The integration of single-cell and bulk RNA-seq atlas reveals ERS-mediated acinar cell damage in acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. METHODS: A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways' activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein-protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. RESULTS: In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. CONCLUSION: We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Epidemiological features and a survival nomogram for primary lymphoma of the male genital tract.

Primary lymphoma of the male genital tract (PLMGT) is rare, and data on its epidemiology and prognosis are lacking. Our study aimed to estimate the incidence and develop a predictive nomogram for PLMGT. We pooled the incidence and survival data of PLMGT over the last 20 years from the Surveillance, Epidemiology, and End Results (SEER) database. Incidence rates were calculated by year of diagnosis, age, race, and histology. Independent prognostic factors selected by Cox regression analysis were used to develop a nomogram for predicting overall survival (OS). Our study enrolled 1312 patients with PLMGT. The overall incidence rate of PLMGT was 0.437/1,000,000 during 2000-2019. OS was associated with age, marital status, histological subtype, Ann Arbor stage, and therapeutic strategy, which were used to construct nomograms to predict 1-, 3-, and 5-year OS rates. Receiver operating characteristic curves, calibration plots, and decision curve analysis showed good performance of the nomogram. Based on the total score of each patient from the nomogram, the patients were clustered into three risk groups, and the risk stratification model was more successful in predicting clinical outcomes than the traditional Ann Arbor staging system. The incidence rate of PLMGT has remained relatively stable over the past two decades. For the OS of patients with PLMGT, we established a novel predictive nomogram involving all independent risk factors obtained from the SEER database and developed a corresponding risk classification system that showed better predictive performance than the Ann Arbor staging system.

Kidney cancer with thyroid metastasis combined with thyroid carcinoma, a case report.

BACKGROUND: Thyroid cancer is the most common malignant tumor of the endocrine system. There have been some reports on kidney cancer with thyroid metastasis. However, kidney cancer has rarely been detected during thyroid cancer surgery. CASE PRESENTATION: We present a rare case of kidney cancer with thyroid metastasis, combined with thyroid carcinoma. A 66-year-old woman was admitted to our hospital in September 2021 due to enlarged left thyroid nodules for two years. The patient was diagnosed with a left thyroid nodule on physical examination in 2012. Extended radical resection of the thyroid cancer was performed. Intraoperatively, two thyroid lesions were identified. Thus, the patient was definitively diagnosed with kidney cancer with thyroid metastasis and papillary thyroid carcinoma. Furthermore, two metastatic nodules due to kidney cancer and one metastatic lymph node lesion due to thyroid cancer were found in the loose connective tissue adjacent to the thyroid. CONCLUSIONS: Kidney cancer with thyroid metastasis and thyroid carcinoma rarely co-occur, and it is difficult to identify the primary tumor. Although clinical examination methods are increasingly updated, the past medical history and physical examination are still very important.

Lung nodule pre-diagnosis and insertion path planning for chest CT images.

Medical image processing has proven to be effective and feasible for assisting oncologists in diagnosing lung, thyroid, and other cancers, especially at early stage. However, there is no reliable method for the recognition, screening, classification, and detection of nodules, and even deep learning-based methods have limitations. In this study, we mainly explored the automatic pre-diagnosis of lung nodules with the aim of accurately identifying nodules in chest CT images, regardless of the benign and malignant nodules, and the insertion path planning of suspected malignant nodules, used for further diagnosis by robotic-based biopsy puncture. The overall process included lung parenchyma segmentation, classification and pre-diagnosis, 3-D reconstruction and path planning, and experimental verification. First, accurate lung parenchyma segmentation in chest CT images was achieved using digital image processing technologies, such as adaptive gray threshold, connected area labeling, and mathematical morphological boundary repair. Multi-feature weight assignment was then adopted to establish a multi-level classification criterion to complete the classification and pre-diagnosis of pulmonary nodules. Next, 3-D reconstruction of lung regions was performed using voxelization, and on its basis, a feasible local optimal insertion path with an insertion point could be found by avoiding sternums and/or key tissues in terms of the needle-inserting path. Finally, CT images of 900 patients from Lung Image Database Consortium and Image Database Resource Initiative were chosen to verify the validity of pulmonary nodule diagnosis. Our previously designed surgical robotic system and a custom thoracic model were used to validate the effectiveness of the insertion path. This work can not only assist doctors in completing the pre-diagnosis of pulmonary nodules but also provide a reference for clinical biopsy puncture of suspected malignant nodules considered by doctors.

