Huang Qin decoction increases SLC6A4 expression and blocks the NFκB-mediated NLRP3/Caspase1/GSDMD pathway to disrupt colitis-associated carcinogenesis.

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Psychobiotics Regulate Purine Metabolism to Influence Host Emotional Behavior.

Purine metabolism plays a pivotal role in numerous biological processes with potential implications for brain function and emotional regulation. This study utilizes gene-edited probiotics and pseudo-germ-free mice to unravel this intricate interplay. Transcriptomic analysis identified a ribonucleoside-diphosphate reductase ß chain (nrdB) as a pivotal gene in purine metabolism within Bifidobacterium breve CCFM1025. Comparative evaluation between the wild-type and nrdB mutant strains revealed CCFM1025's effective reduction of xanthine and xanthosine levels in the serum and brain of stressed mice. Concomitantly, it downregulated the expression of the adenosine receptor gene (Adora2b) and inhibited the overactivation of microglia. These findings emphasize the potential of psychobiotics in modulating emotional responses by regulating purine metabolites and adenosine receptors. This study sheds light on novel pathways that influence emotional well-being through gut microbiota interactions and purine metabolic processes.

Modulation of SEMA4D-modified titanium surface on M2 macrophage polarization via activation of Rho/ROCK-mediated lactate release of endothelial cells: In vitro and in vivo.

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation.

Nomogram for the prediction of tigecycline-induced hypofibrinogenaemia in a Chinese population.

BACKGROUND: Tigecycline has been widely used for multi-drug-resistant bacterial infections in China. Although many studies have reported the risk factors for tigecycline-induced hypofibrinogenaemia, it remains unknown whether valproic acid or voriconazole in combination with tigecycline is associated with the decrease in fibrinogen, as both drugs could lead to coagulation disorders. The aim of this study was to develop a nomogram for the prediction of tigecycline-induced hypofibrinogenaemia. METHODS: This was a multi-centre retrospective case-control study. The primary outcome was the accurate prediction of tigecycline-induced hypofibrinogenaemia. Nomograms were developed from logistic regression models with least absolute shrinkage and selection operator regression for variable selection. Model performance was assessed via calibration plots, and models were validated internally using bootstrapping on a validation cohort. RESULTS: In total, 2362 patients were screened, of which 611 were eligible for inclusion in this study. These 611 patients were divided into the training cohort (n=488) and the validation cohort (n=123). Predictors included in the nomogram for the total population were total dose, age, fibrinogen, prothrombin time (PT), comorbidity, and concomitant use of voriconazole. Total dose, fibrinogen, PT, activated partial thromboplastin time, white blood cell count, and concomitant use of voriconazole were selected to predict hypofibrinogenaemia in patients with malignant haematologic diseases. Both models were calibrated adequately, and their predictions were correlated with the observed outcome. The cut-offs for treatment duration in the total population and the subgroup were 10 and 6 days, respectively. CONCLUSIONS: Tigecycline in combination with voriconazole could increase the risk of hypofibrinogenaemia, and tigecycline-induced hypofibrinogenaemia is more likely to occur in patients with malignant haematologic diseases.

AGR2 and FOXA1 as prognostic markers in ER-positive breast cancer.

BACKGROUND: The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status. METHODS: AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale. RESULTS: Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups. CONCLUSIONS: There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.

Premetastatic Niche Mimicking Bone-On-A-Chip: A Microfluidic Platform to Study Bone Metastasis in Cancer Patients.

Primary cancer modulates the bone microenvironment to sow the seeds of dormancy and metastasis in tumor cells, leading to multiple organ metastasis and death. In this study, 3D printing and bone-on-a-chip (BOC) are combined to develop a BOC platform that mimics the pre-metastatic niches (PMNs) and facilitates elucidation of the interactions between bone-resident cells and metastatic tumor cells under the influence of primary cancer. Photocrosslinkable gelatin methacrylate (GelMA) is used as a 3D culturing hydrogel to encapsulate cells, and circulate tumor culture medium (CM) adjacent to the hydrogel to verify the critical role of mesenchymal stem cells (MSCs) and osteoclasts (RAW264.7s). Three niches: the dormancy niche, the perivascular niche, and the "vicious cycle" niche, are devised to recapitulate bone metastasis in one chip with high cell viability and excellent nutrient exchange. With respect to tumor dormancy and reactivation, the invadopodia formation of A549 lung cancer cells in communication with MSCs and RAW264.7 via the cortactin pathway is researched. As a proof of concept, the functionality and practicality of the platform are demonstrated by analyzing the invadopodia formation and the influence of various cells, and the establishment of the dynamic niches paves the way to understanding PMN formation and related drug discovery.

Feasibility of 4D HDR brachytherapy source tracking using x-ray tomosynthesis: Monte Carlo investigation.

