Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer.

BACKGROUND: The development of laparoscopic technology has provided a new choice for surgery of gastric cancer (GC), but the advantages and disadvantages of laparoscopic total gastrectomy (LTG) and laparoscopic-assisted total gastrectomy (LATG) in treatment effect and safety are still controversial. The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC, and to provide a basis for clinical decision-making. AIM: To compare the efficacy of totally LTG (TLTG) and LATG in the context of radical gastrectomy for GC. Additionally, we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique. METHODS: Literature on comparative studies of the above two surgical methods for GC (TLTG group and LATG group) published before September 2022 were searched in the PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. In addition, the following search keywords were used: Gastric cancer, total gastrectomy, total laparoscopy, laparoscopy-assisted, esophagojejunal anastomosis, gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopy assisted/laparoscopically assisted, and esophagojejunostomy/esophagojejunal anastomosis. Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. RESULTS: After layer-by-layer screening, 258 pieces of literature were recovered, and 11 of those pieces were eventually included. This resulted in a sample size of 2421 instances, with 1115 cases falling into the TLTG group and 1306 cases into the LATG group. Age or sex differences between the two groups were not statistically significant, according to the meta-analysis, however the average body mass index of the TLTG group was considerably higher than that of the LATG group (P = 0.01). Compared with those in the LATG group, the incision length in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly lower (P = 0.003), the number of lymph nodes removed was significantly greater (P = 0.04), and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter (P = 0.03 and 0.02, respectively). There were no significant differences in tumor size, length of proximal incisal margin, total operation time, anastomotic time, postoperative pain score, postoperative anal exhaust time, postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage), or overall postoperative complication rate (P > 0.05). CONCLUSION: TLTG and esophagojejunostomy are safe and feasible. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, and faster postoperative recovery, and TLTG is also suitable for obese patients.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study.

BACKGROUND: Early gastric cancer (EGC) is a common malignant tumor of the digestive system, and its lymph node metastasis and survival prognosis have been concerning. By retrospectively analyzing the clinical data of EGC patients, we can better understand the status of lymph node metastasis and its impact on survival and prognosis. AIM: To evaluate the prognosis of EGC patients and the factors that affect lymph node metastasis. METHODS: The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study. There were 561 males and 450 females. The mean age was 58 ± 11 years. The patient underwent radical gastrectomy. The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens. The outcomes were as follows: (1) Lymph node metastasis in EGC patients; (2) Analysis of influencing factors of lymph node metastasis in EGC; and (3) Analysis of prognostic factors in patients with EGC. Normally distributed measurement data are expressed as mean ± SD, and a t test was used for comparisons between groups. The data are expressed as absolute numbers or percentages, and the chi-square test was used for comparisons between groups. Rank data were compared using a nonparametric rank sum test. A log-rank test and a logistic regression model were used for univariate analysis. A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis. The Kaplan-Meier method was used to calculate the survival rate and construct survival curves. A log-rank test was used for survival analysis. RESULTS: Analysis of influencing factors of lymph node metastasis in EGC. The results of the multifactor analysis showed that tumor length and diameter, tumor site, tumor invasion depth, vascular thrombus, and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC (odds ratios = 1.80, 1.49, 2.65, 5.76, and 0.60; 95%CI: 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, and 0.48-0.76, respectively; P < 0.05). Analysis of prognostic factors in patients with EGC. All 1011 patients with EGC were followed up for 43 (0-13) months. The 3-year overall survival rate was 97.32%. Multivariate analysis revealed that age > 60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC (hazard ratio = 9.50, 2.20; 95%CI: 3.31-27.29, 1.00-4.87; P < 0.05). Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged > 60 years and ≤ 60 years were 99.37% and 94.66%, respectively, and the difference was statistically significant (P < 0.05). The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42% and 97.92%, respectively, and the difference was statistically significant (P < 0.05). CONCLUSION: The lymph node metastasis rate of EGC patients was 23.64%. Tumor length, tumor site, tumor infiltration depth, vascular cancer thrombin, and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients. Age > 60 years and lymph node metastasis are independent risk factors for EGC prognosis.

Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK1 receptors.

