[Effect of Friday surgery on clinical outcome of elderly patients with hip fracture under multidisciplinary treatment].

Objective: To assess the impact of Friday surgery on clinical outcomes in elderly patients with hip fracture under multidisciplinary treatment. Methods: A retrospective cohort study. The clinical data of 414 geriatric patients with hip fractures admitted to Zhongda Hospital Affiliated with Southeast University from January 2018 to March 2021 were analyzed retrospectively, including 126 males and 288 females with a mean age of (81.3±7.6) years. The patients were divided into two groups based on whether they underwent surgery on Friday or not. The Friday group(n=69) and the non-Friday group(n=345) were compared in terms of general information, American Society of Anesthesiologists(ASA) classification, fracture type, injury to admission time, preoperative waiting time, surgical method, anesthesia type and use of intensive care unit (ICU) fast track. Propensity score matching (PSM) was performed based on age, ASA grade, time from injury to admission, preoperative waiting time, hemoglobin and albumin levels at admission. Clinical outcomes were collected and compared between the two groups, including length of hospital stay, total hospitalization cost and 30-day, 90-day and 1-year mortality rates, and postoperative complications. Multivariate logistic regression analyses were conducted to identify influencing factors for 1-year mortality in geriatric patients with hip fracture. Results: Baseline data showed statistically significant differences in hemoglobin, albumin and preoperative waiting time between the two groups (all P<0.05). After PSM matching, 69 patients were included in each group, and no significant differences were observed in baseline data between the two groups (all P>0.05). There was no significant differences in 30-day mortality rate (4.3% vs 0, P=0.080), 90-day mortality rate (7.2% vs 1.4%, P=0.095), length of hospital stay [(10.85±4.45)d vs (10.92±3.68)d, P=0.919], total hospitalization cost [(60.9±15.4) thousands yuan vs (59.1±15.4) thousands yuan, P=0.489], postoperative complications [pneumonia (11.6% vs 13.0%, P=0.796), cardio-cerebrovascular complications (11.6% vs 8.7%, P=0.573) and delirium (5.7% vs 2.9%, P=0.245)] between the Friday group and the non-Friday group (all P>0.05). However, the 1-year mortality rate was higher in the Friday group than that in the non-Friday group(18.8% vs 4.3%, P=0.008). Multivariate analysis revealed that surgery on Friday (OR=11.222, 95%CI: 2.198-57.291, P=0.004), low hemoglobin levels at admission (OR=0.920, 95%CI: 0.875-0.967, P=0.001), hemiarthroplasty treatment (OR=5.127, 95%CI: 1.308-20.095, P=0.019) and longer surgery duration (OR=0.958, 95%CI: 0.927-0.989, P=0.009) were influencing factors for 1-year mortality in geriatric patients with hip fracture. Conclusions: In the context of multidisciplinary treatment, Friday surgery does not increase short-term mortality, length of hospital stay, total hospitalization cost or incidence of complications in geriatric patients with hip fracture. However, it remains a influencing factor for 1-year mortality in those patients.

[Research progress in transcriptional and immunological biomarkers associated with tuberculosis infection].

Tuberculosis (TB) is an infectious disease that poses a serious threat to human health. About a quarter of the world's population were infected with Mycobacterium tuberculosis in 2020, and the majority of them were latently infected. Approximately 5%-10% of the population with latent tuberculosis infection may progress to active TB disease. Identifying latent TB infection from active TB by biomarkers and screening people with latent TB infection at high risk of progression for preventive treatment by biomarkers that can reliably predict the progression is one of the most effective strategies to control TB. This article reviews the progress of research on transcriptional and immunological biomarkers for identifying TB infection and predicting the progression from latent infection to active TB, with the aim of providing new ideas for tuberculosis control.

[Analysis of safety and efficacy of laparoscopic surgery for gallbladder carcinoma].

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

Primary cilia are not calcium-responsive mechanosensors.

