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Bone defect (BD) caused by trauma, infection, congenital defects, or neoplasia is a major cause of physical limitation. Distraction osteogenesis (DO) is a highly effective procedure for bone regeneration, while the concrete mechanism remains unknown. In this study, canine DO and BD models of the mandible were established. The results of micro-computed tomography and histological staining revealed that DO led to an increased mineralized volume fraction and robust new bone formation; in contrast, BD demonstrated incomplete bone union. Mesenchymal stem cells (MSCs) from DO and BD calluses were isolated and identified. Compared with BD-MSCs, DO-MSCs were found to have a stronger osteogenic capability. Single-cell RNA sequencing analysis was further performed to comprehensively define cell differences between mandibular DO and BD calluses. Twenty-six clusters of cells representing 6 major cell populations were identified, including paired related homeobox 1-expressing MSCs ( PRRX1 + MSCs), endothelial cells (ECs), T cells, B cells, neutrophils, and macrophages. Interestingly, 2 subpopulations in PRRX1 + MSCs in the DO group were found to express the marker of neural crest cells (NCCs) and were associated with the process of epithelial-mesenchymal transition. The immunofluorescence assay was performed to further corroborate these results in vivo and in vitro, experimentally validating that continuous distraction maintained the PRRX1 + MSCs in an embryonic-like state. Finally, we used CRISPR/Cas9 to knock out (KO) PRRX1 in the context of DO, which significantly blunted the capability of jawbone regeneration, resulting in a diminished NCC-like program and reduction of new bone volume. In addition, the ability of osteogenesis, cell migration, and proliferation in cultured PRRX1 KO MSCs was inhibited. Taken together, this study provides a novel, comprehensive atlas of the cell fates in the context of DO regeneration, and PRRX1 + MSCs act essential roles.

Background: Mucormycosis is a lethal fungal infection with increasing incidence. The epidemiology of mucormycosis in current mainland China has not been fully elucidated., Objectives: To investigate the epidemiology, risk factors, manifestations, diagnosis, treatment and prognosis of mucormycosis in mainland China., Methods: We searched for published mucormycosis case reports/series in mainland China in the PubMed, WanFang and China National Knowledge Infrastructure databases from January 2001 to July 2020. Cases of proven/probable mucormycosis were included., Results: A total of 390 cases were included in this review. Most of the patients were male (61.3%), and diabetes was the most common predisposing factor (37.2%). Pulmonary mucormycosis (42.1%) was the most common form followed by cutaneous infection (21.0%). Of 390 patients, 24 died before therapy. Among the remaining 366 patients, 208 (56.8%) received antifungal drugs alone, 16 (4.4%) received surgery alone, and 142 (38.8%) received a combination of drugs and surgery, the mortality of the last group is much lower (34/142, 23.9%). The overall mortality was 37.2%. A multivariate analysis indicated that factors associated with increased mortality included corticosteroid use alone as immunosuppressive therapy, rhino-orbito-cerebral or disseminated mucormycosis (compared with pulmonary mucormycosis), and drug administration other than amphotericin B (AmB), posaconazole (POS) and itraconazole (ITR) (compared with the use of conventional AmB), while factors associated with decreased mortality included cutaneous mucormycosis and surgical therapy. Combination or sequential antifungal therapy of AmB and POS or ITR did not reduce mortality compared with conventional AmB monotherapy., Conclusion: In mainland China, mucormycosis is a serious fungal infection with high mortality. Corticosteroid use, rhino-orbito-cerebral and disseminated mucormycosis were adverse prognostic factors. Antifungal therapy combined with surgery could improve the prognosis., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Acne vulgaris is a chronic inflammatory dermatosis affecting approximately 85% of adolescents. There are many factors contributing to the development of this ailment. A recent study indicated that gut microbiota takes part in the pathogenesis of acne. We aimed to investigate the link between acne vulgaris and gut microbiota. A total of 31 moderate to severe acne vulgaris patients and 31 healthy controls were enrolled. We collected their feces, and gut microbiota was evaluated by the hypervariable regions of 16S rRNA genes through high-throughput sequencing. We identified links between acne vulgaris and changes of gut microbiota. At the phylum level, Actinobacteria (0.89% in acne patients and 2.84% in normal controls, P = 0.004) was decreased and Proteobacteria (8.35% in acne patients and 7.01% in normal controls, P = 0.031) was increased. At the genus level, Bifidobacterium, Butyricicoccus, Coprobacillus, Lactobacillus and Allobaculum were all decreased. The observed difference in genera between acne patients and healthy controls provides a new insight into the link between gut microbiota changes and acne vulgaris risk., (© 2018 Japanese Dermatological Association.)