Expression Levels of MicroRNA-300/BCL2L11 in Papillary Thyroid Cancer and Their Clinical Diagnostic Values.

INTRODUCTION: This research aims to explore the expression levels of microRNA (miRNA)-300/BCL-2-like protein 11 (BCL2L11) and their values in the clinical diagnosis of papillary thyroid cancer (PTC). METHODS: Pathological tissues that were surgically removed for thyroid disease were selected. miR-300 and BCL2L11 expression levels in the samples were measured. Receiver operating characteristic (ROC) curves were plotted to analyze miR-300 and BCL2L11 predictive values for PTC. Upon silencing miR-300 and silencing BCL2L11 in PTC cells, the corresponding miR-300 and BCL2L11 expression levels were tested, followed by examining PTC cell activities. The targeting relationship of miR-300 and BCL2L11 was detected by the bioinformatics website and luciferase activity assay. RESULTS: miR-300 expression levels were elevated and BCL2L11 expression levels were reduced in PTC tissues. miR-300 and BCL2L11 expression levels in PTC tissues had a correlation with TNM stage and lymph node metastasis. The results of ROC curve revealed that both miR-300 and BCL2L11 had clinical predictive values for PTC. Mechanistically, miR-300 negatively regulated BCL2L11. The functional assays unveiled that silencing miR-300 impeded PTC cell activities, and silencing BCL2L11 induced PTC cell activities. In the rescue experiment, silencing BCL2L11 reversed the impacts of silencing miR-300 on PTC cell development. CONCLUSION: This study underlines that miR-300 expression is increased and BCL2L11 expression is declined in PTC. miR-300 and BCL2L11 both have clinical predictive values for diagnosing PTC.

Evaluation of a Precision Approach to Intraoperative Ropivacaine Nerve Block to Improve Postoperative Analgesia in 120 Patients Undergoing Thyroid Surgery.

BACKGROUND This study aimed to compare a precision approach to intraoperative nerve block with traditional analgesia to reduce postoperative pain in 120 patients during thyroid surgery. The precision intraoperative technique used 0.3% ropivacaine to block the lower branch of the transverse cervical nerve and the inner branches of the supraclavicular nerve. MATERIAL AND METHODS A total of 120 patients were prospectively enrolled in this study. All patients were randomly and evenly divided into 3 groups. In the precision group, 0.3% ropivacaine was used through the wound during surgery. In the traditional group, a superficial cervical plexus nerve block was performed before surgery. Saline was injected in the control group. The valuation of postoperative pain was assessed using the visual analogue scale (VAS). RESULTS Two hours after surgery, the VAS scores in the precision group, traditional group, and control group were 1.4±0.5, 1.6±0.7, and 2.8±1.0 (P<0.001), respectively. Then, the pain improvement was more significant after 6 h, as the VAS scores in the precision, traditional, and control groups were 1.0±0.5, 1.2±0.6, and 2.6±1.1 (P<0.001), respectively. Twenty-four hours after surgery, the VAS scores in the precision, traditional, and control groups were 0.7±0.3, 0.6±0.4, and 1.9±1.1 (P<0.001), respectively. CONCLUSIONS At a single center, the use of a precision intraoperative ropivacaine nerve block significantly reduced postoperative pain when compared with traditional analgesia for patients undergoing thyroid surgery.

Dual effect of IL-7/IL-7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis.

The IL-7/IL-7R pathway plays a vital role in the immune system, especially in the inflammatory response. Monocytes/macrophages (osteoclast precursors) have been recently recognized as important participants in the osteoclastogenesis of rheumatoid arthritis (RA) patients. Here, we aimed to investigate the therapeutic potential of IL-7/IL-7R pathway in RA and to determine whether it could restrain osteoclastogenic functions and therefore ameliorate RA. Firstly, collagen-induced arthritis (CIA) mice were administered with IL-7Rα-target antibodies to assess their therapeutic effect on arthritis. We found that blockade of the IL-7/IL-7R pathway protected CIA mice from bone destruction in addition to inducing inflammatory remission, by altering the RANKL/RANK/OPG ratio and consequently decreasing osteoclast formation. To explore the effect and mechanism of this pathway, bone marrow cells were induced to osteoclasts and treated with IL-7, a STAT5 inhibitor or supernatants from T cells. The results showed that the IL-7/IL-7R pathway played a direct inhibitory role in osteoclast differentiation via STAT5 signalling pathway in a RANKL-induced manner. We applied flow cytometry to analyse the effect of IL-7 on T-cell RANKL expression and found that IL-7/IL-7R pathway had an indirect role in the osteoclast differentiation process by enhancing the RANKL expression on T cells. In conclusion, the IL-7/IL-7R pathway exhibited a dual effect on osteoclastogenesis of CIA mice by interacting with osteoimmunology processes and could be a novel therapeutic target for autoimmune diseases such as RA.