Primary cilia are solitary, generally non-motile, hair-like protrusions that extend from the surface of cells between cell divisions. Their antenna-like structure leads naturally to the assumption that they sense the surrounding environment, the most common hypothesis being sensation of mechanical force through calcium-permeable ion channels within the cilium. This Ca(2+)-responsive mechanosensor hypothesis for primary cilia has been invoked to explain a large range of biological responses, from control of left-right axis determination in embryonic development to adult progression of polycystic kidney disease and some cancers. Here we report the complete lack of mechanically induced calcium increases in primary cilia, in tissues upon which this hypothesis has been based. We developed a transgenic mouse, Arl13b-mCherry-GECO1.2, expressing a ratiometric genetically encoded calcium indicator in all primary cilia. We then measured responses to flow in primary cilia of cultured kidney epithelial cells, kidney thick ascending tubules, crown cells of the embryonic node, kinocilia of inner ear hair cells, and several cell lines. Cilia-specific Ca(2+) influxes were not observed in physiological or even highly supraphysiological levels of fluid flow. We conclude that mechanosensation, if it originates in primary cilia, is not via calcium signalling.

[Comparative analysis of work-related musculoskeletal disorders catalogues].

Work-related musculoskeletal disorders (WMSDs) refer to musculoskeletal disorders caused by work or work as the main cause, which are characterized by high prevalence and heavy burden of disease as a global problem. The classification and catalog of occupational diseases is of great significance for guiding the prevention and control of occupational diseases and safeguarding the rights and interests of workers. The types of WMSDs included in the list of occupational diseases vary greatly from country to country, and the regulations on specific pathogenic factors are also inconsistent. By sorting out and analyzing the lists and characteristics of WMSDs at home and abroad, and using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) in occupational health to standardize of WMSDs in various countries, which would lay the foundation for future multi-country WMSDs occupational health registration and disease burden research, and provide a reference for China to revise the WMSDs list.

Anti-biofilm potential of kefir-derived Lactobacillus paracasei L10 against Vibrio parahaemolyticus.

Vibrio parahaemolyticus, a kind of biofilm-forming foodborne bacterium, presents formidable challenges to the effectiveness of antimicrobial agents. Increasingly, the safety of chemical antimicrobials has aroused the widespread attention of the public. The development of the novel nature antimicrobial agents has become critical for controlling biofilm-related pollution and infections. In this paper, we investigated the antibacterial activity of Lactobacillus paracasei L10, and evaluated the inhibition and eradication effects of the cell-free supernatant (CFS) of the strain on V. parahaemolyticus biofilms in detail. We found that the CFS exhibited marked antibacterial activity against all tested pathogenic bacteria. In co-cultural assay, L. paracasei L10 could notably reduce cell viability in both plankton and biofilm of V. parahaemolyticus and this antagonism effect in biofilm was greater than that in planktonic state. Meanwhile, the growth of V. parahaemolyticus was completely inhibited when 6% (v/v) of the CFS was added, and the supernatant also showed a concentration-dependent manner to inhibit and eradicate the biofilms of V. parahaemolyticus while decreased the metabolic activity of the biofilm in the same way. Moreover, the fluorescence microscopic and confocal laser scanning microscopy images confirmed the anti-biofilm activity of the CFS. This study elucidates that L. paracasei L10 displays a significant anti-biofilm effect on V. parahaemolyticus and the mechanism of its antagonism merits further study, which provides theoretical support for further development and application of L. paracasei L10 as anti-biofilm agents.

Optical Shielding of Destructive Chemical Reactions between Ultracold Ground-State NaRb Molecules.

We propose a method to suppress the chemical reactions between ultracold bosonic ground-state ^{23}Na^{87}Rb molecules based on optical shielding. By applying a laser with a frequency blue-detuned from the transition between the lowest rovibrational level of the electronic ground state X^{1}Σ^{+}(v_{X}=0,j_{X}=0), and the long-lived excited level b^{3}Π_{0}(v_{b}=0,j_{b}=1), the long-range dipole-dipole interaction between the colliding molecules can be engineered, leading to a dramatic suppression of reactive and photoinduced inelastic collisions, for both linear and circular laser polarizations. We demonstrate that the spontaneous emission from b^{3}Π_{0}(v_{b}=0,j_{b}=1) does not deteriorate the shielding process. This opens the possibility for a strong increase of the lifetime of cold molecule traps and for an efficient evaporative cooling. We also anticipate that the proposed mechanism is valid for alkali-metal diatomics with sufficiently large dipole-dipole interactions.

