Background:Tumor deposits (TDs), nodules in the peritumoral adipose tissue with no architectural residue of lymph node, have previously been described in colorectal adenocarcinomas with poor prognosis. However, the significance of TD has not been fully investigated in patients with papillary thyroid carcinoma (PTC). Method:We retrospectively enrolled 541 patients undergoing surgery between 2015 and 2021. The patients were classified into two groups according to TD status (TD vs non-TD), and the clinicopathologic characteristics and disease-free survival (DFS) were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the primary cohort's prognostic factors for DFS. A nomogram was constructed for clinicians as a quantitative tool for estimating DFS. Result:In our cohort, TD were identified in 16.1% of patients and had higher rate of aggressive features, including microscopic and gross extrathyroidal extension, invasion of the recurrent laryngeal nerve and esophagus, prevertebral fascia involvement or encasement of the carotid artery/internal jugular vein, extranodal extension, advanced clinical stage, tumor recurrence and distant metastasis (all P < 0.05). Univariate and multivariate Cox regression analyses confirmed TD as an independent prognostic factor for DFS, with a 2.501-fold increased risk of recurrence (P < 0.001). The nomogram, incorporating TD and other significant factors, demonstrated good discrimination and calibration (C-index = 0.79). Conclusion:The presence of TD was significantly associated with poor prognosis in PTC patients. TD showed promising efficacy as a potential prognostic indicator for PTC patients.

Background. Approximately 25% of patients with stage III colorectal cancer experience liver metastasis after radical resection; however, there is currently a lack of methods to predict liver metastasis. This study aims to develop and validate a pathomics nomogram to predict liver metastasis in patients with stage III colorectal cancer. Methods. A total of 318 enrolled patients were divided into three cohorts: a training cohort (n = 139), a validation cohort (n = 69), and an external cohort (n = 110). A competitive risk nomogram was established by the pathomics signature and clinicopathological characteristics and assessed by calibration, discrimination, and clinical usefulness. Results. A significant correlation between the pathomics signature and liver metastasis in stage III colorectal cancer was found. Multivariate Fine-Gray analysis indicated that preoperative carcinoembryonic antigen level, postoperative chemotherapy, and pathomics signature were independent predictors of liver metastasis. A competitive risk nomogram was developed to predict liver metastasis in patients with stage III colorectal cancer. The predicting nomogram shows good discrimination and calibration, with C-indexes of 0.811 (95% confidence interval [CI] 0.651-0.971), 0.759 (95% CI 0.531-0.987), and 0.845 (95% CI 0.641-0.999), with area under the receiver operating characteristic (AUROC) curves at 5 years of 0.833 (95% CI 0.742-0.925), 0.760 (95% CI 0.652-0.893), and 0.812 (95% CI 0.692-0.931) in the training, validation, and external cohorts, respectively. Compared with the clinicopathological nomogram, the nomogram combined with the pathomics signature had better performance (AUROC 0.823 [95% CI 0.764-0.881] vs. 0.678 [95% CI 0.606-0.751]; p < 0.001). Conclusions. The pathomics signature is a predictive indicator for liver metastasis in patients with stage III colorectal cancer, and the integrated nomogram can be used to predict liver metastasis better than the clinicopathological nomogram alone.

Purpose Inflammation is recognized as a hallmark of Hashimoto’s thyroiditis (HT). Although inflammation is an important pathogenic factor that leads to thyroid follicular epithelial cell injury after HT, anti-inflammatory treatments remain controversial in the management of HT. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of HT remain ambiguous.Methods The current study investigated the genes and pathways involved in HT by transcriptome sequencing analysis. Furthermore, western blot assays, ELISA and immunohistochemical staining were conducted to validate the expression levels of dysregulated proteins.Results HT was found to be associated with the enrichment of genes related to the inflammatory response, pyroptosis, and regulation of the lipid metabolic process. Further analysis revealed that genes associated with the interleukin (IL)-18 signaling pathway and the NLRP3 inflammasome were upregulated, and the expression levels of the IL-18, NLRP3, and APOC1 proteins were increased.Conclusion The transcriptome data obtained from HT patient samples revealed notable genes and pathways that may be novel therapeutic targets for the treatment of HT.

