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There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0–25% and 25–70%. Tumour proportion score distribution was as follows: tumour proportion score 5% in 10.6%. Combined positive score distribution was as follows: combined positive score 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (

Abstract Background This study aimed to explore the clinical features and prognosis of cardiac metastatic tumors. In addition, whether continuing antitumor therapy after the development of cardiac metastases can benefit patients and the response of cardiac metastases were investigated. Methods A retrospective analysis was conducted on patients with malignancies who were admitted to Fujian Cancer Hospital and Fujian Provincial Hospital from January 2007 to September 2022, and the follow-up period ended in March 2023. Clinical data were gathered, treatment efficacy was evaluated, and survival analysis was performed. Results After the patients developed cardiac metastasis, the overall 30-day, 3-month, 6-month, and 12-month survival rates were 85.00%, 59.00%, 51.00% and 38.00%, respectively. With continued treatment, the average survival time was 27.33 months (95% confidence interval [CI]: 16.88–37.79), which exceeded the 6.6 months (95% confidence interval [CI]: 0.03–13.69) observed for patients who withdrew from treatment (P

The ultramafic rock located on the northern slope of Lüliang Mountain in the northwestern region of North Qaidam Orogen is altered to serpentinite. The occurrence of disseminated chromite within the serpentinite holds significant implications for understanding the petrogenesis of the protolith. This work provides strong evidence of a distinct zonal texture in the chromite found in the ultramafic rock, using petrographic microstructure and electron probe composition analysis. The core of the chromite is characterized by high contents of Cr#, with enrichment in Fe3+# (Fe3+/(Cr + Al + Fe3+)) and depletion in Al2O3 and TiO2. The Cr2O3 content ranges from 51.64% to 53.72%, while the Cr# values range from 0.80 to 0.84. The FeO content varies from 24.9% to 27.8%, while the Fe2O3 content ranges from 5.19% to 8.74%. The Al2O3 content ranges from 6.70% to 9.20%, and the TiO2 content is below the detection limit (# values ranging from 0.13 to 0.25 and Fe3+# values ranging from 0.07 to 0.12. The mineral chemistry of the chromite core in the ultramafic rock suggests it to be from an ophiolite. This ophiolite originated from the fore-arc deficit asthenosphere in a supra-subduction zone. The estimated average crystallization temperature and pressure of the chromite are 1306.02 °C and 3.41 GPa, respectively. These values suggest that the chromite formed at a depth of approximately 110 km, which is comparable to that of the asthenosphere. The chromite grains are surrounded by thick rims composed of Cr-rich magnetite characterized by enrichment in Fe3+# contents and depletions in Cr2O3, Al2O3, TiO2, and Cr#. The FeO content ranges from 28.25% to 31.15%, while the Fe2O3 content ranges from 44.94% to 68.92%. The Cr2O3 content ranges from 0.18% to 23.59%, and the Al2O3 and TiO2 contents are below the detection limit (# values ranging from 0.90 to 1.00, Mg# values ranging from 0.01 to 0.06, and Fe3+# values ranging from 0.64 to 1.00, indicating late-stage alteration processes. The LA-ICP-MS zircon U-Pb dating of the ultramafic rock yielded an age of 480.6 ± 2.4 Ma (MSWD = 0.46, n = 18), representing the crystallization age of the ultramafic rock. This evidence suggests that the host rock of chromite is an ultramafic cumulate, which is part of the ophiolite suite. It originated from the fore-arc deficit asthenosphere in a supra-subduction zone during the northward subduction of the North Qaidam Ocean in the Ordovician period. Furthermore, clear evidence of Fe-hydrothermal alteration during the post-uplift-denudation stage is observed.