Streptomyces-derived actinomycin D inhibits biofilm formation via downregulating ica locus and decreasing production of PIA in Staphylococcus epidermidis.

AIM: The objective of this study was to investigate the biofilm inhibitory activity of Streptomyces-derived actinomycin D against biofilm formation by Staphylococcus epidermidis. METHODS AND RESULTS: The microtitre plate method and microscopy were used to detect the biofilm formation of S. epidermidis. And an attempt was made to detect the effect of actinomycin D on important biofilm components, exopolysaccharides (EPS) in S. epidermidis using precolumn derivation HPLC. Also cell surface hydrophobicities of S. epidermidis were assessed to explore action mechanisms. The qPCR was performed to demonstrate the genetic mechanisms of biofilm formation by S. epidermidis. Unlike other antibiotics, actinomycin D (1·5 µg ml-1 ) from Streptomyces luteus significantly inhibited biofilm formation by S. epidermidis. Additionally, it effectively inhibited S. epidermidis cells from adhering to glass slides. Actinomycin D downregulated ica locus and then the reduced polysaccharide intercellular adhesin production caused S. epidermidis cells to become less hydrophobic, thus supporting its anti-biofilm effect. CONCLUSION: Streptomyces-derived actinomycin D is active in inhibiting the biofilm formation of S. epidermidis. SIGNIFICANCE AND IMPACT OF THE STUDY: Actinomycin D can be used as a promising antibiofilm agent in inhibiting S. epidermidis biofilm formation. The study is also the first insight into how actinomycin D inhibited the biofilm formation of S. epidermidis. Actinomycin D could potentially be used to reduce the risk of biofilm-associated infections. Our study also suggests that the metabolites from Actinomycete strains keep further attention as potential antibiofilm agents against biofilm formation of S. epidermidis, even biofilm infections of the other bacteria.

[Preliminary application of postoperative fast track transfer to intensive care unit for the geriatric hip fractures under enhanced recovery after surgery].

Objective: To develop a fast track transfer to intensive care unit (ICU) for the perioperative high-risk elderly patients after hip fracture surgery and analyze the preliminary clinical effect of the application. Methods: From January 2014 to December 2017, before the application of postoperative fast track transfer to ICU, the clinical data of 195 elderly patients with hip fracture were included in a retrospective analysis. Among 195 hip fracture patients, 18 were transferred to ICU post operation (non-fast track group). Multivariate logistic regression analysis was applied to investigate relevant risk factors for transferring to ICU after hip fracture surgery. Based on risk factors acquired from the analysis and clinical experience, the fast track transfer to ICU for the perioperative high-risk elderly patients after hip fracture surgery was constructed according to the preliminary and experiential criteria. From January 2018 to December 2019, the clinical data of 70 patients (fast track group) who were transferred to ICU after hip fracture surgery through the fast track were collected and compared with non-fast track group. Results: Multivariate regression analysis revealed that American Society of Anesthesiologists classification(≥Ⅲ) (OR=4.260, 95%CI:1.157-15.683, P=0.029), pre-hospital stage (≥48 h) (OR=4.301, 95%CI:1.212-15.266, P=0.024), hemoglobin concentration at admission(<90 g/L) (OR=7.979, 95%CI:1.936-32.889, P=0.004), coronary heart disease as one comorbidity(OR=6.063, 95%CI:1.695-21.693, P=0.006) were independent risk factors for transferring to ICU after hip fracture surgery. There were no significant difference in gender, age, fracture type, hemoglobin concentration at admission and time of pre-hospital stage between the non-fast track group and fast track group(all P>0.05). However, the number of comorbidities in the fast track group was significantly higher than that in the non-fast track group (Z=-1.995, P=0.046). The time to surgery, postoperative hospital stay, and length of hospital stay in fast track group were all significantly less than those in non-fast track group (Z=-2.121, -2.726, -3.130, all P<0.05). Also, there were fewer medical consultations needed and fewer patients who stayed in ICU more than or equal to 2 nights in fast track group than that in non-fast track group(all P<0.05). There were no significant difference in the rate of patients who transferred from the general ward to ICU after transferring from ICU to the general ward, the proportion of patients who received more than or equal to 4 departments, operation time, hospitalization expense, mortality during hospitalization, 30-day mortality and 90-day mortality after operation between the two groups(all P>0.05). Conclusions: The fast track constructed in this study can reduce time to surgery, postoperative hospitalization stay and length of hospitalization stay for the perioperative high-risk elderly patients with hip fractures and is a specific clinical application of eras concept based on multidisciplinary team.

