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".

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.

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.

Objective To investigate the expression and significance of matrix metalloproteinases (MMPs) and toll-like receptor 9 (TLR9) in patients with acute leukemia. Methods A total of 44 patients with acute lymphoblastic leukemia (ALL) were enrolled in the ALL group, 30 patients with acute myeloid leukemia (AML) were included in AML group, and 44 healthy individuals undergoing physical examination during the same period were included in the control group. Serum levels of MMP-2, MMP-7, and MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA) in all three groups. The expression of TLR9 mRNA and TLR9 protein in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Spearman's rank correlation analysis was used to explore the correlations of the malignancy of different clinical subtypes of acute leukemia with the expression levels of MMPs and TLR9 protein. Results Serum levels of MMP-2, MMP-7, and MMP-9 were significantly higher in the ALL and AML groups compared to the control group, with the AML group showing higher levels than the ALL group (P < 0.01). The relative expressions of TLR9 mRNA and TLR9 protein in PBMCs in both the ALL and AML groups were significantly lower than those in the control group, and the AML group had lower expression than the ALL group (P < 0.01). Spearman's rank correlation analysis revealed positive correlations of serum levels of MMP-2, MMP-7, and MMP-9 with the malignancy of both ALL and AML (P < 0.05), while the relative expression of TLR9 protein was negatively correlated with the malignancy of both ALL and AML (P < 0.05). Conclusion Serum levels of MMP-2, MMP-7, and MMP-9 are significantly elevated in patients with acute leukemia, while TLR9 expression is significantly reduced in PBMCs. The abnormal overexpression of MMPs may promote extramedullary infiltration and immune escape of acute leukemia cells by inhibiting TLR9 expression, thereby accelerating the malignant progression of the tumor.

The APOBEC3 (A3) family plays a pivotal role in the immune system by performing DNA/RNA single-strand deamination. Cancers mostly arise from the accumulation of chronic mutations in somatic cells, and recent research has highlighted the A3 family as a major contributor to tumor-associated mutations, with A3A being a key driver gene leading to cancer-related mutations. A3A helps to defend the host against virus-induced tumors by editing the genome of cancer-associated viruses that invade the host. However, when it is abnormally expressed, it leads to persistent, chronic mutations in the genome, thereby fueling tumorigenesis. Notably, A3A is prominently expressed in innate immune cells, particularly macrophages, thereby affecting the functional state of tumor-infiltrating immune cells and tumor growth. Furthermore, the expression of A3A in tumor cells may directly affect their proliferation and migration. A growing body of research has unveiled that A3A is closely related to various cancers, which signifies the potential significance of A3A in cancer therapy. This paper mainly classifies and summarizes the evidence of the relationship between A3A and tumorigenesis based on the potential mechanisms, aiming to provide valuable references for further research on the functions of A3A and its development in the area of cancer therapy.