Identification of Significant Genes and Pathways in Acute Pancreatitis via Bioinformatical Analysis.

BACKGROUND AND AIMS: Acute pancreatitis (AP) is one of the common acute abdominal diseases with complicated pathogenesis. The purpose of this study is to identify the differentially expressed genes (DEGs) in the pancreas and underlying mechanisms. METHODS: Gene expression profiles of GSE109227 and GSE65146 were available from GEO database. Then, an integrated analysis of these genes was performed, including gene ontology (GO) and KEGG pathway enrichment analysis, protein-protein interaction (PPI) network construction, core gene correlation analysis, transcription factors (TFs) prediction, and expression level evaluation in human organs. RESULTS: A total number of 92 differential expressed genes were screened from the datasets, including 81 up-regulated genes and 11 down-regulated genes. The up-regulated genes were mainly enriched in the biological process, such as sarcomere organization, actin cytoskeleton organization, tumor necrosis factor biosynthetic process, response to cytokine, cell-cell adhesion, and the cell migration, and also involved in some signaling pathways, including leukocyte transendothelial migration, proteoglycans in cancer, thyroid cancer, cell adhesion, tight junction, bladder cancer, amoebiasis, glycerolipid metabolism, and VEGF signaling pathway, while down-regulated genes were significantly enriched in the endoplasmic reticulum unfolded protein response, the oxidation-reduction, and no significant signaling pathways. CDH1 and CLDN4 were identified as core genes by PPI network analysis with MCODE plug-in, as well as GO and KEGG re-enrichment. For validation in Gene Expression Profiling Interactive Analysis (GEPIA), CDH1 and CLDN4 were interacting with each other and regulated by the predictive common TFs FOXP3 or USF2. The two core genes and USF2 were expressed in varied human organs including the pancreas, while FOXP3 was not detected in the normal human pancreatic tissues. CONCLUSIONS: This study implied that core gene CDH1 and CLDN4, which might be regulated by FOXP3 or USF2, played a significant role in acute pancreatitis. They could be potential diagnostic and therapeutic targets for AP patients.

Prognostic value of the creatinine-albumin ratio in acute pancreatitis debridement.

BACKGROUND: Increases in the levels of serum C-reactive protein (CRP) and creatinine (Cr) and decreases in those of albumin (Alb) are commonly observed in acute pancreatitis (AP). We aimed to evaluate the efficacy of the Cr/Alb and CRP/Alb ratios in the prediction of surgical treatment effect in AP patients. METHODS: This study retrospectively analyzed clinical data obtained from 140 AP patients who underwent debridement from January 2008 to November 2018 in Shanghai Ruijin Hospital. The Cr/Alb and CRP/Alb ratios at admission and before surgery were assessed in the analysis of clinical statistics, prediction of prognoses, and logistic regression analysis. RESULTS: The admission Cr/Alb had the best predictive value of the four ratios. This value was significantly higher in patients with re-operation and those who died (P < 0.05) and was correlated with the Acute Physiology and Chronic Health Evaluation (APACHE II) score, admission CRP/Alb, preoperative Cr/Alb, and post-operative complications. The admission Cr/Alb could predict the risk of AP-related re-operation and mortality with sensitivities, specificities and areas under the curve of 86.3%, 61.7% and 0.824, and 73.4%, 81.3% and 0.794, respectively. At a cut-off value of 3.43, admission Cr/Alb values were indicative of a worse clinical state, including impaired laboratory test values, APACHE II scores, rates of post-operative complications and re-operation, and mortality (P < 0.05). In the logistic regression analysis, admission Cr/Alb values were independently related to the APACHE II score, post-operative renal failure, and mortality. CONCLUSION: Cr/Alb is a novel but promising, easy-to-measure, reproducible, non-invasive prognostic score for the prediction of the effect of debridement in AP patients.

