A method for isolating and culturing ectopic epithelial and stromal cells to study human adenomyosis.

PURPOSE: Although adenomyosis is a common and benign gynecological disease, the specific pathogenesis of this condition is yet to be fully elucidated. It is difficult to culture primary cells of the ectopic endometrial epithelia and stroma from human adenomyosis lesions. Most of the previous of studies on adenomyosis were based on primary eutopic endometrium cells. However, as yet, no efficient protocols have been developed for the isolation, culture or purification of primary ectopic epithelial and stromal cells from human adenomyosis lesions. Therefore, the present study aimed to develop an efficient protocol for the isolation and culture of primary ectopic epithelial and stromal cells from human adenomyosis lesions. METHODS: In the present study, we aimed to obtain ectopic endometrium tissue from human adenomyosis foci and use a simple and operable type I collagenase digestion method for primary culture. Cells were isolated by sterile cell strainer filtration and flow cytometry was performed to identify, purify, and evaluate the viability of isolated ectopic endometrial cells. RESULTS: Using our method, we successfully isolated and cultured highly purified and active ectopic endometrial epithelial and stromal cells from human adenomyosis foci. Ep-CAM was expressed in ectopic epithelial cells of human adenomyosis with a purity of 93.74% and a viability of 80.58%. In addition, CD10 were robustly expressed by ectopic stromal cells in human adenomyosis. Cellular purity and viability were determined to be 96.37 and 93.49%, respectively. CONCLUSION: Our method provides a new experimental model for studying the molecular pathogenesis of human adenomyosis.

Comparison of Postoperative Scarring in Asian Women After Supra-brow and Sub-brow Blepharoplasty: A Retrospective Study.

BACKGROUND: Supra-brow and sub-brow blepharoplasty are two types of upper eyelid blepharoplasties that are commonly performed in middle-aged Asian women to correct skin laxity of the upper eyelid; the postoperative scar formation of the two procedures may be different. Therefore, we designed this retrospective study to explore the differences in postoperative scarring between patients receiving supra- or sub-brow blepharoplasty. METHODS: We identified 52 patients who underwent supra-brow blepharoplasty and 54 patients who underwent sub-brow blepharoplasty. For each patient, the scar quality was assessed using photographs, the Observer Scar Assessment Scale (OSAS), and the Patient Scar Assessment Scale (PSAS) 1 year following surgery. RESULTS: For OSAS, higher scores for pigmentation, thickness, relief, pliability, surface, and overall opinion were observed in patients who underwent supra-brow blepharoplasty (p < 0.05) except for the "vascular score" (p = 0.148). The average overall opinion scores of the supra- and sub-brow blepharoplasty were 3.90 ± 0.41 and 2.33 ± 0.48, respectively, indicating that acceptance of postoperative scars in patients who underwent supra-brow blepharoplasty was worse than that in patients who underwent sub-brow blepharoplasty. Significantly higher scores were observed in all items of PSAS items for patients with supra-brow blepharoplasty (p < 0.05). CONCLUSIONS: The postoperative scars in patients who underwent supra-brow blepharoplasty were more obvious than those in sub-brow blepharoplasty. From the perspective of postoperative scar formation, sub-brow blepharoplasty may be a more suitable choice for patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Recepteur d'origine nantais contributes to the development of endometriosis via promoting epithelial-mesenchymal transition of a endometrial epithelial cells.

Endometriosis is a benign, chronic inflammatory disease that commonly occurs in reproductive-aged women. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells plays an important role in the development of endometriosis. Recepteur d'origine nantais (RON), a receptor tyrosine kinase, has been reported to promote EMT and progression in tumours. However, whether and how RON mediates the EMT and endometriosis development is not known. Here, we found that RON activation could improve the migratory and invasive capabilities, change cellular morphologies, and decrease expression of E-cadherin and increase expression of N-cadherin in endometrial epithelial cells. Inhibition or knockdown of RON expression suppressed the migration and invasion of endometrial epithelial cells. Our studies also indicated that RON played its part in endometrial epithelial cells through protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways. Treatment with a RON inhibitor could decrease the number of ectopic lesions in a mouse model of endometriosis and mediate expression of EMT markers in endometriotic lesions. These data suggest that RON contributed to endometriosis development by promoting EMT of endometrial epithelial cells. Therefore, RON may be a new therapeutic target for endometriosis.

Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective.

Coronary arterial disease is the most common cardiovascular disease. Myocardial ischemia-reperfusion injury caused by the initial interruption of organ blood flow and subsequent restoration of organ blood flow is an important clinical problem with various cardiac reperfusion strategies after acute myocardial infarction. Even though blood flow recovery is necessary for oxygen and nutrient supply, reperfusion causes pathological sequelae that lead to the aggravation of ischemic injury. At present, although it is known that injury will occur after reperfusion, clinical treatment always focuses on immediate recanalization. Mitochondrial fusion, fission, biogenesis, autophagy, and their intricate interaction constitute an effective mitochondrial quality control system. The mitochondrial quality control system plays an important role in maintaining cell homeostasis and cell survival. The removal of damaged, aging, and dysfunctional mitochondria is mediated by mitochondrial autophagy. With the help of appropriate changes in mitochondrial dynamics, new mitochondria are produced through mitochondrial biogenesis to meet the energy needs of cells. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of ischemia/reperfusion (I/R) injury, which play a crucial role in the pathophysiological process of myocardial injury. This review aimed at elucidating the mitochondrial quality control system and establishing the possibility of using mitochondria as a potential therapeutic target in the treatment of I/R injuries.

Inhibition of Notch Intracellular Domain Suppresses Cell Activation and Fibrotic Factors Production in Hypertrophic Scar Fibroblasts Versus Normal Skin Fibroblasts.

BACKGROUND: Hypertrophic scar (HS) is the most common complication after skin injury with unknown etiopathogenesis. There is increasing evidence to suggest that aberrant Notch signaling contributes directly to skin pathogenesis and altered expression of the Notch intracellular domain (NICD) identified in HS. Therefore, the aim of this study was to investigate the effects of Notch signaling pathway in HS pathogenesis. METHODS: Hypertrophic scar and normal skin samples were collected. Notch intracellular domain expression was detected by immunohistochemistry staining and fibroblasts were separated from the samples. We compared fibrotic factors production, cell viability, migration and apoptosis of HS fibroblasts (HFB) versus normal skin fibroblasts (NFB) by real time quantitative polymerase chain reaction, MTS, cell scratch assay and flow cytometry respectively under the impact of inhibition of Notch signaling by NICD-small-interfering RNA (SiRNA). RESULTS: The results showed that NICD was overexpressed in the dermis of HS tissues. Inhibition of Notch signaling by NICD-SiRNA suppressed the production of the fibrotic factors including collagen 1, collagen 3, α-SMA, and TGF-ß1 by HFB and NFB. Cell viability and migration were reduced in NICD-SiRNA-treated NFB and HFB, whereas cell apoptosis was enhanced by NICD-SiRNA. CONCLUSIONS: Conclusively, the study demonstrates a potential role for Notch signaling in HS progression, and targeting this pathway may provide a novel strategy for treatment of HS.

A new trick for an old dog: The application of mifepristone in the treatment of adenomyosis.

Adenomyosis is also called internal endometriosis and affects about 20% of reproductive-aged women. It seriously reduces life quality of patients because current drug therapies face with numerous challenges. Long-term clinical application of mifepristone exhibits wonderful therapeutic effects with mild side-effects in many disorders since 1982. Since adenomyosis is a refractory disease, we investigate whether mifepristone can be applied in the treatment of adenomyosis. In this study, we investigated the direct effects of mifepristone on human primary eutopic endometrial epithelial cells and stromal cells in adenomyosis. We found that mifepristone causes cell cycle arrest through inhibiting CDK1 and CDK2 expressions and induces cell apoptosis via the mitochondria-dependent signalling pathway in endometrial epithelial cells and stromal cells of adenomyosis. Furthermore, mifepristone inhibits the migration of endometrial epithelial cells and stromal cells through decreasing CXCR4 expression and restricts the invasion of endometrial epithelial cells via suppression of epithelial-mesenchymal transition in adenomyosis. We also found that mifepristone treatment decreases the uterine volume, CA125 concentration and increases the haemoglobin concentration in serum for adenomyosis patients. Therefore, we demonstrate that mifepristone could serve as a novel therapeutic drug in the treatment of adenomyosis, and therefore, the old dog can do a new trick.

