BACKGROUND:Indolepropionic acid has been shown to reduce diabetes-induced central nervous system inflammation.However,there is a lack of research on whether to inhibit microglia M1 polarization for the treatment of spinal cord injury. OBJECTIVE:To investigate the mechanism of indolepropionic acid inhibition of microglial cell M1 polarization for the treatment of spinal cord injury through cell and animal experiments. METHODS:(1)In vitro experiments:BV2 cell viability was assessed using the CCK-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,BV2 cells were categorized into control group,administration group(50 μmol/L indolepropionic acid),lipopolysaccharide group(100 ng/mL lipopolysaccharide),and treatment group(100 ng/mL lipopolysaccharide + 50 μmol/L indolepropionic acid).Nitric oxide content was quantified using the Griess method.Real-time quantitative PCR and western blot assay were employed to measure mRNA and protein levels of pro-inflammatory factors.Cell immunofluorescence staining was conducted to assess inducible nitric oxide synthase expression.The Seahorse assay was employed to assess glycolytic stress levels in BV2 cells.(2)In vivo experiments:30 SD rats were randomly divided into three groups:sham surgery group,spinal cord injury group,and indolepropionic acid group.Motor function recovery in rats after spinal cord injury was assessed using BBB scoring and the inclined plane test.Immunofluorescence staining of spinal cord tissue was conducted to evaluate the expression of inducible nitric oxide synthase in microglial cells.ELISA was employed to measure protein expression levels of the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in spinal cord tissue. RESULTS AND CONCLUSION:(1)In vitro experiments:Indolepropionic acid exhibited significant suppression of BV2 cell viability when its concentration exceeded 50 μmol/L.Indolepropionic acid achieved this by inhibiting the activation of the nuclear factor κB signaling pathway,thereby suppressing the mRNA and protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α),as well as the M1 polarization marker,inducible nitric oxide synthase,in BV2 cells.Additionally,indolepropionic acid notably reduced the glycolytic level in BV2 cells induced by lipopolysaccharides.(2)In vivo experiments:Following indolepropionic acid intervention in spinal cord injury rats,there was a noticeable increase in BBB scores and the inclined plane test angle.There was also a significant decrease in the number of M1-polarized microglial cells in spinal cord tissue,accompanied by a marked reduction in the protein expression levels of pro-inflammatory cytokines(interleukin-1β and tumor necrosis factor-α).(3)These results conclude that indolepropionic acid promotes functional recovery after spinal cord injury by improving the inflammatory microenvironment through inhibition of microglia M1 polarization.

The biomolecular mechanisms that regulate tooth root development and odontoblast differentiation are poorly understood. We found that Atp6i deficient mice (Atp6i^-/-) arrested tooth root formation, indicated by truncated Hertwig's epithelial root sheath (HERS) progression. Furthermore, Atp6i deficiency significantly reduced the proliferation and differentiation of radicular odontogenic cells responsible for root formation. Atp6i^-/- mice had largely decreased expression of odontoblast differentiation marker gene expression profiles (Col1a1, Nfic, Dspp, and Osx) in the alveolar bone. Atp6i^-/- mice sample RNA-seq analysis results showed decreased expression levels of odontoblast markers. Additionally, there was a significant reduction in Smad2/3 activation, inhibiting transforming growth factor-β (TGF-β) signaling in Atp6i^-/- odontoblasts. Through treating pulp precursor cells with Atp6i^-/- or wild-type OC bone resorption-conditioned medium, we found the latter medium to promote odontoblast differentiation, as shown by increased odontoblast differentiation marker genes expression (Nfic, Dspp, Osx, and Runx2). This increased expression was significantly blocked by anti-TGF-β1 antibody neutralization, whereas odontoblast differentiation and Smad2/3 activation were significantly attenuated by Atp6i^-/- OC conditioned medium. Importantly, ectopic TGF-β1 partially rescued root development and root dentin deposition of Atp6i^-/- mice tooth germs were transplanted under mouse kidney capsules. Collectively, our novel data shows that the prevention of TGF-β1 release from the alveolar bone matrix due to OC dysfunction may lead to osteopetrosis-associated root formation via impaired radicular odontoblast differentiation. As such, this study uncovers TGF-β1 /Smad2/3 as a key signaling pathway regulating odontoblast differentiation and tooth root formation and may contribute to future therapeutic approaches to tooth root regeneration.
Female ; Animals ; Mice ; Transforming Growth Factor beta1 ; Odontoblasts ; Culture Media, Conditioned ; Cell Differentiation ; Signal Transduction ; Disease Models, Animal ; Tooth Root

Programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced non-small cell lung cancer(NSCLC), but patients with low PD-L1 expression have limited objective response and survival benefits. Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world. Therefore, researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different sub-groups in NSCLC. Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC. In addition to exploring different emerging combination options, how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy. This article reviews the mechanism of action, research progress, predictive biomarkers and future exploration directions of dual immunotherapy.
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B7-H1 Antigen/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunotherapy ; Lung Neoplasms/drug therapy* ; Prognosis

Objective To investigate the clinicopathological characteristics and independent risk factors of hepatocellular carcinoma (HCC) differentiation.  Methods A total of 108 HCC patients who underwent operation and treatment were reviewed and classified into low differentiation group (n= 29, 26.85%), medium differentiation group (n=53, 49.07%) and high differentiation group (n=26, 24.07%) according to pathological diagnosis. The clinicopathological characteristics and the expression levels of Ki67 and P53 in each group were compared and analyzed. Logistic regression model was used to analyze the risk factors for low differentiation of HCC.  Results The proportion of cirrhosis, the positive rate of P53 and Ki67 expression level in different degrees of HCC differentiation were statistically significant (P<0.05). However, there were no significant differences in age, sex, tumor diameter, and hepatitis virus infection or tumor involvement of liver capsule between groups (P>0.05). Multivariate logistic analysis showed that cirrhosis (OR=3.408), high expression of Ki67 (OR=11.113) and positive P53 (OR=9.711) were the main risk factors for poorly differentiated HCC.  Conclusion There are differences in clinical characteristics and expressions of Ki67 and P53 in HCC patients with different degrees of differentiation. Logistic regression analysis can identify clinicopathological risk factors affecting the degree of differentiation of HCC, which can provide criterion support for accurate diagnosis and prognostic treatment.

Objective To monitor the dynamic change of soluble myeloid cells trigger receptor 1 (sTREM-1)and the clearance rate of sTREM-1 (sTREM-1 c) in patients with sepsis shock and to explore its value in assessing the prognosis.Methods A total of 54 patients from January to December 2016 were divided into improved group and death group,sTREM-1 and sTREM-1c level at 1,5,7 and 9 d were monitored and the receiver-operating characteristic curve analysis was used to judge its value in prognosis.Results Comparison of baseline of APACHE Ⅱ score,PCT and age in 2 groups was statistically significant.After treatment,the sTREM-1 level declined,especially in improved group.Similarly,sTREM-1c in improved group at 5,7 and 9 d dropped more significantly than that in death group (P ＜ 0.05).At different time points,sTREM-1 7 topped the predictive value of AUC on the prognosis,followed by APACHE Ⅱ and sTREM-1 5,PCT,sTREM-1 9,sTREM-1c 9 and sTREM-1 1,and sTREM-1c 5 and sTREM-1c 7 were the minimum.Conclusion Effect of dynamic monitoring of sTREM-1 and sTREM-1c analysis in clinic is better than that of simply monitoring of sTREM-1.

Age-related macular degeneration (AMD) is a common cause of blindness among people over 65 in developed countries.With the rapidity of population aging process,the prevalence of AMD will be further increased.The application of anti-vascular endothelial factor growth medicine in ophthalmology has made great progress in the therapeutic effect and prognosis of wet AMD.In this context,many countries and regions have successively formulated guidelines for the AMD clinical diagnosis and treatment,especially the United States,Europe and Australia.Through the analysis of AMD clinical guidelines of American Academy of Ophthalmology (AAO) in 2015,and by comparing it with AMD analysis and treatment guidelines of European Society of Retina Specialists (EURETINA) in 2014,this paper provides an accurate,effective and comprehensive diagnosis strategy and lays a foundation for providing AMD patients with quality diagnosis and treatment plans.

