A Bibliometrics of the Treatment of Alopecia Areata in the Past Twenty Years.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder characterized by hair loss on the scalp, face, and other body areas. Despite affecting approximately 2% of the global population, there has been no previous bibliometric analysis specifically focusing on AA treatment that can guide researchers in exploring promising treatment options and directing future research efforts. SUMMARY: This study conducted a bibliometric analysis of AA treatment research, encompassing publications from 2003 to 2022. A total of 1,323 papers from 65 countries, predominantly led by the USA and China, were included in the analysis. The number of publications related to AA treatment showed a notable increase over the years. Prominent research institutions included the University of Manchester, Icahn School of Medicine at Mount Sinai, University of Miami, and Columbia University. Among the journals, Dermatologic Therapy stood out as the most popular, while the Journal of the American Academy of Dermatology appeared as the most frequently co-cited publication.

Identification of nonfunctional SPATA20 causing acephalic spermatozoa syndrome in humans.

Acephalic spermatozoa syndrome (ASS) is a rare and severe type of teratozoospermia characterized by the predominance of headless spermatozoa in the ejaculate. However, knowledge about the causative genes associated with ASS in humans is limited. Loss-of-function of SPATA20 has been suggested to result in the separation of the sperm head and flagellum in mice, whereas there have been no cases reporting SPATA20 variants leading to human male infertility. In this study, a nonsense mutation in SPATA20 (c.619C > T, p.Arg207*) was first identified in an ASS patient. Moreover, this variant contributed to the degradation of SPATA20 and was associated with decreased expression of SPATA6, which plays a vital role in the assembly of the sperm head-tail conjunction in humans. In addition, the infertility caused by loss-of-function mutation of SPATA20 might not be rescued by intracytoplasmic sperm injection (ICSI). Collectively, our findings suggested that SPATA20 might be required for sperm head-tail conjunction formation in humans, the nonfunction of which may lead to male infertility related to ASS. The discovery of the loss-of-function mutation in SPATA20 enriches the gene variant spectrum of human ASS, further contributing to improved diagnosis, genetic counseling and prognosis for male infertility.

Predictive value of circulating cystatin C level in patients with acute coronary syndrome: a meta-analysis.

Circulating cystatin C level has been identified as a predictor of adverse outcomes in patients with coronary artery disease (CAD). This meta-analysis aimed to investigate the value of circulating cystatin C level for predicting adverse outcomes in patients with acute coronary syndrome (ACS). We comprehensively searched articles indexed in Pubmed and Embase databases from their inceptions to 30 November 2019. All available observational studies that investigated the association between circulating cystatin C level and major adverse cardiovascular events [MACE] (including death, heart failure, re-infarction, target vascular revascularization, angina and stroke) or all-cause mortality in patients with ACS were included. The prognostic value was expressed by pooling the multivariable-adjusted hazard risk (HR) with 95% confidence interval (CI) for the highest versus the lowest category of cystatin C level. Eleven eligible studies (12 articles) with 4600 ACS patients were identified. Meta-analysis indicated that the highest versus lowest category of cystatin C level was associated with higher risk of MACE (HR 2.28; 95% CI 1.92-2.71) and all-cause mortality (HR 2.89; 95% CI 1.43-5.83) after adjustment for estimated glomerular filtration rate (eGFR) or creatinine. Subgroup analysis by subtypes of patients, study design, follow-up duration and cutoff level of cystatin C further confirmed the value of cystatin C level for predicting MACE. Elevated circulating cystatin C level at baseline is strongly and independently associated with an increased risk of MACE and all-cause mortality in patients with ACS. Determination of circulating cystatin C level has potential to improve risk stratification of ACS patients.

The Stromal Vascular Fraction Improves Maintenance of the Fat Graft Volume: A Systematic Review.

BACKGROUND AND OBJECTIVES: With the continued application of fat grafting in plastic surgery, many studies have focused on various factors to improve maintenance of the fat graft volume, such as platelet-rich plasma, adipose-derived stromal/stem cells, and the stromal vascular fraction (SVF). In addition, many review articles have investigated the functions of platelet-rich plasma and adipose-derived stromal/stem cells in fat grafting, although the usefulness of the SVF remains unclear. The aim of the present review was to determine whether SVF use could maintain a fat graft. METHODS: A systematic review was conducted of the PubMed, Cochrane Central Register of Controlled Trials, and Embase databases of original articles published up to February 2018. RESULTS: Relevant articles were identified by screening the abstracts. A total of 58 full texts were initially identified. After exclusion, 17 articles, including 6 animal studies and 11 clinical studies, were included for analysis. CONCLUSIONS: Most studies found a significant and measurable long-term effect of SVF-enhanced fat grafting on breast augmentation and defects, wound healing, scaring, and facial aesthetic outcomes. Stromal vascular fraction use did not result in a higher instance of complications and, thus, can be considered a safe option for fat grafting.

Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy.

OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. METHODS: Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. RESULTS: We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. CONCLUSION: A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

Effects of promethazine or dexamethasone pretreatment on mivacurium-induced histamine release in children.

OBJECTIVE: To determine the effects of pretreatment with either promethazine or dexamethasone on mivacurium-induced histamine release in children. METHODS: Eighty ASA I-II children (4-10 years of age) scheduled for tonsillectomy and/or adenoidectomy were randomly divided into 4 groups (n = 20 per group) designated as either the rocuronium, mivacurium, dexamethasone (DXM), or promethazine group. Children in the DXM and promethazine groups were treated separately with intramuscular DXM 0.2 mg·kg(-1) or promethazine 0.5 mg·kg(-1) injections 60 min before operation. Radial artery blood samples were collected to quantify plasma histamine concentrations 1 min before and 1, 3, and 5 min after administration of the relaxant. Mean arterial pressure (MAP), heart rate (HR), and skin flushing were recorded at the same time. RESULTS: No significant decreases in plasma histamine concentrations were observed between groups; however, more stable MAP and HR and less skin flushing were observed in DXM group participants compared with individuals in the mivacurium group (P < 0.05). By contrast, children in the promethazine group had significantly decreased plasma histamine concentrations and stable MAP and HR (without a significant increase in HR) compared with patients in mivacurium group. In addition, skin flushing was significantly decreased compared with that observed in the rocuronium group (P < 0.05). CONCLUSIONS: Pretreatment with promethazine significantly decreased mivacurium-induced histamine release in children and provided stable hemodynamics during administration of anesthesia.

Resurfacing of multiple adjacent defects with free multipaddle SCIAP flaps.

BACKGROUND: The efficient resurfacing of multiple adjacent defects (MADs) requires precise reconstructive strategy. Various approaches (e.g., several flap transferring or prelamination of the recipient site) have been reported, but recipient-site impairments, pain, long hospitalization, and low cost-benefit results fatefully considered them as compromise approaches. This study aims to evaluate the feasibility of MADs reconstruction with free multipaddle superficial circumflex iliac artery perforator (SCIAP) flaps. METHODS: From Dec 2015 to Dec 2020, we enrolled patients with upper and lower extremity defects treated with various multipaddle SCIAP flaps (2-paddle, 3-paddle, and 4-paddle). Patient demographics and outcomes of each group were collected. RESULTS: Thirty-two, 21, and 6 patients underwent 2-paddle, 3-paddle, and 4-paddle SCIAP flaps transfers, respectively. All multipaddle SCIAP flaps survived without vascular problems, and the donor sites were closed directly. Except for 3 cases of 2-paddle SCIAP flaps drained by superficial circumflex iliac vein venous return, most cases (n = 56) were drained by venae comitans. Minor complications, including partial flap necrosis (4 cases) and lateral femoral cutaneous nerve palsies (11 cases), were treated conservatively. All patients were satisfied with the reconstructive outcome. CONCLUSION: Multiple adjacent defects reconstruction is still a Gordian knot and lacks a golden standard. The free multipaddle SCIAP flap was demonstrated as a promising alternative, not only enriching its versatility but also initially highlighting the "replace need with need" reconstructive demand.

Novel variations in TENT5D lead to teratozoospermia in infertile patients.

