Reversal of T-cell exhaustion: Mechanisms and synergistic approaches.

T cells suffer from long-term antigen stimulation and insufficient energy supply, leading to a decline in their effector functions, memory capabilities, and proliferative capacity, ultimately resulting in T cell exhaustion and an inability to perform normal immune functions in the tumor microenvironment. Therefore, exploring how to restore these exhausted T cells to a state with effector functions is of great significance. Exhausted T cells exhibit a spectrum of molecular alterations, such as heightened expression of inhibitory receptors, shifts in transcription factor profiles, and modifications across epigenetic, metabolic, and transcriptional landscapes. This review provides a comprehensive overview of various strategies to reverse T cell exhaustion, including immune checkpoint blockade, and explores the potential synergistic effects of combining multiple approaches to reverse T cell exhaustion. It offers new insights and methods for achieving more durable and effective reversal of T cell exhaustion.

Branched-Chain Amino Acids in Liver Diseases: Complexity and Controversy.

Branched-chain amino acids (BCAAs), as essential amino acids, engage in various physiological processes, such as protein synthesis, energy supply, and cellular signaling. The liver is a crucial site for BCAA metabolism, linking the changes in BCAA homeostasis with the pathogenesis of a variety of liver diseases and their complications. Peripheral circulating BCAA levels show complex trends in different liver diseases. This review delineates the alterations of BCAAs in conditions including non-alcoholic fatty liver disease, hepatocellular carcinoma, cirrhosis, hepatic encephalopathy, hepatitis C virus infection, and acute liver failure, as well as the potential mechanisms underlying these changes. A significant amount of clinical research has utilized BCAA supplements in the treatment of patients with cirrhosis and liver cancer. However, the efficacy of BCAA supplementation in clinical practice remains uncertain and controversial due to the heterogeneity of studies. This review delves into the complicated relationship between BCAAs and liver diseases and tries to untangle what role BCAAs play in the occurrence, development, and outcomes of liver diseases.

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.

Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure. METHODS: The whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335). RESULTS: Anlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels. CONCLUSIONS: CircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Investigation of the Association between Air Pollution and Non-Alcoholic Fatty Liver Disease in the European Population: A Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent chronic liver disease worldwide. At the same time, the relationship between air pollution and the likelihood of developing NAFLD has been a subject of debate due to conflicting findings in previous observational research. Our objective was to examine the potential correlation between air pollutant levels and the risk of NAFLD in the European population by employing a two-sample Mendelian randomization (MR) analysis. The UK Biobank Consortium provided the summary statistics for various air pollution indicators (PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2, and NOx). Additionally, information on NAFLD was obtained from three studies, including one derivation set and two validation sets. Heterogeneity, pleiotropy, and sensitivity analyses were performed under different MR frameworks, and instrumental variables associated with confounders (such as education, smoking, alcohol, and BMI) were detected by tools. In the derivation set, causal relationships between PM2.5, NO2, and NAFLD were observed in univariable Mendelian randomization (UVMR) (Odds Ratio (OR) = 1.99, 95% confidence interval (95% CI) = [1.22-3.22], p = 0.005; OR = 2.08, 95% CI = [1.27-3.40], p = 0.004, respectively). After adjustment for air pollutants or alcohol intake frequency in multivariable Mendelian randomization (MVMR), the above genetic correlations disappeared. In validation sets, the null associations remained in UVMR. Our findings from MR analysis using genetic data did not provide evidence for a causal association between air pollution and NAFLD in the European population. The associations observed in epidemiological studies could be partly attributed to confounders.

A highly sensitive and specific Homo1-based real-time qPCR method for quantification of human umbilical cord mesenchymal stem cells in rats.

BACKGROUND: Owing to the characteristics of easier access in vitro, low immunogenicity, and high plasticity, human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered as a promising cell-based drugs for clinical application. No internationally recognized technology exists to evaluate the pharmacokinetics and distribution of cell-based drugs in vivo. METHODS: We determined the human-specific gene sequence, Homo1, from differential fragments Homo sapiens mitochondrion and Rattus norvegicus mitochondrion. The expression of Homo1 was utilized to determine the distribution of UC-MSCs in the normal and diabetic nephropathy (DN) rats. RESULTS: We observed a significant correlation between the number of UC-MSCs and the expression level of Homo1. Following intravenous transplantation, the blood levels of UC-MSCs peaked at 30 min. A large amount of intravenously injected MSCs were trapped in the lungs, but the number of them decreased rapidly after 24 h. Additionally, the distribution of UC-MSCs in the kidneys of DN rats was significantly higher than that of normal rats. CONCLUSIONS: In this study, we establish a highly sensitive and specific Homo1-based real-time quantitative PCR method to quantify the distribution of human UC-MSCs in rats. The method provides guidelines for the safety research of cells in preclinical stages.

