Elastin expression in the conjoint fascial sheath and levator palpebrae superioris muscle of children with unilateral severe congenital ptosis with different muscle strengths.

Elastin expression in the conjoint facial sheath (CFS) of patients of different ages with severe ptosis has been extensively studied, but its expression in the CFS of pediatric patients with severe ptosis with different muscle strengths remains poorly understood. The aim of the present study was to investigate the expression of elastin in the CFS and levator palpebrae superioris muscle (LM) of children with severe congenital ptosis with different LM strengths. In total, 20 pediatric patients with unilateral severe congenital ptosis (20 eyes) were included, who underwent CFS + LM complex suspension surgery from June 2020 to February 2022. Among these patients, the LM strength was 0-1 mm in 10 patients and 2-3 mm in the other 10 patients. Excess CFS and LM tissue samples were obtained from the patients during surgery, before the protein expression levels of elastin in the specimens were measured by western blotting. During the 6-month postoperative follow-up period, the good correction rate, the degree of incomplete eyelid closure and the incidence of complications were observed. Western blotting results showed that, compared with that in the 0-1 mm group, elastin expression was not significantly different in the CFS, whereas it was significantly increased (P=0.021) in the LM of the 2-3 mm group. In addition, elastin expression in the CFS was markedly higher compared with that in the LM in both groups (in the 0-1 mm group, P=0.005; in the 2-3 mm group, P=0.009). Additionally, the curative effect evaluation revealed that the good correction rates in the 0-1 and 2-3 mm groups were 90 and 100%, respectively. In total, 3 patients experienced conjunctival prolapse during the follow-up period, including 2 patients in the 0-1 mm group and 1 patient in the 2-3 mm group, but there were no other complications. To conclude, elastin expression in the CFS was found to be higher compared with that in the LM of children with severe congenital ptosis. Although elastin expression in the LM was positively associated with LM strength, its expression in the CFS displayed no clear association with LM function. Therefore, these observations suggested that CFS + LM complex suspension surgery is viable to correct severe congenital ptosis in pediatric patients.

Development and Characterization of a Novel Carbon-11 Labeled Positron Emission Tomography Radiotracer for Neuroimaging of Sirtuin 1 with Benzoxazine-Based Compounds.

Introduction: Sirtuins (SIRTs) comprise a group of histone deacetylase enzymes crucial for regulating metabolic pathways and contributing significantly to various disease mechanisms. Sirtuin 1 (SIRT1), among the seven known mammalian homologs, is extensively investigated and understood, playing a key role in neurodegenerative disorders and cancer. This study focuses on potential as a therapeutic target for conditions such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). Methods: Utilizing positron emission tomography (PET) as a noninvasive molecular imaging modality, we aimed to expedite the validation of a promising sirtuin 1 inhibitor for clinical trials. However, the absence of a validated sirtuin 1 PET radiotracer impedes clinical translation. We present the development of [11C]1, and 11C-labeled benzoxazine-based derivative, as a lead imaging probe. The radiosynthesis of [11C]1 resulted in a radiochemical yield of 31 ± 4%. Results: Baseline studies demonstrated that [11C]1 exhibited excellent blood-brain barrier (BBB) penetration capability, with uniform accumulation throughout various brain regions. Self-blocking studies revealed that introducing an unlabeled compound 1, effectively blocking sirtuin 1, led to a substantial reduction in whole-brain uptake, emphasizing the in vivo specificity of [11C]1 for sirtuin 1. Discussion: The development of [11C]1 provides a valuable tool for noninvasive imaging investigations in rodent models with aberrant sirtuin 1 expression. This novel radiotracer holds promise for advancing our understanding of sirtuin 1's role in disease mechanisms and may facilitate the validation of sirtuin 1 inhibitors in clinical trials.

Carbon Chain Length Determines Inhibitory Potency of Perfluoroalkyl Sulfonic Acids on Human Placental 3ß-Hydroxysteroid Dehydrogenase 1: Screening, Structure-Activity Relationship, and In Silico Analysis.