Objective PCT and sTREM-1 combined with APACHE Ⅱ score for assessing diagnosis of sepsis and prognostic value.Methods The clinical data for related patients who had hospitalized between January and October 2015 were collected by prospective study methods.According to China guidelines for treatment of severe sepsis/septic shock (2014).The patients were divided into SIRS group,sepsis group,severe sepsis group,septic shock group,and control group.Results Levels of CRP and sTREM-1 were significantly higher in total sepsis group and subgroups than in SIRS group and control group,with a statistical difference (P ＜ 0.05);but there were no significant differences among he subgroups.Lactic acid level differed statistically between both total sepsis group and its subgroups and both control group and SIRS group,so did level of lactic acid between the other groups and septic shock group (P ＜ 0.05).PCT was significantly higher in total sepsis group and its subgroups than in the control group and SIRS group,so did it in septic shock and severe sepsis group than in sepsis group.PCT level was significantly higher in septic shock than in severe sepsis (P ＜ 0.05).APACHE Ⅱ scores were markedly in total sepsis group and its subgroups than in SIRS group and the control group;and it differed statistically between septic shock group and sepsis group (P ＜ 0.05).According to the ROC curve analysis,the area under the curve was 0.935,0.877,0.816,and 0.856 for PCT,sTREM-1,APACHE Ⅱ,CRP,and lactic acid,respectively.Conclusions Detection of serum PCT and sTREM-1 combined with APACHE Ⅱ score can be used to assess diagnosis of sepsis and prognostic value,which has more benefit to the diagnosis and treatment of sepsis.

Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions . Methods Retrospectively analyzed the contrast-enhanced ultrasound model and angiographic predictive model of 465 cases of the A prospective multicenter study of breast nodules contrast-enhanced ultrasound" that led the Sichuan Provincial People′s Hospital from January 2016 to April 2017 ,which included 69 cases of breast precancerous lesions and 396 other types benign lesions ,and the sensitivity ,specificity and accuracy of the diagnosis of breast precancerous lesions were calculated . Results The sensitivity of ultrasound predictive model for the diagnosis of precancerous lesions was 60 .9％ and AUC was 0 .681 . Precancerous lesions mainly showed non-concentricity , increased homogeneity , and increased lesions;other types of benign lesions mainly showed non-centripetal ,high uniformity enhancement and lesion size unchanged . Conclusions Contrast-enhanced ultrasound shows a potential value in the differential diagnosis of precancerous lesions and other types of benign lesions ,that can help clinicians to take early intervention measures for breast precancerous lesions ,but there are still many problems to be solved .