New Opportunities and Challenges for Forensic Medicine in the Era of Artificial Intelligence Technology.

ABSTRACT: Traditional forensic identification relies on forensic experts to manually extract information and provide identification opinions based on medicine, biology and other fields of knowledge combined with personal work experience, which is not only time-consuming and require great effort, but also affected by subjective factors that are difficult to overcome. In the era of big data, the booming development of artificial intelligence brings new ideas to forensic medicine. In recent years, forensic researchers at home and abroad have conducted many studies based on artificial intelligence technology, such as face recognition, age and gender identification, DNA analysis, postmortem interval estimation, injury and cause of death identification, showing the feasibility and advantages of using artificial intelligence technology to solve forensic identification problems. As a new means of technology that has adapted to the development of the times, artificial intelligence has brought new vitality to forensic medicine, but at the same time also some new challenges. How to deal with these challenges scientifically and form a new mode of 'artificial intelligence plus forensic medicine' with artificial intelligence and forensic medicine developing collaboratively is a new direction for the development of forensic medicine in the era of big data.

Antibiofilm activity of three Actinomycete strains against Staphylococcus epidermidis.

This study sought to identify novel and nontoxic biofilm inhibitors from the Actinomycete library for attenuating biofilm formation by Staphylococcus epidermidis. After investigating the antibiofilm activities of spent media from 185 Actinomycete strains using two S. epidermidis strains (ATCC 35984 and a clinical strain 5-121-2) as target bacteria, three strains of tested Actinomycete (TRM 46200, TRM 41337, and TRM 46814) showed a significant inhibition against S. epidermidis biofilm formation without affecting the growth of planktonic cells. The characteristics of three strains of supernatants suggested that hydrophilic compound possibly extracellular peptides or proteins from these three strains, confer the biofilm reduction in S. epidermidis. An attempt was made to assess their effects on biofilm components and cell surface hydrophobicities in order to disclose acting mechanisms. The crude proteins from spent media of three strains degraded not only exopolysaccharides but also extracellular DNA in S. epidermidis biofilm. The active substances in crude proteins caused S. epidermidis cells to become less hydrophobic. Given these results, the metabolites from Actinomycete strains should keep further attention as potential antibiofilm agents against biofilm formation of S. epidermidis, even biofilm infections of the other bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Staphylococcus epidermidis infections are frequently associated with biofilms that are difficult to eradicate with conventional antibiotics. The new biofilm inhibitors from Actinomycete will have a great value in the prevention and treatment of dairy cow mastitis and other biofilm-related infections.

[Suprapubic-assisted laparoendoscopic single-site surgery in nephroureterectomy A case series of 4 patients].