Nanoparticle Targeting in Chemo-Resistant Ovarian Cancer Reveals Dual Axis of Therapeutic Vulnerability Involving Cholesterol Uptake and Cell Redox Balance.

Platinum (Pt)-based chemotherapy is the main treatment for ovarian cancer (OC); however, most patients develop Pt resistance (Pt-R). This work shows that Pt-R OC cells increase intracellular cholesterol through uptake via the HDL receptor, scavenger receptor type B-1 (SR-B1). SR-B1 blockade using synthetic cholesterol-poor HDL-like nanoparticles (HDL NPs) diminished cholesterol uptake leading to cell death and inhibition of tumor growth. Reduced cholesterol accumulation in cancer cells induces lipid oxidative stress through the reduction of glutathione peroxidase 4 (GPx4) leading to ferroptosis. In turn, GPx4 depletion induces decreased cholesterol uptake through SR-B1 and re-sensitizes OC cells to Pt. Mechanistically, GPx4 knockdown causes lower expression of the histone acetyltransferase EP300, leading to reduced deposition of histone H3 lysine 27 acetylation (H3K27Ac) on the sterol regulatory element binding transcription factor 2 (SREBF2) promoter and suppressing expression of this key transcription factor involved in the regulation of cholesterol metabolism. SREBF2 downregulation leads to decreased SR-B1 expression and diminished cholesterol uptake. Thus, chemoresistance and cancer cell survival under high ROS burden obligates high GPx4 and SR-B1 expression through SREBF2. Targeting SR-B1 to modulate cholesterol uptake inhibits this axis and causes ferroptosis in vitro and in vivo in Pt-R OC.

Acousto-optofluidic 3D single cell imaging of macrophage phagocytosis of Pseudomonas Aeruginosa.

Understanding how immune cells such as monocytes or macrophages within our blood and tissue engulf and destroy foreign organisms is important for developing new therapies. The process undertaken by these cells, called phagocytosis, has yet to be observed in real-time at the single cell level. Microfluidic-based imaging platforms offer a wide range of tools for precise fluid control and biomolecule manipulation that makes regulating long term experiments and data collection possible. With the compatibility between acoustofluidics and light-sheet fluorescent microscopy (LSFM) previously demonstrated, here an acousto-optfluidic device with on-chip fluid flow direction control was developed. The standing surface acoustic waves (SSAWs) were used to trap, load and safeguard individual cells within a highly controllable fluid loop, created via the triggering of on-chip PDMS valves, to demonstrate multiple rounds of live single cell imaging. The valves allowed for the direction of the fluid flow to be changed (between forward and reverse operation) without altering the inlet flow rate, an important factor for performing reproducible and comparable imaging of samples over time. With this high-resolution imaging system, volumetric reconstructions of phagocytosed bacteria within macrophages could be resolved over a total of 9 rounds of imaging: totalling 19 reconstructed images of the cell membrane with visible intracellular bacteria.

Metabolic characteristics of granulosa cell tumor: role of PPARγ signaling†.

Granulosa cell tumors are relatively rare, posing challenges for comprehension and therapeutic development due to limited cases and preclinical models. Metabolic reprogramming, a hallmark of cancer, manifests in granulosa cell tumors with notable lipid accumulation and increased expression of peroxisome proliferator-activated receptor gamma (PPARγ), a key lipid metabolism regulator. The roles of these features, however, remain unclear. In our previous work, we established a granulosa cell tumor model in mice by introducing a constitutively active Pik3ca mutant in oocytes, enabling the study of predictable tumor patterns from postnatal day 50. In this study, we characterized metabolic alterations during tumorigenesis (postnatal day 8 to day 50) and tumor growth (day 50 to day 65) in this model and explored the impact of PPARγ antagonism on human granulosa cell tumor proliferation. The tumor exhibited significant lipid accumulation, with PPARγ and the proliferation marker Ki67 co-localizing at postnatal day 65. Transcriptome analysis demonstrates that pathways for lipid metabolism and mitochondrial oxidation are promoted during tumorigenesis and tumor growth, respectively. Overlappingly upregulated genes during tumorigenesis and tumor growth are associated with lipid metabolism pathways. Correspondingly, mouse granulosa cell tumor shows overexpression of peroxisome proliferator-activated receptor gamma and DGAT2 proteins at postnatal day 65. Furthermore, GW9662 reduces the proliferation of KGN human granulosa cell tumor cells and decreases the phosphorylation of AKT and SMAD3. Our findings identify metabolic abnormalities in ooPIK3CA* granulosa cell tumor model and suggest peroxisome proliferator-activated receptor gamma as a potential driver for primary granulosa cell tumor growth.