Objectives: This study explores the correlation between serum cholesterol, interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and post-intracerebral hemorrhage (post-ICH) depression in patients with acute ICH. Methods: 35 patients with acute primary supratentorial ICH were recruited. Serum cholesterol, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC), IL-10, and MIF were measured in the first morning after admission. Additionally, a 24-item Hamilton Depression Scale (HAMD-24) was used to detect depressive symptoms one week after admission. HAMD scores > 8 indicated a diagnosis of post-ICH depression. Results: The levels of TC were significantly lower in ICH patients with depression compared to those without [169.26(139.23-215.67) mg/dL vs. 200.46(182.81-224.74) mg/dL, P = 0.010]. Similarly, levels of LDLC [102.18(78.39-137.28) mg/dL vs. 135.14(120.22-170.63) mg/dL, P = 0.001] and IL-10 [17.56 (16.03-22.52) pg/mL vs. 31.17(23.42-37.53) pg/mL, P = 0.001] were also lower in patients with postICH depression. Furthermore, the levels of TC (r = -0.433, P = 0.009), TG (r = -0.345, P = 0.043), LDLC (r = -0.549, P = 0.001), and IL-10 levels (r = -0.603, P < 0.001) showed negative correlations with the HAMD scores. Logistic regression analysis indicated that higher IL-10 levels (OR = 0.847, 95 % CI = 0.71 7-0.999, P = 0.049) were indicative of protection against post-ICH depression in the acute phase. Conclusion: Lower levels of TC, LDLC, and IL-10 were associated with post-ICH depression during the acute phase. Furthermore, decreased levels of IL-10 may serve as a promising predictor for post-ICH depression. (c) 2024 International Hemorrhagic Stroke Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license.

Objective: To evaluated the safety and feasibility of dissection of lymph nodes posterior to right recurrent laryngeal nerve (ⅥB compartment) in endoscopic thyroidectomy through gasless axillary posterior approach. Methods: A total of 350 cases with right lobe papillary thyroid carcinoma (PTC) who underwent endoscopic lobectomy, isthmusectomy and central compartment neck dissection via gasless axillary posterior approach based at the Department of General Surgery, Nanfang Hospital, Southern Medical University from June 2020 to December 2022 were retrospectively analyzed. Summarize the clinical, pathological characteristics, and postoperative complications of the patients. SPSS 25.0 was used for statistical analysis of the data. Results: All 350 patients underwent endoscopic surgery successfully, with no conversion to open surgery. There were 303 females and 47 males, with an average age of (36.3±9.2) years. Of those, 287 patients were in pT1a stage, 62 in pT1b stage, and one patient in pT2 stage. There was no T3 or T4 stage patient. The mean numbers of yielded lymph nodes in right central compartment and ⅥB compartment were 8.11±4.65 (range, 1-31) and 2.62±1.86 (range, 1-12), respectively. ⅥB compartment metastasis was detected in 52 (14.86%) of 350 patients. The incidence of transient recurrent laryngeal nerve injury was 0.86%(3/350). Postoperative hematoma occurred in three patients (0.86%). Conclusion: The dissection of ⅥB compartment in endoscopic thyroidectomy through gasless axillary posterior approach is safe and feasible in selected PTC patients.

