantly lower incidence of breakthrough pain compared to the SACB group [9 cases (30.00%) vs. 17 cases (56.67%); P<0.05). However, there was no significant difference in the timing of breakthrough pain occurrence and opioid consumption between the two groups ( P>0.05). Four cases in the SACB group and 7 cases in the CACB group experienced adverse events, with no significant difference in the incidence of adverse events between the two groups ( P>0.05). The CACB group had significantly better knee joint mobility than the SACB group at 1 and 2 days after operation ( P<0.05). There was no significant difference between the two groups in knee joint mobility on 0 day after operation and quadriceps muscle strength and OKS and HSS scores at different time points ( P>0.05). Conclusion: In UKA, the analgesic effects and knee joint function recovery are similar when compared between LIA combined with SACB and LIA combined with CACB. However, SACB is simpler to perform and can avoid adverse events such as catheter displacement and dislocation. Therefore, SACB may be a better choice.

Fluid-Dynamic Culture of Tumour and Immune Cells for More Predictive Infiltration Studies and Immunotherapy Drug Screening.

Immunotherapies represent one of the current most promising challenges in cancer treatment. They are based on the boost of natural immune responses, aimed at cancer eradication. However, the success of immunotherapeutic approaches strictly depends on the interaction between immune cells and cancer cells. Preclinical drug tests currently available are poor in fully predicting the actual safety and efficacy of immunotherapeutic treatments under development. Indeed, conventional 2D cell culture underrepresents the complexity of the tumour microenvironment, while in vivo animal models lack in mimicking the human immune cell responses. In this context, predictability, reliability, and complete immune compatibility still represent challenges to overcome. For this aim, novel 3D, fully humanized in vitro cancer tissue models have been recently optimized by adopting emerging technologies, such as organ-on-chips (OOC) and 3D cancer cell-laden hydrogels. In particular, a novel multi-in vitro organ (MIVO) OOC platform has been recently adopted to culture 3D clinically relevant size cancer tissues under proper physiological culture conditions to investigate anti-cancer treatments and immune-tumour cell crosstalk.The proposed immune-tumour OOC-based model offers a potential tool for accurately modelling human immune-related diseases and effectively assessing immunotherapy efficacy, finally offering promising experimental approaches for personalized medicine.

Integrative approach using network pharmacology, bioinformatics, and experimental methods to explore the mechanism of cantharidin in treating colorectal cancer.

Cantharidin, a terpenoid produced by blister beetles, has been used in traditional Chinese medicine to treat various ailments and cancers. However, its biological activity, impact, and anticancer mechanisms remain unclear. The Cantharidin chemical gene connections were identified using various databases. The GSE21815 dataset was used to collect the gene expression information. Differential gene analysis and gene ontology analyses were performed. Gene set enrichment analysis was used to assess the activation of disease pathways. Weighted gene co-expression network analysis and differential analysis were used to identify illness-associated genes, examine differential genes, and discover therapeutic targets via protein-protein interactions. MCODE analysis of major subgroup networks was used to identify critical genes influenced by Cantharidin, examine variations in the expression of key clustered genes in colorectal cancer vs. control samples, and describe the subject operators. Single-cell GSE188711 dataset was preprocessed to investigate Cantharidin's therapeutic targets and signaling pathways in colorectal cancer. Single-cell RNA sequencing was utilized to identify 22 cell clusters and marker genes for two different cell types in each cluster. The effects of different Cantharidin concentrations on colorectal cancer cells were studied in vitro. One hundred and ninety-seven Cantharidin-associated target genes and 480 critical genes implicated in the development of the illness were identified. Cantharidin significantly inhibited the proliferation and migration of HCT116 cells and promoted apoptosis at certain concentrations. Patients on current therapy develop inherent and acquired resistance. Our study suggests that Cantharidin may play an anti-CRC role by modulating immune function.

