Biallelic mutations in LSS in autosomal-recessive mutilating palmoplantar keratoderma.

Mutilating palmoplantar keratoderma (PPK) is a heterogeneous genetic disease that poses enormous challenges to clinical diagnosis and genetic counselling. Lanosterol synthase (LSS) gene encodes LSS involved in the biosynthesis pathway of cholesterol. Biallelic mutations in LSS were found to be related to diseases such as cataracts, hypotrichosis and palmoplantar keratoderma-congenital alopecia syndrome. The aim of this study was to investigate the contribution of the LSS mutation to mutilating PPK in a Chinese patient. The clinical and molecular characteristics of the patient were evaluated. A 38-year-old male patient with mutilating PPK was recruited in this study. We identified biallelic variants in the LSS gene (c.683C > T, p.Thr228Ile and c.779G > A, p.Arg260His). Immunoblotting revealed that the Arg260His mutant showed a significantly reduced expression level while Thr228Ile showed an expression level similar to that of the wild type. Thin layer chromatography revealed that mutant Thr228Ile retained partial enzymatic activity and mutant Arg260His did not show any catalytic activity. Our findings show the correlation between LSS mutations and mutilating PPK.

InDel marker detection by integration of multiple softwares using machine learning techniques.

BACKGROUND: In the biological experiments of soybean species, molecular markers are widely used to verify the soybean genome or construct its genetic map. Among a variety of molecular markers, insertions and deletions (InDels) are preferred with the advantages of wide distribution and high density at the whole-genome level. Hence, the problem of detecting InDels based on next-generation sequencing data is of great importance for the design of InDel markers. To tackle it, this paper integrated machine learning techniques with existing software and developed two algorithms for InDel detection, one is the best F-score method (BF-M) and the other is the Support Vector Machine (SVM) method (SVM-M), which is based on the classical SVM model. RESULTS: The experimental results show that the performance of BF-M was promising as indicated by the high precision and recall scores, whereas SVM-M yielded the best performance in terms of recall and F-score. Moreover, based on the InDel markers detected by SVM-M from soybeans that were collected from 56 different regions, highly polymorphic loci were selected to construct an InDel marker database for soybean. CONCLUSIONS: Compared to existing software tools, the two algorithms proposed in this work produced substantially higher precision and recall scores, and remained stable in various types of genomic regions. Moreover, based on SVM-M, we have constructed a database for soybean InDel markers and published it for academic research.

Preterm Births in Peking Union Medical College Hospital in the Past 25 Years.

Objective To investigate the changes in preterm birth rate,its gestational age distribution,and possible contributors in Peking Union Medical College Hospital (PUMCH) over the last 25-year period. Methods The clinical data of premature deliveries,both singleton and twins,in PUMCH from January 1,1990 to December 31,2014 were retrospectively analyzed. We counted the number of premature fetuses and assessed the changes of preterm birth rate and its gestational age distribution (including extremely preterm birth,early preterm birth,and late preterm birth) over time. The etiologies (including spontaneous and iatrogenic) of preterm birth were also surveyed. Results The overall preterm birth rate was 7.8% in PUMCH,showing a slightly up-trend in both singletons and twins. Twin prematurity accounted for 23.8% of total preterm births,increased from 15.1% to 28.5%. Preterm births subgrouped by gestational age included 26 cases (0.7%) of extreme prematurity (<28 weeks),1199 cases (33.9%) of early preterm birth (28- 33+6 weeks),and 2310 cases (65.3%) of late preterm birth (34- 36+6 weeks). The gestational age distribution in singletons and twins showed no significant difference(z=0.844,P=0.398). Changes in the proportion of preterm birth before 28 weeks was little,gradually increased in the 28- 33+6 weeks group (from 23.8% to 36.1%) and gradually decreased in the 34- 36+6 weeks group (from 75.5% to 63.3%). Trends of gestational age distribution of singleton and twins were similar to that of the total. Spontaneous preterm labor,preterm premature rupture of membrane,and medically indicated (iatrogenic) preterm birth accounted for 20.2%,38.9%,and 40.9% respectively. There was no difference in singletons and twins(χ2=1.071,P=0.301).The proportion of iatrogenic preterm was increased. Common reasons for iatrogenic preterm birth included gestational hypertension,fetal indications (including fetal distress,fetal growth restriction),placenta previa,and pregnancy complicated by heart disease. Conclusions The overall preterm birth rate shows an upward trend in the general hospital as a result of more multifetal gestations and more medically indicated preterm births. Reducing multifetal gestations and effective control of pregnancy complications should be the priorieties in preterm birth intervention.

High frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma.

To study high-frequency ultrasound features and pathological characteristics of medullary thyroid carcinoma (medullary thyroid carcinoma, MTC) with the purpose to improve the diagnostic accuracy of this disease. The clinical data of 20 cases of patients with MTC confirmed by the clinical surgery were retrospectively analyzed. And the high-frequency ultrasound features were analyzed and compared with the pathological characteristics. There were 16 cases with tumor invasion into one side of the thyroid gland; 17 cases with tumor in the middle-upper pole of the thyroid gland. And 8 cases were detected with uneven echo of high frequency ultrasound appearance and pathological manifestations of cystic degeneration to necrosis seen under the light microscope or normal thyroid tissue within part of the lump. 16 cases were tested with even echo of high frequency ultrasound appearance, and tumor cells were formed in the solid and block-like shape under the light microscope. And 18 cases were manifested with low echo, with proliferation of fibrous tissue within the intercellular substance under the light microscope. 18 cases could be seen the calcification points and often amyloid-like content deposited in the intercellular substance seen under the light microscope. In addition, the pathological manifestations of the 8 cases combined with lymph node metastasis were the "lash tumor" of the metastatic lymph nodes and primary tumor. MTC was commonly located in the middle-upper region of the thyroid gland and in one leaf of the thyroid gland, combined with lymph node metastasis. The high frequency ultrasound appearance was the even low-echo tumor in round or quasi-circular shape, with obscure boundary and often combined with rough calcification. High frequency ultrasound could be used as the prior physical diagnostic method for medullary thyroid carcinoma.

[Analysis of differentially expressed genes in placental tissues of early-onset severe preeclampsia patients].

OBJECTIVE: To explore the differentially expressed genes(DEG)involved in the pathogenesis of preeclampsia (PE). METHODS: The gene expression profiles of placental tissues from 7 severe PE patients and 7 preterm controls from June to December 2012 were assessed using microarray. Gene ontology (GO) enrichment analysis and pathway analysis were performed to explore the genes and pathways involved in the pathogenesis of PE. Four DEG involved in these biological processes were further verified by quantitative real-time PCR. RESULTS: A total of 308 transcripts were significantly differentially expressed. Of these DEG, 81 genes(LEPTIN, PAPPA2, CRH, PLIN2, INHA, BCL6, FLT1, CCR7, etc) were up-regulated, and 227 genes (CXCL12, CXCL9, etc)were down-regulated. GO enrichment analysis indicated that the top 3 GO molecular functions were immune response (GO: 0006955, 17 DEG), positive regulation of apoptosis (GO: 0043065, 11 DEG) and inflammatory response (GO: 0006954, 11 DEG). Pathway analysis showed that the top 3 pathways were cell adhesion molecules (11 DEG), cytokine- cytokine receptor interaction (11 DEG), chemokine signaling pathway (8 DEG). Many genes (LEP, FLT1, TFRC, SH3PXD2A, CYP11A1, SEPP1, and so on) involved in oxidative stress were found to be significantly changed. Of these genes, LEP were significantly up- regulated with a fold change of 61.5. The fold changes of FLT1, SH3PXD2A, SEPP1, CYP11A1, TFRC were 8.6, 2.2, -2.0, 2.7 and -2.8. Four DEG involved in oxidative stress were further verified by quantitative real-time PCR. CONCLUSIONS: A DEG signature was identified in severe preeclampsia placentas compared with normal controls. The DEG mainly involved in the molecular mechanisms of immune response, oxidative stress and inflammatory response, and were closely associated with the pathogenesis of PE.

[Value of second trimester maternal serum sFlt-1, PlGF and their ratio in the prediction of preeclampsia].