PURPOSE: High dose rate (HDR) brachytherapy rapidly delivers dose to targets with steep dose gradients. This treatment method must adhere to prescribed treatment plans with high spatiotemporal accuracy and precision, as failure to do so may degrade clinical outcomes. One approach to achieving this goal is to develop imaging techniques to track HDR sources in vivo in reference to surrounding anatomy. This work investigates the feasibility of using an isocentric C-arm x-ray imager and tomosynthesis methods to track Ir-192 HDR brachytherapy sources in vivo over time (4D). METHODS: A tomosynthesis imaging workflow was proposed and its achievable source detectability, localization accuracy, and spatiotemporal resolution were investigated in silico. An anthropomorphic female XCAT phantom was modified to include a vaginal cylinder applicator and Ir-192 HDR source (0.5 × 0.5 × 5.0 mm3 ), and the workflow was carried out using the MC-GPU Monte Carlo image simulation platform. Source detectability was characterized using the reconstructed source signal-difference-to-noise-ratio (SDNR), localization accuracy by the absolute 3D error in its measured centroid location, and spatiotemporal resolution by the full-width-at-half-maximum (FWHM) of line profiles through the source in each spatial dimension considering a maximum C-arm angular velocity of 30° per second. The dependence of these parameters on acquisition angular range (θtot = 0°-90°), number of views, angular increment between views (Δθ = 0°-15°), and volumetric constraints imposed in reconstruction was evaluated. Organ voxel doses were tallied to derive the workflow's attributable effective dose. RESULTS: The HDR source was readily detected and its centroid was accurately localized with the proposed workflow and method (SDNR: 10-40, 3D error: 0-0.144 mm). Tradeoffs were demonstrated for various combinations of image acquisition parameters; namely, increasing the tomosynthesis acquisition angular range improved resolution in the depth-encoded direction, for example from 2.5 mm to 1.2 mm between θtot = 30o and θtot = 90o , at the cost of increasing acquisition time from 1 to 3 s. The best-performing acquisition parameters (θtot = 90o , Δθ = 1°) yielded no centroid localization error, and achieved submillimeter source resolution (0.57 × 1.21 × 5.04 mm3 apparent source dimensions, FWHM). The total effective dose for the workflow was 263 µSv for its required pre-treatment imaging component and 7.59 µSv per mid-treatment acquisition thereafter, which is comparable to common diagnostic radiology exams. CONCLUSIONS: A system and method for tracking HDR brachytherapy sources in vivo using C-arm tomosynthesis was proposed and its performance investigated in silico. Tradeoffs in source conspicuity, localization accuracy, spatiotemporal resolution, and dose were determined. The results suggest this approach is feasible for localizing an Ir-192 HDR source in vivo with submillimeter spatial resolution, 1-3 second temporal resolution and minimal additional dose burden.

Five new species of Schizoporaceae (Basidiomycota, Hymenochaetales) from East Asia.

Five new wood-inhabiting fungi, Lyomycesalbopulverulentus, L.yunnanensis, Xylodondaweishanensis, X.fissuratus, and X.puerensisspp. nov., are proposed based on a combination of morphological features and molecular evidence. Lyomycesalbopulverulentus is characterized by brittle basidiomata, pruinose hymenophore with a white hymenial surface, a monomitic hyphal system with clamped generative hyphae, and ellipsoid basidiospores. Lyomycesyunnanensis is characterized by a grandinioid hymenial surface, the presence of capitate cystidia, and ellipsoid basidiospores. Xylodondaweishanensis is characterized by an odontioid hymenial surface, a monomitic hyphal system with clamped generative hyphae, and broad ellipsoid-to-subglobose basidiospores. Xylodonfissuratus is characterized by a cracking basidiomata with a grandinioid hymenial surface, and ellipsoid basidiospores. Xylodonpuerensis is characterized by a poroid hymenophore with an angular or slightly daedaleoid configuration, and ellipsoid-to-broad-ellipsoid basidiospores. Sequences of ITS and nLSU rRNA markers of the studied samples were generated and phylogenetic analyses were performed with the maximum likelihood, maximum parsimony, and Bayesian inference methods. The phylogram based on the ITS+nLSU rDNA gene regions (Fig. 1) included six genera within the families Chaetoporellaceae, Hyphodontiaceae, Hymenochaetaceae, and Schizoporaceae (Hymenochaetales)-Fasciodontia, Hastodontia, Hyphodontia, Kneifiella, Lyomyces, and Xylodon-in which the five new species were grouped into genera Lyomyces and Xylodon. The phylogenetic tree inferred from the ITS sequences highlighted that Lyomycesalbopulverulentus formed a monophyletic lineage and was then grouped closely with L.bambusinus, L.orientalis, and L.sambuci; additionally, L.yunnanensis was sister to L.niveus with strong supports. The topology, based on the ITS sequences, revealed that Xylodondaweishanensis was retrieved as a sister to X.hyphodontinus; X.fissuratus was grouped with the four taxa X.montanus, X.subclavatus, X.wenshanensis, and X.xinpingensis; and X.puerensis was clustered with X.flaviporus, X.ovisporus, X.subflaviporus, X.subtropicus, and X.taiwanianus.