Analgesic efficacy of local infiltration anaesthesia versus femoral nerve block in alleviating postoperative wound pain following total knee arthroplasty: A systematic review and meta-analysis.

Total knee arthroplasty (TKA) often involves significant postoperative pain, necessitating effective analgesia. This meta-analysis compares the analgesic efficacy of local infiltration anaesthesia (LIA) and femoral nerve block (FNB) in managing postoperative wound pain following TKA. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was structured around the PICO framework, assessing studies that directly compared LIA and FNB in TKA patients. A comprehensive search across PubMed, Embase, Web of Science and the Cochrane Library was conducted without time restrictions. Studies were included based on specific criteria such as participant demographics, study design and outcomes like pain scores and opioid consumption. Quality assessment utilized the Cochrane Collaboration's risk of bias tool. The statistical approach was determined based on heterogeneity, with the choice of fixed- or random-effects models guided by the I2 statistic. Sensitivity analysis and evaluation of publication bias using funnel plots and Egger's linear regression test were also conducted. From an initial pool of 1275 articles, eight studies met the inclusion criteria. These studies conducted in various countries from 2007 to 2016. The meta-analysis showed no significant difference in resting and movement-related Visual Analogue Scale scores post-TKA between the LIA and FNB groups. However, LIA was associated with significantly lower opioid consumption. The quality assessment revealed a low risk of bias in most studies, and the sensitivity analysis confirmed the stability of these findings. There was no significant publication bias detected. Both LIA and FNB are effective in controlling postoperative pain in TKA patients, but LIA offers the advantage of lower opioid consumption. Its simplicity, cost-effectiveness and opioid-sparing nature make LIA the recommended choice for postoperative analgesia in knee replacement surgeries.

Network Pharmacology and Bioinformatics Analyses Identify the Core Genes and Pyroptosis-Related Mechanisms of Nardostachys Chinensis for Atrial Fibrillation.

BACKGROUND: Nardostachys chinensis is an herbal medicine widely used in the treatment of atrial fibrillation (AF), but the mechanism is unclear. OBJECTIVE: To explore the molecular mechanism of N. chinensis against AF. METHODS: The TCMSP was used to screen the active N. chinensis compounds and their targets. Differentially expressed genes (DEGs) for AF were identified using open-access databases. Using Venn diagrams, the cross-targets of N. chinensis, pyroptosis, and AF were obtained. The genes underwent molecular docking as well as gene set enrichment analysis (GSEA). A nomogram based on candidate genes was constructed and evaluated with the clinical impact curve. After that, the immune infiltration of the dataset was analyzed by single sample GSEA (ssGSEA). Finally, microRNAs (miRNAs) and transcription factors (TFs) were predicted based on candidate genes. RESULTS: Tumor necrosis factor (TNF) and caspase-8 (CASP8) were obtained as candidate genes by taking the intersection of DEGs, targets of N. chinensis, and pyroptosis-related genes. Tolllike receptor (TLR) and peroxisome proliferator-activated receptor (PPAR) signaling pathways were linked to candidate genes. Additionally, immune cell infiltration analysis revealed that CASP8 was associated with natural killer T cells, natural killer cells, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSC), macrophages, CD8 T cells, and CD4 T cells. Finally, miR-34a-5p and several TFs were found to regulate the expression of CASP8 and TNF. CONCLUSION: CASP8 and TNF are potential targets of N. chinensis intervention in pyroptosisrelated AF, and the TLR/NLRP3 signaling pathway may be associated with this process.

[Evaluation of early effectiveness of local infiltration anesthesia with compound betamethasone in total knee arthroplasty].