OBJECTIVE: To study the value of second trimester maternal serum soluble Fms-like tyrosine kinase 1 (sFlt-1), placenta grouth factor (PlGF) and their ratio in the prediction of preeclampsia. METHODS: In this nested case-control study, we collected second trimester maternal serum samples at 15-20 weeks and 24-28 weeks of gestation from those who developed gestational hypertensive disorders. Maternal serum sFlt-1 and PlGF were measured by electrochemiluminescence immunoassay on an automated platform. The value of sFlt-1, PlGF and their ratio were compared between gestational hypertensive group and the control group. RESULTS: Totally 41 patients with preeclampsia, 44 patients with gestational hypertension and 88 women with normal pregnancy outcomes were included in this study. There was no difference of age, gravidity, parity and preconception body mass index (BMI) between these three groups (P > 0.05) .Gestational week at delivery and neonatal birth weight were different between preeclampsia group and the control group (P < 0.01). The mean value of sFlt-1, PlGF and sFlt-1/PlGF ratio was (1 658 ± 488) µg/L, (141 ± 80) µg/L and 17 ± 9 in preeclampsia group, (1 945 ± 575) µg/L, (143 ± 52) µg/L and 15 ± 6 in gestational hypertension group, and (2 084 ± 741) µg/L, (65 ± 58) µg/L and 16 ± 9 in the control group at 15-20 weeks of gestation. There was no difference of sFlt-1, PlGF value and their ratio among the three groups at 15-20 weeks of gestation (P > 0.05) . The median value of sFlt-1, PlGF and sFlt-1/PlGF ratio were 8 525 µg/L, 35 µg/L and 398.0 in preeclampsia group, 905 µg/L, 336 µg/L and 2.7 in gestational hypertension group, 1 028 µg/L, 477 µg/L and 2.3 in the control group at 24-28 weeks of gestation. The value of sFlt-1, PlGF and their ratio was significantly different between preeclampsia group and the control group at 24-28 weeks of gestation (P < 0.01) . PlGF value was different between gestational hypertension group and the control group (P < 0.01) . The sensitivity and specificity of serum sFlt-1, PlGF and sFlt-1/PlGF ratio at 24-28 weeks of gestation to predict preeclampsia were 93% and 99% for sFlt-1 (cut off value 2 500 µg/L), 92% and 77% for PlGF (cut off value 270 µg/L) , 89% and 99% for sFlt-1/PlGF ratio (cut off value 11) . CONCLUSION: The value of sFlt-1, PlGF and their ratio at 24-28 weeks of gestation was significantly changed before clinical onset of preeclampsia.Use these serum indicators to predict preeclampsia will hopefully provide objective evidence for the management of patients who will develop preeclampsia later.

Preparation, characterization, and release properties of Rosa roxburghii Tratt seed oil and ß-carotene-coloaded proliposomes.

Rosa roxburghii Tratt seed oil (RSO) and ß-carotene (ßC) were chosen to prepare proliposomes by the thin-film dispersion method. The characteristics of unloaded proliposome, RSO proliposome (L-R), ßC proliposome (L-ß), and RSO/ßC proliposome (L-R-ß) were analyzed, and their antioxidant activity, storage stability, and release properties were investigated. The proliposomes had an encapsulation efficiency (RSO, ßC) higher than 83.10%, nanometer size, smooth surface, and irregular structure. L-R-ß showed better dispersibility, stability, and antioxidant activity than L-R and L-ß. Simultaneous encapsulation of RSO and ßC reduced the phospholipid oxidation of proliposomes and improved the retention rate of RSO in storage environments of 4, 25, and 40°C. Moreover, the RSO and ßC release kinetics of proliposomes in the simulated saliva fluid and gastric fluid phases can be described by the first-order model, and the Korsmeyr-Peppas method was applied to describe their release mechanism in the simulated intestinal fluid phase.