Objective: To evaluate the feasibility and clinical value of suprapubic-assisted laparoendoscopic single-site surgery (SA-LESS) in nephroureterectomy using method of transvaginal natural orifice specimen extraction (NOSE) (SA-LESS+TV-NOSE NU). Methods: Four patients (three cases of renal pelvic carcinoma and one case of ureteral carcinoma) undergoing SA-LESS+TV-NOSE NU were enrolled between April 2015 and January 2016. After general anesthesia, the patients were placed in the lithotomy position with the affected side elevated by 60°. Two trocars were inserted at the medial margin of umbilicus, and the third one was inserted into abdominal cavity at the superior margin of pubic symphysis. The operation was performed under a direct vision with a 5.4 mm 0° flexible-tip laparoscope. Firstly, the distal ureter was isolated completely and blocked by a Hem-O-lok clip. Then, the laparoscopic nephrectomy was performed according to the standard method. Finally, the bladder cuff excision was executed and the incision was sutured. The intact specimen was placed inside a homemade bag and removed through the incision at posterior vaginal fornix. Results: All the procedures were successfully performed. The median operative time was 150 (range: 120 to 210) minutes, and the median estimated blood loss was 180 (range: 80 to 350) ml. No major perioperative complications occurred. The mean visual analogue score (VAS) of 24 hours and 48 hours after operation were 3.25 (range: 2 to 5) and 2.25 (range: 2 to 3). All the patients resumed ambulation on postoperative day 1. Pelvic drainage tube was removed on postoperative day 2-4. On postoperative day 7, urethral catheter was removed. The patients were discharged on postoperative day 7-9. During the follow-up of 20-29 months, the patient recovered well with no case of incisional hernia and pelvic, abdominal infections. The vaginal fornix incision healed well, and the umbilical and suprapubic puncture scars were not obvious. All the patients completed the patient-assessed acromegaly symptom questionnaire PASQ. The average PSAQ score of 3 months after surgery was 34.5. Three of them restarted their sex lives, with an average female sexual function index score of 16.0, which was not significantly different with that of preoperation (15.6). There was no tumor recurrence, metastasis and implantation in all cases. Conclusion: SA-LESS+TV-NOSE NU is safe and feasible for upper tract urothelial carcinoma with faster postoperative recovery, less pain, shorter hospitalization time, better cosmetic results, and does not cause negative effect on the female sexual function.

Detection of Ancestry Information of Urumqi Mongolians Based on the AIM-InDels Loci Multiplex System.

ABSTRACT: Objective To explore the genetic background and structure of Urumqi Mongolians, the previously developed 39-AIM-InDels panel for ancestry inference was utilized in the present study. Methods The blood samples of 145 unrelated healthy Urumqi Mongolian individuals were collected and genotyped. The compositions of ancestry information of Urumqi Mongolians were studied with 17 different populations from three continents （East Asia, Europe and Africa） as reference populations. Then, multiple population genetics and bioinformatics analysis methods were applied, the Fst and DA values between matched populations were compared and analyzed, PCA analysis was performed and a phylogenetic tree was constructed. The proportions of ancestry information components of Urumqi Mongolians were analyzed with Structure software, etc. Results The ancestry information components of Urumqi Mongolian group in different intercontinental populations accounted for 89%, 7%, and 3% of East Asian, European, and African populations, respectively. Compared with other intercontinental populations, Urumqi Mongolian group and East Asian populations have lower Fst and DA values, and they were in the same cluster in PCA analysis as well. In a phylogenetic tree, the Urumqi Mongolian group was in the same branch as East Asian populations. Conclusion Urumqi Mongolian group had relatively close genetic relationships with East Asian populations, and the proportion of its East Asian ancestry was about 89%.

Effect of LSR polymorphism on blood lipid levels and age-specific epistatic interaction with the APOE common polymorphism.

The lipolysis stimulated lipoprotein receptor (LSR) is an apolipoprotein (Apo) B and ApoE receptor that participates in the removal of triglyceride-rich lipoproteins during the postprandial phase. LSR gene is located upstream of APOE, an important risk factor for cardiovascular disease (CVD). Since the APOE common polymorphism significantly affects the variability of lipid metabolism, this study aimed to determine the potential impact of a functional SNP rs916147 in LSR gene on lipid traits in healthy subjects and to investigate potential epistatic interaction between LSR and APOE. Unrelated healthy adults (N = 432) and children (N = 328, <18 years old) from the STANISLAS Family Study were used. Age-specific epistasis was observed between APOE and LSR, reversing the protective effect of APOE ε2 allele on cholesterol, ApoE and low-density lipoprotein levels (ß: .114, P: .777 × 10-8 , ß: .125, P: .639 × 10-3 , ß: .059, P: .531 × 10-3 , respectively). This interaction was verified in an independent adult population (n = 1744). These results highlight the importance of the LSR polymorphism and reveal the existence of complex molecular links between LSR and ApoE for the regulation of lipid levels, revealing potential new pathways of interest in type III hyperlipidemia and its involvement in CVD pathology.

The development of CotA mediator cocktail system for dyes decolorization.

