Predictive value of the surgical pleth index for the hemodynamic responses to trachea intubation and skin incision.

Surgical pleth index (SPI) has been widely investigated in assessing the nociceptive level. The aim of this study was to investigate the relationship between SPI level and patient responses to trachea intubation and skin incision. A total of 40 patients undergoing open abdominal general surgery were recruited for analyses. The patients were monitored with electrocardiogram, non-invasive blood pressure, SpO2, invasive blood pressure and SPI before anesthesia induction. Anesthesia was induced with midazolam, propofol, sufentanil and rocuronium and maintained with sufentanil and sevoflurane. Blood pressure, heart rate and SPI were recorded for analyses during the peri-intubation and peri-incision periods. A receiver operating characteristic (ROC) curve analysis was performed to analyze the predictive value of blood pressure, heart rate (HR) and SPI for hemodynamic responses for trachea intubation and skin incision. SPI had a similar changing trend to systolic blood pressure (SBP) and diastolic blood pressure (DBP). The SPI level was linearly correlated with SBP, DBP and HR. SPI increased significantly after intubation and incision in patients with positive but not negative responses to intubation and incision. The ROC analysis showed that only SBP level is predictive of intubation responses. These data suggested that SPI elevated under the noxious stimulation by intubation and incision, but it was not predictive of the hemodynamic responses to intubation and incision.

CD155 blockade improves survival in experimental sepsis by reversing dendritic cell dysfunction.

Immunosuppression is involved in septic processes, and results in an inability to eradicate the primary infection as well as a propensity to acquire secondary infections. In the present study, we found that the expression of CD155 on dendritic cells (DCs) and TIGIT on T cells were strikingly increased in septic mice. Furthermore, anti-CD155 antibody treatment could improve survival rate in mouse sepsis models through deceasing bacterial burden in both blood and peritoneal lavage fluid. Meanwhile, CD155 blockade efficiently increased the expression of TNF-a, IL-6 and decreased the level of IL-10 in blood and peritoneal lavage fluid of septic mice. In addition, overexpression of CD155 did not affect DCs maturation marker genes, but significantly increased the production of IL-10 and reduced the production of IL-12p40 and IL-12p70. Consequently, our data suggest that increase of CD155 on DCs promotes immunosuppressive effects by modulating cytokine production in sepsis.

Mixed probiotics reduce the severity of stress-induced depressive-like behaviors.

In recent years, the gut microbiome has gained significant attention in the spheres of research and public health. As a result, studies have increasingly explored the potential of probiotic dietary supplements as treatment interventions for conditions such as anxiety and depression. The present study examined the effect of mixed probiotics (Lacticaseibacillus rhamnosus and Enterococcus faecium) on inflammation, microbiome composition, and depressive-like behaviors in a macaque monkey model. The mixed probiotics effectively reduced the severity of depressive-like behaviors in macaque monkeys. Further, treatment with mixed probiotics gradually increased the abundance of beneficial bacteria in the gut, improving the balance of the gut microbiota. Additionally, macaques treated with the mixed probiotics showed decreased serum levels of inflammatory factors (P < 0.05), an increased rate of L-tryptophan metabolism (P < 0.05), and the restoration of 5-HT and 5-HTP levels (P < 0.05). Correlation analysis confirmed that Lacticaseibacillus and other beneficial bacteria exhibited a negative correlation with inflammation in the body (P < 0.05), and a positive correlation with tryptophan metabolism (P < 0.05). In conclusion, the mixed probiotics effectively restored intestinal homeostasis in macaques and enhanced tryptophan metabolism, ultimately alleviating inflammation and depressive-like behaviors.

Machine learning methods for accurately predicting survival and guiding treatment in stage I and II hepatocellular carcinoma.