Objective: To evaluate the early effectiveness of local infiltration anesthesia (LIA) with compound betamethasone in total knee arthroplasty (TKA). Methods: The clinical data of 102 patients with knee osteoarthritis who were treated by TKA and met the selection criteria between May 2022 and March 2023 were retrospectively analyzed. They were divided into control group and study group according to whether LIA preparation was added with compound betamethasone, with 51 cases in each group. There was no significant difference of baseline data, such as age, gender, body mass index, operative side, preoperative range of motion (ROM), Knee Society Score (KSS), white blood cell (WBC), and hematocrit between the two groups ( P>0.05). The intraoperative total blood loss and hidden blood loss were recorded, and WBC was recorded on the 1st, 2nd, and 3rd days after operation. Pain was assessed by visual analogue scale (VAS) score on the 1st, 2nd, and 3rd days after operation and morphine intake milligrames equivalent within 48 hours after operation. Passive ROM, maximum extension and flexion angles of knee joint were measured on the 3rd day after operation; the early postoperative complications were recorded. Results: There was no significant difference in total blood loss and hidden blood loss between the two groups ( P>0.05). The postoperative pain levels in both groups were relatively mild, and there was no significant difference in VAS scores in the first 3 days after operation and in morphine intake milligrams equivalent within 48 hours after operation between the two groups ( P>0.05). The WBC in the first 3 days after operation was significantly improved in both groups ( P<0.05). The WBC in the study group was significantly higher than that in the control group on the 1st and 2nd days after operation ( P<0.05), but there was no significant difference between the two groups on the 3rd day after operation ( P>0.05). On the 3rd day after operation, the maximum extension angle of knee joint in the study group was smaller than that in the control group, while the maximum flexion angle and passive ROM of knee joint in the study group were larger than those in the control group, and the differences were significant ( P<0.05). There were 6 cases of fever and 17 cases of deep venous thrombosis in the control group, and 1 case and 14 cases in the study group, respectively. There was no poor wound healing and periprosthetic joint infection in the two groups, and there was no significant difference in the incidence of complications between the two groups ( P>0.05). Conclusion: The application of compound betamethasone in LIA during TKA is a safe and optimal strategy to promote the early postoperative rehabilitation of patients.

Bioinformatics and Network Pharmacology Explore the Role of Immune Cells in the Occurrence of Anti-Vascular Endothelial Growth Factor (VEGF) Resistance in Patients with Neovascular Age-Related Macular Degeneration(nAMD) and the Application of Complementary Medicine Treatment.

PURPOSE: This study explores the immune cells' role in anti-VEGF resistance in nAMD patients, and the potential of Zi-Yin-Jiang-Huo-Tang (ZYJHT), a Traditional Chinese Medicine formula, as complementary therapy. METHODS: Aqueous humor proteomics data from 10 nAMD patients with anti-VEGF resistance and 10 nAMD patients without anti-VEGF resistance were analyzed, investigating immune cells's role in anti-VEGF resistance and its underlying mechanism. Network pharmacology methods are employed to analyze the active ingredients in ZYJHT that contribute to therapeutic effects and their mechanisms. Real-time PCR (polymerase chain reaction) was used to detect changes in the expression of SOD1 (superoxide dismutase 1) after treatment with compounds targeting SOD1 in ARPE-19 cells. RESULTS: nAMD patients with anti-VEGF resistance showed enhancement of biological processes linked to the positive regulation of immune function, along with decreased cellular resistance to oxidative stress. Infiltration of B cells memory, plasma cells, CD8+and γδ-T cells were higher in nAMD patients with anti-VEGF resistance. SOD1 was identified as a hub gene in the occurrence of anti-VEGF resistance and a core therapeutic target of ZYJHT, negatively correlated with B and T cell infiltration. Compounds diosgenin, naringenin, and liquiritin in ZYJHT can bind to SOD1 and upregulating SOD1 expression in ARPE-19 cells.

Zhoushi Qi Ling decoction inhibits the progression of castration-resistant prostate cancer in vivo by regulating macrophage infiltration via IL6-STAT3 signaling.

