Recent progress in hair follicle stem cell markers and their regulatory roles.

Hair follicle stem cells (HFSCs) in the bulge are a multipotent adult stem cell population. They can periodically give rise to new HFs and even regenerate the epidermis and sebaceous glands during wound healing. An increasing number of biomarkers have been used to isolate, label, and trace HFSCs in recent years. Considering more detailed data from single-cell transcriptomics technology, we mainly focus on the important HFSC molecular markers and their regulatory roles in this review.

Construction of a ferroptosis-related signature based on seven lncRNAs for prognosis and immune landscape in clear cell renal cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are involved in regulating tumor cell ferroptosis. However, prognostic signatures based on ferroptosis-related lncRNAs (FRLs) and their relationship to the immune microenvironment have not been comprehensively explored in clear cell renal cell carcinoma (ccRCC). METHODS: In the present study, the expression profiles of ccRCC were acquired from The Cancer Genome Atlas (TCGA) database; 459 patient specimens and 69 adjacent normal tissues were randomly separated into training or validation cohorts at a 7:3 ratio. We identified 7 FRLs that constitute a prognostic signature according to the differential analysis, correlation analysis, univariate regression, and least absolute shrinkage and selection operator (LASSO) Cox analysis. To identify the independence of risk score as a prognostic factor, univariate and multivariate regression analyses were also performed. Furthermore, CIBERSORT was conducted to analyze the immune infiltration of patients in the high-risk and low-risk groups. Subsequently, the differential expression of immune checkpoint and m6A genes was analyzed in the two risk groups. RESULTS: A 7-FRLs prognostic signature of ccRCC was developed to distinguish patients into high-risk and low-risk groups with significant survival differences. This signature has great prognostic performance, with the area under the curve (AUC) for 1, 3, and 5 years of 0.713, 0.700, 0.726 in the training set and 0.727, 0.667, and 0.736 in the testing set, respectively. Moreover, this signature was significantly associated with immune infiltration. Correlation analysis showed that risk score was positively correlated with regulatory T cells (Tregs), activated CD4 memory T cells, CD8 T cells and follicular helper T cells, whereas it was inversely correlated with monocytes and M2 macrophages. In addition, the expression of fourteen immune checkpoint genes and nine m6A-related genes varied significantly between the two risk groups. CONCLUSION: We established a novel FRLs-based prognostic signature for patients with ccRCC, containing seven lncRNAs with precise predictive performance. The FRLs prognostic signature may play a significant role in antitumor immunity and provide a promising idea for individualized targeted therapy for patients with ccRCC.

[Effect of thunder-fire moxibustion combined with vibration training on low back pain of primary osteoporosis].

OBJECTIVE: To compare the therapeutic effect of thunder-fire moxibustion combined with vibration training and simple vibration training on low back pain of primary osteoporosis by Young's modulus of ultrasonic wave, and seek an objective evaluating method. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each one. The patients in the two groups were treated with vibration training using whole body vibration treatment bed. In the observation group, thunder-fire moxibustion was applied at Yaoyangguan (GV 3), Mingmen (GV 4), Ganshu (BL 18), Shenshu (BL 23) and Dachangshu (BL 25). The treatment was given once every other day, 3 times a week for 4 weeks. The visual analogue score (VAS), real-time shear wave elastography (RTSWE) and medical outcomes study 36-item short-form hearth survey (SF-36) were used to evaluate pain intensity, multifidus muscle tone (Young's modulus) and quality of life before treatment, after 4-week treatment and 1 month after treatment. RESULTS: Compared before treatment, the VAS scores, Young's modulus of multifidus muscle and 5 dimensions of SF-36 (physical condition, body pain, general health, social function and mental health) after 4-week treatment and 1 month after treatment were significantly improved in the two groups (all P<0.05), the physiological role in the observation group after 4-week treatment and 1 month after treatment were improved (both P<0.05). In the observation group, the VAS scores, Young's modulus of multifidus muscle and 3 dimensions of SF-36 (physiological role, body pain and general health) after 4-week treatment and 1 month after treatment were superior to the control group (all P<0.05). CONCLUSION: The therapeutic effect of thunder-fire moxibustion combined with vibration training is superior to simple vibration training in relieving low back pain intensity and multifidus muscle tone, and improving quality of life for primary osteoporosis. RTSWE technique can be an objective examination method to evaluate pain.