AIMS: The increasing use of dyes leads to serious environmental concerns, it is significant to explore eco-friendly and economic approaches for dye decolorization. This study aimed to develop mediator cocktail (AS and ABTS) for enhancing the capability of laccase-mediator system in the removal of dyes. METHODS AND RESULTS: By mediator screening, the mediators of ABTS and AS (ABTS, 2, 2'-azino-bis-(3-ethylbenzothiazo-thiazoline-6-sulphonic acid); AS, acetosyringone) were combined for dyes decolorization. The Box-Behnken Design and response surface analysis was performed to optimize experiment conditions. Comparing the CotA-ABTS-AS cocktail system with CotA-single mediator system showed that the coupling of ABTS and AS could increase the decolorization rate 15 times higher, save a third of the cost and shorten the reaction time by 50%. In addition, our studies revealed that sequential oxidation may occur in CotA-ABTS-AS system. CONCLUSIONS: Compared with CotA laccase-single mediator system, the CotA-ABTS-AS cocktail system showed advantages including higher efficiency, lower cost and shorter reaction time. SIGNIFICANCE AND IMPACT OF THE STUDY: This was the first report on the dyes decolorization by laccase mediator cocktail system. These results paved the curb for the application of laccase mediator system in various industrial processes.

[CTAB-PEG DNA Extraction from Fungi with High Contents of Polysaccharides].

Polysaccharides influence concentration and purity of extracted DNA. Here we present rapid and efficient protocol for DNA extraction from samples rich in polysaccharides. The technique has been developed using cultures of Schizophyllum commune and involves a modification of known Cetyltrimethyl Ammonium Bromide (CTAB) protocol. To remove polysaccharides, Polyethylene Glycol (PEG) 8000 was added during DNA precipitation. Genomic DNA obtained with the CTAB-PEG method had high integrity, with average fragment size >30 kb, the concentration higher than 100 ng/µL, and the yield more than 30 µg/g. Presented technique is suitable for DNA extraction from fungi, bacteria, archaea or even mollusks with high polysaccharide content.

[Experimental studies on correlation between nucleolus spindle-related protein 1 and the malignant progression and prognosis of human glioblastoma multiforme].

Objective: To investigate the correlation between nucleolus spindle-related protein 1 (NUSAP1) and malignant progression and prognosis of human glioblastoma multiforme (GBM). Methods: RT-PCR and immunohistochemical technique were applied to analyze NUSAP1 expression level in GBM surgical specimens. Correlations between NUSAP1 expression and molecular classification and survival of patients with GBM were also investigated in TCGA database. The gene silencing technique was used to silence NUSAP1 expression in U87 cells, CCK-8 assay was used to detect cell proliferation, flow cytometry was used to detect cell cycle changes, and in vivo tumorigenicity was evaluated after NUSAP1 silencing in tumor-bearing mice. Results: NUSAP1 expression level in GBM was higher than that in non-tumor brain tissue. Survival curve analysis showed that the survival time of GBM patients with high NUSAP1 expression decreased significantly (P<0.01). NUSAP1 expression was relatively lower in mesenchymal and neural molecular subtypes of GBM, when compared with the other two molecular subtypes. And it was closely related with specific genetic aberrations (such as PTEN loss and IDH1 mutation). Silencing NUSAP1 inhibited G2/M cell cycle progression of GBM cells, and inhibited cell proliferation both in vitro and in vivo. Conclusion: Expression of NUSAP1 is closely related to progress and prognosis of GBM, and can be a biomarker reflecting GBM prognosis and act as a therapeutic target with potential clinical application value.

MicroRNA-155 is a biomarker of T-cell activation and immune dysfunction in HIV-1-infected patients.

