The Hyperproliferation Mechanism of Cholesteatoma Based on Proteomics: SNCA Promotes Autophagy-Mediated Cell Proliferation Through the PI3K/AKT/CyclinD1 Signaling Pathway.

Cholesteatoma is a chronic inflammatory ear disease with abnormal keratinized epithelium proliferation and tissue damage. However, the mechanism of keratinized epithelium hyperproliferation in cholesteatoma remains unknown. Hence, our study sought to shed light on mechanisms affecting the pathology and development of cholesteatoma, which could help develop adjunctive treatments. To investigate molecular changes in cholesteatoma pathogenesis, we analyzed clinical cholesteatoma specimens and paired ear canal skin with mass spectrometry-based proteomics and bioinformatics. From our screen, alpha-synuclein (SNCA) was overexpressed in middle ear cholesteatoma and might be a key hub protein associated with inflammation, proliferation, and autophagy in cholesteatoma. SNCA was more sensitive to lipopolysaccharide-induced inflammation, and autophagy marker increase was accompanied by autophagy activation in middle ear cholesteatoma tissues. Overexpression of SNCA activated autophagy and promoted cell proliferation and migration, especially under lipopolysaccharide inflammatory stimulation. Moreover, inhibiting autophagy impaired SNCA-mediated keratinocyte proliferation and corresponded with inhibition of the PI3K/AKT/CyclinD1 pathways. Also, 740Y-P, a PI3K activator reversed the suppression of autophagy and PI3K signaling by siATG5 in SNCA-overexpressing cells, which restored proliferative activity. Besides, knockdown of SNCA in RHEK-1 and HaCaT cells or knockdown of PI3K in RHEK-1 and HaCaT cells overexpressing SNCA both resulted in attenuated cell proliferation. Our studies indicated that SNCA overexpression in cholesteatoma might maintain the proliferative ability of cholesteatoma keratinocytes by promoting autophagy under inflammatory conditions. This suggests that dual inhibition of SNCA and autophagy may be a promising new target for treating cholesteatoma.

Immunoglobulin G4 (IgG4) Positive Associated Liver Disease.

BACKGROUND: The goal was to explore the cognition of diagnosis and treatment level of IgG4-related diseases mainly involving lymph nodes. METHODS: The clinical manifestations, laboratory indicators, histopathology, and therapeutic effects of a patient with IgG4-RD suspected of lymphoma were analyzed and the relevant literature was reviewed. RESULTS: Lymph node biopsy showed reactive hyperplasia of lymph node tissue. The liver biochemical indexes were abnormal and the bone marrow smear showed atypical lymphocytes. Lymph node section: IgG4+ cells > 100/HPF (IgG4/IgG > 40%). The serum IgG4 level was 17,200 mg/L, and the diagnosis was IgG4-RD. Oral glucocorticoids took effect after 2 weeks, and no significant enlargement of lymph nodes was observed. CONCLUSIONS: For the diagnosis of IgG4-RD, at present, histopathology is still the gold standard, but a single result cannot diagnose the disease. Comprehensive judgment should be made by combining clinical symptoms, serum IgG4 level and imaging results to prevent misdiagnosis and missed diagnosis, and to avoid over-diagnosis. Short-term hormonal diagnostic therapy may be used in highly suspected patients who cannot be diagnosed. Once diagnosed, standardized medication, adhere to follow-up, regular review, to prevent recurrence and adverse drug reactions.

Comprehensive Analyses of PANoptosome with Potential Implications in Cancer Prognosis and Immunotherapy.

Cell death resistance significantly contributes to poor therapeutic outcomes in various cancers. PANoptosis, a unique inflammatory programmed cell death (PCD) pathway activated by specific triggers and regulated by the PANoptosome, possesses key features of apoptosis, pyroptosis, and necroptosis, but these cannot be accounted for by any of the three PCD pathways alone. While existing studies on PANoptosis have predominantly centered on infectious and inflammatory diseases, its role in cancer malignancy has been understudied. In this comprehensive investigation, we conducted pan-cancer analyses of PANoptosome component genes across 33 cancer types. We characterized the genetic, epigenetic, and transcriptomic landscapes, and introduced a PANoptosome-related potential index (PANo-RPI) for evaluating the intrinsic PANoptosome assembly potential in cancers. Our findings unveil PANo-RPI as a prognostic factor in numerous cancers, including KIRC, LGG, and PAAD. Crucially, we established a significant correlation between PANo-RPI and tumor immune responses, as well as the infiltration of diverse lymphoid and myeloid cell subsets across nearly all cancer types. Moreover, a high PANo-RPI was consistently associated with improved immunotherapy response and efficacy, as evidenced by re-analysis of multiple immunotherapy cohorts. In conclusion, our study suggests that targeting PANoptosome components and modulating PANoptosis may hold tremendous therapeutic potential in the context of cancer.

