Objective:This study investigated the underlying causes of discordance between multiplex fluorescence polymerase chain reaction (PCR)-capillary electrophoresis in determining MSI and immunohistochemistry (IHC) for mismatch repair (MMR) protein evaluation in gastrointestinal adenocarcinomas, aiming to improve interpretation accuracy and guide clinical precision treatment strategies.Methods:A retrospective analysis was conducted on 511 surgically resected or biopsied specimens (161 gastric adenocarcinomas and 350 colorectal adenocarcinomas) diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to June 2024. MMR protein expression of tumors was evaluated by IHC, while MSI status was assessed using the 2B3D National Cancer Institute (NCI) Panel through multiplex fluorescence PCR-capillary electrophoresis on tumor DNA and matched normal DNA. The concordance between the two methods was analyzed, and factors contributing to the discordance were investigated. Cases with unstable dinucleotide loci only in the 2B3D NCI Panel, focal MMR protein loss, or unexplained discrepancies underwent validation using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis markers or next-generation sequencing (NGS).Results:In the 511 gastrointestinal adenocarcinomas, the results of the two methods were discordant in 15 cases (2.9%), with a significantly higher discordantrate in gastric cancers (7.5%, 12/161) compared to colorectal cancers (0.9%, 3/350; P＜0.001). Key contributors to the discordance included: sampling limitations (6 cases), 2B3D NCI Panel design constraints (3 cases),tumor heterogeneity (3 cases),isolated MSH6 deficiency (1 case),and unexplained discrepancies (2 cases).Validation studies demonstrated that cases with dinucleotide-only instability showed concordance with IHC after using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis and NGS verifications. Specimens with focal MMR protein loss and unexplained discrepancies aligned with initial PCR results upon NGS validation. Unexplained cases harbored Kirsten rat sarcoma class Ⅰ variants and multiple class Ⅱ genetic alterations. Conclusions:Colorectal adenocarcinoma demonstrated higher concordance between PCR-capillary electrophoresis and IHC than gastric adenocarcinoma.Discordant results require systematic evaluation including technical review, specimen quality control, and supplemental NGS analysis to resolve discrepancies.

Chronic heart failure (CHF) is a pathological state in which the cardiac ejection fraction is insufficient to meet an individual's metabolic needs owing to changes in the cardiac structure or function. Various etiologies such as myocardial infarction and inflammation are implicated, and the main symptoms are dyspnea, lower limb edema, fatigue, and discomfort during rest or exercise. CHF is the primary outcome of cardiovascular disease, and the increasing morbidity and mortality rates highlight the significant risks of this condition. According to traditional Chinese medicine, the pathogenesis of CHF is deficiency of heart qi and heart yang, which predominantly affects the heart, but may also impede the function of other zang-organs such as the spleen and kidney, and aggravate the symptoms of heart failure. With technological advancements and enhanced awareness of health conditions and disease prevention, China has promoted traditional medicine practices such as medicine and food homology (MFH), which has received increasing attention in recent years. This concept stipulates that certain medicines and foods have the same origin; ergo, these foods have medicinal properties, with many being used in the prevention and treatment of CHF. However, the efficacy and safety of MHF substances have yet to be determined, and there is no consensus regarding the development of disease prevention and treatment strategies. This article therefore reviews the current evidence for MFH in the prevention and treatment of CHF by summarizing the therapeutic potential of this practice and discussing treatment strategies and aims to improve the understanding of Chinese medicine and food homologous substances in the treatment of this condition, as well as highlight the current literature and avenues for future research.