Activation of ATF3/AP-1 signaling pathway is required for P2X3-induced endometriosis pain.

STUDY QUESTION: Does P2X ligand-gated ion channel 3 (P2X3) play a role in endometriosis pain? SUMMARY ANSWER: Upregulation of P2X3 in dorsal root ganglia (DRG) tissues via the activating transcription factor 3 (ATF3)/activator protein (AP)-1 pathway contributed to endometriosis-associated hyperalgesia, which could be attenuated by the chitosan oligosaccharide stearic acid (CSOSA)/liposomes (LPs)/SP600125 delivery system. WHAT IS KNOWN ALREADY: Infiltrating nerve fibers and elevated nociceptors in endometriotic lesions are associated with endometriosis pain. P2X3 has been demonstrated to play an important role in neuropathic pain. STUDY DESIGN, SIZE, DURATION: A rat model of endometriosis was used to investigate the signaling pathways involved in P2X3-induced pain. PARTICIPANTS/MATERIALS, SETTING, METHODS: Degrees of hyperalgesia, endogenous adenosine 5'-triphosphate (ATP) contents and P2X3 expression levels in endometriotic lesions and DRG tissues were detected in a rat model of endometriosis. The expression levels of ATF3 and P2X3 were measured using qRT-PCR, western blot analysis and immunofluorescence analysis after adenosine 5'-diphosphate (ADP) exposure in DRG cells. Plasmids encoding ATF3 and its siRNA were used to investigate the role of ATF3 on ADP-induced P2X3 upregulation. The activity of ATF binding to the P2X3 promoter was evaluated by using chromatin immunoprecipitation (CHIP) and luciferase assays. SP600125, an inhibitor of c-JUN N-terminal kinase, was wrapped in CSOSA/LPs delivery system and its inhibitory effects on ADP-induced upregulation of P2X3 in DRG cells and endometriosis-induced hyperalgesia in rats were tested. MAIN RESULTS AND THE ROLE OF CHANCE: The concentrations of endogenous ATP and expression levels of P2X3 were significantly increased in both endometriotic lesions and DRG tissues in endometriosis rat models and were found to be positively correlated with the severity of hyperalgesia. In DRG cells, P2X3 expression levels were elevated by ADP stimulation, but dramatically inhibited by blocking ATF3 with its siRNA and SP600125. CHIP and luciferase assay showed that ADP increased the binding of ATF3 to the P2X3 promoter, resulting in an increase in P2X3 expression levels. In the CSOSA/LPs/SP600125 delivery system, the drug could be effectively concentrated in endometriotic lesions, and it could alleviate endometriosis-induced hyperalgesia, reduce the size of endometriotic lesions and attenuate upregulated P2X3 expression levels in endometriosis rat models. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Changes in the sensitivity and function of P2X3 caused by endometriosis need to be further investigated. WIDER IMPLICATIONS OF THE FINDINGS: This study indicates that ATP and the P2X3 receptor are involved in endometriosis pain, thus providing a novel therapeutic approach for the treatment of endometriosis pain by targeting the P2X3 receptor. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by National Key R&D Program of China (Grant No. 2017YFC1001202) and National Natural Science Foundation of China (Grant Nos. 81974225, 81671429 and 81471433). There are no competing interests.

Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer.

