ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.

Objective To investigate the distribution and evolutionary patterns of traditional Chinese medicine(TCM)syndromes and syndrome elements during the malignant transformation from chronic pancreatitis(CP)to pancreatic intraepithelial neoplasia(Pan IN)and pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was conducted on 710 patients(330 of CP,104 of Pan IN,276 of PDAC)diagnosed pathologically or clinically at Shanxi Institute of Traditional Chinese Medicine from January 2021 to June 2024.Data including demographics,laboratory results,and TCM diagnostic information were recorded using EpiData 3.1.Syndrome and syndrome-element patterns were determined via factor analysis and K-means clustering using SPSS 27.0.Results The study identifies seven TCM syndrome types in CP,Pan IN,and PDAC.Among CP patients,the syndrome distribution was primarily liver-gallbladder damp-heat syndrome(22.42％)and gastrointestinal excess-heat syndrome(20.91％),with excess syndromes accounting for a higher proportion(43.33％);the syndrome elements were mainly heat(51.52％)and dampness(35.15％),with the disease location in the pancreas,related to the liver,spleen,and stomach.In Pan IN patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(23.08％)and liver-gallbladder damp-heat syndrome(17.31％),with mixed deficiency-excess syndrome accounting for a higher proportion(30.00％);the syndrome elements were mainly heat(41.35％),dampness(40.38％),and qi deficiency(37.50％),with the disease location in the pancreas,related to the spleen and liver.In PDAC patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(29.71％)and qi-blood deficiency syndrome(20.29％),with deficiency syndromes accounting for a higher proportion(49.82％);the syndrome elements were mainly qi deficiency(50.00％)and dampness(36.23％),with the disease location in the pancreas,related to the spleen,kidney,and liver.Chi-square tests revealed significant differences in syndrome types(TCM syndromes:x2=100.419,P＜0.001;deficiency-excess syndromes:x2=73.722,P＜0.001),syndrome elements(x2=117.384,P＜0.001),and disease locations(x2=127.191,P＜0.001)across different stages of CP malignant transformation.During CP malignant progression,the proportion of excess syndromes gradually decreased(43.33％→12.32％),while deficiency syndromes increased(26.67％→49.82％).Excess syndrome elements(fire,heat,qi stagnation,blood stasis)decreased(53.48％→25.36％),whereas deficiency syndrome elements(qi deficiency,yin deficiency,yang deficiency,blood deficiency)increased(25.15％→49.64％).The disease location shifted from primarily the liver,spleen,and stomach in the inflammatory stage to the spleen and kidney in the cancerous stage.Conclusion The malignant transformation of CP basically involves the pancreas,is correlated early with liver and spleen-stomach and later with kidney,and exhibits a progression from excess to deficiency in the pattern of"deficiency interweaved with excess syndrome,transition from excess to deficiency,and progressive spleen deficiency".

Objective:To examine the mid - and long-term outcomes of surgical treatment of brachiocephalic Takayasu arteritis.Methods:This is a retrospective case series study. The clinical data of 39 patients,which had been diagnosed as brachiocephalic Takayasu arteritis (244 cases),who underwent surgical treatment,were analyzed between July 2012 to November 2022 at Department of Endoluminal Vascular Surgery, the First Affiliated Hospital of Zhengzhou University. There were 5 males and 34 females, aged (37.9±14.0)years (range:13 to 71 years). Despite medical treatment, the patients suffered severe ischemic symptoms continually and then underwent surgical interventions. Among them, 20 patients underwent endovascular procedures, 11 underwent open surgical procedures, and 8 underwent hybrid procedures. Patients were followed up through outpatient visits at 1, 3, 6 months after surgery and once every year later. Follow-up was conducted until November 2022. Operation status, postoperative complications and re-intervention of patients were recorded and the Kaplan-Meier survival curves were used to analyze postoperative vascular patency rates.Results:All 39 surgeries were successful, with no intraoperative death or serious complications. The follow-up period was (48.8±38.2) months(range:1 to 123 months). Thirty-three patients experienced symptom relief after surgery, and 6 patients required secondary surgical interventions. The patency rates for the endovascular treatment group at 1-, 3-, 5-, and 10-year were 95.0%, 75.2%, 60.2%, and 60.2%, respectively, while the patency rates for open surgery were all 90.9%. In the hybrid surgery group, the patency rates at 1-, 3-, 5-, and 8-year were all 87.5%.Conclusion:For patients with brachiocephalic Takayasu arteritis, choice of an appropriate blood flow revascularization intervention should be based on the patient′s condition,and the mid-and long-term outcomes are satisfactory.