Outcomes of ankle arthrodesis in adult patients with ankle osteoarthritis in Kashin-Beck disease.

PURPOSE: We retrospectively evaluated the characteristics of these patients and the effectiveness of ankle arthrodesis in the treatment of ankle arthritis caused by Kashin-Beck disease (KBD). METHODS: A retrospective study of KBD patients with ankle osteoarthritis who underwent ankle arthrodesis between December 2012 and January 2022 was performed. A total of 46 patients were included. The general characteristics, clinical manifestations and imaging features of the patients were recorded and summarized. measured using the VAS score, and ankle function was assessed by the AOFAS ankle-hindfoot score. RESULTS: Multiple subchondral cystic changes were found in 42(91.3%) patients. The VAS scores for both resting and weight-bearing conditions were 6.28 ± 1.30 vs. 2.09 ± 1.12 (P < .001) and 6.87 ± 1.01 vs. 2.17 ± 0.98 (P < .001), respectively. The AOFAS scores were 59.17 ± 5.50 and 88.39 ± 1.42, respectively (P < .001). CONCLUSIONS: The subchondral multiple cystic transformation of the ankle KBD has a certain suggestive role.Arthrodesis is an effective method to reduce ankle pain and improve ankle function in KBD patients with ankle osteoarthritis.

The value of gadolinium-enhanced MRI in predicting the development of sudden hearing loss into Ménière's disease.

OBJECTIVE: To compare the clinical features of sudden hearing loss (SHL) in patients with and without endolymphatic hydrops (EH), and to investigate the association between SHL with EH and Ménière's disease (MD). METHODS: The clinical data of 63 SHL patients with first symptoms were evaluated retrospectively. Patients were separated into two groups based on the results of gadolinium-enhanced magnetic resonance imaging: EH and non-EH groups. Independent sample t-test and U-test were used to compare groups for continuous variables, and the chi-squared test, corrected chi-squared test and Bonferroni correction test were used to compare groups for binary and ordinal variables. The binary logistic regression model was utilised for univariate and multivariate analysis of follow-up patient prognosis. RESULTS: The EH and non-EH groups contained 32 and 31 patients, respectively. The EH group had a higher prevalence of low-tone descending hearing loss. Fifty-one patients were followed for more than 2 years. In the EH group, 11 and 15 patients were diagnosed with sudden sensorineural hearing loss (SSNHL) and MD, respectively, while in the non-EH group, 24 patients were diagnosed with SSNHL and only one with MD. EH, low-tone descending hearing loss and vertigo were risk factors for the diagnosis of MD in a subgroup univariate regression analysis of patients experiencing SHL. EH was found to be a risk factor for the progression of SHL into MD in a multifactor regression analysis. CONCLUSIONS: Patients with SHL who have EH are more likely to present with low-tone descending hearing loss. EH is a risk factor for the subsequent development of MD.

[Progress in gene-modified stem cell therapy for penile erectile dysfunction].

Erectile dysfunction (ED) is a common disorder in men and lacks effective treatment. Stem cell (SC) possess the potential in self-renewal and multi-directional differentiation, and secrete a variety of active substances. Stem cell therapy, as a promising option for the treatment of ED, is a focus in regenerative medicine research. However, the effect of stem cell therapy alone on ED is limited due to the complexity of the condition and the limitations of SC. Gene modification can enhance the performance of SC in multiple aspects and play the role of targeted genes, and therefore can better improve ED and its related pathological changes than SC therapy alone. In recent years, gene-modified stem cell therapy has become a hotspot in andrological research. This review summarizes the advances in the studies of gene-modified SC in the treatment of ED, aiming to provide some ideas for further research.