Neuroendocrine pathogenesis of perimenopausal depression.

With the development of social economics and the increase of working pressure, more and more women are suffering from long-term serious stress and showing symptoms of perimenopausal depression (PMD). The incidence rate of PMD is increasing, and the physical and mental health are seriously affected. However, due to the lack of accurate knowledge of pathophysiology, its diagnosis and treatment cannot be accurately executed. By consulting the relevant literature in recent years, this paper elaborates the neuroendocrine mechanism of perimenopausal depression from the aspects of epigenetic changes, monoamine neurotransmitter and receptor hypothesis, glial cell-induced neuroinflammation, estrogen receptor, interaction between HPA axis and HPG axis, and micro-organism-brain gut axis. The purpose is to probe into new ways of treatment of PMD by providing new knowledge about the neuroendocrine mechanism and treatment of PMD.

Association between stress hyperglycaemia and in-hospital cardiac events after coronary artery bypass grafting in patients without diabetes: A retrospective observational study of 5450 patients.

AIMS: To investigate the impact of stress hyperglycaemia (SH) on in-hospital adverse cardiac events after coronary artery bypass grafting (CABG) in patients without diabetes. MATERIALS AND METHODS: In total, 5450 patients without diabetes who underwent CABG were analysed. SH was defined as any two instances in which the random blood glucose level was >7.8 mmol/L after CABG in the intensive care unit (ICU). The primary outcome was major adverse cardiac events (MACEs), including in-hospital mortality, acute myocardial infarction, stroke and acute renal failure. Secondary outcomes included surgical site infection (SSI) and length of ICU stay. RESULTS: Patients with SH had higher rates of MACEs (5.7% vs. 2.3%, p < .0001) and higher SSI (3.3% vs. 1.4%, p = .0003) and longer ICU stays (2.6 ± 2.0 vs. 1.3 ± 1.3 days, p < .0001) than those without SH. Furthermore, SH was associated with a higher risk of MACEs [odds ratio (OR): 2.32, 95% confidence interval (CI): 1.38-3.90], SSI (OR: 2.21, 95% CI: 1.20-3.95) and longer ICU stay (OR: 12.27, 95% CI: 9.41-16.92) after adjusting for confounders. Subgroup analysis showed that patients with SH >10 mmol/L or SH that occurred in the ICU and lasted more than 48 h had increased risks of postoperative complications (p < .05). CONCLUSIONS: SH was significantly associated with an increased risk of MACEs, SSI and longer ICU stay after CABG in patients without diabetes. In addition, SH >10 mmol/L or that occurred in the ICU and lasted more than 48 h increased the risk of adverse outcomes.

Association of Enolase-1 with Prognosis and Immune Infiltration in Breast Cancer by Clinical Stage.

Purpose: Enolase-1 (ENO1) plays a key role in malignancies. Previous studies on the association between ENO1 expression and breast cancer prognosis had yielded inconsistent results. In the present study, we assessed the prognostic effect of ENO1 in breast cancer using Guangzhou Breast Cancer Study (GZBCS) cohort with full consideration of the potential confounders and the modification effects. The results were further validated in the TCGA-BRCA cohort and explained by tumor immunity. Methods: ENO1 protein expressions were evaluated by immunohistochemistry in tissue microarrays from 961 patients with primary invasive breast cancer. Chi-square tests were used to assess the association of ENO1 levels with the patient's characteristics. Cox regression models were applied to assess the prognostic effects. The TCGA-BRCA cohort was utilized to validate the results and explore the potential mechanisms. The immune infiltration was determined using the CIBERSORT and ssGSEA algorithms; the correlation between ENO1 expression and the abundance of tumor-infiltrating immune cells (TIICs) and scores of immune-related functions was evaluated by Wilcoxon signed-rank tests and Spearman's rank test. Results: ENO1 protein expression exerted a protective effect on OS in stage I/II patients (HR=0.58, 95% CI: 0.35-0.96) but not in stage III patients (HR=1.42, 95% CI: 0.81-2.49, P interaction=0.04) in GZBCS; consistent results were obtained at mRNA levels in TCGA cohort. Immune infiltration analyses revealed that ENO1 was positively correlated with multiple antitumor TIICs (including M1 macrophages, B cells, CD8 T cells, T helper 2 cells, and NK cells) only in stage I/II but not stage III patients. Conclusion: A higher expression of ENO1 was associated with a better prognosis only in early-stage breast cancer, which may be related to the different effects of ENO1 on immune infiltration, suggesting that ENO1 may be a promising target for precision immunotherapy in breast cancer.