Objective: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3ß-hydroxysteroid dehydrogenase 1 (3ß-HSD1), aromatase, and rat 3ß-HSD4 activities. Methods: Human and rat placental 3ß-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. Results: PFSA inhibited human 3ß-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC 50: 9.03 ± 4.83 µmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 µmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 µmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 µmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3ß-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 µmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3ß-HSD1 in a carbon chain length-dependent manner. All 100 µmol/L PFSA solutions did not affect rat 3ß-HSD4 and human placental aromatase activity. Conclusion: Carbon chain length determines inhibitory potency of PFSA on human placental 3ß-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.

Efficacy of cell-free DNA methylation-based blood test for colorectal cancer screening in high-risk population: a prospective cohort study.

BACKGROUND: Although colonoscopy is the standard screening test for colorectal cancer (CRC), its use is limited by a poor compliance rate, the need for extensive bowel preparation, and the risk of complications. As an alternative, an FDA-approved stool-based DNA test, Cologuard, has demonstrated satisfactory detection performance for CRC, but its compliance rate remains suboptimal, primarily attributable to individuals' reluctance to provide stool samples. METHODS: We developed a noninvasive blood-based CRC test, ColonSecure, based on cell-free DNA containing cancer-specific CpG island methylation patterns. We initially screened publicly available datasets for differentially methylated CpG sites in CRC with prediction potential. Subsequently, we performed two sequential bisulfite-free methylation sequencing on blood samples obtained from CRC patients and non-cancer controls. Through rigorous evaluation of each marker and machine learning-assisted feature selection, we identified 149 hypermethylated markers from over 193,000 CpG sites. These markers were then utilized to construct the ColonSecure model, enabling accurate CRC detection. RESULTS: We validated the efficacy of our cell-free DNA methylation-based blood test for CRC screening with 3493 high-risk individuals identified from 114,136 urban residents. The ColonSecure test identified 89 out of 103 CRC patients diagnosed by the follow-up colonoscopy, outperforming CEA, CRP, and CA19-9 (with a sensitivity of 86.4% compared to 45.6%, 39.8%, and 25.2% for CEA, CRP, and CA19-9 respectively; an AUROC of 0.956 compared to an AUROC of < 0.77 for other methods). CONCLUSION: Our observations emphasize the potential of our multiple cfDNA methylation marker-based test for CRC screening in high-risk populations.

Application and Mechanisms of Internet-Based Cognitive Behavioral Therapy (iCBT) in Improving Psychological State in Cancer Patients.

This review article is an overview of the effectiveness of internet-based cognitive behavioral therapy (iCBT) in Improving Psychological State in Cancer Patients. iCBT's effectiveness has been investigated in treating and managing conditions like depression, psychiatric disorders, generalized anxiety disorder (GAD), panic disorder, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), adjustment disorder, bipolar disorder, chronic pain, and phobias. iCBT's role in the treatment of medical conditions such as diabetes mellitus with comorbid psychiatric illnesses was also explored. We conducted a thorough literature search using PubMed, Embase, Google Scholar, and Wanfang with no restrictions on the date. iCBT's role in treating and controlling psychiatric illnesses in cancer patients has been established in the literature. Development and popularization of iCBT, treament forms of iCBT, platforms for iCBT, application of iCBT, strategies and efficacy of iCBT for insomnia in cancer patients, current status of iCBT application, and genetic researches on iCBT for anxiety disorders were all reviewed and discussed in this review. From the data compiled, we conclude that iCBT is useful in treating or improving psychological state in cancer patients.

Efficacy of combined conjoint fascial sheath and levator muscle composite flap suspension for congenital severe ptosis.