l-Arginine is a nutritionally essential amino acid for spermatogenesis and plays versatile roles in animal health and can be utilized as a potential agent to improve reproductive performance of boars under high ambient temperature. The present study aimed to determine whether dietary l-arginine could alleviate heat stress-induced infertility in boars. In all, 20 boars (PIC 1040; 248.59±3.84 kg BW and 407.65±6.40 days of age) were selected and randomly assigned to four groups (group 0.0%, basal diet; group 0.6%, 0.8% or 1.0%, basal diet added with 0.6%, 0.8% or 1.0% l-arginine (wt:wt), respectively.) The four diets were made isonitrogenous by addition of appropriate amounts of l-alanine. Boars were pre-fed the corresponding experimental diet for 42 days. Then, the semen characteristics and libido were accessed for 6 weeks during the hot summer period (25.5° to 33.0°C). Results show that dietary l-arginine remarkably improved sperm motility, normality, total sperm number and effective total sperm number. Also, dietary l-arginine improved semen antioxidant capacity, such as decrease of malondialdehyde and 8-Hydroxy-2'-deoxyguanosine content in sperm (P<0.05), increase of the ratio of glutathione and oxidized glutathione, total antioxidant capacity, glutathione peroxidase and catalase activities in seminal plasma (P<0.05). Most of mitochondria contained intact ultrastructure in l-arginine-supplemented group which also accompany with higher ATP content than the 0.0% group. The boars fed 0.8% l-arginine show increased levels of estradiol-17β and testosterone and exhibit improved libido performance than boars in the 0.0% group. Adding dietary l-arginine linearly increased (P=0.002) nitric oxide content (as l-arginine increased). The scrotal surface temperature in the 0.6%, 0.8% and 1.0% group were decreased by 0.9°C, 0.9°C and 0.4°C, respectively, compared with the 0.0% group. l-Arginine levels caused linear effect on semen quality and antioxidant capacity, also caused quadratic effect on libido performance. During the hot summer months, the predicted optimal l-arginine levels for best semen quality and antioxidant capacity was 0.8% to 1.0% and for best libido performance was 0.8%. It can be concluded that l-arginine can be used as an effective agent to alleviate heat stress-induced infertility of boar, and that 0.8% to 1.0% can be considered as the optimum dosage.

Background: Many studies demonstrated that the expression level of HOTTIP in cancerous tissues was significantly higher than that in adjacent normal tissues. Increased expression of HOTTIP was associated with metastasis and a poor prognosis., Methods: The current meta-analysis collected all relevant articles and explored the association of HOTTIP expression levels with lymph node metastasis (LNM), distant metastasis (DM), and overall survival (OS) in multiple cancers. Literature collections were conducted by searching a number of electronic databases (up to December 31, 2015). The Meta-analysis was conducted using RevMan5.3 software and Stata SE12.0., Results: A total of 602 patients with cancer from seven studies were included. The Meta-analysis results showed that lymph node metastasis occurred more frequently in patients with high HOTTIP expression than in patients with low HOTTIP expression (OR = 2.22, 95% CI: 1.47 - 3.37, p = 0.0002, fixed-effects model), and a similar result was observed between HOTTIP expression and distant metastasis (OR = 3.30 (95% CI: 1.78 - 6.12, p = 0.0001, fixed-effects model). Moreover, we found that cancer patients with high HOTTIP expression had a poorer overall survival than those with low HOTTIP expression (HR = 2.23, 95% CI: 1.64 - 2.83, p = 0.000, fixed-effects model)., Conclusions: HOTTIP may serve as an independent biomarker for predicting the clinical outcome of cancer patients.

Background: Numerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients., Results: A total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43-1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59-2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09-4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06-4.30), distant metastasis (OR = 3.14, 95% CI: 1.77-5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08-3.68)., Materials and Methods: A comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis., Conclusions: High expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors., Competing Interests: The authors declared that there are no conflicts of interest regarding the publication of this paper.