Background and aim: Prostate cancer is a leading malignant tumor in men, associated with a high rate of mortality. Androgen deprivation therapy is commonly used to treat prostate cancer, which contributes to the progression of castration-resistant prostate cancer (CRPC). The current therapy has a low survival rate in patients with CRPC. Our study aims to develop a novel effective approach for CRPC treatment and improve survival benefits. Experimental procedure: CRPC cell line PC-3-Luc expressing luciferase and the CRPC cell line PC-3-IL6-Luc stably overexpressing IL-6 were used to establish the xenograft tumor mouse model. The tumor was monitored weekly using Bioluminescence imaging. Infiltrated macrophages were quantified by fluorescence-activated cell sorting using flow cytometry. IL6 mRNA level was determined using quantitative real-time PCR. The protein levels of total STAT3 and phosphorylated STAT3 were determined using Western blot. Results and conclusion: Zhoushi Qi Ling decoction (ZQD) treatment significantly reduced PC3 the xenograft tumor progression and the number of infiltrated macrophages when compared with saline treatment. IL6 mRNA level was remarkedly suppressed by ZQD treatment. Notably, the protein level of phosphorylated STAT3 was significantly decreased in PC3 the xenograft tumor treated with ZQD compared to saline treatment. Our findings demonstrated that ZQD treatment significantly reduced the progression of prostate cancer, evidenced by the reduced population of infiltrated macrophages and the inhibition of the IL6/STAT3 pathway.

Efficacy of the TuttleNumbNow Intraosseous Method for Pulpal Anesthesia in the Mandibular First Molar: A Prospective, Randomized, Crossover Study.

INTRODUCTION: Previous studies on intraosseous (IO) anesthesia as a primary injection have shown high success rates. The TuttleNumbNow (TNN; Orem, UT) is a new primary IO injection technique that has not been scientifically evaluated. Therefore, the purpose of this prospective randomized, crossover study was to evaluate the anesthetic efficacy of the TNN IO technique using the Septoject Evolution needle (Septodont, Saint-Maur-des-Fosses, France) compared with buccal infiltration for pulpal anesthesia in mandibular first molars. METHODS: One hundred four healthy subjects were randomly assigned to 2 treatment groups separated by at least 2 weeks. One set of injections consisted of buccal infiltration of the mandibular first molar using 1.8 mL 4% articaine with 1:100,000 epinephrine followed by a mock TNN injection distal to the mandibular first molar. The other set of injections was a mock buccal infiltration of the mandibular first molar followed by a TNN injection of 1.8 mL 4% articaine with 1:100,000 epinephrine distal to the mandibular first molar. Statistical analyses were performed. RESULTS: For the mandibular first molar, which had a 42% anesthetic success rate (highest 80 reading) with buccal infiltration compared with 49% with the TNN, no statistically significant difference in success was observed (P = .2115). CONCLUSIONS: The TNN technique has been advocated as an IO injection. However, the inability to deliver anesthetic solution to the cancellous bone resulted in an anesthetic success rate of 49%. The success was statistically similar to a buccal infiltration (42%) and would not provide adequate pulpal anesthesia as a primary injection.

L-lysine supplementation attenuates experimental autoimmune hepatitis in a chronic murine model.

The incidence of autoimmune hepatitis (AIH) has increased significantly worldwide. The present study aims to explore the protective effect of L-lysine supplementation against AIH and to investigate its potential underlying mechanisms. A chronic experimental AIH mouse model was established by repeated tail vein injection of human cytochrome P450 2D6 (CYP2D6) plasmid. Starting from day 14 of the modeling, mice in the CYP2D6-AIH +L-lysine group were given 200 µl of purified water containing 10 mg/kg L-lysine by gavage until day27, once a day, and mice in the healthy control group and model group were given an equal volume of purified water by gavage. Our results showed that L-lysine supplementation partially reversed the liver injury mediated by CYP2D6 overexpression. These effects were consistent with the restraining impacts of L-lysine supplementation on decreasing pro-inflammatory cytokines expression level and CD4+ and CD8+ T lymphocytes infiltration, as well as curbing hepatic oxidative stress. Furthermore, L-lysine supplement relieved liver fibrosis in the context of AIH. In conclusion, L-lysine supplementation attenuates CYP2D6-induced immune liver injury in mice, which may serve as a novel nutrition support approach for AIH.