OBJECTIVES: MicroRNA-155 (miR-155) regulates T-cell differentiation and activation. It has also been associated with HIV infection. However, it remains unclear whether miR-155 is related to the T-cell response in HIV-infected individuals (e.g. T-cell activation and exhaustion). METHODS: We performed a cross-sectional study involving 121 HIV-1-infected patients on highly active antiretroviral therapy (HAART) and 43 HAART-naïve patients. MiR-155 levels in the peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (PCR). T-cell immune activation, exhaustion, and homeostasis were measured by determining the expression of CD38, programmed death 1 (PD-1) and CD127 via flow cytometry. RESULTS: The levels of miR-155 in total peripheral blood mononuclear cells, CD4 T cells and CD8 T cells from HIV-1-infected patients were increased (P < 0.01). Nonresponders and HAART-naïve patients also exhibited a higher percentage of CD8+ CD38+ T cells and a lower percentage of CD4+ CD127+ and CD8+ CD127+ T cells (P < 0.05). We also found higher levels of PD-1 expression on the CD4+ and CD8+ T cells of HIV-1-infected patients (P < 0.05). CONCLUSIONS: Our findings suggest that miR-155 levels in the peripheral blood of HIV-1-infected patients are increased and associated with T-cell activation. Therefore, miR-155 is a potential biomarker of the immune response following HIV-1 infection.

Immunotolerant indoleamine-2,3-dioxygenase is increased in condyloma acuminata.

BACKGROUND: The tryptophan-depleting enzyme indoleamine-2,3-dioxygenase (IDO) is critical for the regulation of immunotolerance and plays an important role in immune-associated skin diseases. OBJECTIVES: To analyse the level of IDO in condyloma acuminata (CA) and its role in this condition. METHODS: IDO expression was assessed in the skin and peripheral blood of healthy controls and patients with CA. To assess the role of skin IDO in immunity, the ability of isolated epidermal cells to metabolize tryptophan and the influence on polyclonal T-cell mitogen (PHA)-stimulated T-cell proliferation were explored. RESULTS: IDO median fluorescence intensities in peripheral blood mononuclear cells from patients with CA were similar to those from healthy controls. Immunohistochemistry showed that IDO+ cells were rare in normal skin and the control skin of patients with CA, but were greatly accumulated in wart tissue. Most fluorescence signals of IDO+ cells did not overlap with those of CD1a+ Langerhans cells. Human papillomavirus (HPV) DNA probe in situ hybridization showed a large number of IDO+ cells in the HPV- site. Keratinocytes in the skin of healthy controls and the circumcised skin of patients with CA could minimally transform tryptophan into kynurenine, but IDO-competent epidermal cells from warts could transform tryptophan. In addition, these IDO-competent epidermal cells could inhibit PHA-stimulated T-cell proliferation. The addition of an IDO inhibitor, 1-methyl-d-tryptophan, restored the inhibited T-cell proliferation. CONCLUSIONS: Abnormally localized high IDO expression might be involved in the formation of a local immunotolerant microenvironment.

[Experimental study of glioma stem cell-mediated immune tolerance in tumor microenvironment].

Objective: To investigate the tumor microenvironment of immune tolerance induced by glioma stem cells (GSC). Methods: Human GSC SU3 cells transfected with red fluorescent protein (SU3-RFP) gene were implanted into the brain, subcutis (armpit and foot), liver and abdominal cavity of transgenic green fluorescence protein (GFP) nude mice to establish RFP(+) /GFP(+) dual fluorescence solid tumor model. The re-cultured cells derived from implanted tumor tissues, SU3-RFP cells co-cultured with peritoneal fluid of transgenic GFP nude mice and malignant ascites of tumor-bearing mice were observed by fluorescence microscopy and real-time video image tracing to analyze the microenvironment of immune tolerance mediated by RFP(+) /GFP(+) implanted tumor. Results: Dual fluorescence labeled frozen section showed that all of cells in the tumor microenvironment were GFP(+) , while the pressed tissue-patch showed that the tumor blood vessels exhibited a RFP(+) /GFP(+) double-positioning yellow. In the GFP single fluorescence labeled tumor tissue, all of cells in the microenvironment were green, including tumor edge, necrotic foci and blood vessel. Among them, CD68(+) , F4/80(+) , CD11c(+) , CD11b(+) and CD80(+) cells were observed. In the dual fluorescence labeled co-cultured cells, the phagocytosis and fusion between green host cells and red tumor cells were also observed, and these fusion cells might transfer to the malignant dendritic cells and macrophages. Conclusions: The tumor microenvironment of immune tolerance induced by GSC is not affected by the tissue types of tumor-inoculated sites, and the immune tolerance mediated by inflammatory cells is associated with the inducible malignant transformation, which may be driven by cell fusion.