Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis.

Objectives: The objective of this network meta-analysis is to systematically compare the efficacy of diverse progestin-based combination regimens in treating patients diagnosed with endometrial cancer or atypical endometrial hyperplasia. The primary goal is to discern the optimal combination treatment regimen through a comprehensive examination of their respective effectiveness. Methods: We systematically searched four prominent databases: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials, for randomized controlled trials addressing the efficacy of progestins or progestin combinations in the treatment of patients with endometrial cancer or atypical endometrial hyperplasia. The search spanned from the inception of these databases to December 2023. Key outcome indicators encompassed survival indices, criteria for assessing efficacy, as well as pregnancy and relapse rate. This study was registered in PROSPERO (CRD42024496311). Results: From the 1,558 articles initially retrieved, we included 27 studies involving a total of 5,323 subjects in our analysis. The results of the network meta-analysis revealed that the mTOR inhibitor+megestrol acetate (MA)+tamoxifen regimen secured the top rank in maintaining stable disease (SD) (SUCRA=73.4%) and extending progression-free survival (PFS) (SUCRA=72.4%). Additionally, the progestin combined with tamoxifen regimen claimed the leading position in enhancing the partial response (PR) (SUCRA=75.2%) and prolonging overall survival (OS) (SUCRA=80%). The LNG-IUS-based dual progestin regimen emerged as the frontrunner in improving the complete response (CR) (SUCRA=98.7%), objective response rate (ORR) (SUCRA=99.1%), pregnancy rate (SUCRA=83.7%), and mitigating progression (SUCRA=8.0%) and relapse rate (SUCRA=47.4%). In terms of safety, The LNG-IUS-based dual progestin regimen had the lowest likelihood of adverse events (SUCRA=4.2%), while the mTOR inhibitor regimen (SUCRA=89.2%) and mTOR inbitor+MA+tamoxifen regimen (SUCRA=88.4%) had the highest likelihood of adverse events. Conclusions: Patients diagnosed with endometrial cancer or atypical endometrial hyperplasia exhibited the most favorable prognosis when undergoing progestin combination therapy that included tamoxifen, mTOR inhibitor, or LNG-IUS. Notably, among these options, the LNG-IUS-based dual progestin regimen emerged as particularly promising for potential application. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024496311.

Allergic Diseases and Chronic Adenotonsillar Diseases: A Mendelian Randomization Study.

OBJECTIVE: The existing epidemiological evidence regarding the intricate relationship between allergic diseases and chronic adenotonsillar diseases (CATD) remains inconclusive. Herein, the objective of our study is to explore the causal association using Mendelian randomization (MR). METHODS: Employing data from large genome-wide association studies, a comprehensive two-sample bidirectional MR study was conducted. The studied traits encompassed allergic rhinitis (cases n = 9707, controls n = 331173), allergic asthma (cases n = 8525, controls n = 193857), allergic conjunctivitis (cases n = 18321, controls n = 324178), atopic dermatitis (cases n = 11964, controls n = 306909), and CATD (cases n = 38983, controls n = 258553). All the patients were of European descent and participants in cohort studies. The primary analysis was executed using inverse-variance-weighted MR. Furthermore, six additional MR methods (MR-Egger, weighted median, simple mode, weighted mode, MR pleiotropy residual sum and outlier, MR robust adjusted profile score) were employed to ensure the reliability and detect potential horizontal pleiotropy within the results. The estimates obtained from the MR analysis were factored into the overall effect calculation. RESULTS: Genetically anticipated outcomes demonstrated a significant association between CATD risk and allergic rhinitis (OR = 1.141, p = 6.30E-06), allergic asthma (OR = 1.115, p = 8.31E-05), allergic conjunctivitis (OR = 1.197, p = 8.69E-07), and a suggestive association with atopic dermatitis (OR = 1.053, p = 0.040). However, no substantial correlation was observed in the reverse direction. CONCLUSIONS: Findings of our study provide evidence supporting a causal role of allergic diseases in the development of CATD, whereas the converse relationship does not appear to hold true. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2653-2658, 2024.