BackgroundThe relationship between allergic diseases and the adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a subject of controversy. This study aimed to investigate the association between allergic diseases and the incidence and severity of symptoms in SARS-CoV-2 infection.MethodsClinical data of individuals, including children and their parents, infected with SARS-CoV-2 from December 2022 to January 2023 in China were retrospectively analyzed. The data were collected through questionnaires. Statistical analysis, including chi-squared tests, nonparametric analysis, one-way ANOVA, and logistic regression analysis, was used to examine the relationship between allergic diseases, prior medication, and the symptoms of SARS-CoV-2 infection.ResultsThere were 3,517 adults and 3,372 children with SARS-CoV-2 infection included in the study. Fever was found to occur at similar rates in children (86.5%) and adults (86.8%). However, other symptoms related to respiratory issues (such as cough and sore throat), neurological symptoms (headache, loss of smell, and loss of taste), and systemic symptoms (muscle soreness and weakness) were observed more frequently in adults (P < 0.001). Additionally, adults exhibited higher overall symptom scores, indicating greater severity. Allergic diseases were found to be associated with the incidence of certain SARS-CoV-2 infection symptoms in both children and adults. Specifically, children with allergic rhinitis (AR) were observed to be more susceptible to upper respiratory symptoms (OR: 1.320, 95% CI: 1.081-1.611, P = 0.006), while asthma patients were found to be more susceptible to severe respiratory symptoms (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). Similar patterns were identified in adults. Furthermore, AR was also suggested to be a risk factor for symptom severity in both children (OR: 1.704, 95% CI: 1.314-2.209, P < 0.001) and adults (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). However, prior medication for allergic diseases did not exhibit a preventive effect on SARS-CoV-2 infection symptoms.ConclusionsBoth children and adults with allergic diseases were found to be more prone to experiencing symptoms of SARS-CoV-2 infection, and these symptoms tended to be more severe.

Obacunone, a natural triterpenoid, is an active component of the herbs Dictamnus dasycarpus Turcz. and Phellodendron amurense Rupr, and an indicator of the herbs’ quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone.

Abstract Background Childhood adenoid hypertrophy (AH) is common and is often associated with allergic asthma, resulting in complications like obstructive sleep apnea syndrome (OSAS). Management of the disease and its complications is often challenging. Case presentation We report here a case of a 10-year-old boy who suffered from severe allergic asthma and rhinitis and was treated with omalizumab. Before the treatment, the childhood asthma control test (C-ACT, 14), visal analog scale (VAS, 7) and lung function (mild obstructive ventilation dysfunction and moderate to severe dysfunction in ventilation in small airway) were seriously affected. Polysomnography showed OSAS (apnea hypopnea index, AHI, 6.4), low hypooxia saturation (lowest pulse oxygen saturation, LoSpO2, 70%), and adenoid hypertrophy (at grade III). After treating with omalizumab for 4 weeks (once treatment), the ventilation function, symptoms of asthma and allergic rhinitis (C-ACT, 24; VAS, 2), and OSAS (AHI: 1.8 and LoSpO2: 92.6%) were all improved, and the adenoids size was also significantly reduced to grade II. And during the following 3 times of treatment, the allergic symptoms continued improving, and the size of adenoid was reduced to grade I. Even 6.5 months after cessation of omalizumab, the size of adenoid remained at grade I. Conclusion This is the first documented case that childhood adenoid hypertrophy can be significantly improved by omalizumab.

Abstract Background The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy. Methods This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy. Results Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526–0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR+) = 5.77]. Conclusion Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations.

