Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the in vivo microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key "switch" in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.

Objective:To explore the relapse-related genes and their clinicopathological connections of diffuse large B cell lymphoma (DLBCL).Methods:Targeted panel sequencing was conducted on 32 eligible DLBCL samples; the patients were diagnosed, treated, and went into complete remission at the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2019, including 14 cases with recurrence (relapsed group) and 18 cases with long-term complete remission of over five years (remission group). Clinical and pathological data were further reviewed. Fisher′s exact test was employed to compare the differences in clinicopathological characteristics and mutation patterns between the two groups.Results:Among the 32 patients, there were 18 males and 14 females, with a male to female ratio of 1.3∶1.0 and a median age of 53 (45.5, 67.0) years. In the relapsed group, PIM1 (11/14), KMT2D (7/14), PRDM1 (6/14), MYD88 (6/14), DTX1 (6/14) emerged as the most frequently mutated genes. In the remission group, while recurrent PIM1, KMT2D and MYD88 mutations were also observed, the TP53 gene exhibited the highest mutation frequency (6/18). Compared to the remission group, relapsed group showed elevated mutation frequencies of PIM1 ( P=0.013) and FAT4 ( P=0.010), alongside a reduced incidence of TP53 mutations. In all 32 patients, DLBCL with CD79B, CCND3, DTX1, KMT2D and PRDM1 mutations demonstrated a propensity towards advanced clinicopathologic stage. Conclusions:Relapsed DLBCL has distinctive clinicopathological and genetic features. PIM1 and FAT4 may be served as potential biomarkers for screening relapsed DLBCL-NOS and as targets for novel therapeutic strategies.

Objective:To explore the clinical and pathological features of EBV-positive diffuse large B cell lymphoma (EBV +DLBCL) and to analyze the prognostic significance of CD30 expression in this entity. Methods:A retrospective analysis was conducted from 34 cases of EBV +DLBCL and 198 cases of EBV -DLBCL diagnosed and treated at the First Affiliated Hospital of Nanjing Medical University, from January 2017 to June 2023. Based on CD30 expression, 34 patients with EBV +DLBCL were categorized into CD30-positive and CD30-negative groups. Fisher exact test and Kaplan-Meier survival curves were employed to analyze the relationship between CD30 expression and clinicopathological parameters as well as its prognostic implications. Chi-square tests were used to compare the clinicopathological features between EBV +DLBCL and EBV -DLBCL. Results:There were 19 males and 15 females with a median age of 69.5 (15-83) years in the EBV +DLBCL group. Compared with EBV -DLBCL, EBV +DLBCL was more likely to present with clinical features such as B symptoms ( χ2=23.818, P<0.001), Ann Arbor stage Ⅲ-Ⅳ ( χ2=8.540, P=0.003), ECOG (Eastern Cooperative Oncology Group Performance Status) score 2-4 ( χ2=6.722, P=0.010), IPI score 3-5 ( χ2=9.953, P=0.002), and involvement of more than one extranodal site ( χ2=6.825, P=0.009). Additionally, EBV +DLBCL exhibited higher frequencies of elevated LDH ( χ2=4.307, P=0.038), CRP ( χ2=5.596, P=0.018), and β2-MG ( χ2=7.008, P=0.008) levels. Histopathologically, EBV +DLBCL was more commonly of the non-GCB subtype ( χ2=12.421, P<0.001), with higher frequencies of CD30-positive ( χ2=62.706, P<0.001),CD10-negative ( χ2=8.687, P=0.003),bcl-6-negative ( χ2=11.123, P<0.001), and bcl-2-negative ( χ2=22.779, P=0.003) expression. Using 20% as the positive threshold for CD30, the CD30-positive group had a higher proliferation index ( P=0.045). No significant differences were observed in overall survival between the two groups. Conclusions:EBV +DLBCL is more prevalent in the elderly and often exhibits aggressive clinical features. The expression of CD30 is not associated with the overall prognosis of EBV +DLBCL.

Objective:To explore the relapse-related genes and their clinicopathological connections of diffuse large B cell lymphoma (DLBCL).Methods:Targeted panel sequencing was conducted on 32 eligible DLBCL samples; the patients were diagnosed, treated, and went into complete remission at the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2019, including 14 cases with recurrence (relapsed group) and 18 cases with long-term complete remission of over five years (remission group). Clinical and pathological data were further reviewed. Fisher′s exact test was employed to compare the differences in clinicopathological characteristics and mutation patterns between the two groups.Results:Among the 32 patients, there were 18 males and 14 females, with a male to female ratio of 1.3∶1.0 and a median age of 53 (45.5, 67.0) years. In the relapsed group, PIM1 (11/14), KMT2D (7/14), PRDM1 (6/14), MYD88 (6/14), DTX1 (6/14) emerged as the most frequently mutated genes. In the remission group, while recurrent PIM1, KMT2D and MYD88 mutations were also observed, the TP53 gene exhibited the highest mutation frequency (6/18). Compared to the remission group, relapsed group showed elevated mutation frequencies of PIM1 ( P=0.013) and FAT4 ( P=0.010), alongside a reduced incidence of TP53 mutations. In all 32 patients, DLBCL with CD79B, CCND3, DTX1, KMT2D and PRDM1 mutations demonstrated a propensity towards advanced clinicopathologic stage. Conclusions:Relapsed DLBCL has distinctive clinicopathological and genetic features. PIM1 and FAT4 may be served as potential biomarkers for screening relapsed DLBCL-NOS and as targets for novel therapeutic strategies.