Efficient rural sewage treatment with manganese sand-pyrite soil infiltration systems: Performance, mechanisms, and emissions reduction.

The application of soil infiltration systems (SISs) in rural domestic sewage (RDS) is limited due to suboptimal denitrification resulting from factors such as low C/N (<5). This study introduced filler-enhanced SISs and investigated parameter impacts on pollutant removal efficiency and greenhouse gas (GHG) emission reduction. The results showed that Mn sand-pyrite SISs, with hydraulic load ratios of 0.003 m3/m2·h and dry-wet ratios of 3:1, achieved excellent removal efficiency of COD (92.7 %), NH4+-N (95.8 %), and TN (76.4 %). Moreover, N2O and CH4 emission flux were 0.046 and 0.019 mg/m2·d, respectively. X-ray photoelectron spectroscopy showed that the relative concentrations of Mn(Ⅱ) in Mn sand and Fe(Ⅲ) and SO42- in pyrite increased after the experiment. High-throughput sequencing indicated that denitrification was mainly performed by Thiobacillus. This study demonstrated that RDS treatment using the enhanced SIS resulted in efficient denitrification and GHG reduction.

Constructing a screening model to obtain the functional herbs for the treatment of active ulcerative colitis based on herb-compound-target network and immuno-infiltration analysis.

The therapeutic effect of most traditional Chinese medicines (TCM) on ulcerative colitis is unclear, The objective of this study was to develop a core herbal screening model aimed at facilitating the transition from active ulcerative colitis (UC) to inactive. We obtained the gene expression dataset GSE75214 for UC from the GEO database and analysed the differentially expressed genes (DEGs) between active and inactive groups. Gene modules associated with the active group were screened using WGCNA, and immune-related genes (IRGs) were obtained from the ImmPort database. The TCMSP database was utilized to acquire the herb-molecule-target network and identify the herb-related targets (HRT). We performed intersection operations on HRTs, DEGs, IRGs, and module genes to identify candidate genes and conducted enrichment analyses. Subsequently, three machine learning algorithms (SVM-REF analysis, Random Forest analysis, and LASSO regression analysis) were employed to refine the hubgene from the candidate genes. Based on the hub genes identified in this study, we conducted compound and herb matching and further screened herbs related to abdominal pain and blood in stool using the Symmap database.Besides, the stability between molecules and targets were assessed using molecular docking and molecular dynamic simulation methods. An intersection operation was performed on HRT, DEGs, IRGs, and module genes, leading to the identification of 23 candidate genes. Utilizing three algorithms (RandomForest, SVM-REF, and LASSO) for analyzing the candidate genes and identifying the intersection, we identified five core targets (CXCL2, DUOX2, LYZ, MMP9, and AGT) and 243 associated herbs. Hedysarum Multijugum Maxim. (Huangqi), Sophorae Flavescentis Radix (Kushen), Cotyledon Fimbriata Turcz. (Wasong), and Granati Pericarpium (Shiliupi) were found to be capable of relieving abdominal pain and hematochezia during active UC. Molecular docking demonstrated that the compounds of the four aforementioned herbs showed positive docking activity with their core targets. The results of molecular dynamic simulations indicated that well-docked active molecules had a more stable structure when bound to their target complexes. The study has shed light on the potential of TCMs in treating active UC from an immunomodulatory perspective, consequently, 5 core targets and 4 key herbs has been identified. These findings can provide a theoretical basis for subsequent management and treatment of active UC with TCM, as well as offer original ideas for further research and development of innovative drugs for alleviating UC.