The genomic and immune landscapes of gastric cancer and their correlations with HER2 amplification and PD-L1 expression.

BACKGROUND: Anti-PD1/PD-L1 antibody plus human epidermal growth factor receptor 2 (HER2) antibody and chemotherapy have become the new first-line therapy for HER2 overexpression-positive advanced gastric cancers (GC), suggesting that HER2 and PD-L1 play a vital role in guiding systemic treatment for patients with GC. This study aimed to depict the genomic and immune landscapes of Chinese patients with GC and investigate their correlations with HER2 amplification and PD-L1 expression. PATIENTS AND METHODS: Next-generation targeted sequencing and PD-L1 immunohistochemistry were performed on tumor samples from 735 patients with pathologically diagnosed GC. The genomic and immune landscapes and their correlations with HER2 amplification and PD-L1 expression were analyzed. RESULTS: The most commonly mutated genes in Chinese GC were TP53 (64%), CDH1 (20%), ARID1A (18%), HMCN1 (15%), KMT2D (11%), and PIK3CA (11%). Seventy-six (10%) patients were HER2 amplification, and 291 (40%) had positive PD-L1 expression. Classifying the total population based on HER2 amplification and PD-L1 expression level, 735 patients were divided into four subgroups: HER2+/PD-L1+ (4.5%), HER2+/PD-L1- (5.9%), HER2-/PD-L1+ (35.1%), and HER2-/PD-L1- (54.5%). The HER2+/PD-L1- and HER2+/PD-L1+ subgroups exhibited dramatically higher rate of TP53 mutations, CCNE1 and VEGF amplifications. The HER2+/PD-L1- subgroup also had a markedly higher rate of MYC amplification and KRAS mutations. The HER2-/PD-L1+ subgroup had significantly higher rate of PIK3CA mutations. HER2+/PD-L1- subgroup had the highest TMB level and HER2-/PD-L1+ subgroup had the highest proportion of patients with microsatellite instability-high than other subgroups. Furthermore, we observed that different HER2 amplification levels had distinct impacts on the correlations between PD-L1 expression and therapeutic genomic alterations, but no impact on the prognosis. CONCLUSION: The combination of HER2 amplification and PD-L1 expression in Chinese patients with GC could stratify the total populations into several subgroups with distinctive genomic and immune landscapes, which should be considered when making personalized treatment decisions.

Non-coding RNA methylation modifications in hepatocellular carcinoma: interactions and potential implications.

RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies. Video Abstract.

Utilization and short-term outcomes of percutaneous left atrial appendage occlusion in patients with cancer.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) has been rapidly evolving since FDA's approval in 2015 and has become more of a same-day-discharge procedure. Cancer patient with atrial fibrillation/flutter (AF) population can benefit from the procedure but the in-hospital outcomes and readmission data were rarely studied. OBJECTIVES: We investigated the utilization, in-hospital and readmission outcomes in cancer patients with AF who underwent LAAO. METHODS: Data were derived from the National Inpatient Sample and National Readmissions Database from 2016 to 2019. Patients with primary diagnosis of AF admitted for LAAO (ICD-10 code 02L73DK) were grouped by cancer as a secondary diagnosis. We assessed in-hospital mortality, length of stay, total hospital charges, and complications. Thirty-day readmission rates were compared. RESULTS: LAAO was performed in 60,380 patients with AF and 3% were cancer patients. There were no differences in in-hospital mortality and total hospital charges; however, cancer patients tended to have longer hospital stay (1.59 ± 0.11 vs. 1.32 ± 0.02, p = 0.013). Among complications, cancer patients had higher rates in open or percutaneous pericardial drainage (adjusted odds ratio [aOR] 2.38; 95% confidence interval [CI] 1.19-4.76) and major bleeding events (aOR 7.07; 95% CI 1.82-27.38). There was no statistical significance of 30-day readmission rates between patients with and without cancer (10.0% vs. 9.1%, p = 0.34). The most common readmission reason in cancer patients was gastrointestinal bleeding. CONCLUSIONS: LAAO is a promising procedure in cancer patients complicated by AF with contraindication to anticoagulation. Readmission rate is comparable between patients with and without cancer.