Chronic primary pain (CPP) occurs in the absence of tissue injury and includes temporomandibular disorders (TMD), fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS). CPP is commonly considered a stress-related chronic pain and often presents as wide-spread pain or comorbid pain conditions in different regions of the body. However, whether prolonged stress can directly result in the development of CPP comorbidity remains unclear. In the present study, we adapted a 21 day heterotypic stress paradigm in mice and examined whether chronic stress induced wide-spread hyperalgesia, modeling comorbid CPP in the clinic. We found that chronic stress induced anxiety- and depression-like behaviors, and resulted in long-lasting wide-spread hyperalgesia over several body regions such as the orofacial area, hindpaw, thigh, upper back and abdomen in female mice. We further found that the expression of cholecystokinin (CCK)1 receptors was significantly increased in the L4-L5 spinal dorsal horn of the female mice after 14 and 21 day heterotypic stress compared with the control animals. Intrathecal injection of the CCK1 receptor antagonist CR-1505 blocked pain hypersensitivity in the subcervical body including the upper back, thigh, hindpaw and abdomen. These findings suggest that the upregulation of spinal CCK1 receptors after chronic stress contributes to the central mechanisms underlying the development of wide-spread hyperalgesia, and may provide a potential and novel central target for clinical treatment of CPP.

A targeting nanoplatform for chemo-photothermal synergistic therapy of small-cell lung cancer.

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

Aluminum scandium nitride on 8-inch Si wafers: material characterization and photonic device demonstration.

The anisotropic optical properties of aluminum scandium nitride (Al1-xScxN) thin films for both ordinary and extraordinary light are investigated. A quantitative analysis of the band structures of the wurtzite Al1-xScxN is carried out. In addition, Al1-xScxN photonic waveguides and bends are fabricated on 8-inch Si substrates. With x = 0.087 and 0.181, the light propagation losses are 5.98 ± 0.11 dB/cm and 8.23 ± 0.39 dB/cm, and the 90° bending losses are 0.05 dB/turn and 0.08 dB/turn at 1550 nm wavelength, respectively.

Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

Calmodulin-like protein MdCML15 interacts with MdBT2 to modulate iron homeostasis in apple.

BTB and TAZ domain proteins (BTs) function as specialized adaptors facilitating substrate recognition of the CUL3-RING ubiquitin ligase (CRL3) complex that targets proteins for ubiquitination in reaction to diverse pressures. Nonetheless, knowledge of the molecular mechanisms by which the apple scaffold protein MdBT2 responds to external and internal signals is limited. Here we demonstrate that a putative Ca 2+ sensor, calmodulin-like 15 (MdCML15), acts as an upstream regulator of MdBT2 to negatively modulate its functions in plasma membrane H+-ATPase regulation and iron deficiency tolerance. MdCML15 was identified to be substantially linked to MdBT2, and to result in the ubiquitination and degradation of the MdBT2 target protein MdbHLH104. Consequently, MdCML15 repressed the MdbHLH104 target, MdAHA8's expression, reducing levels of a specific membrane H+-ATPase. Finally, the phenotype of transgenic apple plantlets and calli demonstrated that MdCML15 modulates membrane H+-ATPase-produced rhizosphere pH lowering alongside iron homeostasis through an MdCML15-MdBT2-MdbHLH104-MdAHA8 pathway. Our results provide new insights into the relationship between Ca2+ signaling and iron homeostasis.

ANGPTL3 accelerates atherosclerotic progression via direct regulation of M1 macrophage activation in plaque.

INTRODUCTION: The N-terminal domain of angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity. Its C-terminal fibrinogen-like (FBN) domain is a ligand of macrophage integrin αvß3. OBJECTIVES: ANGPTL3 might home to plaque where it directly regulates macrophage function via integrin αvß3 for atherosclerosis progression. METHODS: Ldlr-/- mice on a high-fat diet and ApoE-/- mice on a chow diet were received adeno-associated virus (AAV)-mediated Angptl3 gene transfer and followed up for 12 weeks. ApoE-/- mice were injected AAV containing FLAG-tagged Angptl3 cDNA for tracing. Atherosclerotic features were compared between Angptl3-/-ApoE-/- mice and ApoE-/- littermates. THP-1 cells were exposed to 0 or 50 µg/ml ANGPTL3 FBN domain for 24 h to evaluate Toll-like receptor (TLR)4 expression using western blot analysis and circulating cytokine and chemokine profiles by the MILLIPLEX MAP assay. Phospho-proteomic profile was established in ANGPTL3-treated macrophages. Integrin ß3 deficient THP-1 cells were obtained by sgRNAs targeting RGD sequence using Lentivirus-Cas9 system. RESULTS: Angptl3 overexpression increased atherosclerotic progression and CD68+ macrophages in plaque (p < 0.05 for all). By immunostaining, FLAG+ cells were identified in plaque of gene transferred ApoE-/- mice. Fluorescent immunostaining detected co-localisation of Angptl3 and CD68 in plaque macrophages. Phospho-proteomic analysis revealed that Angptl3 induced phosphorylation of proteins that were involved in the IL-17 signalling pathway in THP-1 cells. In vitro, ANGPTL3 treatment increased the production of interleukin (IL)-1ß and tumour necrosis factor-α in THP-1 cells (p < 0.05 for both). Exposure of ANGPTL3 to THP-1 cells induced Akt phosphorylation which was weakened in integrin ß3 deficient ones. ANGPTL3 elevated TLR4 expression via Akt phosphorylation. In response to lipopolysaccharide, nuclear factor-κB activity was 2.2-fold higher in THP-1 cells pre-treated with ANGPTL3 than in untreated cells (p < 0.05). CONCLUSIONS: Targeting ANGPTL3 could yield a dual benefit of lowering lipid levels in the blood and suppressing macrophage activation in plaque.