BACKGROUND: Conjoint fascial sheath (CFS) suspension has been gradually recognized and accepted for the treatment of congenital severe blepharoptosis in recent years. To address the problem of postoperative upper eyelid position regression of only CFS suspension, we designed and implemented a CFS combined Levator muscle (CFS+LM) complex flap. This research aims to analyze the surgical efficacy of CFS+LM and FMF suspension surgery. METHODS: Patients diagnosed with congenital severe ptosis with levator muscle function ≦4 mm were enrolled. According to the surgical method, the patients were divided into the CFS+LM and FMF groups. To compare and statistically analyze the postoperative effect between CFS+LM and FMF suspension. RESULTS: Data from 182 patients (220 eyes) were collected in this study, including 89 patients (103 eyes) in the CFS+LM group and 93 patients (117 eyes) in the FMF group. The full correction rate, patient satisfaction, postoperative upper eyelid excursion and lagophthalmos in the CFS+LM group were significantly better than those in the FMF group. The eyelid retraction rate was significantly higher in the FMF group than in the CFS+LM group. The complication rate in the CFS+LM group was significantly lower than that in the FMF group. CONCLUSION: CFS+LM suspension had better outcomes than FMF. Considering that the CFS tissue could be weak in patients under 5 years old and have poor muscle elasticity in patients with levator muscle function ≤1 mm, FMF suspension is firstly recommended. For patients over 5 years old with severe ptosis, CFS+LM suspension is recommended.

Blood tau-PT217 contributes to the anesthesia/surgery-induced delirium-like behavior in aged mice.

INTRODUCTION: Blood phosphorylated tau at threonine 217 (tau-PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms and consequences of acute changes in blood tau-PT217 remain largely unknown. METHODS: We investigated the effects of anesthesia/surgery on blood tau-PT217 in aged mice, and evaluated the associated changes in B cell populations, neuronal excitability in anterior cingulate cortex, and delirium-like behavior using positron emission tomography imaging, nanoneedle technology, flow cytometry, electrophysiology, and behavioral tests. RESULTS: Anesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery-induced changes. DISCUSSION: Acute increases in blood tau-PT217 may contribute to brain dysfunction and postoperative delirium. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.

Risk of Metachronous Advanced Colorectal Neoplasia After Removal of Diminutive Versus Small Nonadvanced Adenomas: A Multicenter Study.

BACKGROUND: Current postpolypectomy guidelines treat 1-9 mm nonadvanced adenomas (NAAs) as carrying the same level of risk for metachronous advanced colorectal neoplasia (ACRN). AIMS: To evaluate whether small (6-9 mm) NAAs are associated with a greater risk of metachronous ACRN than diminutive (1-5 mm) NAAs. METHODS: We retrospectively evaluated 10,060 index colonoscopies performed from July 2011 to June 2019. A total of 1369 patients aged ≥ 40 years with index NAAs and having follow-up examinations were categorized into 5 groups based on size and number of index findings: Group 1, ≤ 2 diminutive NAAs (n = 655); Group 2, ≤ 2 small NAAs (n = 529); Group 3, 3-4 diminutive NAAs (n = 78); Group 4, 3-4 small NAAs (n = 65); and Group 5, 5-10 NAAs (n = 42). Size was classified based on the largest NAA. ACRN was defined as finding an advanced adenoma or colorectal cancer at follow-up. RESULTS: The absolute risk of metachronous ACRN increased from 7.2% in patients with all diminutive NAAs to 12.2% in patients with at least 1 small NAA (P = 0.002). Patients in Group 2 (adjusted odds ratio [AOR] 1.89; 95% confidence interval [CI], 1.21-2.95), Group 3 (AOR 2.40; 95% CI 1.78-4.90), Group 4 (AOR 2.77; 95% CI 1.35-5.66), and Group 5 (AOR 3.71; 95% CI 1.65-8.37) were associated with an increased risk of metachronous ACRN compared with Group 1. CONCLUSIONS: Patients with small NAAs have an increased risk of metachronous ACRN. Postpolypectomy guidelines should consider including risk stratification between small and diminutive adenomas.

Concurrent definitive chemoradiation incorporating intensity-modulated radiotherapy followed by adjuvant chemotherapy in high risk locally advanced cervical squamous cancer: a phase II study.