Plain Language summary An inter-delivery interval (IDI) that is too short or too long increases the risk of adverse maternal and neonatal outcomes. However, the optimal IDI for trial of labor after cesarean delivery (TOLAC) remains unclear. We performed a multicenter, electronic medical record-based, retrospective cohort study that included 1080 pregnant women who had one or two cesarean deliveries and underwent TOLAC. Data on maternal and neonatal outcomes were collected from the electronic record system. In multivariable analysis, the incidences of postpartum hemorrhage, preterm birth, and low birth weight were significantly increased in women with an IDI of

Abstract Background The incidence of placenta preiva is rising. Cesarean delivery is identified as the only safe and appropriate mode of delivery for pregnancies with placenta previa. Anesthesia is important during the cesarean delivery. The aim of this study is to assess maternal and neonatal outcomes of patients with placenta previa managed with neuraxial anesthesia as compared to those who underwent general anesthesia during cesarean delivery. Methods A retrospective cohort study was performed of all patients with placenta preiva at our large academic institution from January 1, 2014 to June 30, 2019. Patients were managed neuraxial anesthesia and general anesthesia during cesarean delivery. Results We identified 1234 patients with placenta previa who underwent cesarean delivery at our institution. Neuraxial anesthesia was performed in 737 (59.7%), and general anesthesia was completed in 497 (40.3%) patients. The mean estimated blood loss at neuraxial anesthesia of 558.96 ± 42.77 ml were significantly lower than the estimated blood loss at general anesthesia of 1952.51 ± 180 ml (p

Abstract Available evidence shows conflicting results regarding the association between hypertensive disorders of pregnancy (HDPs)/preeclampsia (PE) and small for gestational age (SGA) and birthweight discordance (BWD). This retrospective study of 2131 twin pregnancies aimed to evaluate the association of HDPs/PE with the presence of SGA and BWD. The eligible pregnancies were categorized into four study groups: concordant pairs without SGA fetuses, discordant pairs without SGA fetuses, concordant pairs with SGA fetuses, and discordant pairs with SGA fetuses. We applied binary logistic regression models to compare the incidence of HDPs/PE and multinomial logit regression models to evaluate the severity of PE between the study groups. The models were adjusted for potential confounders. Increases in HDPs were observed in concordant (aOR, 2.33; 95% CI: 1.46–3.73) and discordant (aOR, 3.50; 95% CI: 2.26–5.43) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.42; 95% CI: 0.81–2.49); increases in PE were also found in concordant (aOR, 1.87; 95% CI: 1.08–3.23) and discordant (aOR, 3.75; 95% CI: 2.36–5.96) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.34; 95% CI: 0.71–2.52). Discordant pregnancies with SGA fetuses were associated with severe PE (aRRR, 3.48; 95% CI: 1.79–6.77), whereas concordant pregnancies with SGA fetuses were associated with only mild PE (aRRR, 2.54; 95% CI: 1.33–4.88). Our results suggest that SGA is associated with the development of HDP/PE, while discordant growth is associated with the severity of PE. These associations need to be further investigated using estimated fetal weight (EFW).

Abstract Background Placenta previa, a serious obstetric issue, should be managed by experienced teams. The safe and appropriate mode of delivery for placenta previa is by cesarean delivery. However, no studies were found comparing either maternal or neonatal outcomes for different skin incision in women with placenta previa. The aim of this study was to compare maternal and neonatal outcomes by skin incision types (transverse compared with vertical) in a large cohort of women with placenta previa who were undergoing cesarean delivery. Methods This was a retrospective cohort study carried out between January 2014 and June 2019. All pregnant women with placenta previa had confirmed by ultrasonologist before delivery and obstetrician at delivery. The primary outcome was the estimated blood loss during the surgery and within the first 24 hours postoperatively. Mean (standard deviation), median (interquartile range) or frequency (percentage) was reported to variables. Appropriate parametric and nonparametric tests were used to analyses. Results The study included 1098 complete records, 332 (30.24%) cases in the vertical skin incision group and 766 (69.76%) cases in the transverse skin incision group. Those with vertical incision showed a higher percentage of preterm delivery, anterior placenta, abnormally invasive placenta, and history of previous cesarean delivery, and a lower percentage of first pregnancy, in vitro fertilization, and emergency cesarean delivery. After controlling for confounding factors, higher incidence of post-partum hemorrhage (OR 5.47, 95% CI 3.84–7.79), maternal intensive care unit (OR 4.30, 95% CI 2.86–6.45), transfusion (OR 5.97, 95% CI 4.15–8.58), and 5-min APGAR< 7 (OR 9.03, 95% CI 1.83–44.49), a more estimated blood loss (β 601.85, 95%CI 458.78–744.91), and a longer length of hospital stay after delivery (β 0.54, 95%CI 0.23–0.86) were found in the vertical skin incision group. Conclusions Our data demonstrated that transverse skin incision group showed the better perinatal outcomes in women with placenta previa. Future collaborative studies are needed to be done by centers for placenta previa to have a better understanding of the characteristics and the outcomes of the disease in the choosing skin incision.