MiR-652-3p promotes malignancy and metastasis of cancer cells via inhibiting TNRC6A in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was one of the most prevalent life-threatening cancers. Metastasis is the leading cause of cancer-related death in HCC. MiRNAs play essential roles in cancer metastasis. METHODS: Expression of miR-652-3p in HCC was assessed. Function experiments of miR-652-3p and trinucleotide repeat-containing gene 6A protein (TNRC6A) were performed both in vitro and in vivo. mRNA sequencing, PCR, and western blot were performed to verify the target genes and pathway of miR-652-3p. The lung metastasis and xenograft cancer model in nude mice was established to investigate the effects of the miR-652-3p and TRNC6A on tumor metastasis in vivo. The relationship between the expression of the miR-652-3p, TNRC6A and the prognosis of HCC patients was analyzed. RESULTS: Upregulated miR-652-3p was found in the tumor tissues of HCC, especially in metastatic HCC patients. Overexpression of miR-652-3p promoted and knockdown of miR-652-3p suppressed HCC metastasis both in vitro and in vivo. MiR-652-3p promoted HCC metastasis via regulating the EMT pathway. TNRC6A was identified as a direct target of miR-652-3p, and the knockdown of TNRC6A restored repressed EMT and HCC metastasis caused by the inhibition of miR-652-3p. Clinical results revealed that high expression of miR-652-3p and low expression of TNRC6A were positively correlated to shortened overall survival and disease-free survival in HCC patients. CONCLUSIONS: MiR-652-3p promotes EMT and HCC metastasis by inhibiting TNRC6A expression in HCC. MiR-652-3p and TNRC6A may serve as potential biomarkers to predict prognosis in HCC patients with metastasis.

A vaccine delivery system promotes strong immune responses against SARS-CoV-2 variants.

Global coronavirus disease 2019 (COVID-19) pandemics highlight the need of developing vaccines with universal and durable protection against emerging SARS-CoV-2 variants. Here we developed an extended-release vaccine delivery system (GP-diABZI-RBD), consisting the original SARS-CoV-2 WA1 strain receptor-binding domain (RBD) as the antigen and diABZI stimulator of interferon genes (STING) agonist in conjunction with yeast ß-glucan particles (GP-diABZI) as the platform. GP-diABZI-RBD could activate STING pathway and inhibit SARS-CoV-2 replication. Compared to diABZI-RBD, intraperitoneal injection of GP-diABZI-RBD elicited robust cellular and humoral immune responses in mice. Using SARS-CoV-2 GFP/ΔN transcription and replication-competent virus-like particle system (trVLP), we demonstrated that GP-diABZI-RBD-prototype vaccine exhibited the strongest and durable humoral immune responses and antiviral protection; whereas GP-diABZI-RBD-Omicron displayed minimum neutralization responses against trVLP. By using pseudotype virus (PsVs) neutralization assay, we found that GP-diABZI-RBD-Prototype, GP-diABZI-RBD-Delta, and GP-diABZI-RBD-Gamma immunized mice sera could efficiently neutralize Delta and Gamma PsVs, but had weak protection against Omicron PsVs. In contrast, GP-diABZI-RBD-Omicron immunized mice sera displayed the strongest neutralization response to Omicron PsVs. Taken together, the results suggest that GP-diABZI can serve as a promising vaccine delivery system for enhancing durable humoral and cellular immunity against broad SARS-CoV-2 variants. Our study provides important scientific basis for developing SARS-CoV-2 VOC-specific vaccines.

Inference of relative permeability curves in reservoir rocks with ensemble Kalman method.

Multiphase flows through reservoir rocks are a universal and complex phenomenon. Relative permeability is one of the primary determinants in reservoir performance calculations. Accurate estimation of the relative permeability is crucial for reservoir management and future production. In this paper, we propose inferring relative permeability curves from sparse saturation data with an ensemble Kalman method. We represent these curves through a series of positive increments of relative permeability at specified saturation values, which guarantees monotonicity within, and boundedness between 0 and 1. The proposed method is validated by the inference performances in two synthetic benchmarks designed by SPE and a field-scale model developed by Equinor that includes certain real field features. The results indicate that the relative permeability curves can be accurately estimated within the saturation intervals having available observations and appropriately extrapolated to the remaining saturations by virtue of the embedded constraints. The predicted well responses are comparable to the ground truths, even though they are not included as the observation. The study demonstrates the feasibility of using ensemble Kalman method to infer relative permeability curves from saturation data, which can aid in the predictions of multiphase flow and reservoir production.