BACKGROUND: Although the prognosis of locally advanced cervical cancer has improved dramatically, survival for those with stage IIIB-IVA disease or lymph nodes metastasis remains poor. It is believed that the incorporation of intensity-modulated radiotherapy into the treatment of cervical cancer might yield an improved loco-regional control, whereas more cycles of more potent chemotherapy after the completion of concurrent chemotherapy was associated with a diminished distant metastasis. We therefore initiated a non-randomized prospective phaseII study to evaluate the feasibility of incorporating both these two treatment modality into the treatment of high risk locally advanced cervical cancer. OBJECTIVES: To determine whether the incorporation of intensity-modulated radiotherapy and the addition of adjuvant paclitaxel plus cisplatin regimen into the treatment policy for patients with high risk locally advanced cervical cancer might improve their oncologic outcomes. STUDY DESIGN: Patients were enrolled if they had biopsy proven stage IIIA-IVA squamous cervical cancer or stage IIB disease with metastatic regional nodes. Intensity-modulated radiotherapy was delivered with dynamic multi-leaf collimators using 6MV photon beams. Prescription for PTV ranged from 45.0 ~ 50.0 Gy at 1.8 Gy ~ 2.0 Gy/fraction in 25 fractions. Enlarged nodes were contoured separately and PTV-nodes were boosted simultaneously to a total dose of 50.0-65 Gy at 2.0- 2.6 Gy/fraction in 25 fractions. A total dose of 28 ~ 35 Gy high-dose- rate brachytherapy was prescribed to point A in 4 ~ 5 weekly fractions using an iridium- 192 source. Concurrent weekly intravenous cisplatin at 30 mg/m2 was initiated on the first day of radiotherapy for over 1-h during external-beam radiotherapy. Adjuvant chemotherapy was scheduled within 4 weeks after the completion of concurrent chemo-radiotherapy and repeated 3 weeks later. Paclitaxel 150 mg/m2 was given as a 3-h infusion on day1, followed by cisplatin 35 mg/m2 with 1-h infusion on day1-2 (70 mg/m2 in total). RESULTS: Fifty patients achieved complete response 4 weeks after the completion of the treatment protocol, whereas 2 patients had persistent disease. After a median follow-up period of 66 months, loco-regional (including 2 persistent disease), distant, and synchronous treatment failure occurred in 4,5, and 1, respectively. The 5-year disease-free survival, loco-regional recurrence-free survival, distant-metastasis recurrence-free survival was 80.5%, 90.3%, and 88.0%, respectively. Four of the patients died of the disease, and the 5-year overall survival was 92.1%. Most of the toxicities reported during concurrent chemo-radiotherapy were mild and transient. The occurrence of hematological toxicities elevated mildly during adjuvant chemotherapy, as 32% (16/50) and 4% (2/50) patients experienced grade 3-4 leukopenia and thrombocytopenia, respectively. Grade 3-4 late toxicities were reported in 3 patients. CONCLUSIONS: The incorporation of intensity-modulated radiotherapy and adjuvant paclitaxel plus cisplatin chemotherapy were highly effective and well-tolerated in the treatment of high-risk locally advanced cervical cancer. The former yields an improved loco-regional control, whereas distant metastases could be effectively eradicated with mild toxicities when adjuvant regimen was prescribed.

The combination of chronic stress and smoke exacerbated depression-like changes and lung cancer factor expression in A/J mice: Involve inflammation and BDNF dysfunction.