Abstract Background Twin birth weight percentiles are less popular in clinical management among twin pregnancies compared with singleton ones in China. This study aimed to compare the incidence and neonatal outcomes of small for gestational age (SGA) twins between the use of singleton and twin birth weight percentiles. Methods This was a retrospective cohort study of 3,027 pregnancies with liveborn twin pairs at gestational age of > 28 weeks. The newborns were categorized as SGA when a birthweight was less than the 10th percentile based on the singleton and twin references derived from Chinese population. Logistic regression models with generalized estimated equation (GEE) were utilized to evaluate the association between SGA twins and neonatal outcomes including neonatal unit admission, neonatal jaundice, neonatal respiratory distress (NRDS), neonatal asphyxia, ventilator support, hypoxic ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intracranial hemorrhage (ICH), culture-proven sepsis, neonatal death within 28 days after birth as well as the composite outcome. Results The incidence of SGA was 33.1 % based on the singleton reference and 7.3 % based on the twin reference. Both of SGA newborns defined by the singleton and twin references were associated with increases in neonatal unit admission, neonatal jaundice and ventilator support. In addition, SGA newborns defined by the twin reference were associated with increased rates of BPD (aOR, 2.61; 95 % CI: 1.18–5.78) as well as the severe composite outcome (aOR, 1.93; 95 % CI: 1.07–3.47). Conclusions The use of singleton birth weight percentiles may result in misdiagnosed SGA newborns in twin gestations and the twin birth weight percentiles would be more useful to identify those who are at risk of adverse outcomes.

ObjectiveTo compare the outcomes between gestational diabetes mellitus (GDM) vs. non-GDM twin gestations.MethodsA retrospective cohort study of 2,151 twin pregnancies was performed in a tertiary hospital in Foshan, China, 2012–2020. Pregnancy and neonatal outcomes were compared between women with vs. without GDM using 1:1 propensity score matching (PSM) and multivariable logistic models. For neonatal outcomes, generalized estimating equation (GEE) approach was used to address the intertwin correlation.ResultsOf the 2,151 participants, 472 women (21.9%) were diagnosed with GDM. Women with GDM were older and more likely to be overweight or obese, and more likely have chronic hypertension, assisted pregnancies and dichorionic twins. In the PSM cohort of 942 pregnancies, there was no statistical difference when comparing GDM twin pregnancies and non-GDM in any of the perinatal outcomes, especially in terms of preterm birth (PTB)