PURPOSE: Teratozoospermia is the main pathogenic factor of male infertility. However, the genetic etiology of teratozoospermia is largely unknown. This study aims to clarify the relationship between novel variations in TENT5D and teratozoospermia in infertile patients. MATERIALS AND METHODS: Two infertile patients were enrolled. Routine semen analysis of patients and normal controls was conducted with the WHO guidelines. Whole-exome sequencing (WES) was conducted to identify pathogenic variants in the two patients. Morphology and ultrastructure analysis of spermatozoa in the two patients was determined by Papanicolaou staining, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The functional effect of the identified variants was analyzed by immunofluorescence staining and western blotting. The expression of TENT5D in different germ cells was detected by immunofluorescence staining. RESULTS: Two new hemizygous variations, c.101C > T (p.P34L) and c.125A > T (p.D42V), in TENT5D were detected in two patients with male infertility. Morphology analysis showed abnormalities in spermatozoa morphology in the two patients, including multiple heads, headless, multiple tails, coiled, and/or bent flagella. Ultrastructure analysis showed that most of the spermatozoa exhibited missing or irregularly arranged '9+2' structures. Further functional experiments confirmed the abrogated TENT5D protein expression in patients. In addition, both p.P34L and p.D42V substitutions resulted in a conformational change of the TENT5D protein. We precisely analyzed the subcellular localization of TENT5D in germ cells in humans and mice. And we found that TENT5D was predominantly detected in the head and flagellum of elongating spermatids and epididymal spermatozoa. CONCLUSIONS: Our results showed further evidence of a relationship between TENT5D mutation and human male infertility, providing new genetic insight for use in the diagnosis and treatment of male infertility.

The role of IL-6 in bone marrow (BM)-derived mesenchymal stem cells (MSCs) proliferation and chondrogenesis.

Rheumatoid arthritis (RA) is the most common degenerative arthritic cartilage and represents a disease where the prospect of stem cell therapy offers considerable hope. Currently, bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs) for cell therapy. In the pathology of RA, the pro-inflammatory cytokines, such as interleukin 6 (IL-6) play a pivotal role. To investigate the direct role of IL-6 in the chondrogenic differentiation of murine MSCs (mMSCs), we isolate MSCs from the murine bone marrow, and induce MSCs chondrogenesis with different concentrations of IL-6 in vitro. Through detecting the histological and histochemical qualities of the aggregates, we demonstrate that IL-6 inhibited the differentiation of MSCs into chondrocytes in the dose-dependence manner. These findings suggest that possible strategies for improving the clinical outcome of cartilage repair procedures.

[Sequencing and analysis of the complete mitochondrial DNA of Chinese moccasin for medicinal use].

OBJECTIVE: To sequence and analyze the complete mitochondrial DNA of Chinese moccasin. METHODS: The circular 17 541 bp sequence of mitochondrial DNA (mtDNA) of Chinese moccasin was determined by Ex-Taq PCR, TA-cloning and primer-walking methods. RESULTS: This mitogenome contained 37 coding genes (including 22 tRNA, 2 rRNA and 13 protein-coding genes) and two control regions (CR and psiCR). The gene content and arrangement of Chinese moccasin mtDNA was similar to those of other vipers reported so far. CONCLUSION: The characteristics of the replication origin and the tRNA arrangement of snake mitochondrial genomes can be used for identification of medicinal snakes.

Negative pressure wound therapy (NPWT) is superior to conventional moist dressings in wound bed preparation for diabetic foot ulcers: A randomized controlled trial.

OBJECTIVES: To compare the efficacy of negative pressure wound therapy (NPWT) and alginate dressings on wound bed preparation prior to split thickness skin graft (STSG) surgery for patients with chronic diabetic foot ulcers (DFUs). METHODS: Between September 2022 and March 2023, we completed a randomized controlled trial in Nanjing First Hospital and PLA 454 Hospital. Patients were divided into 2 groups: i) the NPWT group (with vacuum-assisted closure, n=50); ii) the control group (with alginates dressings, n=50). Once DFU wound was filled with healthy granulation tissues, STSG surgery was performed. The time to STSG surgery was regarded as the primary outcome. The survival rates of skin graft, the wound blood perfusion, the wound neutrophil extracellular traps (NETs) formation, and polarization of M1 and M2 macrophages in DFU wounds were regarded ad secondary outcomes. RESULTS: Patients in the NPWT group had less time to STSG surgery than the control group. The patients in the NPWT group had prominently increased survival rates of skin graft, increased wound blood perfusion, and decreased NET formation in comparison with the control group. The macrophages in DFU wounds switched from M1 to M2 phenotype in the NPWT group. CONCLUSION: Negative pressure wound therapy is superior to conventional moist dressings in wound bed preparation prior to STSG surgery for patients with chronic DFUs.

Identification of biallelic variations of CEP70 in patients with male infertility.