OBJECTIVE: Depression is positively correlated with the high incidence and low survival rate of cancers, while more cancer patients suffer depression. However, the interaction between depression and cancer, and possible underline mechanisms are unclear. METHODS: Chronic unpredictable mild stress (CUMS) was used to induce depression, and smoke to induce lung cancer in lung cancer vulnerable AJ mice. After 8 weeks, sucrose preference and forced swimming behaviors were tested. Blood corticosterone concentration, and levels of cytokines, lung cancer-related factors, brain-derived neurotrophic factor (BDNF) and apoptosis-related factors in the lung, amygdala and hippocampus were measured. RESULTS: Compared to control group, CUMS or smoke decreased sucrose consumption and increased immobility time, which were deteriorated by stress+smoke. CUMS, smoke or both combination decreased mononuclear viability and lung TNF-α concentration, increased serum corticosterone and lung interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10, IL-12 and HSP-90α concentrations. Furthermore, stress+smoke caused more increase in corticosterone and IL-10, but decreased TNF-α. In parallel, in the lung, Bcl-2/Bax and lung cancer-related factors CDK1, CDC20, P38α etc were significantly increased in stress+smoke group. Moreover, CUMS decreased BDNF, while CUMS or smoke increased TrkB and P75 concentrations, which were exacerbated by stress+smoke. In the amygdala, except for CUMS largely increased Bax/Bcl-2 and decreased TrkB, each single factor decreased BDNF and IL-10, but increased P75, IL-1ß, IL-12, TNF-α concentrations. Changes in Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination. In the hippocampus, except for CUMS largely increased P75 concentration, each single factor significantly increased Bax/Bcl-2 ratio, IL-1ß and TNF-α, but decreased BDNF, TrkB and IL-10 concentrations. Changes in Bax, Bax/Bcl-2, IL-10 and TNF-α were further aggravated by the combination. CONCLUSION: These results suggest that a synergy between CUMS and smoke exposure could promote the development of depression and lung cancer, through CUMS increased the risk of cancer occurrence, and conversely lung cancer inducer smoke exposure deteriorated depressive symptoms.

Modified conjoint fascial sheath suspension for the correction of severe congenital blepharoptosis in pediatric patients at different ages.

Objective: To evaluate the surgical outcomes of modified combined fascia sheath (CFS) and levator muscle (LM) complex suspension for the correction of severe congenital blepharoptosis in pediatric patients. Methods: Pediatric patients with severe congenital blepharoptosis were enrolled form July 2017 to July 2021. All patients were divided into two groups according to their age (group A ≤ 7 years; group B > 7 years) and received CFS + LM suspension surgery. Main surgical outcome indexes include margin reflex distance 1 (MRD1) and MRD1 regression. Postoperative complications such as lagophthalmos (LAG), conjunctival prolapse, exposure keratopathy and trichiasis were documented. Results: Fifty patients (60 eyes) were enrolled, including 17 patients (18 eyes) in group A and 33 patients (42 eyes) in group B. The MRD1 in group A was 3.06 ± 0.64 mm at 6 months after the operation, and the MRD1 in group B was 2.64 ± 0.69 mm 6 months postoperatively which is significantly lower than that of group A (P = 0. 044). At the last visit, however, the MRD1 in group A was 3.00 ± 0.69 mm and the MRD1 in group B was 2.64 ± 0.70 mm. There was no significant difference in MRD1 between two groups in long term (P = 0.255). Additionally, there were a variety of degrees of MRD1 regression, especially in the first month after the operation in both groups (both P < 0.001). Moreover, there were 9 cases of postoperative complications in group A and 13 cases in group B. The overall occurrence of postoperative complications in group A was significantly lower than that in groups B (χ 2 = 4.413, P = 0.036). Conclusions: CFS + LM suspension, a modified CFS-based surgery, is an effective treatment for severe congenital blepharoptosis in pediatric patients. Moreover, CFS + LM suspension demonstrate excellent long-term outcomes, including good movement of the eyelid, satisfied eyelid closure and fewer postoperative complications.

Eight hub genes as potential biomarkers for breast cancer diagnosis and prognosis: A TCGA-based study.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor in women. AIM: To investigate BC-associated hub genes to obtain a better understanding of BC tumorigenesis. METHODS: In total, 1203 BC samples were downloaded from The Cancer Genome Atlas database, which included 113 normal samples and 1090 tumor samples. The limma package of R software was used to analyze the differentially expressed genes (DEGs) in tumor tissues compared with normal tissues. The cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of upregulated and downregulated genes. Univariate Cox regression was conducted to explore the DEGs with statistical significance. Protein-protein interaction (PPI) network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape software. Survival analyses of the hub genes were carried out using the Kaplan-Meier method. The expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database. RESULTS: A total of 1317 DEGs (fold change > 2; P < 0.01) were confirmed through bioinformatics analysis, which included 744 upregulated and 573 downregulated genes in BC samples. KEGG enrichment analysis indicated that the upregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, cell cycle, and the p53 signaling pathway (P < 0.01); and the downregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor signaling pathway, and AMP-activated protein kinase signaling pathway (P < 0.01). CONCLUSION: In view of the results of PPI analysis, which were verified by survival and expression analyses, we conclude that MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.