The mTOR-RUNX1 pathway regulates DC-SIGN expression in renal tubular epithelial cells.

Renal tubular epithelial cells (RTECs) play pivotal roles in the innate immune response in kidneys. Dendritic cell specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) functions as both the innate immune recognition receptor and the adhesion molecule. In our previous study, we found that DC-SIGN expression was induced in RTECs during renal inflammation. However, the underlying mechanism remains unclear. Here, we used the human renal proximal tubular epithelial cell lines (HK-2) to investigate the mechanism of TNF-α-induced expression of DC-SIGN. Our results showed that TNF-α up-regulated the expressions of DC-SIGN and Runt-related transcription factor 1 (RUNX1) in a time-dependent manner and that it up-regulated DC-SIGN promoter-driven luciferase activity in a dose-dependent manner. The mTOR inhibitor rapamycin and mTOR siRNA blocked the TNF-α-induced up-regulation of DC-SIGN expression. Meanwhile, DC-SIGN expression was also inhibited by RUNX1 siRNA and its inhibitor Ro5-3335. In addition, both mTOR and RUNX1 inhibitors attenuated TNF-α-induced the increase in DC-SIGN promoter-driven luciferase activity. Finally, we found that HK-2 cells exposed to rapamycin or mTOR siRNA reduced the TNF-α-induced up-regulation of RUNX1. In conclusion, these results indicated that the mTOR-RUNX1 pathway participates in the regulation of TNF-α-induced DC-SIGN expression in RTECs.

Analysis of risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a study of 268 patients.

BACKGROUND: To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. METHODS: We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. RESULTS: Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). CONCLUSION: Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.

Paeoniflorin ameliorates collagen-induced arthritis via suppressing nuclear factor-κB signalling pathway in osteoclast differentiation.

Paeoniflorin (PF), extracted from the root of Paeonia lactiflora Pall, exhibits anti-inflammatory properties in several autoimmune diseases. Osteoclast, the only somatic cell with bone resorbing capacity, was the direct cause of bone destruction in rheumatoid arthritis (RA) and its mouse model, collagen-induced arthritis (CIA). The objective of this study was to estimate the effect of PF on CIA mice, and explore the mechanism of PF in bone destruction. We demonstrated that PF treatment significantly ameliorated CIA through inflammatory response inhibition and bone destruction suppression. Furthermore, PF treatment markedly decreased osteoclast number through the altered RANKL/RANK/OPG ratio and inflammatory cytokines profile. Consistently, we found that osteoclast differentiation was significantly inhibited by PF through down-regulation of nuclear factor-κB activation in vitro. Moreover, we found that PF suppressed nuclear factor-κB activation by decreasing its translocation to the nucleus in osteoclast precursor cells. Taken together, our new findings provide insights into a novel function of PF in osteoclastogenesis and demonstrate that PF would be a new therapeutic modality as a natural agent for RA treatment and other autoimmune conditions with bone erosion.

Intravenous Vitamin C attenuates hemorrhagic shock-related renal injury through the induction of SIRT1 in rats.

To investigate the effect of intravenous Vitamin C (VC) on hemorrhagic shock (HS)-associated rat renal injury and the involved mechanism. Thirty SD rats were randomly assigned to the sham surgery (sham), hemorrhagic shock (HS), HS+100 mg/kg VC (H + VL), HS+500 mg/kg VC (H + VH) and HS+100 mg/kg VC + EX527 (H + VL + E) groups. Tissue and blood samples were collected 6 h after surgery. Kidney pathological changes were scored. Creatinine (CRE), blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels in serum and Vitamin C levels and superoxide dismutase (SOD) activity and the ability to suppress hydroxyl radical (RAFHR) in plasma were measured. The expression of Sirtuin1 (SIRT1), Acetyl-NF-κB (Ace-NF-κB), heme oxygenase-1 (HO-1), TNF-α, and IL-1ß in tissues was analyzed by ELISA or western-blot. In the HS group, the kidney pathological score and CRE, BUN, TNF-α, and IL-1ß levels in serum were significantly higher than in the Sham group (P < 0.05), while SOD and RAFHR were significantly decreased in the plasma (P < 0.05). SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group (P < 0.05), while MDA, TNF-α, and IL-1ß concentrations and Acetyl-NF-κB andHO-1 expression in the kidney showed a noteworthy increase compared to the Sham group (P < 0.05). Compared to the HS group, VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α, and IL-1ß levels (P < 0.05), and a significant increase in Vitamin C, SOD, and RAFHR levels in the plasma (P < 0.05). Additionally, MDA, TNF-α, IL-1ß and Acetyl-NF-κB expression levels were decreased in the kidney (P < 0.05), while SOD, SIRT1 and HO-1 levels were notably enhanced. There were no differences between the H + VL and H + VH groups aside from plasma Vitamin C levels. The effect of Vitamin C was decreased after the addition of EX527, which inhibits SIRT1. Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway, and it appears that there were no differences in the effects between the high and low doses.