Introduction: Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited. Methods: Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis. Results: In this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70-/- male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice. Conclusions: Biallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.

A novel splicing mutation identified in a DMD patient: a case report.

Background: Duchenne muscular dystrophy (DMD, ORPHA:98896) is a lethal X-linked recessive disease that manifests as progressive muscular weakness and wasting. Mutations in the dystrophy gene (DMD) are the main cause of Duchenne muscular dystrophy. Case presentation: This study aims to determine novel mutations of DMD and help preimplantation genetic diagnosis (PGD) for family planning. Here present a 4-year-old Chinses boy with DMD, whole-exome sequencing (WES) was performed to identify the molecular basis of the disease. It was confirmed that the boy carried a novel hemizygous mutation of NC_000023.11(NM_004006.3): c.5912_5922 + 19delinsATGTATG in DMD which inherited from his mother. This led to the aberrant splicing of DMD which demonstrated by a minigene splicing assay and further resulted in the impairment of the dystrophy protein. Conclusions: Our study discovered a novel splicing mutation of DMD in a DMD patient, which expands the variant spectrum of this gene and provide precise genetic diagnosis of DMD for timely therapy. Meanwhile, this finding will supply valuable information for preimplantation genetic diagnosis.

Sutures positioning technique enhances the predictability and concordance between preoperative simulation and actual outcomes in rhinoplasty.

BACKGROUND: The predictability and concordance between simulated and actual outcomes in rhinoplasty are uncertain. Here, we introduce a suture positioning technique (SPT), a simple and low-cost method to minimize the gap between the simulated and actual outcomes of rhinoplasty. METHODS: Seventy patients were enrolled in this study between January 2018 and January 2021. Preoperative simulations were performed using Adobe Photoshop. The control group underwent surgery using simulation and intuition. In the SPT group, sutures were used to assist in the preoperative identification of the ideal nasal tip position. The SPT effectiveness was tested by measuring the nasal parameters and using the patient's subjective satisfaction questionnaire at T1 (Time 1, immediately postoperatively) and T2 (Time 2, at least 1 year postoperatively). RESULTS: The intraclass correlation coefficient test showed a satisfactory correlation between simulation and postoperative outcomes in both groups. However, the SPT group had a higher correlation than the control group, especially for the nasal length (16% higher at T1 and 15% higher at T2). The mean absolute difference (MAD) between the outcomes and simulation indicated that the MAD of nasal tip projection between T2 and simulation and MAD of nasal length between T1 (or T2) and simulation were statistically significant between groups. Additionally, the SPT group was more satisfied with the postoperative outcomes and were consistent with the preoperative simulation. CONCLUSION: This study demonstrated the effectiveness of SPT in intraoperative quality control. This technique may be adopted by surgeons to achieve good concordance between simulated and actual surgical outcomes.

Promoter methylation of p16, Runx3, DAPK and CHFR genes is frequent in gastric carcinoma.

AIMS AND BACKGROUND: Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including gastric cancer. A number of reports on methylation of various genes in gastric cancer have been published, but most of these studies focused on cancer tissues or only a single gene. In this study, we determined the promoter hypermethylation status and mRNA expression of 4 genes: p16, Runx3, DAPK and CHFR. METHODS: Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of p16, Runx3, DAPK and CHFR gene promoters in cancer and adjacent normal gastric mucosa specimens from 70 patients with gastric cancer, as well as normal gastric biopsy samples from 30 people without cancer serving as controls. In addition, the mRNA expression of p16, Runx3, DAPK and CHFR was investigated in 34 gastric cancer patients by RT-PCR. Bisulfite DNA sequence analysis was applied to check the positive samples detected by MSP. RESULTS: When carcinoma specimens were compared with adjacent normal gastric mucosa samples, a significant increase in promoter methylation of p16, Runx3, DAPK and CHFR was observed, while all 30 histologically normal gastric specimens were methylation free for all 4 genes. The methylation rate of the 4 genes increased from normal stomach tissue to tumor-adjacent gastric mucosa to gastric cancer tissue. Concurrent methylation in 2 or more genes was found in 22.9% of tumor-adjacent normal gastric mucosa and 75.7% of cancer tissues. No correlation was found between hypermethylation and other clinicopathological parameters such as sex, age, and tumor location. However, the frequency of DAPK and CHFR methylation in cancer tissues was significantly associated with the extent of differentiation and lymph node metastasis (P < 0.05) and the frequency of Runx3 methylation was significantly associated with tumor size (P < 0.05). Weak expression and loss of expression of the 4 genes was observed in cancer tissues and was significantly associated with promoter hypermethylation (P < 0.05). CONCLUSIONS: Promoter hypermethylation of p16, Runx3, DAPK and CHFR is frequent in gastric cancer. DAPK and CHFR promoter hypermethylation may be an important help in evaluating the differentiation grade and lymph node status of gastric cancer. Weak gene expression and loss of gene expression due to promoter hypermethylation may be a cancer-specific event.