Objective To investigate the safety and effectiveness of establishing a transaxillary lumpectomy space for lumpectomy thyroid surgery without inflatable posterior approach based on the deep cervical fascial anatomy.Methods The clinical data of 276 consecutive patients admitted to the Department of Thyroid Hernia Surgery,Southern Hospital of Southern Medical University from June to December 2021 who underwent transaxillary lumpectomy thyroid surgery were retrospectively analyzed,and the surgical space was established based on fascial anatomy.Intraoperative and postoperative conditions were observed and recorded,and follow-up was performed on the second day after surgery and at 3 and 6months after surgery.Results The operative time was 80.5（60-115） min and the operative space was established in 18（12-26） min.Intraoperative bleeding was 5（1-15） mL.There were 2 cases of intraoperative extra-jugular venous and genera expenditure blood and 1 case of intraoperative anterior jugular vein bleeding.The postoperative hospital stay was 2.5（1-4） d.Sensory recovery scores in the clavicular region were assessed on the second postoperative day:221（80.1%） S3,55（19.9%） S2,no S4,S3+,S1 or S0 cases;3 months postoperatively:245（88.8%） S3+/S4,30（10.9%） S3 and 1（0.4%） S2;6 months postoperatively:270（97.8%） S3+/S4,6（2.2%） S2,no postoperative flap area effusion.Follow-up was completed in all cases.Two patients had temporary hoarseness after surgery and voice was restored at the 3-month postoperative follow-up.There were no postoperative lymphatic fistulas,Horner’s syndrome,postoperative bleeding or swelling of the sternocleidomastoid muscle,and no recurrent cases.Conclusion The fascial anatomy-based method of transaxillary uninflated lumpectomy thyroid surgery space creation is safe and effective and can be used as a routine method.

Background In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. Methods The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. Result After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto’s thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). Conclusion Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.

Background: Inferior mesenteric artery lymph node (station 253 node) metastasis occurs in approximately 0.3% to 13.9% of rectal cancer patients. This study examined whether carbon nanoparticles could aid in harvesting more station 253 nodes and evaluated the relationship between the number of station 253 nodes retrieved and station 253 node metastasis. Method: A total of 480 consecutive rectal cancer patients were enrolled in this prospective cohort study between August 2014 and October 2018. Ninety-one patients (18.96%) received a preoperative submucosal injection of carbon nanoparticles (CN+ group), and 389 patients did not receive an injection (CN- group). The number of lymph node retrievals was analyzed, and the relevant risk factors for station 253 node metastasis were identified using univariate and multivariate analyses. Results: The mean number of station 251, 252, and 253 lymph nodes and total lymph nodes retrieved in the CN+ group were higher than that retrieved in the CN- group. The percentage of patients with >= 4 station 253 nodes retrieved (54.0% vs 28.3%, P = .004) were higher in the CN+ group than in the CNgroup. Retrieval of >= 4 station 253 nodes was an independent risk factor for station 253 node metastasis (OR: 2.40, 95% CI: 1.22-4.74, P = .012). Conclusion: The preoperative submucosal injection of carbon nanoparticles was helpful for increasing the number of station 253 nodes harvested, and a minimum of 4 examined station 253 nodes was necessary for standard D3 lymph node dissection in rectal cancer. (C) 2021 Elsevier Inc. All rights reserved.

Excessive keratinocyte apoptosis leads to impaired wound healing. Recently, advanced oxidation protein products (AOPP) have been recognized as a marker of oxidative stress and a potent inducer of apoptosis. Previously, we have demonstrated that extracellular AOPP accumulation induced keratinocyte apoptosis, and we discovered that autophagy was involved. To further elucidate the role and mechanism of autophagy in AOPP-induced-apoptosis of keratinocytes, we treated HaCaT cells with increasing concentrations of AOPP-human serum albumin or with AOPP-human serum albumin for increasing durations. Cyto-ID solution staining was used to assess cell autophagy using confocal laser scanning microscopy. Autophagy-related protein interactions were investigated using western blot analysis. Exposure of HaCaT cells to AOPP decreased the expression of mammalian target of rapamycin (mTOR) and increased the expression of autophagy-related proteins Beclin-l and LC3, and eventually led to autophagy. Furthermore, an autophagy agonist significantly decreased the expression of apoptosis-related proteins. Taken together, we showed that accumulation of extracellular AOPP induced autophagy in HaCaT cells via a reactive oxygen species-dependent, mTOR-Beclin-1-mediated pathway, and that excessive autophagy-mediated apoptosis, which resulted in delayed wound healing.