NUPR1 promotes the proliferation and migration of breast cancer cells by activating TFE3 transcription to induce autophagy.

Recurrence and metastasis affect the survival rate of breast cancer patients. The fundamental reason lies in the lack of understanding of the mechanism of breast cancer metastasis. In this study, the proliferation, migration and invasion abilities of breast cancer cells were evaluated. The mechanism of NUPR1/TFE3 signaling pathway on autophagy-related proteins and migration-invasion-related proteins was examined in cell model in vitro. The effects of NUPR1 on malignancy formation and metastasis were investigated in vivo. We found that NUPR1 was upregulated in breast cancer cells and tissues. NUPR1 knockdown inhibited the proliferation, migration and invasion of ZR-75-30 cells and inhibited malignancy formation and metastasis in vivo. Mechanically, NUPR1 promoted autophagy by activating of TFE3 transcription, thereby regulating breast cancer metastasis. This paper indicates that NUPR1 activates autophagy through the TFE3 signaling pathway to promote breast cancer metastasis, and provides a biological basis for the intervention of blocking distant metastasis.

A Case of Acute Mixed Cell Leukemia Resembling AML1-ETO Positive Acute Myeloid Leukemia.

BACKGROUND: The aim of the study was to improve the understanding of complex karyotype acute mixed cell leukemia containing pseudo Chediak-Higashi granules. METHODS: A case of acute mixed cell leukemia resembling AML1-ETO positive acute myeloid leukemia was reported. The results of morphological, immunophenotypic, and cytogenetic tests were analyzed by reviewing relevant literature. RESULTS: The patient was a young boy with clinical manifestations of recurrent fever. Bone marrow smear: Granulocyte system hyperplasia is obvious, visible at each stage, primitive cells account for 12%. These cells are large in volume, mostly round or class round, with abundant cell mass, stained gray blue, unbalanced development of some nuclear plasma, abnormal cytoplasmic staining, and visible "sunrise red" -like changes. Typical Auer bodies, pseudo Chadiak-Higashi granules and phagocytic erythroid substances were observed. The nuclei are irregular in shape, distorted and depressed, with fine chromatin and prominent large nucleoli. Bone marrow was extracted 3 days later, the bone marrow smear showed 65% primitive cells. The morphology of primitive cells was similar to that of 3 days ago. The results of flow cytometry showed that the primary/naive T cells in the samples possessed nuclear cells. Flow cytometry showed two groups of abnormal cells. One group accounted for 3.87% of nuclear cells and was a primitive/naive T-cell phenotype, mainly expressing: CD34+, CD7+, CD5+, CD2dim+, MPO-, CCD3 + part, CD3-, CD4-, CD8 -, CD117 -, CD13-, CD33-, HLA - DR -, CD10-, CD11b-, CD56-. The other group which accounted for 79.8% of the nuclear cells was monocyte phenotype, mainly expressing: CD34-, CD117-, CD13+ small amount, CD33+, HLA-DR-, CD11b+, CD14+, CD15+, CD36+, CD56+, CD64+, CD4+, CD85J+, CD85K + part. It matched the immunophenotype of acute mixed cell leukemia (T/MMPAL). Immunophenotypic leukemia-related fusion genes were negative, and karyotype analysis results were 45, XY, T (11; 12)(p13; Q13), -12-17, + mar [12]/90 < n > 4, idem x 2 [6]/46, XY. Combined with the above results, acute mixed cell leukemia was diagnosed. CONCLUSIONS: The flow cytometry is the gold standard in the diagnosis of acute mixed cell leukemia. The diagnosis of acute mixed cell leukemia requires the combination of clinical manifestations, cellular morphology, immunology, cytogenetics and molecular biology, and the comprehensive diagnosis efficiency is obviously better than that of morphology.

FBXW7 inhibits the progression of ESCC by directly inhibiting the stemness of tumor cells.