A number of studies have demonstrated that the expression level of actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) was upregulated in various cancers. High expression of AFAP1-AS1 is associated with an increased risk of metastasis and a poor prognosis in cancer patients. The electronic search was conducted in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang database. We collected relevant articles to explore the association between the expression levels of AFAP1-AS1 and lymph node metastasis, distant metastasis, overall survival, relapse-free survival, and progression-free survival. A total of 1,017 patients from eight studies were finally included. The results showed that cancer patients with high AFAP1-AS1 expression suffered an increased risk of developing lymph node metastasis (odds ratio =3.19, 95% confidence interval [CI]: 2.11-4.83, P<0.00001) and distant metastasis (odds ratio =3.05, 95% CI: 1.84-5.04, P<0.0001). Moreover, we found that patients with high AFAP1-AS1 expression also had a poorer overall survival (hazard ratio [HR]: 1.98, 95% CI: 1.57-2.38, P=0.000), a worse progression-free survival (HR: 1.73, 95% CI: 1.11-2.35, P=0.000), and a shorter recurrence-free survival (HR: 1.96, 95% CI: 1.02-2.90, P=0.000) than those with low AFAP1-AS1 expression. High expression of AFAP1-AS1 was associated with poor clinical outcome. AFAP1-AS1 might serve as a potential novel biomarker for indicating the clinical outcomes in human cancers.

Purpose: To explore the association between HOTAIR rs4759314 and cancer risk., Methods: A comprehensive online search was conducted using PubMed, EMBASE, and CNKI databases to identify relevant studies. The case-control studies related to HOTAIR rs4759314 polymorphism and cancer risk were selected according to the inclusion and exclusion criteria. The retrieval time was until November 2015. After extracting the basic data information and performing an evaluation of the quality of the literature, the meta-analysis was performed using STATA 12.0 software, by calculating the odds ratio (OD) and 95% confidence interval (95% CI), and further subgroup analysis, literature publication bias testing, and sensitivity analysis., Results: The studies included a total of 5025 patients with cancer and 5657 controls. The results found no significant association between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population (G vs A, OR=1.06, 95% CI :0.87-1.30 ; GG/GA vs AA, OR=1.07, 95% CI: 0.87-1.32; GG vs GA/AA, OR=0.75, 95% CI:0.39-1.43; GA vs AA, OR=1.08, 95% CI: 0.88-1.33; GG vs AA, OR=0.76, 95% CI:0.39-1.45) (all p<0.05). However, A allelic gene was associated with lower risk of gastric cancer, while G allelic gene may act as a genetic susceptibility factor for gastric cancer in Chinese population., Conclusion: No significant association was noted between the HOTAIR rs4759314 polymorphism and cancer risk in a Chinese population.

Introduction: A number of studies in gastric carcinoma have demonstrated that cancerous tissues have a significant higher HOTAIR level than that in noncancerous tissues. Overexpression of HOTAIR is associated with the development in gastric cancer., Evidence Acquisition: We collected all relevant articles and explored the association of HOTAIR expression with clinicopathological features and prognosis in patients with gastric cancer. Literature collections were conducted by searching a number of electronic databases (up to November 15, 2015). The meta-analysis was conducted by using RevMan v.5.3 software and Stata SE 12.0., Evidence Synthesis: A total of 832 patients with gastric cancer based on 10 studies were included. The Meta-analysis results showed that high-expression of HOTAIR is significantly associated with clinicopathological features in gastric cancer patients, especially in the depth of tumor invasion, lymph node metastasis, vessel invasion, lymphatic vessel involvement and TNM stage, but there is no association between HOTAIR overexpression and other clinicopathological features. In addition, aberrant HOTAIR expression is also significantly associated with the prognosis in gastric cancer patients., Conclusions: There is an association between HOTAIR expression and clinicopathological features and prognosis in gastric cancer patients. High expression of HOTAIR in cancerous tissue could predict poor clinical outcome in gastric cancer, suggesting HOTAIR abundance may serve as a novel candidate biomarker for the clinical outcome in gastric cancers.