BACKGROUND:Transanal total mesorectal excision (TaTME) allows patients with ultralow rectal cancer to be treated with sphincter-saving surgery. However, accurate delineation of the distal resection margin (DRM), which is essential to achieve R0 resection for low rectal cancer in TaTME, is technically demanding.AIM:To assess the feasibility of optical biopsy using probe-based confocal laser endomicroscopy (pCLE) to select the DRM during TaTME for low rectal cancer.METHODS:A total of 43 consecutive patients who were diagnosed with low rectal cancer and scheduled for TaTME were prospectively enrolled from January 2019 to January 2021. pCLE was used to determine the distal edge of the tumor as well as the DRM during surgery. The final pathological report was used as the gold standard. The diagnostic accuracy of pCLE examination was calculated.RESULTS:A total of 86 pCLE videos of 43 patients were included in the analyses. The sensitivity, specificity and accuracy of real-time pCLE examination were 90.00% [95% confidence interval (CI): 76.34%-97.21%], 86.96% (95%CI: 73.74%-95.06%) and 88.37% (95%CI: 79.65%-94.28%), respectively. The accuracy of blinded pCLE reinterpretation was 86.05% (95%CI: 76.89%-92.58%). Furthermore, our results show satisfactory interobserver agreement (κ = 0.767, standard error = 0.069) for the detection of cancer tissue by pCLE. There were no positive DRMs (≤ 1 mm) in this study. The median DRM was 7 mm [interquartile range (IQR) = 5-10 mm]. The median Wexner score was 5 (IQR = 3-6) at 6 mo after stoma closure.CONCLUSION:Real-time in vivo pCLE examination is feasible and safe for selecting the DRM during TaTME for low rectal cancer (clinical trial registration number: NCT04016948).

Anastomotic ischemia can affect healing and eventually lead to anastomotic leakage, and confocal laser endomicroscopy (CLE) can offer detailed observations at the subcellular level. We aimed to evaluate the anastomotic microcirculation in different anastomotic perfusion models using CLE. Anastomotic perfusion models were established using twelve rabbits distributed into two groups: group A (good perfusion, n = 6) and group B (poor perfusion, n = 6). Afterward, intraoperative detection of anastomotic perfusion was carried out using CLE, and quantitative analysis of blood cells was performed. Rabbits that satisfied the criteria underwent a second exploratory operation and specimens were stained by hematoxylin and eosin. Enhanced with fluorescein sodium, capillaries were obviously highlighted in group A, while few capillaries were viewed in group B. Delayed development of fluorescence occurred in group B. The average flow of blood cells was 37.0 ± 5.93 per minute in group A and 6.33 ± 2.16 per minute in group B (p < 0.001). In addition, during the second exploratory surgery, rabbits with inadequate anastomotic perfusion exhibited more serious intestinal adhesion and ischemia. Anastomotic leakage and abdominal infection occurred in all rabbits in group B. CLE can realize real-time imaging of the anastomotic microcirculation and is a feasible technique for performing intraoperative evaluation in different anastomotic perfusion situations. This animal experiment provides the groundwork for future in vivo research in humans.

Background The relationship between collagen features (CFs) in the tumor microenvironment and the treatment response to neoadjuvant chemoradiotherapy (nCRT) is still unknown. This study aimed to develop and validate a perdition model based on the CFs and clinicopathological characteristics to predict the treatment response to nCRT among locally advanced rectal cancer (LARC) patients. Methods In this multicenter, retrospective analysis, 428 patients were included and randomly divided into a training cohort (299 patients) and validation cohort (129 patients) [7:3 ratio]. A total of 11 CFs were extracted from a multiphoton image of pretreatment biopsy, and a support vector machine (SVM) was then used to construct a CFs-SVM classifier. A prediction model was developed and presented with a nomogram using multivariable analysis. Further validation of the nomogram was performed in the validation cohort. Results The CFs-SVM classifier, which integrated collagen area, straightness, and crosslink density, was significantly associated with treatment response. Predictors contained in the nomogram included the CFs-SVM classifier and clinicopathological characteristics by multivariable analysis. The CFs nomogram demonstrated good discrimination, with area under the receiver operating characteristic curves (AUROCs) of 0.834 in the training cohort and 0.854 in the validation cohort. Decision curve analysis indicated that the CFs nomogram was clinically useful. Moreover, compared with the traditional clinicopathological model, the CFs nomogram showed more powerful discrimination in determining the response to nCRT. Conclusions The CFs-SVM classifier based on CFs in the tumor microenvironment is associated with treatment response, and the CFs nomogram integrating the CFs-SVM classifier and clinicopathological characteristics is useful for individualized prediction of the treatment response to nCRT among LARC patients.