Growth Differentiation Factor-15 Orchestrates Inflammation-Related Diseases via Macrophage Polarization.

Macrophage polarization is a critical determinant of disease progression and regression. Studies on macrophage plasticity and polarization can provide a theoretical basis for the tactics of diagnosis and treatment for macrophage-related diseases. These include inflammation-related diseases, such as sepsis, tumors, and metabolic disorders. Growth differentiation factor-15 (GDF-15) or macrophage inhibitory cytokine-1, a 25 kDa secreted homodimeric protein, is a member of the transforming growth factor-ß (TGF-ß) superfamily that is released in response to external stressors. GDF-15 regulates biological effects such as tumor occurrence, inflammatory response, tissue damage, angiogenesis, and bone metabolism. It has been shown to exert anti-inflammatory and pro-inflammatory effects in inflammation-related diseases. Moreover, inflammatory stimuli can induce GDF-15 expression in immune and parenchymal cells. GDF-15 exhibits a feedback inhibitory effect by inhibiting tumor necrosis factor-α secretion during the macrophage activation anaphase, suggesting that there may be a close association between the two. GDF-15 directly induces CD14+ monocytes to produce the M2-like macrophage phenotype, inhibits monocyte-derived macrophage for M1-like polarization, and induces monocyte-derived Mφ for M2-like polarization. This review summarizes the macrophage polarization mechanism of GDF-15 under the conditions of sepsis, colon cancer, atherosclerosis, and obesity. An improved understanding of the role and molecular mechanisms of action of GDF-15 could greatly elucidate the mechanism of disease occurrence and development and provide new ideas for targeted disease prevention and treatment. An advanced understanding of the function and molecular mechanisms of action of GDF-15 may be helpful in the assessment of its potential value as a therapeutic and diagnostic target.

Independent prognostic value of CLDN6 in bladder cancer based on M2 macrophages related signature.

M2 macrophages are associated with the prognosis of bladder cancer. CLDN6 has been linked to immune infiltration and is crucial for predicting the prognosis in multi-tumor. The effect of CLDN6 on M2 macrophages in bladder cancer remains elusive. Here, we compared a total of 40 machine learning algorithms, then selected optimal algorithm to develop M2 macrophages-related signature (MMRS) based on the identified M2 macrophages related module. MMRS predicted the prognosis better than other models and associated to immunotherapy response. CLDN6, as an important variable in MMRS, was an independent factor for poor prognosis. We found that CLDN6 was highly expressed and affected immune infiltration, immunotherapy response, and M2 macrophages polarization. Meanwhile, CLDN6 promoted the growth of bladder cancer and enhanced the carcinogenic effect by inducing polarization of M2 macrophages. In total, CLDN6 is an independent risk factor in MMRS to predict the prognosis of bladder cancer.

Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.

Temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) may present as comorbid conditions, but treatment options are ineffective. The purpose of this study was to investigate whether valproate (VPA) attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress, which represents a model of pain associated with TMD and FMS comorbidity, and to explore the potential mechanisms. The results showed that VPA inhibited somatic hyperalgesia induced by orofacial inflammation combined with stress, and down-regulated the interleukin-6 (IL-6) expression in the L4-L5 spinal dorsal horn of female rats. The anti-nociceptive effect of VPA was blocked by single or 5 consecutive day intrathecal administration of recombinant rat IL-6. Orofacial inflammation combined with stress up-regulated the ratio of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) to STAT1 (p-STAT1/STAT1) in the spinal cord. VPA did not affect the STAT1 expression, while it down-regulated the ratio of p-STAT1/STAT1. The expression of STAT3 and the ratio of p-STAT3/STAT3 were not affected by orofacial inflammation combined with stress and VPA treatment. Intrathecal administration of exogenous IL-6 up-regulated the ratio of p-STAT1/STAT1. These data indicate that VPA attenuated somatic hyperalgesia induced by orofacial inflammation combined with stress via inhibiting spinal IL-6 in female rats, and the mechanism may involve the alteration of activation status of spinal STAT1. Thus, VPA may be a new candidate analgesic that targets IL-6 and STAT1 for the treatment of pain associated with the comorbidity of TMD and FMS.

Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Doublecortin-like kinase 3 (DCLK3) is associated with bad clinical outcome of patients with gastric cancer and regulates the ferroptosis and mitochondria function in vitro and in vivo.

BACKGROUND: Doublecortin-like kinase 3 (DCLK3), a member of tubulin superfamily, has been proved to be closely associated with the pathogenesis of numerous human tumors. However, the expression pattern and regulatory mechanisms of DCLK3 in gastric cancer (GC) remain unknown. MATERIALS AND METHODS: DCLK3 expression in GC cells was assessed by RT-qPCR and western blotting. The correlation between DCLK3 levels and the overall survival of GC patients was assessed via TCGA, ACLBI, and Kaplan-Meier plotter databases. Additionally, key proteins (TCF4) involved in the regulation of DCLK3 on GC progression were screened by ACLBI database. Cell proliferation, ferroptotic cell death, and oxidative stress markers were measured by EdU staining, immunofluorescence, ELISA, and western blotting assays. RESULTS: DCLK3 was upregulated in GC, and high DCLK3 expression was significantly associated with poor survival of GC patients. Here, DCLK3 knockdown reduced GC cell proliferation, induced ferroptotic cell death, and exacerbated oxidative stress level. Logistic regression analysis showed that TCF4 was an independent prognostic indicator of GC. Mechanistically, DCLK3 promoted TCF4 expression and subsequently upregulated the expression of TCF4 downstream target genes (c-Myc and Cyclin D1). Furthermore, DCLK3 overexpression enhanced GC cell proliferation, but mitigating ferroptotic cell death and oxidative stress. The regulatory mechanism may involve the upregulation of TCF4, c-Myc, and cyclin D1. CONCLUSIONS: Our research suggests that DCLK3 modulates the levels of iron and reactive oxygen and may involve regulation of TCF4 pathway, thereby promoting the GC cell growth, indicating that DCLK3 may use as a prognostic marker and therapeutic target for GC patients.

Primary Angiosarcoma of the Breast Diagnosed on Core Needle Biopsy: A Diagnostic Challenge.

Primary angiosarcoma of the breast is very rare and difficult to pathologically diagnose especially on core needle biopsy. Only 11 cases of breast primary angiosarcoma diagnosed on core needle biopsy have been reported in English literature of last 5 years. We reported a case of primary angiosarcoma of the breast diagnosed on core needle biopsy and summarized the useful morphological clues in literature which prompted the diagnosis of angiosarcoma. A 50-year-old woman presented with a palpable mass in her left breast for a year. She never received breast surgery or radiotherapy before. Microscopically, the core needle biopsy specimen displayed interanastomosing vascular spaces that dissected through the mammary stroma and adipose tissue. The vascular channels were mostly lined by a single layer of endothelial cells with a mild degree of nuclear atypia, whereas focally, the endothelia were multilayered, with tufting and formation of glomerulus-like structures. CD31, CD34, and ERG immunochemical stain highlighted the endothelial cells lining on the vascular spaces. The Ki67 index was about 10%, and MYC was negative. Primary angiosarcomas have significant overlaps of morphological features with benign and borderline vascular lesions. Anastomosing vascular spaces, cytologic atypia, endothelial mitotic activity, infiltration of glandular parenchyma, elevated Ki-67, and high cellularity are all useful clues to diagnose angiosarcomas. Among them, anastomosing vascular spaces with infiltrated growth pattern especially invasion into the breast intralobular stroma and adipose tissue was the most common character of angiosarcomas which alert the possibility of malignancy in core needle biopsy. However, an accurate diagnosis demands integration of various histological clues and multidisciplinary discussion.

A prospective comparison of a modified miniaturised hand-held epifluorescence microscope and touch imprint cytology for evaluation of axillary sentinel lymph nodes intraoperatively in breast cancer patients.

BACKGROUND: The management of axillary lymph nodes in early-stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro-metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW-M) to assess SLN status intraoperatively for improved diagnostic efficiency. METHODS: A prospective, side-by-side comparison of intraoperative SLN evaluation between MEW-M and TIC was performed. RESULTS: A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW-M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW-M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 2 (classifying results into macro-metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW-M compared with TIC were 0.055 (95% CI, 0.018-0.160) and 0.074 (95% CI, 0.029-0.190) in model 1; and 0.019 (95% CI, 0.003-0.130) vs 0.020 (95% CI, 0.003-0.140) in model 2, respectively. CONCLUSIONS: MEW-M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision-making in axillary surgery.