Down-regulated expression of miR-99a is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background: Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of microRNA-99 (miR-99) family have been previously reported. This study sought to investigate the predictive value of miR-99a for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC). Methods: Patients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of miR-99a in the samples. Differential expression levels of miR-99a were compared between the 2 groups using independent sample t-test. Furthermore, the associations between miR-99a expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher's exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method. Results: There were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of miR-99a in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of miR-99a was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated miR-99a and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of miR-99a was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015-0.979; P=0.048). Patients with downregulated miR-99a tended to have more unfavorable overall survival, but the difference did not reach statistical significance. Conclusions: MiR-99a plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.

Research on the expression of elastin in the conjoint fascial sheath for the correction of severe unilateral congenital blepharoptosis.

BACKGROUND: To investigate the expression of elastin in the conjoint facial sheath (CFS) in patients with severe unilateral congenital blepharoptosis in different age groups. METHODS: Twenty-seven cases of severe unilateral congenital blepharoptosis (27 eyes) were treated with CFS + LM complex suspension from January 2020 to July 2020. Within that sample, 9 patients were over 18 years old, 9 patients were 13 to 17 years old and 9 patients were 5 to 12 years old. CFS and LM specimens were collected during CFS + LM complex suspension surgery. In the CFS specimens, the elastic fibers were observed by Victoria Blue staining. The elastin expression levels of the three groups of specimens were determined and analyzed by immunofluorescent staining and Western blotting. RESULTS: Victoria Blue staining showed that elastic fibers were abundant in CFS tissue. Moreover, immunofluorescent staining showed strong positive expression of elastin in the CFS and LM. Furthermore, in the child group, the Western blot results demonstrated that the expression of elastin was higher in the CFS than in the LM (P < 0.05). Additionally, the expression of elastin was significantly higher in the CFS of children than in that of adults or adolescents (P < 0.001). CONCLUSIONS: The CFS and LM are rich in elastic fibers and elastin, although elastin expression in the CFS decreases with age. Thus, it is feasible to apply CFS + LM complex suspension to cure severe unilateral congenital blepharoptosis.

Deep Orbital Hyaluronic Acid Gel Filler for Volume Augmentation in Orbital Dysplasia.

PURPOSE: Orbital dysplasia is caused by congenital microphthalmos, anophthalmos, or eye atrophy. Orbital volume growth is known to parallel ocular growth and the absence of an eye results in noticeable hemifacial deformity that affects patients' lives. The aim of this study was to observe the effects of injections of hyaluronic acid gel into the orbit combined with ocular prosthesis to treat orbital dysplasia. METHODS: Three patients with orbital dysplasia who were 3 to 7 years old treated in our department. Each year, the hyaluronic acid gel was injected into each patient intraconal and extraconal posterior orbit and each wore an ocular prosthesis. The length of the palpebral fissure and orbital volume were measured before and after the injections. RESULTS: A total of 9 injections were performed on 3 patients ages 7, 5, and 4 years old, respectively. The follow-up periods were 5, 5, and 2 years. The authors observed significant improvements in patient appearance. The length of the palpebral fissure and the volume of the orbit increased linearly with the increasing age, and there were no complications, such as intraorbital hemorrhage or local hyperplastic stimulation. CONCLUSIONS: Orbital hyaluronic acid gel injection and combined with an ocular prosthesis is a safe, convenient, and effective treatment for orbital dysplasia.

Interleukin-10 Attenuates Behavioral, Immune and Neurotrophin Changes Induced by Chronic Central Administration of Interleukin-1ß in Rats.