Objective To investigate the role of Helicobacter pylori (HP) on the regulation of NF-κB/IL-17 signaling, mechanisms underlying apoptosis in human megakaryocyte cell lines Dami. Methods Firstly, the mouse model of immune thrombocytopenia (ITP) was established. Then, the mice were subjected to gastric perfusion with HP. Next, the changes in platelet and bone marrow megakaryocyte classification were assessed in each group. Human megakaryocyte Dami cells were treated with HP in vitro for 3, 6, or 9 h; and the rates of apoptosis in each group were then evaluated with flow cytometry. Fluorescent quantitative PCR and Western blotting were implemented for assessing the expression of Bcl-2 and Bax, which are related to apoptosis, and p65, which is associated with the NF-κB pathway. The expression of these proteins was also evaluated after treatment with PDTC, an inhibitor of the NF-κB pathway inhibitor. Results In vivo, exogenous administration of HP was found to increase the optical density value for the anti-HP antibody in HP-infected BALB/c mice. Meanwhile, the platelet counts in the HP-infected ITP mice model were significantly reduced compared with non-infected ITP mice. In vitro, the apoptotic rate of Dami cells increased gradually with the prolongation of the exposure to HP; the most noticeable change was at 6 h, and there was a significant difference between 0 h and 6 h. The expression of Bax, p-p65, and IL-17 also increased progressively with the prolongation HP exposure, while the expression of anti-apoptotic Bcl-2 protein decreased gradually, especially at 6 h, and the expression of total p65 did not change significantly compared with baseline. Anecdotally, these effects were reversed by the application of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling. Conclusion HP can promote platelet destruction in ITP mice, and the underlying mechanisms may be related to accelerating apoptosis of megakaryocytes by the activation of the NF-κB/IL-17 pathway.

The cure of acute leukemia by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is closely linked to major complications leading to adverse outcomes, including graft-versus-host disease (GVHD), disease relapse and death. This study retrospectively investigated a consecutive series of 312 adult patients with acute leukemia receiving allo-HSCT by using a novel concept of GVHD-free/relapse-free survival (GRFS), and further evaluated the impact of clinical factors on GRFS. Results indicated that the 1- and 2-year GRFS were 54.8% and 51.5%, respectively. In multivariable analysis, recipient age > 35 years (HR 1.676; p = 0.006), diagnosis of acute lymphoblastic leukemia (HR 1.653; p = 0.027) and acute biphenotypic leukemia (HR 2.175; p = 0.010), advanced disease (HR 2.702; p < 0.001), and donor age > 35 years (HR 1.622; p = 0.008) were significantly associated with inferior GRFS post-HSCT. GRFS of haploidentical-related donor transplant was comparable to that of matched sibling donor or matched unrelated donor transplant. Furthermore, prophylactic donor lymphocyte infusion (DLI) had an overall beneficial effect on GRFS (HR 0.645, p = 0.044). Collectively, with a better understanding of these significant prognostic factors which impacted on GRFS, we can effectively evaluate the risk and probability of real recovery after allo-HSCT, further optimizing the therapeutic avenues for acute leukemia.

γδ regulatory T cells are able to inhibit the activation and function of T cells involved in antigen-specific immune responses. This study aimed to investigate the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). We measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts. In addition, we evaluated the ability of γδ regulatory T cells to inhibit the proliferation of CD4+CD25- T cells and detected the expression of immunoregulatory-associated molecules. We found that the levels of γδ regulatory T cells from the peripheral blood in patients of MM were significantly higher than those in healthy donors. Comparison of γδT regulatory cells function in MM and healthy donors showed similarly inhibitory effects on the proliferation of T cells. Additionally, TLR8 expression level increased significantly in MM patients compared to healthy donors, while the expression levels of Foxp3, CD25, CTLA4, GITR, GATA3 and Tbet in MM patients and healthy donors showed no significant difference. Taken together, our study reveals the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in MM patients.