TiO2nanotubes induce early mitochondrial fission in BMMSCs and promote osseointegration.

Nanotopography can promote osseointegration, but how bone marrow mesenchymal stem cells (BMMSCs) respond to this physical stimulus is unclear. Here, we found that early exposure of BMMSCs to nanotopography (6 h) caused mitochondrial fission rather than fusion, which was necessary for osseointegration. We analyzed the changes in mitochondrial morphology and function of BMMSCs located on the surfaces of NT100 (100 nm nanotubes) and ST (smooth) by super-resolution microscopy and other techniques. Then, we found that both ST and NT100 caused a significant increase in mitochondrial fission early on, but NT100 caused mitochondrial fission much earlier than those on ST. In addition, the mitochondrial functional statuses were good at the 6 h time point, this is at odds with the conventional wisdom that fusion is good. This fission phenomenon adequately protected mitochondrial membrane potential (MMP) and respiration and reduced reactive oxygen species. Interestingly, the MMP and oxygen consumption rate of BMMSCs were reduced when mitochondrial fission was inhibited by Mdivi-1(Inhibition of dynamin-related protein 1 fission) in the early stage. In addition, the effect on osseointegration was significantly worse, and this effect did not improve with time. Taken together, the findings indicate that early mitochondrial fission plays an important role in nanotopography-mediated promotion of osseointegration, which is of great significance to the surface structure design of biomaterials.

Dual-responsive nanoparticles loading bevacizumab and gefitinib for molecular targeted therapy against non-small cell lung cancer.

The combination of vascular endothelial growth factor (VEGF) inhibitors and tyrosine kinase inhibitors (TKIs) is newly available for molecular targeted therapy against non-small cell lung cancer (NSCLC) in clinic. However, the therapeutic benefits remain unsatisfying due to the poor drug delivery to targets of interest. In this study, we developed bevacizumab-coated gefitinib-loaded nanoparticles (BCGN) with dual-responsive drug release for inhibiting tumor angiogenesis and phosphorylation of epidermal growth factor receptor (EGFR). Through an exogenous corona strategy, bevacizumab is easily coated on gefitinib-loaded nanoparticles via electrostatic interaction. After intravenous injection, BCGN are efficiently accumulated in NSCLC tumors as confirmed by dual-model imaging. Bevacizumab is released from BCGN upon oxidation in tumor microenvironment, whereas gefitinib is released after being internalized by tumor cells and disassembled in reduction cytoplasm. The dual-responsive release of bevacizumab and gefitinib significantly inhibits tumor growth in both A549 and HCC827 human NSCLC models. Our approach provides a promising strategy to improve combinational molecular targeted therapy of NSCLC with precisely controlled drug release.

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. METHODS: The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan-Meier (K-M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. RESULTS: A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K-M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p < 0.05) and Tgds (p < 0.01) was higher in the high-risk group than in the low-risk group. Spearman's correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. CONCLUSION: In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.

The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing.

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

Laparoscopic vs. open colectomy for T4 colon cancer: A meta-analysis and trial sequential analysis of prospective observational studies.

Background: To evaluate short- and long-term outcomes of laparoscopic colectomy (LC) vs. open colectomy (OC) in patients with T4 colon cancer. Methods: Three authors independently searched PubMed, Web of Science, Embase, Cochrane Library, and Clinicaltrials.gov for articles before June 3, 2022 to compare the clinical outcomes of T4 colon cancer patients undergoing LC or OC. Results: This meta-analysis included 7 articles with 1,635 cases. Compared with OC, LC had lesser blood loss, lesser perioperative transfusion, lesser complications, lesser wound infection, and shorter length of hospital stay. Moreover, there was no significant difference between the two groups in terms of 5-year overall survival (5y OS), and 5-year disease-free survival (5y DFS), R0 resection rate, positive resection margin, lymph nodes harvested ≥12, and recurrence. Trial Sequential Analysis (TSA) results suggested that the potential advantages of LC on perioperative transfusion and the comparable oncological outcomes in terms of 5y OS, 5y DFS, lymph nodes harvested ≥12, and R0 resection rate was reliable and no need of further study. Conclusions: Laparoscopic surgery is safe and feasible in T4 colon cancer in terms of short- and long-term outcomes. TSA results suggested that future studies were not required to evaluate the 5y OS, 5y DFS, R0 resection rate, positive resection margin status, lymph nodes harvested ≥12 and perioperative transfusion differences between LC and OC.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022297792.