Successful Treatment of Refractory Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome with Baricitinib, a Janus Kinase Inhibitor.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare immune-mediated inflammatory disease, poses diagnostic and therapeutic challenges owing to its multi-system involvement, high heterogeneity, and lack of specific laboratory tests. Additionally, lacking evidence-based treatment recommendations, with the primary approach focusing on symptomatic relief. Herein, we report the case of a 32-year-old Chinese woman who presented with recurrent, generalized multiple osteoarticular pain lasting over one year and skin erythema pustulosis for 11 months. Traditional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and other traditional approaches, yielded no significant effects. Despite the prior use of adalimumab and acitretin capsules, the treatment remained unsatisfying, especially regarding the skin lesions. Considering the complex pathogenesis of SAPHO syndrome, the patient was orally administered baricitinib (2 mg), a Janus kinase (JAK) inhibitor, twice daily. A notable improvement in both skin lesions and osteoarticular pain was observed within two weeks of treatment initiation. Subsequently, the dosage of baricitinib was halved and continued for an additional three months, during which regular follow-ups revealed neither disease recurrence nor adverse effects. Collectively, the successful treatment of refractory SAPHO syndrome with baricitinib presents a promising implication for addressing the therapeutic challenges of this rare autoimmune condition, offering a potential breakthrough in managing its complex manifestations.

Aligned cryogel fibers incorporated 3D printed scaffold effectively facilitates bone regeneration by enhancing cell recruitment and function.

Reconstructing extensive cranial defects represents a persistent clinical challenge. Here, we reported a hybrid three-dimensional (3D) printed scaffold with modification of QK peptide and KP peptide for effectively promoting endogenous cranial bone regeneration. The hybrid 3D printed scaffold consists of vertically aligned cryogel fibers that guide and promote cell penetration into the defect area in the early stages of bone repair. Then, the conjugated QK peptide and KP peptide further regulate the function of the recruited cells to promote vascularization and osteogenic differentiation in the defect area. The regenerated bone volume and surface coverage of the dual peptide-modified hybrid scaffold were significantly higher than the positive control group. In addition, the dual peptide-modified hybrid scaffold demonstrated sustained enhancement of bone regeneration and avoidance of bone resorption compared to the collagen sponge group. We expect that the design of dual peptide-modified hybrid scaffold will provide a promising strategy for bone regeneration.

OSBPL2 compound heterozygous variants cause dyschromatosis, ichthyosis, deafness and atopic disease syndrome.

PURPOSE: In this study, we identified and diagnosed a novel inherited condition called Dyschromatosis, Ichthyosis, Deafness, and Atopic Disease (DIDA) syndrome. We present a series of studies to clarify the pathogenic variants and specific mechanism. METHODS: Exome sequencing and Sanger sequencing was conducted in affected and unaffected family members. A variety of human and cell studies were performed to explore the pathogenic process of keratosis. RESULTS: Our finding indicated that DIDA syndrome was caused by compound heterozygous variants in the oxysterol-binding protein-related protein 2 (OSBPL2) gene. Furthermore, our findings revealed a direct interaction between OSBPL2 and Phosphoinositide phospholipase C-beta-3 (PLCB3), a key player in hyperkeratosis. OSBPL2 effectively inhibits the ubiquitylation of PLCB3, thereby stabilizing PLCB3. Conversely, OSBPL2 variants lead to enhanced ubiquitination and subsequent degradation of PLCB3, leading to epidermal hyperkeratosis, characterized by aberrant proliferation and delayed terminal differentiation of keratinocytes. CONCLUSIONS: Our study not only unveiled the association between OSBPL2 variants and the newly identified DIDA syndrome but also shed light on the underlying mechanism.

Magnesium/gallic acid bioMOFs laden carbonized mushroom aerogel effectively heals biofilm-infected skin wounds.

Biofilm-infected acute skin wounds are still one of the significant challenges that need to be solved urgently in wound healing. Herein, we reported a magnesium/gallic acid bio-MOFs laden carbonized mushroom aerogel (QMOFs-PCMA) combined with photothermal therapy for eradicating biofilms in skin wounds. The design of bioMOFs is mainly responsible for regulating immunity. In vitro, it exhibited ROS clearance and antioxidant ability. In vivo, it could regulate local immune responses from pro-inflammatory status to pro-regenerative status, resulting in decreased inflammatory cytokines expression and increased anti-inflammatory cytokines expression. The carbonized mushroom aerogel is mainly responsible for photothermal therapy (PTT), and the polydopamine and bioMOFs could enhance the photothermal conversion efficiency and stability of carbonized aerogels. The carbonized aerogel in combination with PTT could eradicate S. aureus biofilm in both in vitro and in vivo studies and clear E. coli biofilms in vitro studies. The biofilm clearance and improved inflammatory responses laid a good foundation for wound healing, resulting in the granulation tissue formation, re-epithelialization, and angiogenesis significantly enhanced in the QMOFs-PCMA + NIR group. Our results indicate that the QMOFs-PCMA combined with photothermal therapy may provide a promising treatment for biofilm-infected skin wounds.