Periarticular Infiltration Compared to Single Femoral Nerve Block in Total Knee Arthroplasty: A Prospective Randomized Study / Infiltração periarticular comparada ao bloqueio do nervo femoral único na artroplastia total de joelho: Um estudo prospectivo randomizado

Abstract Objective To compare patients undergoing total knee arthroplasty (TKA) under spinal anesthesia and single femoral nerve block (FNB) with subjects undergoing TKA under spinal anesthesia and periarticular infiltration (PAI). Materials and Methods A total of 100 patients undergoing primary TKA were randomized into two groups. Group 1 included patients undergoing surgery under FNB associated with spinal anesthesia, while group 2 included patients undergoing TKA under IPA and spinal anesthesia. The assessment of these subjects in the early postoperative period included pain, active flexion, active extension, elevation of the extended limb, and morphine use. Results There was no significant difference in the types of analgesia concerning pain, the elevation of the extended limb, and morphine use. Active flexion and extension were better in the PAI group (p = 0.04 and p = 0.02 respectively). Conclusion We conclude that the techniques are similar regarding pain control, limb elevation, and morphine use. The use of IPA provided better active flexion and extension during the hospital stay compared to single FNB in patients undergoing TKA.

Resumo Objetivo Avaliar pacientes submetidos a artroplastia total do joelho (ATJ) sob raquianestesia e bloqueio do nervo femoral (BNF) único e comparar com pacientes que submetidos a ATJ sob raquianestesia e infiltração periarticular (IPA). Materiais e Métodos Um total de 100 pacientes submetidos a ATJ foram randomizados em dois grupos. O grupo 1 incluiu pacientes submetidos a ATJ sob BNF associado à raquianestesia, ao passo que o grupo 2 incluiu pacientes submetidos a ATJ sob IPA associada à raquianestesia. Os indivíduos foram avaliados no pós-operatório precoce quanto à dor, à flexão e extensão ativas, à elevação do membro estendido e ao uso de morfina. Resultados Não se observou diferença significativa associada ao tipo de analgesia em relação à dor, à elevação do membro em extensão e ao consumo de morfina. Houve melhor flexão e extensão ativas no grupo que recebeu IPA (p = 0,04 e p = 0,02, respectivamente). Conclusão Concluímos que as técnicas utilizadas são semelhantes quanto ao controle da dor, à elevação de membro e ao uso de morfina. O uso de IPA proporcionou uma melhor flexão e extensão ativas durante o período de internação hospitalar comparado ao uso de BNF único em pacientes submetidos a ATJ.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration.

OBJECTIVE: Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC). METHODS: An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method. RESULTS: We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38. CONCLUSION: Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Reliability of the electric pulp tester as an indicator of pulpal anesthesia in primary maxillary posterior teeth to assess the need for supplemental injections: An observational clinical study.

Background: The primary maxillary molars occasionally remain sensitive during operative procedures even post the buccal supraperiosteal injection. This could be due to the widely flared palatal roots receiving accessory innervation from the palatal nerves. Identifying inadequate anesthesia upfront using the electric pulp test (EPT) would give vital information to the clinician on the need of a supplemental palatal injection. Aim: The aim of this study was to assess and evaluate the reliability of the EPT as an indicator of pulpal anesthesia in primary maxillary molars. Methodology: Fifty one primary maxillary molars were subjected to the EPT following a buccal supraperiosteal injection. During the operative procedure, the " Face Legs Activity Cry Consolability" (FLACC) scores were recorded. The outcome of the EPT was correlated with the results of the FLACC score using Pearson's Chi-square test.Results: The EPT results were correlated to the FLACC scores. Five out of the 10 primary maxillary second molars which responded to the EPT scored 0 on the FLACC scale. The remaining 5 teeth scored 1 on the FLACC scale. The P value was 0.056 which was not statistically significant. This infers that the EPT is not a reliable tool to assess the adequacy of pulpal anesthesia in primary maxillary second molars. Conclusion: From the results of the present study, it can be concluded that the EPT is not a reliable tool to be used as an indicator of pulpal anesthesia in primary maxillary molars.