Accurately predicting survival in patients with early hepatocellular carcinoma (HCC) is essential for making informed decisions about treatment and prognosis. Herein, we have developed a machine learning (ML) model that can predict patient survival and guide treatment decisions. We obtained patient demographic information, tumor characteristics, and treatment details from the SEER database. To analyze the data, we employed a Cox proportional hazards (CoxPH) model as well as 3 ML algorithms: neural network multitask logistic regression (N-MLTR), DeepSurv, and random survival forest (RSF). Our evaluation relied on the concordance index (C-index) and Integrated Brier Score (IBS). Additionally, we provided personalized treatment recommendations regarding surgery and chemotherapy choices and validated models' efficacy. A total of 1136 patients with early-stage (I, II) hepatocellular carcinoma (HCC) who underwent liver resection or transplantation were randomly divided into training and validation cohorts at a ratio of 3:7. Feature selection was conducted using Cox regression analyses. The ML models (NMLTR: C-index = 0.6793; DeepSurv: C-index = 0.7028; RSF: C-index = 0.6890) showed better discrimination in predicting survival than the standard CoxPH model (C-index = 0.6696). Patients who received recommended treatments had higher survival rates than those who received unrecommended treatments. ML-based surgery treatment recommendations yielded higher hazard ratios (HRs): NMTLR HR = 0.36 (95% CI: 0.25-0.51, P < .001), DeepSurv HR = 0.34 (95% CI: 0.24-0.49, P < .001), and RSF HR = 0.37 (95% CI: 0.26-0.52, P = <.001). Chemotherapy treatment recommendations were associated with significantly improved survival for DeepSurv (HR: 0.57; 95% CI: 0.4-0.82, P = .002) and RSF (HR: 0.66; 95% CI: 0.46-0.94, P = .020). The ML survival model has the potential to benefit prognostic evaluation and treatment of HCC. This novel analytical approach could provide reliable information on individual survival and treatment recommendations.

GABA induced by sleep deprivation promotes the proliferation and migration of colon tumors through miR-223-3p endogenous pathway and exosome pathway.

BACKGROUND: Research has indicated that long-term sleep deprivation can lead to immune dysfunction and participate in the occurance and progression of tumors. However, the relationship between sleep deprivation and colon cancer remains unclear. This study explored the specific mechanism through which sleep deprivation promotes the proliferation and migration of colon cancer, with a focus on the neurotransmitter GABA. METHODS: Chronic sleep deprivation mice model were used to investigate the effect of sleep disorder on tumors. We detected neurotransmitter levels in the peripheral blood of mice using ELISA. CCK-8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the effect of GABA on colon cancer cells, while immunofluorescence showed the distribution of macrophages in lung metastatic tissues. We isolated exosomes from a GABA-induced culture medium to explore the effects of GABA-induced colon cancer cells on macrophages. Gain- and loss-of-function experiments, luciferase report analysis, immunohistochemistry, and cytokine detection were performed to reveal the crosstalk between colon cancer cells and macrophages. RESULTS: Sleep deprivation promote peripheral blood GABA level and colon cancer cell proliferation and migration. Immunofluorescence analysis revealed that GABA-induced colon cancer metastasis is associated with enhanced recruitment of macrophages in the lungs. The co-culture results showed that GABA intensified M2 polarization of macrophage induced by colon cancer cells. This effect is due to the activation of the macrophage MAPK pathway by tumor-derived exosomal miR-223-3p. Furthermore, M2-like macrophages promote tumor proliferation and migration by secreting IL-17. We also identified an endogenous miR-223-3p downregulation of the E3 ligase CBLB, which enhances the stability of cMYC protein and augments colon cancer cells proliferation and migration ability. Notably, cMYC acts as a transcription factor and can also regulate the expression of miR-223-3p. CONCLUSION: Our results suggest that sleep deprivation can promote the expression of miR-223-3p in colon cancer cells through GABA, leading to downregulation of the E3 ligase CBLB and inhibition of cMYC ubiquitination. Simultaneously, extracellular miR-223-3p promotes M2-like macrophage polarization, which leads to the secretion of IL-17, further enhancing the proliferation and migration of colon cancer cells.