Clinical application of super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction: a pilot study.

OBJECTIVE: This study aimed to evaluate the clinical application and efficacy of a super-low-positioned intestinal decompression tube in the treatment of intestinal obstruction. METHODS: A total of 130 patients with postoperative small bowel obstruction were included in this study. The patients were divided into a super-low-positioned intestinal decompression group and a conventional intestinal decompression group. The clinical data, treatment outcomes, and complications were compared between the two groups. RESULTS: The technical success rate of placing the super-low-positioned intestinal decompression tube was 100%, with no intraoperative complications. The patients in the super-low-positioned intestinal decompression group had a significantly shorter hospital stay (8.3 ± 5.2 vs 17.7 ± 13.3, P < 0.001) and a higher non-operative treatment success rate (83.6% vs 57.9%, P = 0.001) compared to the conventional intestinal decompression group. Multivariate logistic regression analysis showed that the placement of a super-low-positioned intestinal decompression tube was an independent protective factor for treatment outcomes (P = 0.001). The hospital stay was significantly shorter in the super-low-positioned intestinal decompression group compared to the conventional group in both successful non-operative treatment patients (6.9 ± 3.0 vs 11.2 ± 7.5, P < 0.001) and failed non-operative treatment patients (16.2 ± 7.4 vs 26.6 ± 14.4, P < 0.001). The super-low-positioned intestinal decompression tube effectively relieved the "Self-strangulation" phenomenon in patients with intestinal obstruction. CONCLUSION: The super-low-positioned intestinal decompression tube is a safe and effective method for the treatment of intestinal obstruction, with better treatment outcomes and shorter hospital stays compared to conventional intestinal decompression. Further prospective studies are needed to validate these findings.

The role of SLC39A4 in the prognosis, immune microenvironment, and contribution to malignant behavior in vivo and in vitro of cervical cancer.

BACKGROUND: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. METHODS: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. RESULTS: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. CONCLUSION: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Total thyroidectomy versus unilateral lobectomy for unilateral multifocal papillary thyroid carcinoma: systematic review and meta­analysis.

The optimal surgical procedure(s) for unilateral multifocal papillary thyroid carcinomas is currently controversial. As such, the present study aimed to compare the efficacies of total thyroidectomy and lobectomy in patients with unilateral multifocal papillary thyroid carcinoma. A literature search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, Wan Fang, and Zhi Wang databases for relevant studies, published from inception to October 31, 2022, was performed. Two researchers independently extracted data from the included studies. Lymph node metastasis, vocal fold paralysis, parathyroid injury, postoperative recurrence, and disease-free survival were evaluated. The meta-analysis included 7 studies comprising 1540 patients, of whom 496 and 1044 underwent lobectomy and total thyroidectomy, respectively. Compared with lobectomy, total thyroidectomy resulted in more vocal cord paralysis (odds ratio [OR] 0.35 [95% confidence interval (CI) 0.13 to 0.96]; P = 0.04) and parathyroid injury (OR 0.11 [95% CI 0.03-0.39]; P = 0.001) but with better disease-free survival (OR 0.21 [95% CI 0.09-0.49]; P = 0.000), although vocal cord paralysis and parathyroid injury, in large part, resolved within 1 year after surgery. In addition, there was no difference in postoperative lymph nodes metastasis (OR 0.74 [95% CI 0.13-4.21]; P = 0.737) and postoperative recurrence (OR 2.37 [95% CI 0.42-13.38]; P = 0.33). Excluding studies that deviated from the general trend, total thyroidectomy was beneficial in reducing recurrence. Compared with lobectomy, total thyroidectomy was beneficial in reducing recurrence and disease-free survival and may be considered a more optimal approach for unilateral multifocal papillary thyroid carcinoma.

S100A10 Overexpression Correlates with Adverse Prognosis, Tumor Microenvironment, and Aggressive Behavior In Vitro and In Vivo of Cervical Cancer.