F-box and WD repeat domain containing 7 (FBXW7) is an aboriginal and high-frequency mutant gene associated with esophageal squamous cell carcinoma (ESCC). This study was designed to determine the clinical value and molecular mechanisms of FBXW7 in the development of ESCC. The clinical significance of FBXW7 was analyzed in ESCC from TCGA data. The effects of FBXW7 on proliferation, colony formation, migration and invasion, angiogenesis, and apoptosis were tested in ESCC cells. PCR-array, sphere formation assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the mechanism of FBXW7. FBXW7 was a significantly mutated gene in ESCC. It was an independent and potential predictor for survival in ESCC patients. In addition, FBXW7 overexpression significantly inhibited ESCC cell proliferation, migration, invasion, angiogenesis, and promoted cell apoptosis. PCR array revealed that FBXW7 overexpression leads to a significant change of gene expressions associated with angiogenesis, cell senescence, and DNA damage and repair. Sphere formation assay and qPCR showed FBXW7 was associated with ESCC stem cell formation. Our results suggest that FBXW7 may act as a tumor suppressor by repressing cancer stem cell formation and regulating tumor angiogenesis, cell senescence, DNA damage, and repair in ESCC.

Investigation of Self-Powered IoT Sensor Nodes for Harvesting Hybrid Indoor Ambient Light and Heat Energy.

Sensor nodes are critical components of the Internet of Things (IoT). Traditional IoT sensor nodes are typically powered by disposable batteries, making it difficult to meet the requirements for long lifetime, miniaturization, and zero maintenance. Hybrid energy systems that integrate energy harvesting, storage, and management are expected to provide a new power source for IoT sensor nodes. This research describes an integrated cube-shaped photovoltaic (PV) and thermal hybrid energy-harvesting system that can be utilized to power IoT sensor nodes with active RFID tags. The indoor light energy was harvested using 5-sided PV cells, which could generate 3 times more energy than most current studies using single-sided PV cells. In addition, two vertically stacked thermoelectrical generators (TEG) with a heat sink were utilized to harvest thermal energy. Compared to one TEG, the harvested power was improved by more than 219.48%. In addition, an energy management module with a semi-active configuration was designed to manage the energy stored by the Li-ion battery and supercapacitor (SC). Finally, the system was integrated into a 44 mm × 44 mm × 40 mm cube. The experimental results showed that the system was able to generate a power output of 192.48 µW using indoor ambient light and the heat from a computer adapter. Furthermore, the system was capable of providing stable and continuous power for an IoT sensor node used for monitoring indoor temperature over a prolonged period.

[Latest Findings on the Pathogenic Mechanisms of Thoracic Aortic Dissection].

Thoracic aortic dissection (TAD) is a cardiovascular disease entailing a high lethality between 65% and 85%. Surgery-assissed implant/interventional stenting is the prevailing treatment of TAD. However, surgical treatment can cause severe postoperative complications and patients incur a relatively higher risk of postoperative mortality. Since the pathogenic mechanism underlying TAD is not clear, effective medication therapies are still not available. In recent years, along with advances in single-cell sequencing and other molecular biological technologies, there have been prelimiary findings suggesting the special role of dysfunctional vascular smooth muscle cells (VSMCs) in the pathogenesis and development of TAD. Furthermore, the molecular mechanisms regulating the dysfunction of VSMCs have been initially explored. It is expected that these new findings will contribute to the development of new strategies to prevent TAD and lead to new ideas for the identifiction of potential drug therapeutic targets. Herein, we summarized the critical role of dysfunctional VSMCs in the pathogenesis and development of TAD and presented in detail the biological factors and the related molecular mechanisms that regulate the dysfunction of VSMCs. We hope this review will provide a reference for further investigation into the central role of dysfunctional VSMCs in the pathogenesis and development of TAD and exploration for effective molecular drug targets for TAD.

N6-methyladenosine-mediated downregulation of miR-374c-5p promotes cadmium-induced cell proliferation and metastasis by targeting GRM3 in breast cancer cells.