BACKGROUND: Previous studies have shown a major green tea polyphenol (-)-epigallocatechin-3-gallate ((-)-EGCG) as a powerful anti-cancer agent. However, its poor bioavailability and requirement of a high dosage to manifest activity have restricted its clinical application. Recently, our team synthesized a peracetate-protected derivative of EGCG, which can act as a prodrug of (-)-EGCG (ProEGCG) with enhanced stability and improved bioavailability in vitro and in vivo. Herein, we tested the therapeutic efficacy of this novel ProEGCG, in comparison to EGCG, toward human endometrial cancer (EC). METHODS: In this study, the effects of ProEGCG and EGCG treatments on cell growth, cell survival and modulation of intracellular signaling pathways in RL95-2 and AN3 CA EC cells were compared. The antiproliferative effect was evaluated by cell viability assay. Apoptosis was measured by annexin/propidium iodide staining. Expression of mitogen-activated protein kinases, markers of proliferation and apoptosis were measured by immunoblot analysis. In addition, the effects of ProEGCG and EGCG on tumor growth, vessel formation and gene expression profiles on xenograft models of the EC cells were investigated. RESULTS: We found that treatment with ProEGCG, but not EGCG, inhibited, in a time- and dose-dependent manner, the proliferation and increased apoptosis of EC cells. Treatment with low-dose ProEGCG significantly enhanced phosphorylation of JNK and p38 MAPK and inhibited phosphorylation of Akt and ERK which are critical mediators of apoptosis. ProEGCG, but not EGCG, elicited a significant decrease in the growth of the EC xenografts, promoted apoptotic activity of tumour cells in the EC xenografts, and decreased microvessel formation, by differentially suppressing anti-apoptotic molecules, NOD1 and NAIP. Notably, no obvious adverse effects were detected. CONCLUSIONS: Taken together, ProEGCG at a low dose exhibited anticancer activity in EC cells through its anti-proliferative, pro-apoptotic and anti-tumor actions on endometrial cancer in vitro and in vivo. In contrast, a low dose of EGCG did not bring about similar effects. Importantly, our data demonstrated the efficacy and safety of ProEGCG which manifests the potential of a novel anticancer agent for the management of endometrial cancer.

The new application of mifepristone in the relief of adenomyosis-caused dysmenorrhea.

Background: Adenomyosis is a quite common gynecological disorder and above 30% of patients have typical secondary and progressive dysmenorrhea. Current treatments still have many disadvantages and thereby the novel treatment aiming to relieve dysmenorrhea still needs to be further investigated. Mifepristone is a wonderful drug because it is effective, safe and cheap in many diseases including adenomyosis. In this study, we aim to investigate if mifepristone could be used in the treatment of adenomyosis-associated dysmenorrhea. Methods: Human primary endometrial epithelial and stromal cells from adenomyosis patients were isolated and treated with mifepristone. RNA-sequencing was then performed to detect the gene changes of pain-related inflammatory mediators. Meanwhile, the effect of mifepristone on the infiltration and degranulation of mast cells were investigated in adenomyosis lesions. Additionally, the role of mifepristone on the density of nerve fibers was also studied in the ectopic endometrium. At last, to evaluate the therapeutic efficacy of mifepristone on dysmenorrhea of adenomyosis, twenty participants were included and the visual analog scale (VAS) score was assessed and compared before and after treatment with mifepristone. Results: We demonstrated that mifepristone reduced the secretion of IL-6 and TNF-α from endometrial epithelial and stromal cells, restricted the infiltration and degranulation of mast cells in eutopic and ectopic endometrium and decreased the density of nerve fibers by inhibiting the migration capacity of nerve cells in adenomyosis. Meanwhile, we found that mifepristone could significantly relieve dysmenorrhea of adenomyosis. Conclusion: The findings demonstrated that mifepristone could be applied in the treatment of dysmenorrhea for the adenomyosis patients.

A Randomized, Controlled Study Comparing Subbrow Blepharoplasty and Subbrow Blepharoplasty Combined with Periorbital Muscle Manipulation for Periorbital Aging Rejuvenation in Asians.