Background: The incidence of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is increasing in women. S100A10 overexpression is commonly reported in various malignancies and is closely associated with tumor cell characteristics and prognosis. Methods: The expression of S100A10 and its prognostic relevance were assessed utilizing RNA-seq data from The Cancer Genome Atlas. S100A10 regulation of CESC cell growth and migration was investigated using CCK-8, colony-forming, and Transwell-based approaches. Xenograft model mice were used to examine the in vivo effects of S100A10, and differentially expressed genes (DEGs) linked to S100A10 were identified to explore its functional role in oncogenesis. Associations between S100A10 levels, chemosensitivity, and the immune microenvironment were assessed, and the mutational and methylation status of S100A10 was evaluated using the cBioPortal and MethSurv databases, respectively. Results: S100A10 was upregulated in CESC samples, and higher S100A10 mRNA levels were associated in poor prognostic outcomes. The area under the curve for S100A10 when diagnosing CESC was 0.935, and S100A10 was found to regulate tumor cell proliferation and metastasis both in vitro and in vivo. Overall, 1125 DEGs enriched in crucial CESC progression-associated signaling pathways were identified. S100A10 expression was also associated with the intratumoral immune microenvironment and immune checkpoint activity. Patients expressing elevated S100A10 levels exhibited distinct chemotherapeutic susceptibility, and methylation of the S100A10 gene was correlated with patient survival outcomes. Conclusion: In summary, this research demonstrated that S100A10 plays a crucial role in regulating CESC development, prognosis, and the intratumoral immune microenvironment. Thus, S100A10 shows potential as a prognostic or diagnostic tool and as a potential target for CESC immunotherapy.

Identification of biomarkers in laryngeal cancer by weighted gene co-expression network analysis. / åº”ç”¨åŠ æƒåŸºå› å ±è¡¨è¾¾ç½‘ç»œåˆ†æžæŽ¢ç´¢å–‰ç™Œæ ‡å¿—ç‰©ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Laryngeal cancer (LC) is a globally prevalent and highly lethal tumor. Despite extensive efforts, the underlying mechanisms of LC remain inadequately understood. This study aims to conduct an innovative bioinformatic analysis to identify hub genes that could potentially serve as biomarkers or therapeutic targets in LC. METHODS: We acquired a dataset consisting of 117 LC patient samples, 16 746 LC gene RNA sequencing data points, and 9 clinical features from the Cancer Genome Atlas (TCGA) database in the United States. We employed weighted gene co-expression network analysis (WGCNA) to construct multiple co-expression gene modules. Subsequently, we assessed the correlations between these co-expression modules and clinical features to validate their associations. We also explored the interplay between modules to identify pivotal genes within disease pathways. Finally, we used the Kaplan-Meier plotter to validate the correlation between enriched genes and LC prognosis. RESULTS: WGCNA analysis led to the creation of a total of 16 co-expression gene modules related to LC. Four of these modules (designated as the yellow, magenta, black, and brown modules) exhibited significant correlations with 3 clinical features: The age of initial pathological diagnosis, cancer status, and pathological N stage. Specifically, the yellow and magenta gene modules displayed negative correlations with the age of pathological diagnosis (r=-0.23, P<0.05; r=-0.33, P<0.05), while the black and brown gene modules demonstrated negative associations with cancer status (r=-0.39, P<0.05; r=-0.50, P<0.05). The brown gene module displayed a positive correlation with pathological N stage. Gene Ontology (GO) enrichment analysis identified 77 items, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 30 related signaling pathways, including the calcium signaling pathway, cytokine-cytokine receptor interaction, neuro active ligand-receptor interaction, and regulation of lipolysis in adipocytes, etc. Consequently, central genes within these modules that were significantly linked to the overall survival rate of LC patients were identified. Central genes included CHRNB4, FOXL2, KCNG1, LOC440173, ADAMTS15, BMP2, FAP, and KIAA1644. CONCLUSIONS: This study, utilizing WGCNA and subsequent validation, pinpointed 8 genes with potential as gene biomarkers for LC. These findings offer valuable references for the clinical diagnosis, prognosis, and treatment of LC.