Citric acid promotes SPARC release in pancreatic cancer cells and inhibits the progression of pancreatic tumors in mice on a high-fat diet.

Over the years, pancreatic cancer has experienced a global surge in incidence and mortality rates, largely attributed to the influence of obesity and diabetes mellitus on disease initiation and progression. In this study, we investigated the pathogenesis of pancreatic cancer in mice subjected to a high-fat diet (HFD) and observed an increase in citric acid expenditure. Notably, citrate treatment demonstrates significant efficacy in promoting tumor cell apoptosis, suppressing cell proliferation, and inhibiting tumor growth in vivo. Our investigations revealed that citrate achieved these effects by releasing secreted protein acidic and rich in cysteine (SPARC) proteins, repolarizing M2 macrophages into M1 macrophages, and facilitating tumor cell apoptosis. Overall, our research highlights the critical role of citric acid as a pivotal metabolite in the intricate relationship between obesity and pancreatic cancer. Furthermore, we uncovered the significant metabolic and immune checkpoint function of SPARC in pancreatic cancer, suggesting its potential as both a biomarker and therapeutic target in treating this patient population.

The significance of short-term preoperative calcium and activated vitamin D3 supplementation in thyroidectomy: a randomized trial and prospective study.

Objective: The aim was to explore the effects of preoperative calcium and activated vitamin D3 supplementation on post-thyroidectomy hypocalcemia and hypo-parathyroid hormone-emia (hypo-PTHemia). Methods: A total of 209 patients were randomly divided into control group (CG) and experimental group (EG). Oral calcium and activated vitamin D3 supplementation were preoperatively administered to EG, whereas a placebo was administered to CG. Data on serum calcium, phosphorus, and PTH concentrations before operation, on postoperative day 1 (POPD1), at postoperative week 3 (POPW3), and on the length of postoperative hospitalization were collected. Results: The serum calcium, phosphorus, and PTH concentrations, as well as the incidence of postoperative hypocalcemia and hypo-PTHemia, did not significantly differ between EG and CG. Subgroup analysis revealed that the serum calcium concentrations of the experimental bilateral thyroidectomy subgroup (eBTS) on POPD1 and POPW3 were higher than that of the control bilateral thyroidectomy subgroup (cBTS) (P < 0.05); the reduction of serum calcium in eBTS on POPD1 and POPW3 was less than those in cBTS (P < 0.05). However, significant differences were not observed between the unilateral thyroidectomy subgroups (UTS) (P > 0.05). Moreover, the incidence of postoperative hypocalcemia in cBTS on POPD1 was significantly higher than that in eBTS (65.9% vs 41.7%) (P < 0.05). The length of hospitalization in cBTS (3.55 ± 1.89 days) was significantly longer than that (2.79 ± 1.15 days) in eBTS (P < 0.05). Conclusion: Short-term preoperative prophylactic oral calcium and activated vitamin D3 supplementation could effectively reduce the incidence of postoperative hypocalcemia and decrease the length of postoperative hospitalization in patients who have undergone bilateral thyroidectomy.

Clinical Efficacy of Intraoperative Ultrasound for Prophylactic Lymphadenectomy of the Lateral Cervical Neck in Stage CN0 Papillary Thyroid Cancer: A Prospective Study.