Promoter methylation of CHFR gene in gastric carcinoma tissues detected using two methods.

BACKGROUND AND OBJECTIVE: Transcriptional silencing induced by CpG island methylation is believed to be one of the important mechanisms of carcinogenesis. Checkpoint with fork head-associated and ring finger (CHFR) governs the transition from prophase to prometaphase in response to mitotic stress. This study was to analyze the relationship between the methylation of CHFR gene and the clinicopathologic features of gastric cancer, and the difference of results between methylation-specific polymerase chain reaction (MSP) and combined bisulfite restriction analysis (COBRA) in detecting aberrant methylation of CHFR gene in gastric cancer. METHODS: Both MSP and COBRA methods were used to detect the promoter methylation of CHFR gene in gastric cancer specimens from 64 patients. The relationship between methylation status of CHFR gene and the clinicopathologic features of gastric cancer were analyzed using SPSS16.0. RESULTS: The methylation rates of CHFR gene promoter were significantly higher in gastric cancer samples than in the corresponding paracancer normal gastric mucosa by MSP (51.6% vs. 18.8%, P < 0.001). However, there was no significant correlation between methylation status of CHFR gene and the clinicopathologic parameters of gastric cancer, including age, gender, tumor size, clinical stage, Borrman type, tumor invasion depth, differentiation, and lymph node metastasis (P > 0.05). Aberrant methylation of the CHFR gene was detected in 27 (42.2%) of the 64 specimens of gastric cancer using COBRA, which did not significantly differ from that using MSP (P > 0.05). CONCLUSIONS: Aberrant methylation of the CHFR gene is a frequent event in the carcinogenesis of gastric cancer. Detecting the methylation of CHFR gene in gastric mucosa may conduce to the diagnosis of gastric cancer. No difference was found between MSP and COBRA in detecting promoter methylation of CHFR gene in gastric cancer.

[Effects of low-dose aspirin on primary prevention of cardiovascular events: a systematic review].

OBJECTIVE: To evaluate the effect and safety of low-dose aspirin for primary prevention of cardiovascular events. METHODS: We searched for randomized controlled trials (RCT) in the following electronic databases: MEDLINE, EMbase, the Cochrane Library (Issue 3, 2008), CBM, CNKI. Quality assessment and data extraction were conducted by two reviewers independently. All data were analyzed using Review Manager 4.2. RESULTS: Six studies (TPT, HOT, PPP, WHS, POPADAD, J-PAD) involving a total of 72,466 participants met the inclusion criteria. Meta-analysis results showed that: (1) Compared with placebo, the incidences of total cardiovascular events (RR = 0.85, 95% CI: 0.80-0.92), stroke (RR = 0.87, 95% CI: 0.77-0.98), nonfatal stroke (RR = 0.81, 95% CI: 0.70-0.95) and transient ischemic attack (RR = 0.76, 95% CI: 0.64-0.90) were significantly lower in low-dose aspirin group than those in placebo control group (all P < 0.05). (2) Nonfatal myocardial infarction (RR = 0.89, 95% CI: 0.77-1.02), death from cardiovascular causes (RR = 0.98, 95% CI: 0.86-1.13) and death from any cause (RR = 0.95, 95% CI: 0.88-1.02) were similar between the 2 groups (all P > 0.05). (3) The risk of coronary heart disease was reduced in low-dose aspirin group in the elderly (RR = 0.81, 95% CI: 0.70-0.94, P < 0.05). (4) The risk of bleeding was higher in low aspirin group compared to placebo group (RR = 1.15, 95% CI: 1.12-1.18, P < 0.01). CONCLUSIONS: Low-dose aspirin use could reduce the incidences of total cardiovascular events, stroke, nonfatal stroke and transient ischemic attack but increase the risk of bleeding, the incidence of nonfatal myocardial infarction, death from cardiovascular causes and death from any cause was not affected by low-dose aspirin use. Low-dose aspirin use was also significantly reduced the risk of coronary heart disease in the elderly.