Success of Pulpal Anesthesia Following Buccal Infiltration of the Maxillary First Molar With 1.8 mL and 3.6 mL of 4% Articaine With 1:100,000 Epinephrine: A Prospective, Randomized Crossover Study.

OBJECTIVE: The purpose of this prospective, randomized crossover study was to compare the peak incidence of success, onset, and incidence over time of pulpal anesthesia in maxillary first molars following a buccal infiltration of 1.8 mL or 3.6 mL of 4% articaine with 1:100 000 epinephrine. METHODS: A total of 118 adults received 1.8 mL or 3.6 mL of 4% articaine with 1:100 000 epinephrine via buccal infiltration of the maxillary first molar at 2 separate appointments. Electric pulp testing (EPT) of the maxillary first molar was performed over 68 minutes. RESULTS: There was no significant difference in the peak incidence of anesthetic success (85% and 92%, respectively) in the maxillary first molar between 1.8 mL and 3.6 mL. The difference in onset times (4.5 min for 1.8 mL vs 4.4 min for 3.6 mL) was not statistically significant. However, the 3.6-mL volume did produce a significantly higher incidence of pulpal anesthesia from minutes 48 to 68 compared with the 1.8-mL volume. CONCLUSION: There was no significant difference in peak incidence or onset of pulpal anesthesia in the maxillary first molar between 1.8 mL and 3.6 mL of articaine with epinephrine. The incidence of pulpal anesthesia was significantly higher with 3.6 mL of articaine at 48 minutes and beyond, but neither volume provided complete pulpal anesthesia for all subjects that lasted at least 60 minutes.

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles.

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

Euphorbia factor L1 suppresses breast cancer liver metastasis via DDR1-mediated immune infiltration.

Euphorbia factor L1 (EFL1), a lathyrane-type diterpenoid from the medicinal herb Euphorbia lathyris L., has been documented to possess various pharmacologic actives. However, the function of EFL1 on breast cancer is not clear. In this study, we explored the effect and mechanism of EFL1 on breast cancer liver metastasis. Female BALB/c mice were subjected to breast cancer-surgical hepatic implantation (SHI) to establish breast cancer liver metastasis model in vivo. At 10 days post-surgery, mice were administrated with EFL1 once daily for a total of 2 weeks. Serum AST and ALT activities, abdominal circumference, peritoneal fluid, tumor weight and volume were determined to assess liver and mesenteric re-metastasis of breast cancer. H&E staining was used to observe morphology changes in tumor, liver and small intestine tissues. ELISA was applied to observe inflammatory levels. Tumor DDR1 expression and immune infiltration were determined using western blotting, immunohistochemistry and flow cytometer methods. Our results showed that EFL1 administration improved liver function (AST and ALT activities), ascites, liver metastasis and mesenteric re-metastasis in SHI mice. Also, SHI-induced inflammatory cell infiltration and IL-1ß, IL-6, TNF-α generation in ascites were decreased by EFL1 treatment. Mechanism study revealed that EFL1 intervention enhanced the ratios of CD4+ and CD8+ and CD49b+(NK) T lymphocytes and decreased Treg cells through downregulating DDR1 in the tumor of SHI mice. Furthermore, overexpression of DDR1 abolished the anti-liver metastasis effect and pro-immune infiltration action of EFL1 in SHI mice. Together, our findings suggested that EFL1 protects against breast cancer liver metastasis in vivo by targeting DDR1-mediated immune infiltration.

Garlic-derived exosome-like nanovesicles as a hepatoprotective agent alleviating acute liver failure by inhibiting CCR2/CCR5 signaling and inflammation.