Effectiveness and safety of Chinese massage therapy (Tui Na) on post-stroke spasticity: a prospective multicenter randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese massage therapy (Tui Na) for patients with post-stroke spasticity. DESIGN: A prospective, multicenter, blinded, randomized, placebo-controlled intervention trial. SUBJECT: A total of 90 patients with post-stroke spasticity were randomly assigned to the experimental (Tui Na therapy) group ( n = 45) or control (placebo Tui Na therapy) group ( n = 45). INTERVENTION: Participants in the experimental group received Tui Na therapy, while those in the control group received placebo-Tai Na (gentle rubbing) for 20-25 minutes per limb, once per day, five days per week for a total of four weeks. All participants in both groups received conventional rehabilitation. MAIN MEASURE: The Modified Ashworth Scale, the Fugl-Meyer Assessment and the Modified Barthel Index were used to assess the severity of spasticity, motor function of limbs and activities of daily living, respectively. Assessments were performed at baseline, at four weeks and at three months. RESULTS: Tui Na group had a significantly greater reduction in Modified Ashworth Scale in only four muscle groups than the control did (elbow flexors, P = 0.026; wrist flexors, P = 0.005; knee flexors, P = 0.023; knee extensors, P = 0.017). Improvements were sustained at three months follow-up. There was no significant difference between the two groups in Fugl-Meyer Assessment ( P = 0.503) and Modified Barthel Index ( P = 0.544). No adverse reaction was recorded in any of the cases mentioned at all study sites. CONCLUSIONS: Tui Na might be a safe and effective treatment to reduce post-stroke spasticity of several muscle groups.

Efficiency of muscle strength training on motor function in patients with coronary artery disease: a meta-analysis.

BACKGROUND: Existing literature has shown that patients with coronary artery disease (CAD) can benefit greatly from the strength training; therefore, the strength training should play a more important role in cardiac rehabilitation. However, the medical community may still have conservation to apply the strength training owing to no comprehensive study so far to compare the effectiveness of the strength training to the other trainings, such as aerobic training. OBJECTIVE: To evaluate the effect of strength training on motor function in patients with CAD. METHODS: Published articles from the earliest date available to July 2015 were identified using electronic searches. Two reviewers selected independently relevant randomized controlled trials (RCTs) investigating exercise program with strength training versus control interventions (exercise without strength training, including aerobic training and no exercise group) for the treatment of CAD patients. We examined effects of exercise with strength training versus control interventions on peak oxygen uptake (VO2peak), duration of exercise test and muscle strength. Two reviewers extracted data independently. RESULTS: Twenty seven trials that represented 1151 participants passed the selection criteria and were evaluated for the effects of strength training in CAD patients. For improving VO2peak [SMD (95%CI) = 0.58 (0.11, 1.06)] and muscle strength [upper limb, SMD (95% CI) =0.44 (0.34, 0.55); lower limb, SMD (95% CI) =0.33 (0.16, 0.50)], exercise program with strength training were significantly more effective than one without it. But there is no significantly difference on duration of exercise test [SMD (95%CI) = 0.17 (-0.04, 0.39)] in strength training group than in control group. CONCLUSIONS: We conclude strength training is effective in improving muscle strength and VO2peak, in CAD patients, when compared to patients with control group. Furthermore, our evaluations suggest that strength training does not compromise clinical trial completion or safety.