Background: Numerous studies have found that the expression levels of long noncoding RNA PVT1 (lncRNA PVT1) were elevated in cancerous tissue, which was significantly higher than those in adjacent noncancerous tissues or corresponding normal tissues. Overexpression of lncRNA PVT1 was correlated with lymph node metastasis and a poor prognosis in various cancers., Methods: This quantitative meta-analysis collected all relevant articles and explored the association of lncRNA PVT1 expression levels with lymph node metastasis and prognosis. The systematic search was conducted through multiple electronic databases (up to December 1, 2015). The meta-analysis was performed by using RevMan5.3 software and Stata SE12.0., Results: A total of 939 patients with cancer from 10 studies were included. The Meta-analysis results showed that cancer patients with high PVT1 have a strong trend for LNM (OR=2.05, 95%CI:0.97-4.30, P=0.06, random-effects model). Moreover, we found that cancer patients with high PVT1 expression had a poorer overall survival (HR=2.07, 95%CI:1.40-2.74, P=0.000, fixed-effects model), a shorter recurrence-free survival (HR=1.70, 95%CI:1.02-2.39, P=0.000, fixed-effects model), and a worse disease-free survival (HR:2.10, 95%CI:0.96-3.23, P=0.000, fixed-effects model)., Conclusions: PVT-1 may serve as a novel molecular marker for lymph node metastasis and prognosis.

Introduction: Recent studies have reported that long non-coding RNA low expression in tumor (lncRNA-LET) was down-regulated in several cancers. The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis., Evidence Acquisition: We collected all relevant papers by searching multiple electronic databases (PubMed, EMBASE, Google Scholar, CNKI, Wanfang Database) and explored the association between the expression levels of lncRNA-LET and lymph node metastasis (LNM), distant metastasis (DM) and overall survival (OS)., Evidence Synthesis: A total of 383 patients from four studies were finally included. The meta-analysis results showed that LNM occurred more frequently in patients from the lncRNA-LET low expression group than in patients from the lncRNA-LET overexpression group (OR=4.56, 95% CI 2.92-7.12, P<0.00001), and a similar result was observed between lncRNA-LET expression and DM (OR=4.77, 95% CI 2.29-9.94, P<0.0001). Additionally, we found that patients with low expression of lncRNA-LET had a poorer OS than those with lncRNA-LET overexpression (HR=2.39, 95% CI 1.57-3.21, P=0.000)., Conclusions: lncRNA-LET may serve as a common molecular marker for metastasis and prognosis in human cancers.

Introduction: Numerous researches have showed that the dysregulation of lncRNA ANRIL play a significant role in cancer progression, and high expression of ANRIL may have important clinical value. This meta-analysis aims to investigate potential clinical application role of ANRIL as a biomarker for cancer prognosis., Evidence Acquistion: The electronic search was conducted in Pubmed, EMBASE, Web of Science, CNKI and Wanfang database (up to January 27, 2016). We collected relevant articles to explore the association between the expression levels of ANRIL and overall survival (OS)., Evidence Synthesis: A total of 519 cancer patients from six studies were finally included. The results showed that cancer patients with high ANRIL expression may have a poorer OS (HR=1.95, 95%CI:1.37-2.53, P=0.000, fixed-effect model) than those with low ANRIL expression., Conclusions: High expression of ANRIL is associated with poor clinical outcome. ANRIL might be act as a novel potential prognostic biomarker in various cancers.

Introduction: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer., Evidence Acquisition: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis., Evidence Synthesis: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05)., Conclusions: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk.

Background: Recent studies have reported that the lncRNA-LET was down-regulated in several cancers.The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis., Methods: We collected all relevant papers by searching multiple electronic databases(Pubmed,EMBASE,Google Scholar,CNKI,Wanfang database) and explored the association between the expression levels of lncRNA-LETand lymph node metastasis (LNM),distant metastasis (DM) and overall survival (OS)., Results: A total of 383 patients from four studies were finally included.The meta-analysis results showed that LNM occurred more frequently in patients with low lncRNA-LET expression group than in patients with high lncRNA-LET expression group(OR=4.56,95%CI:2.92-7.12,p<0.00001),and a similar result was observed between lncRNA-LET expression and DM,the OR was 4.77(95%CI:2.29-9.94, p<0.0001).Additionally,we found that patient with low lncRNA-LET expression had a poorer OS than those high lncRNA-LET expression (HR=2.39,95 %CI:1.57-3.21,p = 0.000)., Conclusion: LncRNA-LETmay serve as a common molecular marker for metastasis and prognosis in human cancers.