BACKGROUND: Improving periorbital aging is, currently, of great concern. The previous literature has reported some surgical methods for periorbital aging. The purpose of this study was to compare subbrow blepharoplasty (SBB) with subbrow blepharoplasty combined with periorbital muscle manipulation (SBB-pm) with regard to improving periorbital aging. METHODS: A prospective, randomized, controlled study was designed to evaluate and compare the effects of two different surgical techniques on upper lid relaxation, brow shape and periorbital wrinkles. Patients were divided into two groups. Group 1 underwent resection of excess skin; group 2 underwent a modified technique that involved resection of an elliptical island of skin, separation of the corrugator supercilii muscle and dissection of the orbicularis oculi muscle, followed by suturing it to the orbital periosteum and cross-fixation with itself. The upper eyelid and eyebrow height, periorbital wrinkle score and patient satisfaction were measured preoperatively and postoperatively. RESULTS: This study included 70 patients (140 eyes). At 1 month, 3 months, 6 months and 12 months after surgery, group 2 was superior to group 1 with regard to the improvement in upper eyelid relaxation at the medial limbus, middle pupil and lateral canthus. The eyebrow assumed a low and flat appearance in group 1. The eyebrow showed a low and flat appearance and then returned to the preoperative level in group 2. When comparing the two surgical techniques, the authors found statistically significant differences in regard to changes in crow's feet and glabellar frown lines. Two patients in group 2 experienced forehead numbness after surgery, which resolved by the 6-month follow-up. Patients in group 2 were significantly more satisfied with their surgery than patients in group 1. CONCLUSION: SBB-pm is more effective than SBB for improving upper eyelid relaxation and preventing secondary brow ptosis after surgery as well as for alleviating periorbital wrinkles, although it is accompanied by transient forehead numbness. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Is there a correlation between inflammatory markers and coagulation parameters in women with advanced ovarian endometriosis?

BACKGROUND: Endometriosis is defined as a chronic inflammatory disease. Recent studies have shown that increased coagulation parameters including fibrinogen and platelets are associated with endometriosis. The objective of this study was to determine the levels of inflammatory markers and coagulation parameters and their correlations in women with endometriomas compared to those with benign ovarian cysts or normal pelvic anatomy. METHODS: Between June 2015 and June 2017, a total of 548 women who underwent laparoscopic/laparotomic surgery for ovarian endometriomas (OMA group, n = 226), non-endometriosis benign ovarian cysts (Cyst group, n = 210) and tubal reanastomosis (Control group, n = 112) were recruited in this study. Inflammatory markers including c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and coagulation parameters including platelet count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time, and plasma fibrinogen as well as CA-125 were determined. RESULTS: Compared with Cyst group and Control group, TT and PT in OMA group were significantly shorter and plasma fibrinogen levels were significantly higher (P < 0.05). Moreover, the levels of plasma fibrinogen were positively correlated with CRP, NLR and PLR (P < 0.05). In addition, the confidence intervals for the area under the curve (AUC) for CA-125 × fibrinogen were significantly higher than those for CA-125 (0.904-0.952 vs. 0.899-0.949) in the diagnosis of endometrioma. CONCLUSIONS: These results indicate that women with endometriomas demonstrate a hypercoagulable status due to the inflammatory nature of endometriosis. The combined determination for CA-125 and fibrinogen demonstrate a higher area under the curve than the single detection of CA-125 in those with endometriomas compared to these with benign ovarian cysts. TRIAL REGISTRATION: This study was approved by the Human Ethics Committee of the Women's Hospital, School of Medicine, Zhejiang University (No.20170174) and all women provided written informed consent.

The clinical dynamic changes of macrophage phenotype and function in different stages of human wound healing and hypertrophic scar formation.