Changes in Corporate Social Responsibility Efficiency in Chinese Food Industry Brought by COVID-19 Pandemic-A Study With the Super-Efficiency DEA-Malmquist-Tobit Model.

Coronavirus disease 2019 (COVID-19) has brought about a significant and far-reaching impact on the world's business environment, corporations, and individuals. In the face of the general shortage of funds caused by the pandemic, assuming corporate social responsibility (CSR) is a problem for every enterprise manager. In the recent years, as corporate social responsibility (CSR) has become a hot topic globally, many enterprises have chosen to incorporate social responsibility into their development strategies. The food industry is a basic industry related to people's livelihood, especially in the pandemic. Its social responsibility efficiency deserves our attention. This article takes 17 sample enterprises whose CSR performance between 2012 and 2020 in China and reports are above the industry level as examples. Constructing the super-efficiency data envelopment analysis (DEA)-Malmquist-Tobit model explores the social responsibility efficiency of these enterprises. It analyzes the pandemic's impact on CSR efficiency. The results show that COVID-19 has promoted the social responsibility efficiency of the sample enterprises in the food industry. Besides, the level of technical efficiency and technological progress in the food industry is relatively high. Still, most enterprises are below the industry's average level. Before the outbreak of the pandemic, the size of enterprises is the key factor affecting the efficiency of CSR. After then, the listing years of enterprises then become the key factor.

Long noncoding RNA SNHG8 promotes chemoresistance in gastric cancer via binding with hnRNPA1 and stabilizing TROY expression.

AIMS: To determine SNHG8's function and potential mechanisms in gastric cancer (GC) chemoresistance. METHODS: We assessed SNHG8 expression in GC cell lines, GC/CDDP cell lines (cell lines treated with cisplatin), and 42 GC tissues and SNHG8 levels in the lncRNA microarray analysis of AGS/CDDP and AGS cell lines. We also examined GC cell viability in vivo and in vitro and its apoptosis level with Flow cytometry assays. SNHG8 was localized in subcells using fluorescence in situ hybridization (FISH) and cell fraction assays, hnRNPA1's link to SNHG8 was determined utilizing RNA immunoprecipitation (RIP) and FISH assays, gene expression profiles were assessed employing RNA transcriptome sequencing, and hnRNPA1's relationship with TROY was ascertained with the RIP assay. RESULTS: SNHG8 increased significantly in GC cell lines and GC tissues. However, a decrease in its expression promoted sensitivity to chemotherapy and inhibited DNA damage repair in vitro and in vivo. SNHG8 appeared to regulate TROY expression via linking with hnRNPA1. Reducing TROY levels considerably stimulated GC cell chemosensitivity, whereas heightening them partially rescued the rate of chemoresistance caused by downregulating SNHG8. CONCLUSION: In summary, the "SNHG8/hnRNPA1-TROY" axis is crucial to GC chemoresistance.

Can an incomplete ERAS protocol reduce postoperative complications compared with conventional care in laparoscopic radical resection of colorectal cancer? A multicenter observational cohort and propensity score-matched analysis.