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Purpose To investigate the clinicopathological features and prognosis of adult large B-cell lymphoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 63 adult LBCL-IRF4r cases were collected.The EnVision two-step method was employed for immunohistochemical staining,and fluorescence in situ hybridization was used to detect rearrangements or deletions of the IRF4,BCL2,MYC,BCL6,and TP53 genes.The relationship be-tween clinicopathological features and prognosis was analyzed and compared with data from 132 adult non-specified dif-fuse large B-cell lymphoma(DLBCL)cases.Results Among the 63 adult LBCL-IRF4r patients,the male to female ratio was 1.1∶1,with a median age of 54.0 years(range 20-84 years),and 14 cases(22.2％)were＜40 years old,24 cases(38.1％)were between 40 and 60 years old,and 25 cases(39.7％)were＞60 years old.18 cases(28.6％)were involved in Waldeyer's ring,along with 8 cases(12.7％)in cervical lymph nodes,7 cases(11.1％)in other lymph nodes and lymphatic organs,13 cases(20.6％)in stomach,4 cases(6.4％)in intestine,and 13 cases(20.6％)in other extranodal sites.63 cases showed IRF4 rearrangements,with no BCL2 and MYC translocations(0/58),30.9％(17/55)had BCL6 translocations,and 16.3％(8/49)had TP53 deletions.59 pa-tients were followed up for a median of 28 months(range 1-65 months).48 patients(81.4％)achieved complete re-sponse,10 patients(16.9％)experienced disease progression or relapse,and 3 patients(5.1％)died.Univariate a-nalysis showed that lactate dehydrogenase level,Ann Arbor stage,international prognostic index(IPI)score,growth pattern,Hans classification,and double expression of BCL2 and C-MYC were significantly associated with progression-free survival.Age,Ann Arbor stage,and IPI score were significantly associated with overall survival.Multivariate Cox regression analysis showed that double expression of BCL2 and C-MYC was an independent prognostic factor for pro-gression-free survival.Adult LBCL-IRF4r had significantly higher complete response rate and progression-free survival than adult DLBCL.Conclusion LBCL-IRF4r occurs in adults of all age groups,commonly affecting Waldeyer's ring,cervical lymph nodes,and gastrointestinal tract,and has a favorable clinical prognosis.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Objective:This study investigated the underlying causes of discordance between multiplex fluorescence polymerase chain reaction (PCR)-capillary electrophoresis in determining MSI and immunohistochemistry (IHC) for mismatch repair (MMR) protein evaluation in gastrointestinal adenocarcinomas, aiming to improve interpretation accuracy and guide clinical precision treatment strategies.Methods:A retrospective analysis was conducted on 511 surgically resected or biopsied specimens (161 gastric adenocarcinomas and 350 colorectal adenocarcinomas) diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to June 2024. MMR protein expression of tumors was evaluated by IHC, while MSI status was assessed using the 2B3D National Cancer Institute (NCI) Panel through multiplex fluorescence PCR-capillary electrophoresis on tumor DNA and matched normal DNA. The concordance between the two methods was analyzed, and factors contributing to the discordance were investigated. Cases with unstable dinucleotide loci only in the 2B3D NCI Panel, focal MMR protein loss, or unexplained discrepancies underwent validation using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis markers or next-generation sequencing (NGS).Results:In the 511 gastrointestinal adenocarcinomas, the results of the two methods were discordant in 15 cases (2.9%), with a significantly higher discordantrate in gastric cancers (7.5%, 12/161) compared to colorectal cancers (0.9%, 3/350; P＜0.001). Key contributors to the discordance included: sampling limitations (6 cases), 2B3D NCI Panel design constraints (3 cases),tumor heterogeneity (3 cases),isolated MSH6 deficiency (1 case),and unexplained discrepancies (2 cases).Validation studies demonstrated that cases with dinucleotide-only instability showed concordance with IHC after using the non-NCI Panel through multiplex fluorescence PCR-capillary electrophoresis and NGS verifications. Specimens with focal MMR protein loss and unexplained discrepancies aligned with initial PCR results upon NGS validation. Unexplained cases harbored Kirsten rat sarcoma class Ⅰ variants and multiple class Ⅱ genetic alterations. Conclusions:Colorectal adenocarcinoma demonstrated higher concordance between PCR-capillary electrophoresis and IHC than gastric adenocarcinoma.Discordant results require systematic evaluation including technical review, specimen quality control, and supplemental NGS analysis to resolve discrepancies.