The pathogenesis of hypertrophic scar (HS) is still poorly understood. Macrophages, especially the polarisation of that to M1 or M2, play a pivotal role in control of the degree of scar formation. Profiling of macrophage phenotypes in human specimens during long-term period of wound healing and HS formation may provide valuable clinical evidence for understanding the pathology of human scars. Human wound and HS specimens were collected, the macrophage phenotype was identified by immunofluorescence, and biomarkers and cytokines associated with M1 and M2 macrophages were detected by RT-PCR. The correlation between the macrophage phenotype and HS characteristics was analysed by linear regression analyses. We found excessive and persistent infiltration by M1 macrophages around the blood vessels in the superficial layer of the dermis at early wound tissues, whereas M2 macrophages predominated in later wound tissues and the proliferative phase of HS and were scattered throughout the dermis. The density of M1 macrophages was positively correlated with mRNA expression levels of tumour necrosis factor-alpha (TNF-α) and IL-6. The density of M2 macrophages was positively correlated with ARG1 and negatively correlated with the duration of HS. The sequential infiltration by M1 macrophage and M2 macrophages in human wound and HS tissues was confirmed.

Optical Fiber Sensors Based on Fiber Ring Laser Demodulation Technology.

A review for optical fiber sensors based on fiber ring laser (FRL) demodulation technology is presented. The review focuses on the principles, main structures, and the sensing performances of different kinds of optical fiber sensors based on FRLs. First of all, the theory background of the sensors has been discussed. Secondly, four different types of sensors are described and compared, which includes Mach-Zehnder interferometer (MZI) typed sensors, Fabry-Perot interferometer (FPI) typed sensors, Sagnac typed sensors, and fiber Bragg grating (FBG) typed sensors. Typical studies and main properties of each type of sensors are presented. Thirdly, a comparison of different types of sensors are made. Finally, the existing problems and future research directions are pointed out and analyzed.

Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway.

Rab11-family interacting proteins (Rab11-FIPs) belong to an evolutionarily conserved protein family and act as effector molecules for the Rab11 family of small GTPases. Recent evidence suggests that Rab11-FIPs have important roles in tumor progression and metastasis. However, the contribution of Rab11-FIPs to colorectal carcinoma (CRC) remains elusive. Our study focuses on elucidating the role of Rab11-FIP2 in the migration and invasion of colorectal cancer cells. We firstly found upregulation of Rab11-FIP2 in CRC tissues compared with peritumor tissues by oncomine data-mining analysis, western blot analysis and immunohistochemistry (IHC) analysis, respectively. Then, we demonstrated that knockdown of Rab11-FIP2 via siRNAs transfection resulted in a decrease in migration and invasion of CRC cells, while overexpression of Rab11-FIP2 via lentiviral infection increased migration and invasion of CRC cells. In addition, we verified that Rab11-FIP2 promoted migration and invasion of CRC cells through upregulating MMP7 expression. Finally, using several kinase inhibitors, our results showed that Rab11-FIP2 regulated MMP7 expression through activating PI3K/Akt signaling. Our data suggested a potential role of Rab11-FIP2 in tumor progression and provided novel insights into the mechanism of how Rab11-FIP2 positively regulated cell migration and invasion in CRC cells.

[Analysis of single nucleotide polymorphisms and haplotypes of FCGR2A gene among patients with ulcerative colitis].

OBJECTIVE: To assess the association of several single nucleotide polymorphisms and haplotypes of the FCGR2A gene with ulcerative colitis (UC) among Chinese patients. METHODS: For 198 UC patients and 356 healthy controls, the alleles and genotypes of the FCGR2A gene (rs1801274, rs10800309 and rs6696854) were detected with a multiplex SNaPshot technique. All subjects were also subjected to linkage disequilibrium and haplotype analyses. RESULTS: The mutant homozygote (CC) of the FCGR2A gene rs1801274 polymorphism was less frequent among UC patients compared with the controls (5.56% vs. 11.80%, P=0.017, OR=0.440, 95%CI: 0.221-0.875). However, the allelic and genotypic distributions of other two SNPs did not differ significantly between the two groups (all P>0.05). Furthermore, no association of the three SNPs (rs1801274, rs10800309 and rs6696854) of the FCGR2A gene with the severity and location of the UC was found (all P>0.05). The three SNPs were shown to be in a strong linkage [rs1801274-rs10800309 (D'=0.863, r2=0.634); rs1801274-rs6696854 (D'=0.753, r2=0.546); rs10800309-rs6696854(D'=0.990, r2=0.802)]. Moreover, the frequency of T-A-T haplotype was higher among the UC patients compared with the controls (67.40% vs. 60.93%, P=0.032, OR=1.326, 95%CI: 1.024-1.717). CONCLUSION: Our findings suggested that the mutant homozygote (CC) of the FCGR2A gene (rs1801274) may have a protective role among Chinese patients with UC. Moreover, the T-A-T haplotype formed by rs1801274, rs10800309 and rs6696854 may confer a higher risk for UC.