Background: The patients undergoing laparoscopic radical colorectomy in many Chinese hospitals do not achieve high compliance with the ERAS (enhanced recovery programs after surgery) protocol. Methods: The clinical data from 1,258 patients were collected and divided into the non-ERAS and incomplete ERAS groups. Results: A total of 1,169 patients were screened for inclusion. After propensity score-matched analysis (PSM), 464 pairs of well-matched patients were generated for comparative study. Incomplete ERAS reduced the incidence of postoperative complications (p = 0.002), both mild (6.7% vs. 10.8%, p = 0.008) and severe (3.2% vs. 6.0%, p = 0.008). Statistically, incomplete ERAS reduced indirect surgical complications (27,5.8% vs. 59, 12.7) but not local complications (19,4.1% vs. 19, 4.1%). The subgroup analysis of postoperative complications revealed that all patients benefited from the incomplete ERAS protocol regardless of sex (male, p = 0.037, 11.9% vs. 17.9%; female, p = 0.010, 5.9% vs. 14.8%) or whether neoadjuvant chemotherapy was administered (neoadjuvant chemotherapy, p = 0.015, 7.4% vs. 24.5%; no neoadjuvant chemotherapy, p = 0.018, 10.2% vs. 15.8%). Younger patients (<60 year, p = 0.002, 7.6% vs. 17.5%) with a low BMI (<22.84, 9.4% vs. 21.1%, p < 0.001), smaller tumor size (<4.0 cm, 8.1% vs. 18.1%, p = 0.004), no fundamental diseases (8.8% vs. 17.0%, p = 0.007), a low ASA score (1/2, 9.7% vs. 16.3%, p = 0.004), proximal colon tumors (ascending/transverse colon, 12.2% vs. 24.3%, p = 0.027), poor (6.1% vs. 23.7%, p = 0.012)/moderate (10.3% vs. 15.3%, p = 0.034) tumor differentiation and no preoperative neoadjuvant radiotherapy (10.3% vs. 16.9%, p = 0.004) received more benefit from the incomplete ERAS protocol. Conclusion: The incomplete ERAS protocol decreased the incidence of postoperative complications, especially among younger patients (<60 year) with a low BMI (<22.84), smaller tumor size (<4.0 cm), no fundamental diseases, low ASA score (1/2), proximal colon tumors (ascending/transverse colon), poor/moderate differentiation and no preoperative neoadjuvant radiotherapy. ERAS should be recommended to as many patients as possible, although some will not exhibit high compliance. In the future, the core elements of ERAS need to be identified to improve the protocol.

Remote ischemic preconditioning protects neurocognitive function of rats following cerebral hypoperfusion.

BACKGROUND: Protection of remote ischemic preconditioning on neurocognitive function caused by bilateral common carotid artery occlusion has been investigated in rats. MATERIAL/METHODS: Thirty-six male Sprague-Dawley rats were divided into 3 groups - control group (Group C, n=12), bilateral carotid arteries occlusion group (Group B, n=12) and remote ischemic precondition group (Group P, n=12). In Group P, remote ischemic preconditioning (RIPC) was performed on the right femoral artery with 3 cycles (10 min) of occlusion/perfusion. After 3 cycles of preconditioning, bilateral carotid arteries were occluded immediately for 60 min. In Group B, ischemic insults were conducted without RIPC. Sham surgeries were performed in Group C. Evaluation of memory and learning capacity was performed on days 5-8 after surgery by Morris water maze testing of spatial learning capacity (n=6 for each group). Apoptosis of cells in the hippocampus region was determined by TUNEL tests and Bcl-2 at this region was determined by ELISA 24 h and 9 days after vessel occlusion (n=6 for each group). RESULTS: Neurocognitive tests showed that latency time was significantly longer in Group B than in Group P on day 7 (p=0.016) and day 8 (p=0.036). Moreover, frequency of platform crossings was significant less in group B than in the other 2 groups on day 9. Bcl-2 level was significantly increased in the hippocampal region of rats in Group P on days 1 and 9 after vessel occlusion. TUNEL test showed that apoptosis could be observed at 24 h after occlusion in Group B, but not in Group P and Group C. No apoptosis was observed on day 9. CONCLUSIONS: Our results suggest that RIPC can protect neurocognitive function of rats after bilateral carotid occlusions, and that Bcl-2 may play an important role in this protective effect.

Association of genetic polymorphisms of CYP 2C19 with hypertension in a Chinese Han population.