TPM3: a novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) has become increasingly prevalent in younger women. Tropomyosin 3 (TPM3), a thin filament actin-binding protein, has been implicated in various malignancies. In this study, TPM3 expression was evaluated using RNA-seq data from The Cancer Genome Atlas (TCGA), and its relationship with CESC prognosis was examined with receiver operating characteristic (ROC) curves. The effects of TPM3 on cellular proliferation and migration were examined in CESC cell lines using Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays, while in vivo effects were assessed in mouse xenograft models. Furthermore, differentially expressed genes (DEGs) associated with TPM3 were investigated to determine their tumorigenic functions. Associations between TPM3, chemosensitivity, and immune infiltration were analyzed, as were links between mutations, methylation, and prognosis using the cBioPortal and MethSurv databases. Upregulation of TMP3 mRNA and protein levels was observed in CESC samples, with elevated mRNA levels associated with reduced overall survival. TPM3 showed an area under the curve (AUC) of 0.946 for CESC diagnosis and was found to regulate tumor proliferation and metastasis in vitro and in vivo. Overall, 3099 DEGs were identified and found to be enriched in key CESC progression-related signaling pathways. TPM3 expression was also correlated with intratumoral immune cell infiltration and immune checkpoint activity. Patients with higher TPM3 expression showed distinctive chemosensitivity profiles, and TPM3 gene methylation was linked to poorer CESC patient prognostic outcomes. In conclusion, TPM3 is a key regulator of CESC progression, prognosis, and the tumor immune microenvironment, suggesting its potential as a diagnostic or prognostic biomarker and target for CESC immunotherapy.

Transoral robotic surgery vs. non-robotic surgeries for oropharyngeal squamous cell carcinoma: systematic review and meta-analysis.

To compare the effectiveness of transoral robotic surgery (TORS) and non-robotic surgeries (NRES) in patients with oropharyngeal squamous cell carcinoma (OPSCC), medical databases were searched including PubMed, Web of Science, Medline, Embase, and Cochrane Library up to January 2023. The methodology follows PRISMA guidelines, including the PRISMA flow diagram. Data from the included studies were extracted independently by two researchers. Seven studies involving five hundred seventy-seven patients were included. Of these, 275 underwent TORS and 302 underwent NRES. The disease-free survival rate was significantly higher in the TORS group than in the NRES group (OR = 3.43, 95% CI 1.92-6.15, P < 0.0001). However, there were no significant differences in positive surgical margins, hospital stays, operation time, blood loss, postoperative bleeding rate, perioperative tracheostomy, perioperative feeding tube, and overall survival rate. These findings can initially guide the preoperative counseling of TORS in patients with OPSCC, and preliminarily confirm that the adoption of TORS deserves careful consideration.

Ligand-Enabled NiII -Catalyzed Hydroxylarylation of Alkenes with Molecular Oxygen.

The use of molecular oxygen as the terminal oxidant in transition metal catalyzed oxidative process is an appealing and challenging task in organic synthetic chemistry. Here, we report a Ni-catalyzed hydroxylarylation of unactivated alkenes enabled by a ß-diketone ligand with high efficiency and excellent regioselectivity employing molecular oxygen as the oxidant and hydroxyl source. This reaction features mild conditions, broad substrate scope and incredible heterocycle compatibility, providing a variety of ß-hydroxylamides, γ-hydroxylamides, ß-aminoalcohols, γ-aminoalcohols, and 1,3-diols in high yields. The synthetic value of this methodology was demonstrated by the efficient synthesis of two bioactive compounds, (±)-3'-methoxyl citreochlorol and tea catechin metabolites M4.

PHF5A regulates the expression of the DOCK5 variant to promote HNSCC progression through p38 MAPK activation.