BACKGROUND: Activated microglia can trigger pro-inflammatory cytokine releases and neuroinflammation, which may inhibit astrocytes to produce neurotrophins and anti-inflammatory factors. Both eventually lead to neuron apoptosis or death. Furthermore, effective antidepressant or anti-dementia treatments can reduce pro-inflammatory cytokines, while enhance interleukin (IL)-10 production. However, the underline mechanism by which IL-10 modulates glial cell function, hence improves cognitive impairment or depression-like behavior is unknown. This study evaluated whether and how IL-10 attenuated chronic IL-1ß administration-induced behavioral changes and the possible involved mechanisms. METHODS: Rats received intracerebroventricular injection of IL-1ß and/or IL-10 for 14 days. Then animal memory and depression-like behavior, pro-inflammatory cytokines, glial activities, expression of brain-derived neurotrophic factor (BDNF), Trk B, p75, and apoptosis-related genes were studied. RESULTS: Compared to controls, significantly increased latent time and swimming distance in the Morris-water-maze, decreased sucrose consumption, and decreased locomotor and center zone entries in the open-field were found in rats administrated with IL-1ß. These changes were associated with the reduction of GFAP expression, and concentrations of BDNF and anti-inflammatory cytokine IL-10, but the increase in the expressions of CD11b, TrkB, p75, and Caspase-3, the ratio of Bax/Bcl-2, and the concentrations of IL-1ß, tumor necrosis factor-α, and IL-6. IL-10 treatment markedly attenuated IL-1ß-induced above changes, except for the expressions of neurotrophin receptors. CONCLUSION: IL-10-improved behavioral changes may be through suppressing microglia activity and inflammation, while restoring astrocyte function and BDNF expression.

Patient-Reported Outcomes and Complications Following Breast Reconstruction: A Comparison Between Biological Matrix-Assisted Direct-to-Implant and Latissimus Dorsi Flap.

BACKGROUND: Implant-based breast reconstruction is increasingly becoming the most common method of postmastectomy breast reconstruction in use today. As the traditional autologous reconstruction technique, latissimus dorsi flap (LDF) is employed by surgeons for reconstruction after breast cancer surgery, including partial mastectomy, modified radical mastectomy, and others. The authors aim to compare patient-reported outcomes (PROs) and complications between the SIS matrix-assisted direct-to-implant (DTI) breast reconstruction and the autologous LDF breast reconstruction. METHODS: Patients undergoing the SIS matrix-assisted DTI reconstruction or mastectomy with LDF reconstruction or partial mastectomy with mini latissimus dorsi flap (MLDF) reconstruction were enrolled in a single institution from August 2010 to April 2019. Patients were included for analysis and divided into three groups: those who underwent LDF reconstruction, those who underwent MLDF reconstruction, and patients who underwent SIS matrix-assisted DTI breast reconstruction. PROs (using the BREAST-Q version 2.0 questionnaire) and complications were evaluated. RESULTS: A total of 135 patients met the inclusion criteria: 79 patients (58.5%) underwent SIS matrix-assisted DTI, 29 patients (21.5%) underwent LDF breast reconstruction, and 27 patients (20%) underwent MLDF breast reconstruction. PROs and complication rates between LDF reconstruction group and MLDF reconstruction group showed no statistically significant differences. Furthermore, BREAST-Q responses found that patients in the whole autologous LDF reconstruction group had better psychosocial well-being, showing a mean score of 84.31 ± 17.28 compared with SIS matrix-assisted DTI reconstruction, with a mean score of 73.52 ± 19.96 (p = 0.005), and expressed higher sexual well-being (69.65 ± 24.64 vs. 50.95 ± 26.47; p = 0.016). But there were no statistically significant differences between the two groups for postoperative complications. CONCLUSION: This retrospective study showed no statistically significant differences between LDF breast reconstruction and MLDF breast reconstruction. However, patients in the whole autologous LDF reconstruction group yielded superior PROs than patients in the SIS matrix-assisted DTI reconstruction group in the psychosocial well-being and sexual well-being domains.

Steroidal saponins from Trillium tschonoskii rhizome repress cancer stemness and proliferation of intrahepatic cholangiocarcinoma.