OBJECTIVES: Cytochrome P450 (CYP) 2C19 is expressed in vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which play a centralrole in regulating renal tubular fluid-electrolyte transport and vascular tone. The purpose of this study is to explore the relationship between the genetic polymorphism and hypertension risk in a Chinese Han population. METHODS: There were 1120 Chinese Han hypertension patients and 1249 age- and sex-matched control subjects genotyped for two tagging single nucleotide polymorphism (rs10509676 and rs11568732) of the human CYP2C19 gene by the use of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Haplotypes were constructed and their frequencies compared between the hypertension patients and the controls. RESULTS: The AA genotype of rs10509676 was found more frequently in the hypertension group than in the control group (p < 0.001). The frequency of the A-G haplotype was significantly higher in hypertensive patients than in control subjects (p < 0.001). The frequency of the T-T genotype was markedly higher in control subjects than in hypertensive patients (p < 0.001). CONCLUSIONS: The present results indicate that hypertension is associated with the AA genotype of rs10509676 in the human CYP2C19 gene. The A-G haplotype appears to be a risk factor and the T-T haplotype may be a protective factor of hypertension in Chinese Han people.

The Role of CSR Engagement in Customer-Company Identification and Behavioral Intention During the COVID-19 Pandemic.

The global coronavirus pandemic has reignited a strategic debate among the business community of the necessity for corporate social responsibility (CSR) engagement in the ever-dynamic social media. Considering the global economic downturn introduced by the COVID-19 pandemic, the present research is devoted to investigating whether CSR engagement in social media can help DiDi (a Chinese shared brand) at stake survive this overwhelming crisis. A theoretical model proposed to describe the hypothesized relationships was tested by a Structural Equation Modeling technique through the empirical online questionnaire. Through findings, we demonstrated that there was a positive relationship between CSR engagement of DiDi on WeChat, customer-company identification (C-C identification), and behavioral intention [purchase intention, brand loyalty, and e-word-of-mouth (eWOM)] of customers. With attention to psychological influence, our empirical statistics also evidenced the mediating role of C-C identification between CSR engagement and behavioral intention of customers. This study highlights the significant role of CSR engagement in a critical period theoretically and offers businesses more open innovation strategies to compete against the COVID-19 pandemic-induced market downturn.

Pandemic Uncertainty and Socially Responsible Investments.

This paper examines the effects of pandemic uncertainty on socially responsible investments. We use the overall corporate sustainability performance index in the Global-100 Most Sustainable Corporations in the World dataset to measure socially responsible investments. The global pandemic uncertainty is also measured by the World Pandemic Uncertainty Index. We focus on the panel dataset from 2012 to 2020, and the results show that the World Pandemic Uncertainty Index is positively related to socially responsible investments. The main findings remain significant when we utilize various panel estimation techniques.

Integration of the Confucian Culture on Cross-Cultural Conflict Management: The Role of the COVID-19 Pandemic.

Cross-culture conflict management is the major challenge for the Chinese enterprises going global along the Belt and Road Initiative. This study explores the feasibility of integrating the Confucian culture into cross-culture conflict management, and a special role is given to the COVID-19 pandemic. We combine the Confucian culture values and Hofstede's cultural dimension theory and adopt the questionnaire survey methods on the Chinese multinational enterprises' employees. The Cronbach's Alpha method is also deployed to test the reliability and validity of the data. We find the significant integration of the Confucian culture into cross-culture conflict management. Furthermore, 16 sub-values of the Confucian culture are suggested to mitigate the cross-culture conflicts in multinational enterprises effectively. The findings imply that Chinese enterprises should consider new strategies to manage the cross-culture conflicts, especially during the COVID-19 pandemic.

Interferon regulatory factor-1 suppresses DNA damage response and reverses chemotherapy resistance by downregulating the expression of RAD51 in gastric cancer.

Recent studies have shown that IRF-1 plays a significant role in various tumour-induced chemoresistance, but its role and mechanism in gastric cancer-associated chemoresistance are not clear. Our study showed that IRF-1 expression could reverse gastric cancer-related chemoresistance. Dysregulated DNA repair is an important cause of chemoresistance. We established a chemoresistant gastric cancer cell line and found that drug-resistant gastric cancer cells had increased DNA repair ability and that IRF-1 regulated DNA damage repair. Further studies showed that IRF-1 inhibited the expression of RAD51 directly by binding to the RAD51 promoter to affect DNA damage repair; this binding reversed resistance. However, restoring the expression of RAD51 halted the inhibitory effect of IRF-1 partially. Also, we revealed that the overexpression of IRF-1 in a mouse model synergized with chemotherapeutic drugs to inhibit tumour growth. Finally, IRF-1 expression correlated with RAD51 expression in gastric cancer specimens. The expression of IRF-1 and RAD51 are both related to the survival duration of patients with gastric cancer. These results suggest that targeting IRF-1-RAD51 could be an effective approach to reversing multidrug resistance in gastric cancer.