BACKGROUND: Previously, we identified an oncogenic splicing variant of DOCK5 in head and neck squamous cell carcinoma (HNSCC); however, the mechanism for the generation of this specific DOCK5 variant remains unknown. This study aims to explore the potential spliceosome genes involved in the production of the DOCK5 variant and validate its role in regulating the progression of HNSCC. METHODS: The differentially expressed spliceosome genes involved in the DOCK5 variant were analysed in The Cancer Genome Atlas (TCGA), and the correlation between the DOCK5 variant and the potential spliceosome gene PHF5A was verified by qRT-PCR. The expression of PHF5A was detected in HNSCC cells, TCGA data and a separate primary tumour cohort. The functional role of PHF5A was examined using CCK-8, colony formation, cell scratch and Transwell invasion assays in vitro and validated in vivo in xenograft models of HNSCC. Western blot analysis was used to explore the potential mechanism of PHF5A in HNSCC. RESULTS: PHF5A was one of the top upregulated spliceosome genes in TCGA HNSCC samples with highly expressed DOCK5 variants. Knockdown or overexpression of PHF5A in HNSCC cells correspondingly altered the level of the DOCK5 variant. PHF5A was highly expressed in tumour cells and tissues and correlated with a worse prognosis of HNSCC. Loss- and gain-of-function experiments demonstrated that PHF5A could promote the proliferation, migration and invasion of HNSCC cells in vitro and in vivo. Moreover, PHF5A inhibition reversed the oncogenic effect of the DOCK5 variant in HNSCC. Western blot analysis showed that PHF5A activated the p38 MAPK pathway, and inhibition of p38 MAPK further reversed the effect of PHF5A on the proliferation, migration and invasion of HNSCC cells. CONCLUSION: PHF5A regulates the alternative splicing of DOCK5 to promote HNSCC progression through p38 MAPK activation, which provides potential therapeutic implications for HNSCC patients.

Integrated analysis of diagnostic, prognostic value and potential drug treatment of GSDME in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSC) poses a global health challenge. Effective biomarkers for early detection are necessary to improve the survival rate of HNSC patient. The purpose of this study was using integrated bioinformatic analysis to investigate the potential biological roles of GSDME in HNSC. METHODS: The Gene Expression Omnibus (GEO) and Cancer Gnome Atlas (TCGA) databases were used to analyze the expression of GSDME in different cancer types. The correlation between GSDME expression and immune cell infiltration or immune checkpoint genes was examined by Spearman correlation analysis. DNA methylation analysis of the GSDME gene was conducted using the MethSurv database. Kaplan-Meier (K-M) survival curves, diagnostic receiver operating characteristic (ROC) curves, nomogram model, and Cox regression analysis were chosen to evaluate the diagnostic and prognostic predictive value of GSDME. Connectivity Map (Cmap) online platform, Protein Data Bank (PDB) database and Chem3D, AutoDock Tool and PyMol software were used to predict and visualize potential molecular drugs aimed for GSDME. RESULTS: GSDME expression level in HNSC was significantly higher than in the controls (p < 0.001). Differentially expressed genes (DEGs) correlation with GSDME were enriched in the GO pathways, such as protein activation cascade, complement activation and classical pathway (p < 0.05). According to GSEA, GSDME-associated differentially expressed genes were significantly enriched in KRAS signaling pathway and cytokine signaling molecule (p < 0.05). There is a significant relation between GSDME expression and immune cell infiltration in HNSC tissues, as well as immune checkpoint genes expression (p < 0.001). DNA methylation status of cg17790129 CpG islands of GSDME gene is correlated with HNSC prognosis (p < 0.05). Based on Cox regression analysis of HNSC patients, GSDME as a potential risk gene has high correlation with overall survival (OS) and disease specific survival (DSS) (p < 0.05). In a ROC curve analysis, HNSC tissues were differentiated from adjacent peritumoral tissues based on GSDME expression levels (AUC = 0.928). Totally six potential drugs targeted for GSDME were screened and the molecular docking tests between GSDME protein and candidate drugs were conducted. CONCLUSIONS: GSDME is a promising therapeutic target as well as a potential clinical biomarker in HNSC patients.

Deep learning-based network pharmacology for exploring the mechanism of licorice for the treatment of COVID-19.