Clinical status and future prospects of single-incision robotic-assisted surgery: a review.

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.

Conductive, water-retaining and knittable hydrogel fiber from xanthan gum and aniline tetramer modified-polysaccharide for strain and pressure sensors.

Herein, we explored strategies for defoaming and controllable adjustment of spinnable and mechanical properties of polyanion polysaccharide-based hydrogels to fabricate conductive, water-retaining, and knittable hydrogel fibers for next-generation flexible electronics. Xanthan gum (XG) and aniline tetramer modified-polysaccharide (TMAT38) were crosslinked with sodium trimetaphosphate (STMP) and subsequently by Fe3+/Fe2+ ions coordination to prepare conductive and spinnable hydrogels. Polypropylene glycol was introduced as chemical antifoam, and solvent displacement method was adopted to improve mechanical and water-retaining properties. The glycerol-immersed XG5-TMAT38-STMP-Fe3+/CA-PPG hydrogel exhibited conductivity of 3.55×10-3-27.30×10-3 S/cm, storage modulus at linear viscoelastic region of 573 Pa-1717 Pa and self-healing percentage of 100 %-108 %. The 2 h glycerol-immersed hydrogel fibers with good flexibility, moisture retention and freezing tolerance were ready to bend and knit into fabrics. The hydrogel fiber braid possessed better conductivity, reliability and durability than the single hydrogel fiber as strain sensors. The hydrogel fiber fabric perceived tiny vibration triggered by swallowing, speaking and writing with good sensitivity and reproducibility. Furthermore, a three-component model was developed to evaluate response sensitivity and recoverability of the hydrogel fiber fabric-based pressure sensors, which facilitated understanding transient response of polymer-based hydrogel strain and pressure sensors.

Covalent organic framework functionalized smart membranes with under-liquid dual superlyophobicity for efficient separation of oil/water emulsions.

The smart membrane with under-liquid dual superlyophobicity, which can achieve on-demand separation of oil/water emulsions only by simple liquid pre-wetting, is of essential value for the treatment of complicated real oil/water systems. Here, we first fabricated a stable suspension of imine-linked covalent organic framework nanospheres (TPB-DMTP-COF), and subsequently fabricated COF functionalized smart membranes with under-liquid dual superlyophobicity by immersing polyacrylonitrile-based (PAN-based) membranes into TPB-DMTP-COF nanosphere suspension. Accordingly, effective switchable separation of both oil-in-water and water-in-oil emulsions by TPB-DMTP-COF/PAN membranes can be achieved by employing pre-wetting processes (both the oil contact angle under water and the water contact angle under oil are over 150°). Specifically, the separation flux and the separation efficiency are higher than 1200 L/m2‧h and 98.0 %, and 2100 L/m2‧h and 97.4 % for the surfactant-stabilized oil-in-water and water-in-oil emulsions, respectively. Furthermore, the ultralow adhesions in liquid contributed to the outstanding reusability and antifouling resistance of the prepared TPB-DMTP-COF/PAN membranes. This work provides a feasible approach for fabricating a smart membrane with under-liquid dual superlyophobicity for oily wastewater treatment.

Single-incision robotic assisted surgery: a nonrandomized cohort pilot study on a novel surgical platform in colorectal surgery.