Cadmium (Cd) is a toxic heavy metal that can facilitate the development and progression of breast cancer (BC). Emerging evidence has indicated that the progression of Cd-exposed BC is related to the dysregulation of microRNAs (miRNAs). The purpose of our study was to investigate the expression pattern and underlying mechanisms of miR-374c-5p in Cd-mediated BC progression. In this study, T-47D cells and MCF-7 cells were treated with different concentrations of Cd (0.1, 1 and 10 µM) for 72 h. MiR-374c-5p expression was downregulated, and transfection of miR-374c-5p mimics significantly decreased BC cell proliferation, migration and invasion induced by 10 µM Cd. Importantly, we used the Cytoscape software plugin cytoHubba to analyse the intersected genes between our RNA-Seq results and the mirDIP database, and six hub genes (CNR1, CXCR4, GRM3, RTN1, SLC1A6 and ZEB1) were identified as potential direct targets of miR-374c-5p in our model; however, luciferase reporter assays indicated that miR-374c-5p only repressed GRM3 by directly binding to its 3'-untranslated region (UTR). Of note, we verified that suppression of N6-methyladenosine (m6A) modification led to miR-374c-5p downregulation by decreasing its RNA transcript stability. Together, these findings demonstrated that m6A modification of pri-miRNA-374c blocks miRNA-374c-5p maturation and then activates GRM3 expression, which drives BC cell metastasis after Cd exposure.

Optimization of loop-mediated isothermal amplification (LAMP) assay for robust visualization in SARS-CoV-2 and emerging variants diagnosis.

Loop-mediated isothermal amplification (LAMP) is widely used in detection of pathogenic microorganisms including SARS-CoV-2. However, the performance of LAMP assay needs further exploration in the emerging SARS-CoV-2 variants test. Here, we design serials of primers and select an optimal set for LAMP-based on SARS-CoV-2 N gene for a robust and visual assay in SARS-CoV-2 diagnosis. The limit of detectable template reaches 10 copies of N gene per 25 µL reaction at isothermal 58℃ within 40 min. Importantly, the primers for LAMP assay locate at 12 to 213 nt of N gene, a highly conservative region, which serves as a compatible test in emerging SARS-CoV-2 variants. Comparison to a commercial qPCR assay, this LAMP assay exerts the high viability in diagnosis of 41 clinical samples. Our study optimizes an advantageous LAMP assay for colorimetric detection of SARS-CoV-2 and emerging variants, which is hopeful to be a promising test in COVID-19 surveillance.

Recent Advances in PROTACs for Drug Targeted Protein Research.

Proteolysis-targeting chimera (PROTAC) is a heterobifunctional molecule. Typically, PROTAC consists of two terminals which are the ligand of the protein of interest (POI) and the specific ligand of E3 ubiquitin ligase, respectively, via a suitable linker. PROTAC degradation of the target protein is performed through the ubiquitin-proteasome system (UPS). The general process is that PROTAC binds to the target protein and E3 ligase to form a ternary complex and label the target protein with ubiquitination. The ubiquitinated protein is recognized and degraded by the proteasome in the cell. At present, PROTAC, as a new type of drug, has been developed to degrade a variety of cancer target proteins and other disease target proteins, and has shown good curative effects on a variety of diseases. For example, PROTACs targeting AR, BR, BTK, Tau, IRAK4, and other proteins have shown unprecedented clinical efficacy in cancers, neurodegenerative diseases, inflammations, and other fields. Recently, PROTAC has entered a phase of rapid development, opening a new field for biomedical research and development. This paper reviews the various fields of targeted protein degradation by PROTAC in recent years and summarizes and prospects the hot targets and indications of PROTAC.

TGF-ß1 induced proliferation, migration, and ECM accumulation through the SNHG11/miR-34b/LIF pathway in human pancreatic stellate cells.

Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas, and activated pancreatic stellate cells (PSCs) play a vital role in the progression of pancreatic fibrosis in CP. It has been reported that long non-coding RNA small nucleolar RNA host gene 11 (SNHG11) is highly expressed in chronic pancreatitis (CP) patients. However, the role of SNHG11 in CP progression is unclear. The purport of the study was to survey the role of SNHG11 in CP. We employed transforming growth factor (TGF)-beta1 (TGF-ß1) to activate human pancreatic stellate cells (PSCs). Expression of SNHG11 was assessed with qRT-PCR. Loss-of-function experiments were executed to evaluate the effects of SNHG11 on the proliferation and migration of TGF-ß1-treated PSCs. Some protein levels were detected by western blotting. The regulatory mechanism of SNHG11 was verified by the dual-luciferase reporter and RIP assays. As a result, SNHG11 was upregulated in plasma of CP patients and TGF-ß1-treated PSCs. Also, SNHG11 inhibition reduced TGF-ß1-induced proliferation, migration, and ECM accumulation in PSCs. Mechanistically, SNHG11 regulated leukemia inhibitory factor (LIF) expression by sponging miR-34b. Furthermore, miR-34b inhibitor abolished SNHG11 silencing-mediated effects on TGF-ß1-treated PSC proliferation, migration, and ECM accumulation. LIF overexpression counteracted the repressive influence of miR-34b mimic on proliferation, migration, and ECM accumulation of TGF-ß1-treated PSCs. In conclusion, SNHG11 knockdown reduced TGF-ß1-induced PSC proliferation, migration, and ECM accumulation by the miR-34b/LIF axis.

Y-Shaped Tendon Graft-A Technique in the Reconstruction of Posttraumatic Chronic Boutonniere Deformity.

PURPOSE: Current reconstruction strategies for chronic posttraumatic boutonniere deformities have variable outcomes and are prone to complications. This study aimed to describe the clinical outcomes of a Y-shaped tendon graft technique. METHODS: In this retrospective case study, we reviewed the files of 18 patients treated with the Y-shaped tendon graft between January 2010 and January 2017. The technique involves release of the central slip, lateral bands, and transverse retinacular ligaments at the proximal interphalangeal (PIP) joint, total excision of scar tissue in the central slip and at the insertion site, and construction of 3 1.5-mm unicortical holes at the base of the middle phalanx, through which a Y-shaped graft of the palmaris longus is inserted to reconstruct the central slip and stabilize the lateral bands in a dorsal position. Clinical evaluations included measuring the active range of motion in the PIP joint and distal interphalangeal (DIP) joint, grip strength, Souter score, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score. RESULTS: The mean age of patients was 36.1 years, and 12 of the 18 patients were men. The average follow-up period was 23 months (range, 13-38 months). The preoperative PIP joint extension deficit was 48.0° ± 5.0° compared with 10.9° ± 9.3° after surgery. The preoperative DIP joint active flexion was 34.4° ± 8.0° compared with 71.4° ± 8.6° after surgery The outcomes based on the Souter score were 11 excellent, 5 good, and 2 poor. The QuickDASH score was 17.7 ± 6.4 before surgery and 11.2 ± 7.2 after surgery. CONCLUSIONS: The Y-shaped tendon graft can be a useful procedure for the correction of chronic boutonniere deformity; in our patient series, this provided good or excellent results in 16 of 18 patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Maternal origins, population structure and demographic history of ten Chinese indigenous goat breeds from Yunnan.

Yunnan as a frontier zone that connects China with South and Southeast Asia, has 11 well-recognized goat breeds. However, the knowledge about maternal origins, population structure and demographic history of Chinese indigenous goats from Yunnan is limited. In this study, we analysed a 481-bp fragment of first hypervariable segment (HVSI) of the mitochondrial DNA (mtDNA) control region sequences of 749 individuals from 10 Yunnan indigenous goat breeds, of which 556 sequences were newly determined. There were 110 polymorphic sites that defined 158 haplotypes among all sequences. The haplotype and nucleotide diversity of these breeds ranged from 0.782 ± 0.079 to 0.982 ± 0.015 and from 0.028 ± 0.003 to 0.043 ± 0.005, respectively. Phylogenetic analysis identified two lineages A and B, of which the lineage A had higher frequency (68.1%) and distributed in all Yunnan breeds. We combined previously reported sequences with our sequences belonging to the lineage B and detected two subclades B1 and B2, in which the B1 subclade shared individuals from Eastern Asia, Southeast Asia and Southern Asia. Given higher level of diversity and more unique haplotypes, the B2 subclade probably originated from Southwestern China. The haplotype network, analysis of molecular variance (AMOVA) and a Mantel test revealed no significant phylogeographic structuring among Yunnan goat breeds. This can be explained by high gene flow and genetic admixture among these breeds from different geographic regions in Yunnan. Additionally, both the lineages A and B reflected different demographic histories. This study will provide a scientific basis for the conservation and utilization of Yunnan indigenous goats.