Licorice, a traditional Chinese medicine, has been widely used for the treatment of COVID-19, but all active compounds and corresponding targets are still not clear. Therefore, this study proposed a deep learning-based network pharmacology approach to identify more potential active compounds and targets of licorice. 4 compounds (quercetin, naringenin, liquiritigenin, and licoisoflavanone), 2 targets (SYK and JAK2) and the relevant pathways (P53, cAMP, and NF-kB) were predicted, which were confirmed by previous studies to be associated with SARS-CoV-2-infection. In addition, 2 new active compounds (glabrone and vestitol) and 2 new targets (PTEN and MAP3K8) were further validated by molecular docking and molecular dynamics simulations (simultaneous molecular dynamics), as well as the results showed that these active compounds bound well to COVID-19 related targets, including the main protease (Mpro), the spike protein (S-protein) and the angiotensin-converting enzyme 2 (ACE2). Overall, in this study, glabrone and vestitol from licorice were found to inhibit viral replication by inhibiting the activation of Mpro, S-protein and ACE2; related compounds in licorice may reduce the inflammatory response and inhibit apoptosis by acting on PTEN and MAP3K8. Therefore, licorice has been proposed as an effective candidate for the treatment of COVID-19 through PTEN, MAP3K8, Mpro, S-protein and ACE2.

Short-term outcomes of a new gastrointestinal decompression tube combined with conservative treatment in patients with esophagojejunal anastomotic leakage after total gastrectomy.

To compare the short-term outcomes of a new gastrointestinal decompression tube combined with conservative treatment in patients with esophagojejunal anastomotic leakage (EJAL) after total gastrectomy. We retrospectively analyzed the data of 81 patients with EJAL who had undergone total gastrectomy and Roux-en-Y reconstruction at Fujian Medical University Union Hospital between January 2014 and December 2021. The patients were divided into experimental (12 patients with new gastrointestinal decompression tube plus conservative treatment) and control (69 patients with conservative treatment) groups, according to the different treatment methods they received. Anatomic defect size linearly correlated with time to clinical success, hospital stay, and hospital cost in the control group. The two groups showed no significant differences in anastomotic defect size, time of defect after surgery, hospitalization cost, and time of antibiotic use. However, the time to clinical success was significantly shorter in the experimental group than in the control group (16.0 ± 8.3 vs. 23.6 ± 17.8, P = 0.04), as was the length of hospital stay (30.1 ± 6.3 vs. 36.8 ± 16.7, P = 0.017). Furthermore, when the defect size was ≥ 4 mm, the time to clinical success, hospital stay, and hospital cost in the experimental group were lower than those in the control group (P < 0.05). Placement of a new gastrointestinal decompression tube is a safe treatment. When the defect size is ≥ 4 mm, the time to clinical success, length of hospital stay, and hospital cost can be reduced.

Ligand-enabled Ni-catalyzed hydroarylation and hydroalkenylation of internal alkenes with organoborons.

The transition metal-catalyzed hydrofunctionalization of alkenes offers an efficient solution for the rapid construction of complex functional molecules, and significant progress has been made during last decades. However, the hydrofunctionalization of internal alkenes remains a significant challenge due to low reactivity and the difficulties of controlling the regioselectivity. Here, we report the hydroarylation and hydroalkenylation of internal alkenes lacking a directing group with aryl and alkenyl boronic acids in the presence of a nickel catalyst, featuring a broad substrate scope and wide functional group tolerance under redox-neutral conditions. The key to achieving this reaction is the identification of a bulky 1-adamantyl ß-diketone ligand, which is capable of overcoming the low reactivity of internal 1,2-disubstituted alkenes. Preliminary mechanistic studies unveiled that this reaction undergoes an Ar-Ni(II)-H initiated hydroarylation process, which is generated by the oxidative addition of alcoholic solvent with Ni(0) species and sequential transmetalation. In addition, the oxidative addition of the alcoholic solvent proves to be the turnover-limiting step.

Stem Cell Therapies for Human Infertility: Advantages and Challenges.