Machinability of high-speed enamel cutting with carbide bur.

The cutting of tooth enamel using a high-speed air-turbine handpiece and carbide bur is a key procedure in oral surgeries, such as the minimally invasive extraction. However, presently little is known about the cutting mechanics and material removal mechanism related to tooth enamel machinability. In this study, the machinability of high-speed enamel cutting with carbide bur is studied by a computer-aided numerical control system. The dynamic cutting forces of enamel of the occlusal, buccal/lingual, and proximal surfaces were measured by the force measuring system. The force ratio, cutting torque, rotating speed, specific cutting energy, and bur wear were analyzed. The microstructure of enamel and carbide burs was observed by the scanning electron microscope, and the relationship between enamel microstructures and machinability was further analyzed. The results show that during the high-speed enamel cutting with carbide bur, the chip thickness is on the nano-scale, and the plastic deformation of the machined surface is obvious. With increased material removal rate, the cutting force, torque, specific cutting energy, and bur wear increases accordingly, whereas the rotating speed decelerates (p < 0.05). The different angles between the cutting direction and the axial direction of the enamel rods give rise to the large differences in the cutting mechanics and mechanism of the proximal, buccal/lingual, and occlusal surfaces of the teeth. When the cutting direction is parallel, vertical, and oblique 45° to the axial direction of the enamel rods, the force required for material fracture and crack propagation increases, and the cutting force increases as a consequence. Parallel and oblique 45° cutting are the main modes of tooth segmentation in the minimally invasive extraction. In comparison with the parallel cutting mode, the cutting force, torque, and cutting ratio of the oblique 45° cutting mode can be significantly increased, and the tool wear is obviously accelerated. This is the lowest priority in segmentation surgery, hence the problems of overload and temperature rise need to be considered. The cutting mechanics and cutting mechanism obtained in this study will provide scientific process guidance for dental cutting operations with the air-turbine handpiece driving bur.

Synthesis, characterization, DNA-binding and antiproliferative activity of Nd(III) complexes with N-(nitrogen heterocyclic) norcantharidin acylamide acid.

Three novel complexes [Nd(L)(NO3)(H2O)2].NO(3).2H2O (HL1 = N-pyrimidine norcantharidin acylamide acid, C12H13N3O4; HL2 = N-pyridine norcantharidin acylamide acid, C13H14N2O4; HL3 = N-phenyl norcantharidin acylamide acid, C14H15NO4) were synthesized. HL1, HL2 and HL3 are the ligand of complex(1), complex(2) and complex(3), respectively. Their structures were characterized by elemental analysis, conductivity measurement, infrared spectra and thermogravimetric analysis. The DNA-binding properties of the complexes have been investigated by fluorescence spectroscopy and viscosity measurements. The results suggest that the complexes can bind to DNA by partial intercalation. The liner Stern-Volmer quenching constant Ksq values are 3.3(+/-0.21)(1), 1.7(+/-0.19)(2) and 0.9(+/-0.04)(3), respectively. Complex (1) and (2) have been found to cleave pBR322 plasmid DNA at physiological pH and temperature. The test of antiproliferation activity indicates that complex(1) has strong antiproliferative ability against the SMMC7721 (IC50 = 131.7 +/- 23.4 micromol x L(-1)) and A549 (IC50 = 128.4 +/- 19.9 micromol x L(-1)) cell lines. The inhibition rates of complex(2) (IC50 = 86.3 +/- 11.3 micromol x L(-1)) are much higher than that of NCTD (IC50 = 115.5 +/- 9.5 micromol x L(-1)) and HL2 (111.0 +/- 5.7 micromol x L(-1)) against SMMC7721 cell lines.