A phytochemical study was carried out on the extract of Trillium tschonoskii rhizomes, resulting in the isolation of thirty-six steroidal glycosides (1-36). Their structures were established mainly by spectroscopic analyses as well as necessary chemical evidence, of which 1-25 were identified as new analogues. Herein, all the isolated analogues were screened for the cytotoxicity against intrahepatic cholangiocarcinoma (ICC) cell lines of HuCCT1 and RBE through tumor colony formation and CCK-8 survival analysis, and the results demonstrated that three compounds 9, 12, and 26 significantly repressed tumor colony and sphere formation in both cell lines, respectively. Furthermore, the three analogues possessed a remarkable inhibitory role of organoid formation established from hydrodynamic induced mouse primary intrahepatic cholangiocarcinoma. Moreover, the functional assays of flow cytometry analysis, cancer stemness related gene expression, and western blotting assays all indicated that compound 26 could significantly repress cancer stem markers. Taken together, these results demonstrate that steroidal glycosides derived from T. tschonoskii rhizomes could be potentially implicated in human ICC therapy.

Primary low-grade extrauterine endometrial stromal sarcoma: analysis of 10 cases with a review of the literature.

BACKGROUND: This study aimed to analyze the clinical and pathological features of extrauterine endometrial stromal sarcoma (EESS) and explore an effective therapeutic regimen to reduce the recurrence rate in low-grade EESS patients. METHODS: Ten LG-EESS patients who were treated at the Chinese Academy of Medical Sciences Cancer Institute and Hospital from June 1999 to June 2019 were collected and analyzed. RESULTS: (1) Patient demographics are summarized in manuscript. Preoperative CA125 examination showed that 8 patients had a median level of 49.5 U/L (15.4-168.0 U/L). (2) All ten patients underwent tumor cytoreductive surgery. Five patients underwent optimal tumor resection and achieved an R0 resection. After the initial surgery, 7 patients who had multiple metastasis were treated with adjuvant chemotherapy, 2 patients with vaginal ESS were treated with chemotherapy and radiation therapy, and 6 patients with ER/PR positive received hormone therapy with or without chemotherapy. (2) Most EESS patients had multiple tumors. The omentum was the most commonly affected site, followed by the ovaries. (3) The median follow-up was 94 (range: 27-228) months, and recurrence was observed in 3 patients (n = 10, 30%) who underwent non-optimal surgery and no hormone therapy. The 5-year and 10-year DFS rates were both 70%, as shown in Fig. 2. OS was both 100% at 5 and 10 years. CONCLUSION: As a conclusion, EESS is a rare disease and LG-EESS has a good prognosis. Surgery remains the available treatment for patients. LG-EESS has a risk of late recurrence which requires a long-term follow-up. With a limited sample size, our study shows optimal tumor reductive surgery and adjuvant hormone therapy may significantly reduce the risk of recurrence.

Clinical outcomes and patient satisfaction with the use of biological and synthetic meshes in one-stage implant-based breast reconstruction.

BACKGROUND: Biological and synthetic meshes were used to cover the damaged muscle and augment the subpectoral pocket in breast reconstruction. However, few studies have directly compared the effects of biological and synthetic meshes. This study analyzed postoperative complications and assessed the patient-reported outcomes with the use of BioDesign® Surgisis and TiLOOP Bra/TiMesh® in one-stage implant-based breast reconstruction. METHODS: Patients undergoing one-stage implant-based breast reconstruction were enrolled in this study. Post-mastectomy breast reconstructions were facilitated with either Surgisis mesh or TiLOOP mesh. Complications were examined and patient-reported quality-of-life outcomes were evaluated using the BREAST-Q questionnaire (ver 2.0). The multivariate linear regression models were used for data analysis. RESULTS: Overall, 79 of 116 patients (68%) received breast reconstruction with Surgisis mesh and 37 (32%) with TiLOOP mesh. There was no difference in complication rates between the two groups postoperatively. But patient-reported satisfaction was higher with the use of Surgisis mesh than with TiLOOP mesh (P = 0.05). CONCLUSIONS: This study reported no difference between the Surgisis group and the TiLOOP group in either complication rates or most patient-reported outcomes postoperatively. Yet the assessment of patient-reported satisfaction showed preference toward Surgisis mesh, a finding with a potential implication for mesh selection.