Combined Blepharoplasty and Brow Fat Pad Transfer for the Correction of Dermatochalasis and Sunken Upper Eyelids.

BACKGROUND: Women commonly experience upper eyelid dermatochalasis and upper eyelid depression with advancing age. Blepharoplasty is a suitable method for treating dermatochalasis, but not sunken eyelid. This study proposed a novel technique for eyelid rejuvenation by simultaneously correcting dermatochalasis and sunken upper eyelids in middle-aged women. METHODS: Forty patients underwent subbrow blepharoplasty combined with brow fat pad transfer. Ellipse-shaped skin and subcutaneous tissue underneath the eyebrow were measured, demarcated, and excised. The orbicularis oculi muscle beneath the subcutaneous tissue was exposed and dissected in the upper-third area. The brow fat pad was turned downward using the lower edge as the pedicle and was fixed in the layer of retro-orbicularis oculi fat to fill the depressed area in the upper eyelid. The lower muscle flap was fixed to the supraorbital rim periosteum and upper musculocutaneous flaps, thereby forming a cross flap for interlocking fixation. The surgical outcomes were evaluated using a three-dimensional imaging device and the Global Aesthetic Improvement Scale. RESULTS: The depth and volume of upper eyelid depression decreased significantly 3 months after the surgery and stabilized within 6 months. Global Aesthetic Improvement Scale scores significantly improved after the surgery, and the postoperative outcomes were acceptable. CONCLUSIONS: The novel technique is simple and effective for simultaneously correcting dermatochalasis and sunken upper eyelids in middle-aged women. The surgical outcomes are predictable and acceptable to most patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

CILP2 promotes hypertrophic scar through Snail acetylation by interaction with ACLY.

BACKGROUND & AIMS: Hypertrophic scar (HS) is a skin fibroproliferative disorder occurring after burns, surgeries or traumatic injuries, and it has caused a tremendous economic and medical burden. Its molecular mechanism is associated with the abnormal proliferation and transition of fibroblasts and excessive deposition of extracellular matrix. Cartilage intermediate layer protein 2 (CILP2), highly homologous to cartilage intermediate layer protein 1 (CILP1), is mainly secreted predominantly from chondrocytes in the middle/deeper layers of articular cartilage. Recent reports indicate that CILP2 is involved in the development of fibrotic diseases. We investigated the role of CILP2 in the progression of HS. METHODS AND RESULTS: It was found in this study that CILP2 expression was significantly higher in HS than in normal skin, especially in myofibroblasts. In a clinical cohort, we discovered that CILP2 was more abundant in the serum of patients with HS, especially in the early stage of HS. In vitro studies indicated that knockdown of CILP2 suppressed proliferation, migration, myofibroblast activation and collagen synthesis of hypertrophic scar fibroblasts (HSFs). Further, we revealed that CILP2 interacts with ATP citrate lyase (ACLY), in which CILP2 stabilizes the expression of ACLY by reducing the ubiquitination of ACLY, therefore prompting Snail acetylation and avoiding reduced expression of Snail. In vivo studies indicated that knockdown of CILP2 or ACLY inhibitor, SB-204990, significantly alleviated HS formation. CONCLUSION: CILP2 exerts a vital role in hypertrophic scar formation and might be a detectable biomarker reflecting the progression of hypertrophic scar and a therapeutic target for hypertrophic scar.