BACKGROUND: The technological barriers and steep learning curve of single-incision laparoscopic surgery had kept it from further applications. A literature review had reported that robotic technology could preserve its advantages while simplifying its difficulties. This nonrandomized cohort pilot study aims to evaluate the feasibility and safety of single-incision robotic assisted colorectal surgery based on a novel robotic surgical platform, the SHURUI Endoscopic Surgical Robotic System (SR-ENS-600). METHOD: This study enrolled 7 patients with colorectal malignancy who underwent single-incision robotic assisted surgery (SIRAS) at a tertiary general surgery center, and retrospectively included 23 patients who underwent robotic assisted surgery from September 2015 to June 2016 and 35 patients who underwent single-incision laparoscopic surgery from June 2017 to March 2018, which were labeled as the initial in-learning-curve attempts from the same surgical team. The technological feasibility and safety of SIRAS were evaluated. Perioperative outcomes, short-term postoperative outcomes, clinicopathologic outcomes, and follow-up were reported. RESULTS: Six SIRAS operations were completed successfully without eventful intraoperative complications, except for one operation that encountered a large-volume of intraoperative hemorrhage. Two SIRAS cases were converted to multiport laparoscopic surgery because of intraoperative hemorrhage and difficulty in retraction. Postoperative pathology reported satisfactory specimen qualities. There were no short-term postoperative complications, no short-term mortality, no tumor recurrence, or metastasis reported. There was one incisional hernia reported half a year after operation. Patients with advanced staging were sent to standard evaluation and chemotherapy, and follow-up is still on-going. CONCLUSIONS: SIRAS can be feasibly performed by a skilled surgical team via the SR-ENS-600 platform for strictly-selected patients, which provides preferable instrument maneuverability and stability in confined surgical fields and overcomes the technical difficulty of multisite dissection through a single-incision. Large-volume investigations and high-level evidences are required to further validate its safety and superiority.

Utility of adjuvant radioactive iodine therapy after reoperation in papillary thyroid carcinoma with cervical lymph node recurrence.

PURPOSE: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. MATERIALS AND METHODS: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RESULTS: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. CONCLUSIONS: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.

3D Printing Model of a Patient's Specific Lumbar Vertebra.

Selective dorsal rhizotomy (SDR) is a difficult, risky, and sophisticated operation, in which a laminectomy should not only expose an adequate surgical field of view but also protect the patient's spinal nerves from injury. Digital models play an important role in the pre-and intra-operation of SDR, because they can not only make doctors more familiar with the anatomical structure of the surgical site, but also provide precise surgical navigation coordinates for the manipulator. This study aims to create a 3D digital model of a patient-specific lumbar vertebra that can be used for planning, surgical navigation, and training of the SDR operation. The 3D printing model is also manufactured for more effective work during these processes. Traditional orthopedic digital models rely almost entirely on computed tomography (CT) data, which is less sensitive to soft tissues. Fusion of the bone structure from CT and the neural structure from magnetic resonance imaging (MRI) is the key element for the model reconstruction in this study. The patient's specific 3D digital model is reconstructed for the real appearance of the surgical area and shows the accurate measurement of inter-structural distances and regional segmentation, which can effectively help in the preoperative planning and training of SDR. The transparent bone structure material of the 3D-printed model allows surgeons to clearly distinguish the relative relationship between the spinal nerve and the vertebral plate of the operated segment, enhancing their anatomical understanding and spatial sense of the structure. The advantages of the individualized 3D digital model and its accurate relationship between spinal nerve and bone structures make this method a good choice for preoperative planning of SDR surgery.

Differential expression of serum mir-363-3p in patients with polycystic ovary syndrome and its predictive value for their pregnancy.

BACKGROUND: This study aimed to investigate the expression of serum miR-363-3p in patients with polycystic ovary syndrome (PCOS) and its predictive value for pregnancy after ovulation induction therapy. METHODS: The expression of serum miR-363-3p was detected by Reverse transcription quantitative polymerase chain reaction (RT-qPCR). PCOS patients were treated with ovulation induction therapy, and after the successful pregnancy was confirmed, they were followed up for 1 year in outpatient department to record the pregnancy outcomes of the patients. The Pearson correlation coefficient was used to evaluate the correlation between the expression level of miR-363-3p and biochemical indicators of PCOS patients. Logistic regression analysis was used to analyze the risk factors of pregnancy failure after ovulation induction therapy. RESULTS: The serum level of miR-363-3p in PCOS group was significantly lower than that in control group. Compared with the control group, both pregnant and non-pregnant groups had lower miR-363-3p levels, while the non-pregnant group had a greater reduction in miR-363-3p levels than the pregnant group. Low levels of miR-363-3p showed high accuracy in distinguishing pregnant and non-pregnant patients. Logistic regression analysis showed that high levels of luteinizing hormone, testosterone (T), prolactin (PRL) and low level of miR-363-3p were independent risk factors for pregnancy failure after ovulation induction in PCOS patients. Additionally, compared with pregnancy outcomes of healthy women, the incidence of premature delivery, macrosomia, and gestational diabetes in PCOS patients increased. CONCLUSIONS: The expression of miR-363-3p in PCOS patients was reduced and correlated with abnormal hormone levels, suggesting that miR-363-3p may be involved in the occurrence and development of PCOS.