Abstract Background Pathological skin scars, caused by cesarean section, affected younger mothers esthetically and psychosocially and to some extent frustrated obstetricians and dermatologists. Umbilical cord mesenchymal stem cells (UC-MSCs), as a population of multipotent cells, are abundant in human tissues, providing several possibilities for their effects on skin scar tissues. Herein, we performed a randomized, double-blind, placebo-controlled, three-arm clinical trial, aiming to assess the efficacy and safety of UC-MSCs in the treatment of cesarean section skin scars among primiparous singleton pregnant women. Methods Ninety primiparous singleton pregnant women undergoing elective cesarean section were randomly allocated to receive placebo, low-dose (3 × 106 cells), or high-dose (6 × 106 cells) transdermal hydrogel UC-MSCs on the surface of the skin incision. The primary outcome was cesarean section skin scars followed after the sixth month, assessed by the Vancouver Scar Scale (VSS). Results All the participants completed their trial of the primary outcome according to the protocol. The mean score of estimated total VSS was 5.52 in all participants at the sixth-month follow-up, with 6.43 in the placebo group, 5.18 in the low-dose group, and 4.71 in the high-dose group, respectively. No significant difference was found between-group in the mean scores for VSS at the sixth month. Additional prespecified secondary outcomes were not found with significant differences among groups either. No obvious side effects or adverse effects were reported in any of the three arms. Conclusion This randomized clinical trial showed that UC-MSCs did not demonstrate the effects of improvement of cesarean section skin scars. Trial registration ClinicalTrials.gov identifier, NCT02772289 . Registered on 13 May 2016.

Allergic and related diseases have a substantial epidemiological impact on the pediatric population. Small molecule-based medicines have been traditionally used to manage the diseases. Omalizumab is the first monoclonal antibody-based medicine used in children's allergy and shows great promises. It binds to free IgE and prevents it from binding to IgE receptors, thus interrupting the IgE-dependent allergic inflammatory cascade. Vast amounts of data demonstrate its effectiveness and well tolerance by patients, including the children. However, the drug was only approved to use in allergic asthma and chronic spontaneous urticaria (CSU), though other applications were explored in clinical trials. In this review, we summarized current pediatric applications of omalizumab in allergic diseases, focusing on its usages beyond asthma and CSU, including allergic rhinitis, allergic bronchopulmonary aspergillosis, vernal keratoconjunctivitis, food allergy and atopic dermatitis. In addition, we highlighted the unmet needs and controversial issues of anti-IgE therapy.

Abstract This retrospective cohort study aimed to investigate the effect of placental location on birthweight discordance among diamniotic-dichorionic twin pregnancies. Medical records and sonographic reports of 978 diamniotic-dichorionic twin pregnancies delivered at Foshan Maternal and Fetal Health Hospital were reviewed. Pregnancies with congenital malformation, intrauterine death or placenta previa were excluded. The placental location for each twin was determined by last sonographic examination before delivery, and the pregnancies were grouped by different versus same placental location in each pregnancy. Maternal and fetal characteristics were summarized. The primary outcome of interest was birthweight discordance (BWD) ≥20%, and secondary outcomes included small for gestational age (SGA) as a binary outcome and mean value and absolute difference in birthweight as continuous outcomes. Student’s t test and the chi-square test were used for univariate analyses, while multivariate regressions were used to adjust for confounders. General estimated equation (GEE) models were used to address the correlation between fetuses when assessing SGA. A total of 866 eligible subjects were included in the analysis. In total, 460 pregnancies had placentas with different locations, and 406 had placentas with same locations. The gestational age at delivery was slightly younger in the same placental location group than in the different placental location group (35.8 ± 0.1 vs. 36.1 ± 0.1 weeks, P = 0.067). Other maternal and fetal characteristics were comparable between the two study groups. There was no significant difference in BWD ≥20% (aOR = 1.06; 95% CI: 0.71–1.59) or SGA (aOR = 1.32; 95% CI: 0.76–2.28) between the same and different placental location groups. Neither the mean value nor the absolute difference in birth weight was associated with placental location combination (P = 0.478 and P = 0.162, respectively). In conclusion, discordant birthweight is not affected by same location of diamniotic-dichorionic placentas.