Efficacy of electrocoagulation in sealing the cystic artery and cystic duct occluded with only one absorbable clip during laparoscopic cholecystectomy.

BACKGROUND: Even though laparoscopic cholecystectomy (LC) emerged over 20 years ago, controversies persist with regard to the best method to ligate the cystic duct and artery. We proposed to assess the effectiveness and safety of electrocoagulation to seal the cystic artery and cystic duct after their occlusion with only one absorbable clip. MATERIALS AND METHODS: We retrospectively compared the clinical data for 635 patients undergoing LC using electrocoagulation to seal the cystic artery and cystic duct that were occluded with only one absorbable clip (Group 1) and 728 patients undergoing LC using titanium clips (Group 2). In parallel, 30 rabbits randomized into six groups underwent cholecystectomy. After cystic duct ligation with absorbable or titanium clips, the animals were sacrificed 1, 3, or 6 months later, and intraabdominal adhesions were assessed after celiotomy. RESULTS: The mean operative time was significantly shorter (41.6 versus 58.9 minutes, P<.01) in Group 1 than in Group 2. No cystic duct leaks occurred in any patients from Group 1, compared with seven leaks among the 728 (0.96%) patients from Group 2 (P<.05). The morbidity was significantly higher in Group 2 than in Group 1 (3.43% versus 1.58%). Mean intraoperative blood loss and hospitalization length were not significantly different between the two groups, and no deaths occurred in either group. In animal experiments, adhesion was tighter for absorbable than for titanium clips, but fibrous tissue encapsulation was thinner at the site of titanium clips. CONCLUSIONS: Electrocoagulation of the cystic artery and cystic duct that were occluded with only one absorbable clip is safe and effective during LC. This approach is associated with shortened operative times and reduced leakage, compared with the standard method using metal clips.

Adenovirus-mediated Wnt5a expression inhibits the telogen-to-anagen transition of hair follicles in mice.

The canonical Wnt/ß-catenin pathway plays an important role in hair cycle induction. Wnt5a is a non-canonical Wnt family member that generally antagonizes canonical Wnt signaling in other systems. In hair follicles, Wnt5a and canonical Wnt are both expressed in cells in the telogen stage. Wnt5a has been shown to be critical for controlling hair cell fate. However, the role that Wnt5a plays in the transition from the telogen to anagen stage is unknown. In this study, using whole-mount in situ hybridization, we show that Wnt5a is produced by several other cell types, excluding dermal papilla cells, throughout the hair cycle. For example, Wnt5a is expressed in bulge and secondary hair germ cells in the telogen stage. Our studies focused on the depilated 8-week-old mouse as a synchronized model of hair growth. Interestingly, overexpression of adenovirus Wnt5a in the dorsal skin of mice led to the elongation of the telogen stage and inhibition of the initiation of the anagen stage. However, following an extended period of time, four pelage hair types grew from hairless skin that was induced by Wnt5a, and the structure of these new hair shafts was normal. Using microarray analysis and quantitative arrays, we showed that the expression of ß-catenin and some target genes of canonical Wnt signaling decreased after Wnt5a treatment. These data demonstrate that Wnt5a may inhibit the telogen stage to maintain a quiescent state of the hair follicle.

Adenovirus-mediated Wnt10b overexpression induces hair follicle regeneration.

Hair follicles periodically undergo regeneration. The balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. We previously reported that Wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. To unveil the roles of Wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. On the basis of this model, we found that Wnt10b could induce the biological switch of hair follicles from telogen to anagen when overexpressed in the skin. The induced hair follicles expressed structure markers and could cycle normally into catagen. Conversely, anagen onset was abrogated by the knockdown of Wnt10b with small interfering RNA (siRNA). The Wnt10b aberrant expression data suggest that it is one of the activators of hair follicle regeneration. The ß-catenin protein is translocated to the nucleus in Wnt10b-induced hair follicles. The biological effects of Wnt10b were abrogated when ß-catenin expression was downregulated with siRNA. These data revealed that Wnt10b might induce hair follicle regeneration in vivo via the enhanced activation of the canonical Wnt signaling pathway. To our knowledge, our data provide previously unreported insights into the regulation of hair follicle cycling and provide potential therapeutic targets for hair follicle-related diseases.