Investigation of the Therapeutic Effect of Salbutamol on Endometriosis in a Mouse Model.

Endometriosis is an immune chronic inflammatory disease, and there are currently no more effective drugs for treating endometriosis due to its unknown etiology. Salbutamol is a ß2-adrenergic receptor (ß2AR) agonist commonly used to treat asthma by selectively activating ß2 receptors on airway smooth muscle and leukocytes, exerting bronchial dilation and synergistic anti-inflammatory effects. In recent years, ß2AR agonists have been used in endometriosis studies, and we speculate that salbutamol may have a therapeutic effect on endometriosis. The purpose of this research was to explore the therapeutic effect of salbutamol on endometriosis mice. The mouse endometriosis model was established and treated with different doses of salbutamol. Endometrial lesions were harvested for pathological diagnosis, immunohistochemistry (IHC), Masson staining, and toluidine blue analysis. We found that the number and size of endometriotic lesions were all significantly decreased after 3 weeks of treatment with different doses of salbutamol on endometriosis model mice (P < 0.05). After Salbutamol treatment, the amount of mast cells (toluidine blue) and macrophages (F4/80) in the lesions as well as the expressions of interleukin (IL)-1ß, tumor necrosis factor (TNF)-ɑ, platelet-derived growth factor subunit B (PDGFB), CD31, transforming growth factor (TGF)-ß, Masson staining, BCL2, TUBB3, substance P (SP), and nerve growth factor (NGF) were significantly reduced (P < 0.05). These results suggested that salbutamol could effectively treat endometriosis in mice by reducing immune inflammatory cells and factors, angiogenesis, and fibrosis, increasing apoptosis of endometriotic lesions, and decreasing neurogenesis.

Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics.

Adenomyosis is a poorly understood gynecological disorder lacking effective treatments. Controversy persists regarding "invagination" and "metaplasia" theories. The endometrial-myometrial junction (EMJ) connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis, but its in-depth study is just beginning. Using single-cell RNA sequencing and spatial profiling, we mapped transcriptional alterations across eutopic endometrium, lesions, and EMJ. Within lesions, we identified unique epithelial (LGR5+) and invasive stromal (PKIB+) subpopulations, along with WFDC1+ progenitor cells, supporting a complex interplay between "invagination" and "metaplasia" theories of pathogenesis. Further, we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin pathways. Cell-cell communication differed markedly between ectopic and eutopic endometrium, with aberrant signaling in lesions involving pleiotrophin, TWEAK, and WNT cascades. This study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified, dysfunctional signaling, and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

Long non coding RNA, C8orf49, a novel diagnostic and prognostic biomarker, enhances PTEN/FZD4-mediated cell growth and metastasis by sponging miR-1323 in endometriosis.

Lack of sensitive biomarkers in the early stages of endometriosis (EMs) results in delayed diagnosis and intervention. Long non-coding RNAs (lncRNAs) have prognostic and diagnostic values in various diseases. However, the prognostic and diagnostic effects of lncRNAs on EMs have rarely been discussed in EMs. In this study, we found that lncRNA C8orf49 was stably overexpressed in EMs tissues/plasma, and its expression greatly influenced dysmenorrhea (p = 2.2605E-9) and the revised American Society for Reproductive Medicine stage (p = 0.040765) of EMs. Multivariate logistic regression results revealed that C8orf49 expression was an independent risk factor for EMs [p = 6.4997E-17, 95% confidence interval (CI) = 0.000559-0.023853]. In primary endometrial stromal cells (ESCs), inhibition of C8orf49 could impede the proliferation and metastasis of ESCs. C8orf49 influenced the expression of PTEN/FZD4 by absorbing miR-1323, thus controlling ESCs activity. The results of a subcutaneous endometriosis animal model showed that the inhibition of C8orf49 restrained endometrial growth. Overall, C8orf49 functioned as an activator of EMs pathogenesis via the C8orf49/miR-1323/PTEN/FZD4 axis.