Abstract Background Gestational weight gain (GWG) has implications for perinatal outcomes, the guidelines for maternal weight gain, however, remain understudied among twin pregnancies. This study aimed to assess the associations between perinatal outcomes and GWG among twin pregnancies, based on the US institute of Medicine (IOM) 2009 guidelines. Methods A retrospective cohort study of pregnant women with viable twins ≥26 weeks of gestation, was conducted in Foshan, China, during July 2015 and June 2018. Maternal BMI was categorized based on Chinese standard and GWG was categorized as below, within and above the IOM 2009 recommendations. Underweight women were excluded for analysis. Perinatal outcomes were compared among these groups. To assess the independent impact of GWG on the perinatal outcomes, conventional multivariable regression and general estimated equation (GEE) were utilized for maternal outcomes and neonatal outcomes, respectively. Results A total of 645 mothers with twin pregnancies were included, of whom 15.0, 41.4 and 43.6% gained weight below, within and above guidelines, respectively. Compared to weight gain within guidelines, inadequate weight gain was associated with increased risks in spontaneous preterm birth 90th percentile and less likely to have fetuses weighted

Objective: To explore the size and shape association of OGTT values with adverse pregnancy complications among women with gestational diabetes mellitus (GDM) in Southern Han Chinese population and further analyze their mediating effects with maternal age in outcomes.Methods: 6,861 women with GDM were included in the study. Logistic regression was used to identify the correlations between OGTT values and adverse pregnancy outcomes of GDM. Restricted cubic spline nested logistic regression was conducted to investigate potential non-linear and linear associations. Mediating effect among maternal age, OGTT and adverse outcomes were explored.Results: Women with GDM had a mean age of 31.83, and 24.49% had advanced maternal age (≥35 years). In logistic regression with adjustment, compared with lower OGTT0 ( 0.05) were observed between OGTT0 and HDP, preterm, neonatal hyperbilirubinemia, and macrosomia in both maternal age groups (

Background/Aims: Genomic adaptations to high altitudes have been well studied in the last several years; however, the roles of microRNAs (miRNAs), which are essential modulators of a variety of genes and key cellular processes, have rarely been explored. Here, we explored the interactions between miRNAs and their target genes as an adaptation to high altitude in an avian species, the great tit (Parus major), which is widely distributed across the Eurasian continent at altitudes between 4500 m and sea level. Because the MAPK signaling pathway plays a crucial role in the hypoxia response in the great tit, we chose MAPK1 as a target candidate gene. Methods: We established a great tit embryonic fibroblast line and subsequently studied the relationship between miRNA-19b-3p and MAPK1 in normoxia and hypoxia groups. Meanwhile, the great tit embryonic fibroblasts (GEFs) were treated or transfected with miR-19b-3p mimics, inhibitors, or si-MAPK1, and their proliferation was subsequently assessed using the MTT assay. The expression of the miRNAs and MAPK1 was measured by real-time PCR and Western blotting. Results: We identified 14 miRNAs in the cardiac tissues of great tits that are related to hypoxia adaptation. MAPK1 binds only to miR-19b-3p of the 14 miRNAs predicted by both TargetScan and miRanda software. Specifically, we validated the computational prediction of miR-19b-3p binding to the 3’UTR of MAPK1 using a luciferase reporter assay. Our results show that miR-19b-3p promotes GEFs proliferation and up-regulates MAPK1 expression. Moreover, miR-19b-3p mimics and MAPK1 knockdown induce GEFs apoptosis and regulate the cell cycle under hypoxic conditions. Conclusions: Our study is the first to describe an important miRNA-mediated regulatory mechanism of high altitude adaptation in a non-model wild songbird and highlights the importance of studies on miRNA-mediated mechanisms of hypoxic adaptations in other animals.

The embryonic surface ectoderm is a simple flat epithelium consisting of cells that express the cytokeratins K8/K18. Before stratification, K5/K14 expression substitutes K8/K18 expression, marking the event called epidermal commitment. Previous studies show that the transcription factor p63 plays an essential role in epidermal commitment. However, detailed expression information of p63 during early epidermal development in mice is still unclear. We systematically studied the expression pattern of p63 in mouse epidermal commitment, together with K8 and K5. We show that p63 expression could be detected as early as E8.5 in mouse embryos preceding epidermal commitment. p63 expression first appears near the newly formed somites and the posterior part of the embryo, further expanding to the whole embryonic surface with particular enrichment in the first branchial arches and the limb buds. ΔNp63 is the major class of isoforms expressed in this period. Relative expression intensity of p63 depends on the embryonic position. In summary, there is a sequential and regular expression pattern of K8, p63 and K5 in mouse epidermal commitment. Our study not only contributes to understanding the early events during epidermal development but also provides a basal tool to study the function of p63 in mammals.