Physical and mental health and hormonal imbalance are associated with the problems related to infertility and reproductive disorders. The rate of infertility has increased globally over the years, due to various reasons. Given the psychosocial implications of infertility and its effects on the life of the affected people, there has been an increased focus on its treatment over the last several years. Assisted reproductive technology can only solve about 50% of the cases. Moreover, it contains significant risks and does not solve the fundamental problem of infertility. As pluripotent stem cells have the potential to differentiate into almost any type of cell, they have been widely regarded as a promising option in the development of stem cell-based fertility treatments, which could even correct genetic diseases in offspring. These advancements in reproductive biotechnology present both challenges and possibilities for solving infertility problems caused by various unexplainable factors. This review briefly presents the different types of infertility disorders and the potential applications of stem cells in the treatment of these reproductive diseases.

Biomechanics of extreme lateral interbody fusion with different internal fixation methods: a finite element analysis.

BACKGROUND: Establishing a normal L3-5 model and using finite element analysis to explore the biomechanical characteristics of extreme lateral interbody fusion (XLIF) with different internal fixation methods. METHOD: The L3-5 CT image data of a healthy adult male volunteer were selected to establish a normal lumbar finite element model (M0). The range of motion (ROM) of L3-4 and L4-5, under flexion, extension, left bending, right bending, left rotation, and right rotation, together with L3-4 disc pressure was analyzed. Then the L4-5 intervertebral disc was excised and implanted with a cage, supplemented by different types of internal fixation, including lateral two-hole plate model (M1), lateral four-hole plate model (M2), VerteBRIDGE plating model (M3), lateral pedicle model (M4), posterior unilateral pedicle screw model (M5) and posterior bilateral pedicle screw model (M6). The ROM,the maximum stress value of the cage, and the maximum stress value of the intervertebral disc of L3-4 were analyzed and studied . RESULTS: The ROM of L3-4 and L4-L5 segments in the validation model under various motion states was basically consistent with previous reports. The lumbar finite element model was validated effectively. After XLIF-assisted internal fixation, the range of activity in L3-4 segments of each internal fixation model was greater than that of the normal model under various working conditions, among which the M5、M6 model had the larger range of activity in flexion and extension. After the internal fixation of L4-5 segments, the mobility in M1-M6 was significantly reduced under various motion patterns. In terms of flexion and extension, the posterior pedicle fixation model (M5、M6) showed a significant reduction,followed by M2. The maximal von mises cage stress of M1 was obviously greater than that of other models (except the left bending). Compared with M0, the intervertebral disc stress of M1-M6 at L3-4 segments was increased. CONCLUSIONS: It is recommended that the posterior bilateral pedicle screw model is the first choice, followed by the lateral four-hole plate model for fixation during XLIF surgery. However, it is still necessary to be aware of the occurrence of adjacent segment degeneration (ASD) in the later stage.

MTDH associates with m6A RNA methylation and predicts cancer response for immune checkpoint treatment.

Immune checkpoint blockade (ICB) persistently provides a prognosis improvement but only in a small fraction of patients with cancer due to immunotherapy resistance induced by the consecutive activated oncogenic pathways, including MAPK, Akt, and WNT pathway partially driven by Metadherin (MTDH). However, there is no study to investigate the potential role and mechanisms of MTDH in ICB-treated cancers. Here, we systematically explored the cohorts from The Cancer Genome Atlas (TCGA) and independent cancer cohorts. Elevated MTDH expression was founded to associate with a worse overall survival and poorer immune response in patients with cancer. Dysregulated tumor-infiltrating immune cells and inhibitory immune checkpoint expression were correlated with MTDH expression. Furthermore, the mutual interactions between epithelial-to-mesenchymal-transition, m6A-RNA-methylation, and MTDH may illustrate the potential mechanisms of MTDH resistant to ICB treatment. Although more designed experiments and trials are needed in the future, targeting MTDH may help to overcome immunotherapy resistance in a wide range of cancers.

Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma.

BACKGROUND: Metastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated. METHODS: PLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU's association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis. RESULTS: PLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all p < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU's function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell. CONCLUSIONS: PLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU's oncogene role in HNSCC.