Background: To evaluate the clinical effectiveness of lateral cervical region (LCR) lymphadenectomy as a preventative procedure for stage CN0 papillary thyroid cancer (PTC).Methods: From December 2019 to October 2021, 108 patients with CN0 stage PTC hospitalized to our general surgery department were recruited. After analysis, the clinical data of these patients were separated into two groups: 57 cases were in the Surgical + lymphatic dissection group and 51 instances were in the surgical group. Total thyroidectomy with central node dissection (TTCD) was carried out on the surgical group, whereas intraoperative ultrasound (IOUS) for prophylactic LCR lymph nodes dissection was carried out on the basis of TTCD in the Surgical + lymphatic dissection group. The postoperative complications, cervical lymph node metastases and recurrent reoperation were analyzed in both groups.Results: In the Surgical + lymphatic dissection group, the rate of lymph node metastasis (LNM) identified by IOUS in the LCR of PTC was 29.82% (17/57). In the central group with >2 lymph node metastases compared to the central group with < 2 lymph node metastases, the rate of LCR LNM was considerably greater (20% vs. 43%). Between the two groups, there was no statistically significant difference in the frequency of postoperative complications (P > 0.05). At the 1-year postoperative follow-up, the recurrence rate in the surgical group was 13.73%, whereas there was no recurrence in the Surgical + lymphatic dissection group.Conclusions: The recurrence/reoperation rate of PTC in individuals with stage CN0 can be decreased by IOUS guided prophylactic lymph node dissection in the LCR.

Generation and characterization of iPS cell line (SYSUSHi002-A) from PBMCs of an AML patient with TP53 mutation.

We have generated an iPSCs line (IPS-AML2-C3, SYSUSHi002-A) from AML cells of a 71-year-old male Acute Myeloid Leukaemia patient with TP53 gene mutation (TP53: c.824G > A, p.Cys275Tyr) using episomal plasmids encoding the factors OCT4, SOX2, KLF4, L-MYC and human miR-302. The IPS-AML2-C3 (SYSUSHi002-A) iPSC line displayed typical embryonic stem cell-like morphology, carried the TP53 gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY), and was capable of forming three germ layer cells in vitro.

Prior skeleton based online deep reinforcement learning for coronary artery centerline extraction.

Coronary centerline extraction is an essential technique for X-ray coronary angiography (XCA) image analysis, which provides qualitative and quantitative guidance for percutaneous coronary intervention (PCI). In this paper, an online deep reinforcement learning method for coronary centerline extraction is proposed based on the prior vascular skeleton. Firstly, with XCA image preprocessing (foreground extraction and vessel segmentation) results, the improved ZhangSuen image thinning algorithm is used to rapidly extract the preliminary vascular skeleton network. On this basis, according to the spatial-temporal and morphological continuity of the angiography image sequence, the connectivity of different branches is determined using k-means clustering, and the vessel segments are then grouped, screened, and reconnected to obtain the aorta and its major branches. Finally, using the previous results as prior information, an online Deep Q-Network (DQN) reinforcement learning method is proposed to optimize each branch simultaneously. It comprehensively considers grayscale intensity and eigenvector continuity to achieve the combination of data-driven and model-driven without pre-training. Experimental results on clinical images and the third-party dataset demonstrate that the proposed method can accurately extract, restructure, and optimize the centerline of XCA images with a higher overall accuracy than the existing state-of-the-art methods.

An exploratory research on antitumor effect of drug-eluting slow-releasing electrospinning membranes.

Objective: To evaluate the long-term inhibition of malignant biliary tumor growth using paclitaxel (PTX)-covered polycaprolactone (PCL) electrospun membranes. Methods: A mixture of PCL, a material used to fabricate polymer stents, and PTX, a widely used chemotherapeutic agent, was synthesized by electrospinning. After preparing the drug-eluting membrane, drug release and fiber degradation were assessed in vitro under different pH conditions. The QBC939 cholangiocarcinoma cell line was cultured to establish a xenograft nude mouse model. Finally, the drug-eluting membrane was implanted into the mouse model, and the relative tumor inhibition rate was evaluated. Results: A new PTX-loaded PCL electrospun fiber membrane was developed. The drug release rate was about 20-40% in the 32-day release cycle, and the release quantity was between 20 and 170 mg. As pH decreased, the release rate increased significantly. The degradation rate of the fiber membranes in vitro was approximately 20-48%, and was positively correlated with the drug loading rate. In animal experiments, the growth of tumors in mice was suppressed using drug-eluting membranes. Conclusion: The PTX-loaded PCL electrospun fiber membrane enhanced the long-term drug release and exhibited excellent antitumor effects in vivo.

Molecular testing raises thyroid nodule fine needle aspiration diagnostic value.

Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16%-24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n=335), 9.6% (n=44), 2.8% (n=13), 4.8% (n=22), and 0.4% (n=2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V-VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III-IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.