Simultaneous Determination of Three Flavonoids in Rat Plasma of Masson Pinus Needles (Pinus massoniana L.) Extracts by UHPLC-MS/MS and Application to Pharmacokinetics Studies after Oral and Transdermal Administration.

Pinus massoniana needles, a traditional herb, were applied to prevent hair loss in China. Studies available mainly focused on pine needle flavonoids with various biological activities. However, there has been no pharmacokinetics study of the flavonoids from Pinus needles extract. A selective and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously quantify taxifolin, quercetin and catechin in rat plasma. To separate the three constituents, an Agilent Extend-C18 column (2.1 mm × 100 mm, 1.8 µm) was used with a mobile phrase of (A) 0.1% formic acid and (B) acetonitrile. The analytes were measured by multiple reaction monitoring in the negative ionization mode. There was good linearity in the established UHPLC-MS/MS method, with a coefficient of determination (r2) of >0.99. The accuracy, intra-day and inter-day precision and recovery were all satisfactory and these 3 compounds were stable under the tested conditions. The validated method in this study was successfully applied to pharmacokinetic study in healthy rats after oral and transdermal administration of Pinus needles extract. The results could provide further research foundation for pine needle extract as external preparations.

A Case of Paradoxical Reactions to Biologic Therapy for Psoriasis.

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease. As our understanding of the pathogenesis of psoriasis has improved, biologic agents have become increasingly important in the treatment of psoriasis. However, the use of biologic agents is associated with cutaneous side effects. A new type of side effect called paradoxical reactions is an emerging threat arising from the increasing use of biologic agents. Case: Here, we present a case of paradoxical skin reactions - pyoderma gangrenosum (PG) and eczema - induced by biologic therapy. The case was successfully and eventually treated with baricitinib. Discussion: PG is a rare inflammatory disease characterised by painful and necrotic ulcerations containing neutrophils. It has been associated with autoimmune diseases such as inflammatory bowel disease (IBD). TNF (tumor necrosis factor) -α inhibitors can effectively treat refractory PG, while IL (interleukin) -17A inhibitors may worsen IBD symptoms. The cause of PG in this case was believed to be secukinumab, not adalimumab. The patient was diagnosed with eczematous dermatitis due to TNF-α inhibitors, and baricitinib was added to treat eczematous dermatitis. Conclusion: Paradoxical reactions are unpredictable events that may occur during treatment with biologics at anytime. They need further research in order to formulate personalised treatment.

Transcriptome analysis of hepatic injury caused by delayed resuscitation following severe burns in rats.

BACKGROUND: Delayed resuscitation (DR) can induce hepatic reperfusion injury after severe burns. The underlying molecular mechanisms of DR-induced hepatic injury remain unidentified. This study sought to predict candidate genes and molecular pathways in a DR-induced hepatic injury preclinical model. METHODS: Rats were randomized into three groups: the sham injury (Sham) group; the DR group, which had third-degree burns covering 30% of the body surface area and DR; and the early resuscitation (ER) group, in which ER was administered. The liver tissue was harvested for the purpose of evaluating hepatic injury and performing transcriptome sequencing. Differentially expressed genes (DEGs) for DR versus Sham and ER versus DR were analyzed respectively. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Ingenuity Pathway Analysis were used. The DEGs and critical module genes were intersected to obtain critical genes. Immune infiltration and competing endogenous RNA networks were also analyzed. Validation was conducted using quantitative real-time polymerase chain reaction. RESULTS: Hepatic injury was evident in DR rats. There were 2,430 DEGs between DR and Sham and 261 DEGs between ER and DR. Differentially expressed genes were mostly enriched in metabolic process for DR versus Sham, and immune and inflammatory processes for ER versus DR. Four critical genes (Tff3, C1galt1, Cd48, and MGC105649) were obtained by screening. Five immune cells were significantly different between DR and Sham, and seven immune cells were significantly different between ER and DR in immunoassays. Three critical genes, 75 miRNAs, 7 lncRNAs, and 197 edges constituted the mRNA-miRNA-lncRNA linkages, which included C1galt1-rno-miR-330-5p-Pvt1, among others. CONCLUSION: This is the first attempt to perform a high-throughput analysis of gene expression profiles in DR-induced hepatic injury. It shows that immunity and inflammation-related RNAs and pathways play an important role in the progression of hepatic injury. It also provides insight into some important RNAs and regulatory targets related to disease.