Aim: Spinal cord injury (SCI) is a serious condition of the central nervous system and it affects the quality of life and even hampers the day-to-day activity of the patient. In the current study, we investigated the efficacy of intrathecal administration of flavopiridol in an experimental animal model of SCI. The study also aimed at exploring the physiological effects of flavopiridol on neurons, astrocytes and cell cycle regulatory proteins., Material and Methods: In vitro scratch wound experiments were performed on female Sprague-Dawley rats (n=23). A complete hemisection to the right of T10 was made, and flavopiridol solution (200 mM, 0.8 nmol flavopiridol/animal) was delivered topically to the lesion site. Cell viability assay, in vitro scratch injury assay, cell cycle analysis using flow cytometry and behavioural assessments were performed., Results: The local delivery of flavopiridol reduced cavity formation and improved regeneration of neurons with improvement in physiological performance. Flavopiridol also inhibited the migration and proliferation of astrocytes, and at the same time, promoted the survival of neurons., Conclusion: Intrathecal administration of flavopiridol can be a promising treatment strategy in patients with SCI and it needs to be validated in patient setting.

Purpose: The association between polymorphism of vascular endothelial growth factor (VEGF)-634 G>C and malignancy risk has been widely studied, and no conclusive result was available up to now., Methods: Twenty-three case-control studies with 21,917 individuals were included in this meta-analysis through searching the databases of Medline, Embase, and CNKI (up to October 1st, 2010). The odds ratio (OR) and 95% confidence interval (95%CI) were used to investigate the strength of the association., Results: Overall, the pooled analysis showed that there was no association between VEGF-634 G>C and risk of malignancy, and the ORs (95%CIs) were 0.98 (0.85-1.12) for GG versus CC, 1.03 (0.90-1.17) for GC versus CC, 1.00 (0.89-1.13) for G carrier versus CC, and 1.08 (0.94-1.23) for C carrier versus GG. Subgroup analyses according to ethnicity, source of control, type of cancer, and sample size were also performed, and results indicated that VEGF-634 G>C was not associated with risk of malignancy for neither Asians [1.06 (0.81-1.38) for GG vs. CC and 1.08 (0.84-1.39) for GC vs. CC] nor Caucasians [0.93 (0.83-1.05) for GG vs. CC and 0.98 (0.87-1.10) for GC vs. CC]. It was also not associated with risk of breast cancer [0.95 (0.81-1.12) for GG vs. CC], gastric cancer [0.93 (0.47-1.84) for GG vs. CC], and colorectal cancer [1.17 (0.93-1.47) for GG vs. CC]., Conclusions: This meta-analysis suggests that VEGF-634 G>C may be not associated with risk of malignancy. More studies with larger sample size were needed to provide more precise evidence.

Objective: To conduct a meta-analysis of randomized controlled trials (RCTs) to clarify whether nutritional intervention (caloric supplementation for at least 2 weeks) can improve the nutritional status and the pulmonary functions, while reduce the frequency of acute exacerbation or mortality of patients with stable COPD., Methods: RCTs were identified from databases including Medline and Embase, and a hand search for references was also conducted. Two reviewers independently selected the trials for inclusion, assessed the methodological quality of each study, and extracted the data Within each trial and for each outcome, an effect size was calculated. The effect sizes were then pooled by a random or fixed effects model according to the heterogeneity tested among the studies., Results: From 143 references, 10 RCTs (including 354 participants) were included in this meta-analysis. The results of the study, which included body weight (BW), mid arm muscle circumference (MAMC), triceps skinfold thickness (TSF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), were expressed in standardized mean difference (SMD, 95% CI): 0.05 (-0.18 - 0.28) kg, -0.16 (-0.57 - 0.25) cm, 0.41 (0.01 - 0.82) cm, 0.04 (-0.39 - 0.48) ml and 0.03 (- 0.40 - 0.46) ml. The effect of energetic nutritional intervention for patients with stable COPD was insignificant; the 95% CI around the pooled effect sizes all included zero., Conclusion: Nutritional intervention by caloric supplementation had no effect on improving the nutritional status and the pulmonary functions in patients with stable COPD. There was no evidence that the frequency of acute exacerbation or mortality could be reduced.