Purpose To investigate the clinical and patho-logical characteristics,molecular characteristics,treatment and prognosis of systemic ALK-negative anaplastic large cell lympho-ma(ALCL).Methods Retrospective analysis was conducted on the clinical pathology,immunophenotype,molecular charac-teristics,treatment and prognosis of 18 cases of systemic ALK-ALCL.HE,immunohistochemistry,FISH,and NGS tests were performed,and relevant literatures were reviewed.Results Systemic ALK-ALCL tended to occur in elderly men,often in the advanced stage,mainly in lymph node lesions.The extran-odal primary sites included the primary pancreas and primary thoracic vertebrae.Morphological examination showed 17 cases belong to common type,1 case belong to"Hodgkin like"type.CD30 was diffuse and strongly positive in tumor cells(＞75％),CD2(16/17),CD3(13/18),CD5(4/18),CD7(8/18),CD4(14/18),TIA-1(16/18),CD8(2/16),GATA-3(10/12),EMA(3/5),MUM1(12/12),CD43(6/6)and CD56(2/8)were positive to varying degrees.The Ki67 proliferation index of 30％to 90％,PD-L1(22C3)(TPS=0-100％),ALK,CD15,CD79α and CD20 were all negative.FISH detection:5 cases of TP63 deficiency and 2 cases of DUSP22 deficiency;NGS detection:16 cases of gene mutations occurred,with a fre-quency of 0-11 gene mutations and an average of 4.2 gene mu-tations;ALK-ALCL with TP63 rearrangement was more likely to occur in women,mostly in lymph nodes,late clinical staging,susceptibility to p53 gene abnormalities,low PD-L1 expression rate and high mortality rate.Conclusion Systemic ALK-ALCL with TP63 rearrangement is associated with many adverse factors,the clinical process is often invasive with poor progno-sis.

Esophageal squamous cell carcinoma(ESCC)is a major histological subtype of esopha-geal cancer with a poor prognosis.Although several serum metabolomic investigations have been reported,ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined.Here,we enrolled 34 treatment-naive patients with ESCC and collected their pre-and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabo-lomic survey.Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites.Notably,postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome.Furthermore,we performed an examina-tion using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans.Notably,among these metabolites,the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization,and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice.Furthermore,this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest.Together,this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitor-ing therapeutic efficacy and disease relapse,presented evidence for refining parenteral nutrition composition,and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Objective:To investigate the relationship between the protein expression of C-MYC, bcl-2 and bcl-6 and the clinicopathological characteristics in patients with de novo CD5-positive diffuse large B cell lymphoma (CD5 +DLBCL). Methods:Fifty seven cases of de novo CD5 +DLBCL were collected at Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from February 2013 to September 2018. The hematoxylin-eosin stained slides were reviewed, and immunohistochemical (IHC) staining and FISH were used to analyze the relationship between C-MYC, bcl-2, bcl-6 expression and the clinicopathologic characteristics of patients. Results:Among these 57 cases, 27 were male and 30 were female. The age of onset was 35-99 years old. The IHC expression rates of C-MYC, bcl-2 and bcl-6 were 50.9% (29/57), 84.2% (48/57), and 75.4% (43/57) respectively; and co-expression rate of C-MYC and bcl-2 proteins was 40.4 (23/57). There was no significant correlation between protein expression and patients′ genders, clinical stage, the level of serum LDH,β2 microglobulin, IPI,B symptoms, bone marrow involvement and central nervous system recurrence ( P>0.05). Univariate analysis showed that the median OS of C-MYC negative patients was significantly longer than C-MYC positive patients ( P<0.05); and the median OS of patients without double expression was significantly longer than that of patients with positive expression ( P<0.05), and bcl-6 positive patients had longer median OS than bcl-6 negative patients ( P<0.05). There was no significant correlation between prognosis and bcl-2 protein expression ( P>0.05) . Cox multivariate analysis showed C-MYC protein expression was an independent predictor of OS in de novo CD5 +DLBCL ( P<0.05). Conclusions:Bcl-2 protein expression has no effect on the prognosis in de novo CD5 +DLBCL whereas bcl-6 expression is correlated with good prognosis. C-MYC protein expression could be used as an independent and effective index to predict the prognosis of patients with de novo CD5 +DLBCL.However, the relationship between protein expression and gene rearrangement of C-MYC, bcl-2 and bcl-6 needs to be further explored.