The Epidermal Barrier Structure and Function of Re-Harvested Skin from Non-Scalp Donor Sites.

AIM: The aim of this study was to explore the epidermal barrier structure and function of re-harvested skin from non-scalp donor sites. METHODS: Six patients with large-area deep burns who met the inclusion and exclusion criteria were subjected to split-thickness skin excision three times on the same healthy non-scalp donor sites, with an interval of 14 days. The donor skin thus harvested was labeled as primary skin (S1), secondary skin (S2), and tertiary skin (S3). The transepidermal water loss (TEWL) and stratum corneum water content (SCH) of donor skin were detected before each surgery, and the donor skin was harvested during the surgery. The donor skin was stained with hematoxylin and eosin (HE) and involucrin, loricrin, filaggrin, small molecule proline-rich protein 3 (SPRR3), ZO-3, JAM-A, and JAM-C, or observed by transmission electron microscopy. RESULTS: The epidermal barrier function of the re-harvested skin from the non-scalp donor sites became impaired. The histopathological structure of the re-harvested skin from non-scalp donor sites became abnormal. The barrier of the epidermal stratum corneum of the re-harvested skin from non-scalp donor sites was damaged. The epidermal tight junction barrier in the re-harvested skin from non-scalp donor sites was damaged. CONCLUSIONS: As the number of harvesting increases, the epidermal barrier function of the skin decreased, and the damage to the barrier structure increased. Hence, it is vitally important to restore the epidermal barrier function for re-harvesting in non-scalp donor sites.

Antibacterial, injectable, and adhesive hydrogel promotes skin healing.

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107 CFU/mL in the blank group and 2.5 × 107 CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107 CFU/mL in the blank group and 8.5 × 107 CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects.

[Clinical analysis of pregnancies after vaginal radical trachelectomy].

OBJECTIVE: To explore the pregnancy outcome and obstetric management of pregnancy and delivery after vaginal radical trachelectomy (VRT). METHODS: Forty-two cases of VRT from December 2003 to May 2012 in Peking Union Medical College Hospital were analyzed retrospectively. Among them ten cases got pregnant successfully. RESULTS: The average age of patient at VRT surgery was (30.6 ± 3.7) years old and average follow-up time was 29.5 months. There were 31 patients attempted conception. Ten of them got fourteen conceptions successfully. Overall conception rate was 45% (14/31). There were four cases of first trimester abortion. Among them, two were miscarriage, two were elective abortion. There was one case of ectopic pregnancy operation and non of second trimester loss. Nine cases reached the third trimester. The total preterm delivery rate was 4/9. There were two cases delivered before 32 gestational weeks (2/9). Cesarean section was performed through a transverse incision in all of nine cases. No uterine rupture and postpartum hemorrhage occurred. All newborns had good outcomes. The average follow-up time after postpartum was 22.9 months. All cases were disease-free. CONCLUSIONS: The conception rate of patients after VRT in our series is 45%. The preterm birth rate of pregnancy after VRT is higher. Routine cerclage of cervix during VRT procedure and pregnancy is not necessary. Cesarean section shortly after full term pregnancy through a transverse incision should be considered as a suitable and safe procedure.

Corrigendum: A community-oriented survey on the association between androgenetic alopecia and metabolic syndrome in Chinese people.

[This corrects the article DOI: 10.3389/fmed.2022.1009578.].

A community-oriented survey on the association between androgenetic alopecia and metabolic syndrome in Chinese people.