Objective To investigate the relationship between the composition of vaginal microbiota and the course of cervical precancerous lesion.Methods A total of 64 vaginal swabs were collected from 22 healthy women, 18 CINⅠ patients and 24 CINⅡ/Ⅲ patients who visited Obstetrics and Gynecology of the Second Xiangya Hospital of Central South University during July 2014 and July 2015.The Bacterial genomic DNA was extracted and the V3 and V4 hypervariable regions of 16S rRNA were amplified and high-throughput sequenced.The abundance and composition of vaginal microbiota were analyzed by Uparse, Mothur and LefSe statistical software.Results There was no significant difference in Alpha diversity index between CINⅡ/Ⅲ group(Chao:63±32;ACE:72±38;Simpson:0.70±0.27;Shannon:0.70±0.63) and control group ( Chao:48±24;ACE:54±25;Simpson:0.71±0.27;Shannon:0.65±0.58)(W=192,P=0.11;W=189,P=0.10;W=281,P=0.72;W=241,P=0.62).The ACE(85±37) and Chao(66±25) values of CINⅠgroup were significantly different from those of the control group (ACE:54±25;Chao:48±24)(W=99,P=0.006;W=113,P=0.02).At the phylum level, 78.69%(309 020/392 722) of the vaginal microbiota in the control group was Firmicutes, 16%(62 846/392 722) was Actinobacteria.Firmicutes was reduced to 64.86%(208 422/321 318) and Actinobacteria increased to 27.71%(89 040/321 318) in CINⅠgroup.The composition of vaginal microbiotain in CINⅡ/Ⅲ group was similar to those of control group.At the genus level, the composition of vaginal microbiota were similar between CINⅡ/Ⅲ group and control group, with Lactobacillus as predominant genus[71.81%(307 658/418 424)], Gardnerella[12.91%(55 299/428 424)], others such as Prevotella, atopobium were less.In the CINⅠ group, the abundance of Lactobacillus was decreased to 56.26%(180 787/321 318), Gardnerella was increased to 19.62%(63 057/321 318), and Listeria was increased to 7.7%(24 746/321 318).The composition of vaginal microbiota in the most samples was classified as CSTⅢ and CSTⅠ, with Lactobacillus inersand and Lactobacillus crispatus were dominant respectively.There was no significant difference in the composition of vaginal microbiota between the three groups(χ2=2.72, P=0.949).LEfSe analysis showed that the abundance of bacteria in CIN group and control group were varied.At the genus level, there were significant differences in the abundance of Geobacter, Atopobium and Ureaplasma (P<0.05, P<0.05, P<0.01, respectively).At the species level, there was significant difference in the abundance of Ureaplasma urealyticum serotype 9 (P<0.01).Conclusion The diversity and the composition of vaginal microbiota were similar between CIN patients and healthy women, but the abundances of some bacteria were varied, with Ureaplasma increased in patients with CIN.

Objective To explore the impact of different doses of dexmedetomidine on the anesthetic sedative and analgesic effect of anesthesia agents in hysterectomy of patients with uterine fibroids under laparoscopy.Methods 90 patients with uterine fibroids with ASA class Ⅰ or Ⅱ who were going to undergoing general intravenous anesthesia laparoscopic hysterectomy were selected and they were divided into group A (dexmedetomidine 0.4μg·kg-1·h-1,n=30) and group B (dexmedetomidine 0.2μg·kg-1·h-1,n=30) and group C (no dexmedetomidine,n=30) by digital random method.The analgesia effect (VAS score) of group A,group B and group C preoperation and postoperative 1h,12h and 24h,and the sedation (Ramsay sedation score) were compared.General information,postoperative blood pressure,heart rate,pulse oxygen saturation,postoperative patients'' satisfaction on analgesic effect and the sedation effect and adverse reactions of the three groups were also compared.Results Age,body mass index and other basic information of three groups had no statistically significant differences (all P＞0.05).The preoperative VAS score of the three groups also had no statistically significant difference (F=0.625,P＞0.05).Postoperative 12h,24h,the VAS scores of group A and group B were lower than those of C group,which of group A were lower than group B (F=11.250,P＜0.05,F=21.181,P＜0.05).The Ramsay sedation score was higher than that of C group[(3.67±0.18) vs.(2.13±0.11)].The satisfaction of group A was significantly higher than group B and group C (96.67％ vs.73.33％,46.67％,χ2=25.953).The Ramsay sedation score and satisfaction were higher than those of group B (all P＜0.05).There were no significant differences in blood pressure (F=0.362,P＞0.05),pulse oxygen saturation (F=0.978,P＞0.05) and heart rate among the three groups before and after operation (F=1.268,P＞0.05).There was no obvious adverse reaction in the three groups.Conclusion Dexmedetomidine can promote anesthetic sedative and analgesic effect of anesthesia agents in hysterectomy of patients with uterine fibroids under laparoscopy,and the dose 0.4μg·kg-1·h-1 of dexmedetomidine has better effect,feasibility and safety,it is worthy of clinical promotion.