Objective:To investigate the overall recurrence rate and the pattern of treatment failure in thoracic esophageal cancer (TEC) patients after minimally invasive esophagectomy (MIE), and to evaluate the significance of adjuvant therapy after MIE.Methods:Clinical data of TEC patients who underwent MIE with or without neoadjuvant chemotherapy in the Fourth Hospital of Hebei Medical University between 2016 and 2018 were retrospectively analyzed. The pathology-based lymph node metastasis (LNM) rate, overall recurrence rate, and pattern of treatment failure following MIE were analyzed by SPSS 26.0 statistical software. Cox regression model was used to identify the high-risk factors for recurrent disease. Propensity score matching was performed to compare the survival of patients between the postoperative radiotherapy group and non-radiotherapy group.Results:A total of 443 eligible patients were enrolled in this study, and the pathology-based LNM rate in all groups was 42.0%. The overall recurrence rate was 34.8%. Regional lymphatic metastasis was the most frequent pattern of recurrence (24.2%), followed by distant metastasis (19.4%). Multivariate Cox regression analysis identified pT 3-4 stage and pN + stage as the independent risk factors for recurrence. At the same time, the total number of lymph nodes dissected ≥12 and the number of lymph nodes dissected ≥7 in the neck clavicle and upper mediastinum could reduce the risk of tumor recurrence. The 1-, 3-, and 5-year disease-free survival (DFS) rates in the postoperative radiotherapy group and non-radiotherapy group were 83.5%, 66.8%, 60.7%, and 79.2%, 61.6%, 57.2%, respectively ( χ2=0.13, P=0.715). The 1-, 3-, and 5-year overall survival (OS) rates in two groups were 92.0%, 72.0%, 67.5% and 84.0%, 68.0%, 55.4% , respectively ( χ2=0.43, P=0.513). Conclusions:Regional lymphatic and distant metastases are the main patterns of recurrence for TEC patients after MIE with or without neoadjuvant chemotherapy. pT 3-4 stage, pN + stage, insufficient total number of lymph node dissection and insufficient number of lymph nodes in neck supraclavicular and upper mediastinal dissection are high-risk factors for postoperative recurrence. The survival rate in the postoperative radiotherapy group tends to be higher than that in the non-radiotherapy group. Adjuvant therapy, including postoperative radiotherapy, may remain necessary.

Non-neoplastic lesions were added in the 5th edition WHO classification of adrenal cortical tumor based on the recent update, including adrenal rests, adrenal cysts, congenital adrenal hyperplasia and adrenocortical nodular disease. A range of tumor concepts were updated or refined based on tumor cell origin, histopathology, oncology and molecular biology. The most significant nomenclature change in the field of adrenal cortical pathology involves the refined classification of adrenal cortical nodular disease, which now includes sporadic nodular adrenocortical disease, bilateral micronodular adrenal cortical disease, and bilateral macronodular adrenal cortical disease. The 5th edition WHO classification endorses the nomenclature of the HISTALDO classification to help the classification of aldosterone producing adrenal cortical lesions, which uses CYP11B2 immunohistochemistry to identify functional sites of aldosterone production. The 5th edition WHO classification does not change the Weiss and Lin-Weiss-Bisceglia histopathologic criteria for diagnosing adrenal cortical carcinomas, and underscores the diagnostic and prognostic impact of angioinvasion in these tumors. Reticulin algorithm and Helsinki scoring system were added to assist the differential diagnosis of adrenal cortical neoplasms in adults. Pediatric adrenal cortical neoplasms are assessed using the Wieneke system. The 5th edition WHO classification places an emphasis on an accurate assessment of tumor proliferation rate using both the mitotic count (mitoses per 10 mm 2) and Ki-67 labeling index which play an essential role in the dynamic risk stratification of affected patients. This review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the adrenal cortex pathologies in the 5th edition WHO classification.