Predicting subsolid pulmonary nodules before percutaneous needle biopsy: a comparison of artificial neural network and biopsy results.

AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.

Generalized granuloma annulare in an infant clinically manifested as papules and atrophic macules: A case report.

BACKGROUND: Granuloma annulare (GA) has diverse clinical manifestations including papules, plaques, and nodules on the extremities that are skin-colored, pink, or purple. Approximately 15% of all GA cases are considered generalized GA. CASE SUMMARY: Herein, we describe the case of a pediatric patient who initially presented with papules and later developed generalized atrophic macules. Upon examination, two different morphologic lesions were histopathologically confirmed: Epithelioid nodular GA and scattered histiocytic infiltrative GA. This patient exhibited rare clinical manifestations that differed throughout the course of the disease. The varying histopathological types and clinical manifestations of GA may be linked to the different stages of the disease. CONCLUSION: This rare case demonstrates the different histopathological features of different stages and clinical manifestations of granuloma annulare in an infant.

Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in laryngeal squamous carcinoma.

In order to construct a prognostic model of ferroptosis-related lncRNA associated with laryngeal carcinoma and to investigate its prognostic value, RNA sequencing, genomic mutation, and clinical data of laryngeal squamous carcinoma patients were collected from the TCGA database. Patients were randomly divided into train and test groups. Cox regression analysis and lasso regression analysis were performed on the data of patients in the training group, and their independent prognostic effect was validated in the test group and the whole cohort. Data from 123 laryngeal squamous carcinoma patients in the TCGA database were collected. According to previous literature, 484 ferroptosis-related genes were collected, and 912 ferroptosis-related lncRNAs were obtained by co-expression. Cox models suggested six lncRNAs involved in ferroptosis (AC083862.2, CYTOR, AC114296.1, LINC02768, GATA2-AS1, CTB-178M22.2). Patients were divided into high-risk and low-risk groups based on median risk scores. Kapkan-Meier survival curve results showed a statistical difference in survival between the high- and low-risk groups. Receiver operating characteristic curves and principal component analysis demonstrated the high accuracy of the model. Univariate and multifactorial Cox regression analyses and column plots demonstrated risk scores as independent prognostic factors. The distribution of prognostic marker risk scores was correlated with clinical staging. Immune infiltration studies suggested the model was associated with immune checkpoints and multiple immune functions. GATA2-AS1 was able to promote cell proliferation, cell migration, and cell invasion. This study identified six lncRNAs associated with ferroptosis in laryngeal squamous carcinoma as prognostic predictors, which may be promising biomarkers involved in the treatment of laryngeal squamous carcinoma.

Value of ctDNA methylation biomarkers in diagnosis of colorectal tumors.

Tweetable abstract DNA methylation alterations have been identified as promising biological markers for early-stage colorectal cancer detection. Here, the authors highlight some recent advances in DNA methylation and its role in the early diagnosis and overall disease course management of colorectal tumors. New insights into DNA methylation biomarkers for colorectal cancer early diagnosis and management are discussed.

CLDN6 inhibits colorectal cancer proliferation dependent on restraining p53 ubiquitination via ZO-1/PTEN axis.

Colorectal cancer (CRC) is one of the most common cancers in the world. Abnormal proliferation is a chief characteristic of cancer and is the initiation of CRC progression. As an important component of tight junctions, CLDN6 regulates the proliferation of multiple tumors. Our previous study showed that CLDN6 was low expressed in CRC, and CLDN6 overexpression inhibited CRC proliferation. However, the specific mechanism of how CLDN6 works remains unclear. This research aimed to reveal the relationship between CLDN6 and clinical features, as well as the molecular mechanism by which CLDN6 inhibited CRC proliferation. We found that low expression of CLDN6 was associated with pathological grade and prognosis of CRC patients, and confirmed that CLDN6 inhibited CRC proliferation dependent on p53. Mechanically, we elucidated that CLDN6 regulated ubiquitination to enhance p53 stability and nuclear import by PTEN/AKT/MDM2 pathway. Through the PDZ-binding motif (PBM), CLDN6 bound to ZO-1 to interact with PTEN, and regulate AKT/MDM2 pathway. Collectively, our data enriched the theoretical basis for CLDN6 as a potential biomarker for diagnosis, therapy and prognosis of CRC.