Intrinsically altered lung-resident γδT cells control lung melanoma by producing interleukin-17A in the elderly.

Cancer is an age-associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung-resident γδT cells was significantly increased with altered gene expression in aged mice (20-24 months) versus young mice (10-16 weeks). Aged lung Vγ4+ and Vγ6+ γδT cells predominantly produced interleukin-17A (IL-17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4+ and Vγ6+ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL-17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL-17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti-tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co-housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age-dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti-tumor immunotherapy.

Thrombospondin-1 inhibits ossification of tissue engineered cartilage constructed by ADSCs.

Cartilage tissue engineering provides a new method in the treatment of cartilage defects, and adipose derived stem cells seem to be an ideal seed cell in cartilage tissue engineering because of its characteristics. However, ossification after in vivo implantation of tissue engineered cartilage remains a challenge. Thrombospondin-1 which has been reported to have an inhibitory effect on angiogenesis, may play an important role in inhibiting the ossification of tissue engineered cartilage constructed by adipose derived stem cells. Therefore, the effect of thrombospondin-1 in inhibiting the ossification of tissue engineered cartilage was evaluated in this study. Lentivirus vectors carrying thrombospondin-1 cDNA were transfected into adipose derived stem cells, and the transfected cells were used in the experiments. The expression of thrombospondin-1 was evaluated by quantitative reverse transcriptase-polymerase chain reaction and western blot, and the effects of thrombospondin-1 over-expression on angiogenesis were analyzed by angiogenesis assays. The quality of tissue engineered cartilage and the degree of ossification were assessed by biomechanical and molecular biology methods. The results showed that thrombospondin-1 infected cells have a high expression of thrombospondin-1 in mRNA and protein level, which inhibited the tube formation of endothelial cells, indicating the anti-angiogenic effects. Gene expression analyses in vitro showed that thrombospondin-1 inhibits the osteogenic differentiation of adipose derived stem cells significantly, and the results of in vivo study revealed that thrombospondin-1 significantly inhibits the expression of osteogenic genes. Compared to that in the control group, tissue engineered cartilage constructed by thrombospondin-1 transfected adipose derived stem cells in vivo showed a higher GAG content and lower compressive modulus, which indicating lower level of ossification. In conclusion, the current study indicated that the anti-angiogenic factor thrombospondin-1 suppresses the osteogenic differentiation of adipose derived stem cells in vitro, and inhibits ossification of tissue engineered cartilage constructed by adipose derived stem cells in vivo.

Clinicopathological and prognostic significance of circulating tumor cells in patients with lung cancer: a meta-analysis.

BACKGROUND: The prognostic significance of circulating tumor cells in patients with lung cancer is controversial. Therefore, we aimed to comprehensively and quantitatively assess the prognostic role of CTCs in patients with lung cancer. METHODS: The relevant literature was searched using PubMed, the Cochrane database and the China National Knowledge Internet database (up to June 2016). Using Review Manager 5.1.2, a meta-analysis was performed using hazard ratio (HR), odds ratio (OR) and 95% confidence interval (CI) as effect values. RESULTS: Thirty studies comprising 2,060 patients with lung cancer were analyzed. The pooled HR values showed that circulating tumor cells were significantly correlated with overall survival (HR =2.63, 95% CI [2.04, 3.39]) and progression-free survival (HR =3.74, 95% CI [2.49, 5.61]) in these patients. Further subgroup analyses were conducted and categorized by sampling time, detection method, and histological type; these analyses showed the same trend. The pooled OR values showed that circulating tumor cells were associated with non small cell lung cancer stage(OR = 2.11, 95% CI [1.42, 3.14]), small cell lung cancer stage (OR = 10.91, 95% CI [4.10, 29.06]), distant metastasis (OR =7.06, 95%CI [2.82, 17.66]), lymph node metastasis (OR =2.31, 95% CI [1.19,4.46]), and performance status(OR =0.42, 95%CI [0.22, 0.78]). CONCLUSION: The detection of circulating tumor cells in the peripheral blood of patients with lung cancer can be indicative of a poor prognosis.