Acute liver failure (ALF) is a life-threatening clinical syndrome mostly induced by viral infections or drug abuse. As a novel therapeutic adjuvant or delivery vehicle, plant-derived exosome-like nanovesicles (PELNVs) have been extensively studied in recent years. This study aimed to develop garlic-derived exosome-like nanovesicles (GaELNVs) in order to ameliorate liver injury induced by LPS/D-GalN in mice, inhibit inflammatory eruption and reduce inflammatory cells infiltration. The results showed that treatment with GaELNVs improved liver pathology and reduced the levels of soluble inflammatory mediators IL-6, IL-1ß and TNF-α in the serum of ALF mice. GaELNVs reversed the upregulation of Cleaved Caspase-9, Cleaved Caspase-3, p53 and Bax expression and decreased Bcl2 activation caused by D-GalN/LPS, and inhibited NF-κB p65 expression and translocation to the nucleus. Meanwhile, treatment with GaELNVs resulted significant reduction in NLRP3 activation and Caspase-1 maturation, as well as decrease in the release of the inflammatory mediator IL-18. Additionally, an upregulation of the expression of proteins related to energy metabolism and autophagy occurrence including Foxo3a, Sirt1, and LC3-II was detected in the liver. Oral administration of GaELNVs also led to significant alteration in the expression of F4/80 and CD11b in the liver. Furthermore, the detection of chemokines in mouse liver tissue revealed that GaELNVs exhibited minimal reduction in the expression of CCL2, CCL3, CCL5 and CCL8. The decreased expression of CCR2 and CCR5 in the liver suggests that GaELNVs have the ability to decrease the recruitment of monocytes from the circulation to the liver. A reduction in the infiltration of F4/80loCD11bhi monocyte-derived macrophages into the liver was also observed. This study provides novel evidence that GaELNVs can ameliorate inflammatory eruptions and hinder the migration of circulating monocytes to the liver, as well as decrease macrophage infiltration by inhibiting CCR2/CCR5 signaling. Consequently, GaELNVs hold promise as a novel therapeutic agent for clinical management of liver disease.

Articaine versus Lidocaine in only buccal infiltration anesthesia for the extraction of mandibular anterior teeth. A prospective split-mouth randomized-controlled clinical study.

OBJECTIVE: To investigate the effectiveness of a single labial infiltration of 4% articaine versus 2% lidocaine for the extraction of mandibular anterior teeth without an additional lingual injection. PATIENTS AND METHODS: A prospective, randomized-controlled, split-mouth clinical study was implemented. Healthy adult patients seeking bilateral extraction of mandibular anterior teeth were included in this study. Teeth extractions were randomly assigned to two equal groups, where one mandibular anterior tooth was extracted using a solitary labial infiltration of either 4% articaine (the study group) or 2% lidocaine (the control group). After 14 days, the other mandibular anterior tooth was extracted using the other local anesthetic agent. The selection of the anesthetic agent injected in the first session was done in a randomized fashion. After 5 min of local anesthetic injection, the tooth was extracted, and each patient was asked to record the intensity of the extraction pain using the Visual Analogue Scale (VAS). RESULTS: Thirty-one patients were included in the study. The efficacy of a single labial injection for mandibular anterior teeth extraction was established by the fact that none of the patients in the study or control group required re-administration of local anesthesia. The mean VAS for pain control during tooth extraction was 1.16 ± 0.93 for the articaine group and 1.71 ± 0.90 for the lidocaine group. The pain score showed a statistically significant decrease in the articaine group compared to that in the lidocaine group (P = 0.017). CONCLUSION: Although the anesthetic effects of only buccal infiltration of 4% articaine and 2% lidocaine for extraction of mandibular anterior teeth were comparable, the use of 4% articaine would have more effective and predictable outcomes. CLINICALTRIALS: ORG: (ID: NCT05223075) 3/2/2022.