Hair follicle stem cells (HFSCs) possess fascinating self-renewal capacity and multipotency, which play important roles in mammalian hair growth and skin wound repair. Although HFSCs from other mammalian species have been obtained, the characteristics of ovine HFSCs, as well as the methods to isolate them have not been well addressed. Here, we report an efficient strategy to obtain multipotent ovine HFSCs. Through microdissection and organ culture, we obtained keratinocytes that grew from the bulge area of vibrissa hair follicles, and even abundant keratinocytes were harvested from a single hair follicle. These bulge-derived keratinocytes are highly positive for Krt15, Krt14, Tp63, Krt19 and Itga6; in addition to their strong proliferation abilities in vitro, these keratinocytes formed new epidermis, hair follicles and sebaceous glands in skin reconstitution experiments, showing that these are HFSCs from the bulge outer root sheath. Taken together, we developed an efficient in vitro system to enrich ovine HFSCs, providing enough HFSCs for the investigations about the ovine hair cycle, aiming to promote wool production in the future.

Hair follicle stem cells (HFSCs) are considered one of the useful donor cell types for skin regenerative medicine owing to their robust proliferative capacity and multipotency. However, methods for easily and effectively obtaining HFSCs from a limited skin biopsy are still lacking. Here we report a novel approach for obtaining a subpopulation of HFSCs from a small skin sample from the rat tail, which uses the sebaceous glands (SGs) to capture the adjacent HFSCs. By means of organ culture, keratinocytes were expanded from the detached SGs, which also included adherent HFSCs from the hair follicle that could be passaged at the single-cell level. These SG-captured keratinocytes strongly expressed the basal layer markers K14, integrin α6, and p63; the bulge stem cell marker K15; and the upper isthmus stem cell marker Plet1. Furthermore, we reconstituted new epidermis, hair follicles, and SGs from the SG-captured keratinocytes using an easily operated, modified skin reconstitution assay based on silicone gel sheeting. This study suggests that the SGs could be an accessible capturer to harvest the adjacent HFSC subpopulation, particularly when the donor tissue is limited.

Hair follicle stem cells (HFSCs) are potentially useful for the treatment of skin injuries and diseases. To achieve clinical application, a prerequisite must be accomplished: harvesting enough HFSCs from limited skin biopsy. The commonly used sorting approach for isolating HFSCs, however, suffers from its intrinsic disadvantages, such as requirement of large-scale skin biopsy. Here, we report an efficient organ culture method to isolate and expand rat HFSCs from limited skin biopsy and these HFSCs could reconstitute the epidermis and the hair follicles (HFs). Seventy-three percent of cultured HFs formed hair follicle stem cell colonies from the bulge, and a single hair follicle provided all the HFSCs used in this research, demonstrating the high efficiency of this method. Quantitative RT-PCR and immunofluorescent staining results revealed that these stem cells obtained from the bulge highly expressed basal layer markers K14 and alpha-6 integrin, epithelial stem cell marker P63, and bulge stem cell marker K15. After long-term culture in vitro, GFP-labeled hair follicle stem cells formed new hair follicles, epidermis, and sebaceous glands following xenotransplantation into the back of nude mice. This study indicated that multipotent hair follicle stem cells could be efficiently harvested through organ culture from limited skin material—even a single hair follicle—and reconstitute hair follicles in vivo after long-term expansion culture, providing the basis for future clinical applications.