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China.

BACKGROUND: Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. METHODS: All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications. RESULTS: The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of ß2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. CONCLUSIONS: Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

[Tolerability of 6-mercaptopurine in children with acute lymphoblastic leukemia].

OBJECTIVE: 6-Mercaptopurine (6-MP) has been the backbone of maintenance chemotherapy for acute lymphoblastic leukemia (ALL), the response to 6-MP is highly variable, adverse events leading to discontinuation or dose-reduction (children intolerant) of 6-MP occur in many children with ALL. The aim of this study was to investigate the tolerability of 6-MP and to optimize thiopurine use. METHODS: The authors evaluated in a prospective manner the tolerance of 6-MP in ALL children from Oct. 1, 2004 to Sept. 30, 2007 who were newly diagnosed in Beijing Children's Hospital, using BCH-ALL-2003 protocols, during the maintenance therapy and followed up to Sept. 30, 2008. All children had a treatment period of at least 3 months for maintenance therapy. RESULTS: Totally 133 children including 81 boys and 52 girls at median age of 67 months (18 - 188 months), 100% of the patients went into complete remission (CR) on day 33 of induction chemotherapy, and the median time to CR was 26 months (6 - 47 months). All the children had maintenance therapy from 3 to 25 months (mean 13.5 +/- 7.4) and 72(54%) received 6-MP standard doses continuously for total courses, the median daily dose of 6-MP was 46 mg/(m(2).d) 6-MP, their WBC was (3 - 4) x 10(9)/L, ANC (1.5 - 2) x 10(9)/L, they had no severe liver toxicity. In 4 children the dose of 6-MP was increased to 125% because WBC was higher than 6 x 10(9)/L, ANC higher than 3 x 10(9)/L. Sixty one children (46%) had poor tolerability to 6-MP, they experienced adverse events that led to discontinuation (n = 19) or dose reduction (n = 42) of 6-MP, the actual mean dose for the 42 cases was 25 - 30 mg/(m(2).d) and the time to occurrence of toxic effects was 2.5 weeks. Reasons for discontinuation or dose reduction were severe myelotoxicity occurred in 48 children, hepatotoxicity in 12, and skin rash in one. CONCLUSIONS: In this cohort of ALL children, the difference of tolerance to oral 6-MP was obvious, 54% of the children well tolerated 6-MP during the whole course at oral standard dose, and severe granulocytopenia did not occur. However, 46% developed severe granulopenia or hepatotoxicity, the dosage had to be reduced in order to decrease the probability of severe toxicity. It is suggested that standard dose of 6-MP is not always the maximum tolerant dose in some children and inadequate dose may be the cause of therapy failure.

[Clinical study of wind-warm and pulmonary heat syndrome treated with integrated traditional Chinese and Western medicine].

OBJECTIVE: To investigate the clinical effectiveness of Toubiao Qingfei (expelling exterior evil and clearing lung) Decoction (TBQFD) on wind-warm and pulmonary heat syndrome. METHODS: Forty-six subjects were randomized into treatment group and control group. Patients in the control group were treated with Western medicines, while patients in the treatment group were treated with Western medicines and TBQFD. The therapeutic effects and improvement of symptoms in both groups were observed. RESULTS: The durations of fever, cough and absorption of pulmonary inflammatory focus in the treatment group were 1.52, 3.52 and 6.25 days respectively, which were significantly shorter than those in the control group (P<0.05). CONCLUSION: TBQFD can improve the symptoms, such as fever and cough, and can promote the absorption of infection and shorten the clinical course of wind-warm and pulmonary heat syndrome.