8-Phenyl-10-oxa-8-aza-tricyclo-[4.3.0.1]decane-7,9-dione.

The reaction of aniline with norcantharidin produced the imide title compound, C(14)H(13)NO(3), which shows no significant hydrogen bonds in the crystal structure. The dihedral angle between the phenyl and pyrrolidine rings is 48.48 (6)°.

catena-Poly[[diaqua-nickel(II)]-µ-7-oxabicyclo-[2.2.1]heptane-2,3-di-carboxyl-ato].

In the crystal structure of the title compound, [Ni(C(8)H(8)O(5))(H(2)O)(2)](n), the Ni(II) cation is in a Jahn-Teller-distorted octahedral coordination environment binding to two O atoms from water molecules, the bridging O atom of the bicycloheptane unit, two carboxylate O atoms from different carboxylate groups and one carboxylate O atom from a symmetry-related bridging ligand. The crystal structure is made up from layers propagating parallel to the bc plane.

Type 2 diabetes affects postextraction socket healing and influences first-stage implant surgery: A study based on clinical and animal evidence.

AIM: To verify the influence of type 2 diabetes mellitus (T2DM) on postextraction socket healing and subsequent first-stage implant surgery. MATERIALS AND METHODS: We analyzed pre-extraction and postextraction cone beam computed tomography images of T2DM patients (n = 75) and paired nondiabetic controls to investigate changes in postextraction socket and ridge dimensions. The types of guided bone regeneration (GBR) surgeries were also compared. Three T2DM pig models were established to compare their postextraction socket healing with that of nondiabetic controls. Healing was quantitatively verified by microcomputed tomography. The osteogenic differentiation of mesenchymal stem cells (MSCs) was also compared. RESULTS: Compared to nondiabetic controls, T2DM patients had higher socket width/depth values postextraction across all groups with different healing times. Among the T2DM patients, 62.7% could not receive first-stage implant surgery within 6 months postextraction, and 54.7% received GBR surgery during first-stage surgery. Ossification was not achieved in the socket center of the T2DM pig models after 3 months of healing. A decrease in osteogenic differentiation was observed in T2DM-MSCs. CONCLUSIONS: T2DM interferes with the healing of the extraction socket and thus delays first-stage implant surgery. This phenomenon may be due to the reduced osteogenic differentiation of MSCs in the sockets.

miR-145-5p suppresses osteogenic differentiation of adipose-derived stem cells by targeting semaphorin 3A.

Adipose-derived stem cells (ADSCs) provide a novel method for bone tissue regeneration, but their adipogenic tendency limits their therapeutic efficacy. MicroRNAs (miRNAs) have been reported to regulate stem cell differentiation and bone tissue regeneration, but the detailed mechanism is poorly investigated. Our study indicated that inhibition of miR-145-5p enhanced the osteogenic potential of ADSCs and reduced the adipogenic differentiation. Osteogenesis- and adipogenesis-associated genes were detected by qRT-PCR indicating a corresponding result. Moreover, semaphorin 3A (sema3A) was found to be a target of miR-145-5p, as confirmed by a luciferase activity assay, qRT-PCR, and western blotting. Inhibition of miR-145-5p promoted migration, as detected by wound healing and Transwell assays, but did not affect proliferation, as detected by CCK-8 and ki-67 assays. The effects of miR-145-5p inhibitors on ADSC progression rescued by siRNA of Sema3a and si-sema3a exerted the same effect as miR-145-5p inhibitors on ADSC progression. Furthermore, siRNA of Sema3a rescued synergistic effects with miR-145-5p inhibitors in ADSCs. qRT-PCR and immunofluorescence assays showed that miR-145-5p activated the Wnt signaling pathway for osteogenic differentiation. In conclusion, miR-145-5p and sema3a represent new targets for improving the osteogenic capacity of ADSCs.