Background: Several studies on Caucasians have revealed a positive relationship between androgenetic alopecia (AGA) and metabolic syndrome (MS). However, this correlation varies in different contexts. Currently, the association of AGA with MS is yet to be studied and elucidated in Chinese people. Objective: To evaluate the association between AGA and MS in the Chinese population. Methods: This study included information on components of MS along with other possible risk factors in a total of 3,703 subjects. The patients' loss of hair was assessed using Hamilton-Norwood and Ludwig classification method. Results: In this study, 29.88% of male and 27.58% of female AGA patients were diagnosed with MS, while the rest were regarded as controls (29.95% of male and 27.89% of female control subjects) (P > 0.05). The AGA males presented significantly higher systolic and diastolic blood pressure than the male control subjects (SP: P = 0.000; DP: P = 0.041). Among females with AGA, waist circumference, hip circumference, and waist-hip ratio elevated the loss of hair compared to that of the female controls (P = 0.000, P = 0.020, P = 0.001, respectively). Conclusion: Our study indicated no direct association between AGA and MS in Chinese people. However, a close relationship was observed between AGA and systolic blood pressure.

Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway.

BACKGROUND: Aging disturbs the skin morphology and function, manifested as thinned epithelium and impaired wound healing. As a major type of skin cells, epidermal stem cells (EpiSCs) are inevitably affected by aging. The effect of age on EpiSCs and wound healing needs to be further explored. METHODS: Skin RNA-seq data of young (5 months) and old (30 months) CB6F1 mice were obtained from GEO Series GSE35322 with 10 in each age group. Differentially expressed genes were analyzed, and EpiSCs-related pathways were enriched by KEGG. The age-related changes of the screened PI3K/Akt pathway were validated by Western Blot and immunofluorescence of epidermis of SD rats (2, 17, and 23 months, n = 6). The expression of upstream protein EGFR was assessed by immunofluorescence in skin of mice (4, 13, and 23 months, n = 6) and human (respectively, 23, 28, 30 years old in the young group and 69, 73, 78 years old in the old group) skin. Inhibitors of EGFR were used to verify its effects on EpiSCs and wound healing. The small molecule drug Tideglusib was tested for its effects on signaling pathways of EpiSCs and wound healing of aged rats. Western Blot was used for the detection of signaling pathways in in vitro experiments. Cell migration assays were used to assess cell migration ability. Flow cytometry was used to detect changes in cell cycle and apoptosis levels. Sulforhodamine B assay and CCK-8 assay were used to evaluate cell proliferation and viability, respectively. Student's t test and one-way analysis of variance (ANOVA) followed by the multiple comparisons Bonferroni test were used for statistical analysis. The 0.05 level of confidence was accepted as a significant difference. RESULTS: EpiSCs-related PI3K/Akt pathway was enriched by KEGG and verified by decreased phosphorylation of Akt (32.1 ± 13.8%, P < 0.01) and mTOR (38.9 ± 11.8%, P < 0.01) in aged epidermis of rats. Furthermore, the expression of PI3K/Akt-upstream EGFR decreased with age in the epidermis of mouse (27.6 ± 5.5%, P < 0.01) and human (25.8 ± 9.3%, P < 0.01). With EGFR blocked by Erlotinib, EpiSCs showed reduced phosphorylation of Akt (30.4 ± 10.6%, P < 0.01) and mTOR (39.8 ± 12.8%, P < 0.01), impaired proliferation and migration after incubated for 24 h and 36 h (P < 0.05), and higher levels of apoptosis (11.9 ± 1.7%, P < 0.05), and rats showed slower wound healing from d7 to d14 after wounding (P < 0.01). In addition to slower wound healing rates, aged rats also showed a decrease in the efficacy of EGF, partly due to the downregulated EGFR expression. By activating PI3K/Akt pathway, Tideglusib promoted the proliferation and migration of EpiSCs with apoptosis inhibited (P < 0.01) and accelerated wound healing in aged rats from d7 to d14 after wounding (P < 0.05). Notably, the combined use of Tideglusib and EGF could further enhance wound healing in aged rats. CONCLUSIONS: The decreased expression of EGFR in epidermis with age resulted in decreased activity of the PI3K/Akt pathway and limited EGF efficacy. Tideglusib could assist wound healing in aged rats via activating PI3K/Akt pathway, which may be considered as an ingredient for medical and cosmetics use.