Objective:To explore the clinical and pathological features of EBV-positive diffuse large B cell lymphoma (EBV +DLBCL) and to analyze the prognostic significance of CD30 expression in this entity. Methods:A retrospective analysis was conducted from 34 cases of EBV +DLBCL and 198 cases of EBV -DLBCL diagnosed and treated at the First Affiliated Hospital of Nanjing Medical University, from January 2017 to June 2023. Based on CD30 expression, 34 patients with EBV +DLBCL were categorized into CD30-positive and CD30-negative groups. Fisher exact test and Kaplan-Meier survival curves were employed to analyze the relationship between CD30 expression and clinicopathological parameters as well as its prognostic implications. Chi-square tests were used to compare the clinicopathological features between EBV +DLBCL and EBV -DLBCL. Results:There were 19 males and 15 females with a median age of 69.5 (15-83) years in the EBV +DLBCL group. Compared with EBV -DLBCL, EBV +DLBCL was more likely to present with clinical features such as B symptoms ( χ2=23.818, P<0.001), Ann Arbor stage Ⅲ-Ⅳ ( χ2=8.540, P=0.003), ECOG (Eastern Cooperative Oncology Group Performance Status) score 2-4 ( χ2=6.722, P=0.010), IPI score 3-5 ( χ2=9.953, P=0.002), and involvement of more than one extranodal site ( χ2=6.825, P=0.009). Additionally, EBV +DLBCL exhibited higher frequencies of elevated LDH ( χ2=4.307, P=0.038), CRP ( χ2=5.596, P=0.018), and β2-MG ( χ2=7.008, P=0.008) levels. Histopathologically, EBV +DLBCL was more commonly of the non-GCB subtype ( χ2=12.421, P<0.001), with higher frequencies of CD30-positive ( χ2=62.706, P<0.001),CD10-negative ( χ2=8.687, P=0.003),bcl-6-negative ( χ2=11.123, P<0.001), and bcl-2-negative ( χ2=22.779, P=0.003) expression. Using 20% as the positive threshold for CD30, the CD30-positive group had a higher proliferation index ( P=0.045). No significant differences were observed in overall survival between the two groups. Conclusions:EBV +DLBCL is more prevalent in the elderly and often exhibits aggressive clinical features. The expression of CD30 is not associated with the overall prognosis of EBV +DLBCL.

Objective:To investigate the clinicopathological and molecular genetic characteristics of Crohn′s disease (CD).Methods:A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes.Results:Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium.Conclusions:CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Humans ; Pyriform Sinus/surgery* ; Thyroid Neoplasms/diagnosis* ; Fistula/surgery* ; Diagnostic Errors ; Pharyngeal Diseases/surgery*

Objective:To explore the application value of wide detector multi-slice spiral CT target scanning technique in the preoperative evaluation of pancreatic cancer.Methods:The clinical data of 22 patients with pancreatic cancer who underwent pancreatic arterial contrast enhanced CT scanning and were diagnosed by pathology in the First Affiliated Hospital of Naval Medical University from September 2019 to October 2019 were analyzed retrospectively. The CT phantom experiment was carried out on the international standard phantom CATPHON500. By changing the scanning radiation dose, scanning mode and scanning field of view, the spatial resolution and density resolution of the image were compared and analyzed. The target scan technical parameters obtained from the experiment were applied to the late arterial phase of MDCT enhanced scan in 22 patients with pancreatic cancer. Executive current, volume scanning mode and small scanning field were used for scanning. The attenuation value (CT value) and noise value (SD value) of pancreatic cancer tissue and normal pancreatic tissue were measured at different phases, the attenuation difference and contrast signal-to-noise ratio (CNR) of the two tissues were calculated, the contrast difference between the two tissues was evaluated, and the CT values of celiac trunk, renal artery and vein, superior mesenteric artery and vein, splenic vein and portal vein were measured, and the display of tumor tissue and peripancreatic important vessels was evaluated.Results:In the phantom experiment, under the condition of the same radiation dose, the image quality of the volume scan mode was better than that of the spiral scan mode (1%@4 mm versus 1%@9 mm at 5 mGy and 1%@2 mm versus 1%@6 mm at 25 mGy). In comparison between pancreatic tumor and pancreatic tissue, the enhancement process of pancreatic tumor tissue was increased at first and then decreased, while that of pancreatic tumor tissue was slightly enhanced. The attenuation difference between pancreatic tissue and tumor tissue and CNR also increased at first and then decreased, reaching the maximum at the late arterial stage [(91.96±29.29)HU, 8.60±5.71]. The differences between each phase were statistically significant ( F values were 47.20 and 19.80 respectively, all P values <0.05). The evaluation of vascular variation and invasion showed that a better arterial phase image could be obtained on the late arterial target scan images, while taking into account the display of splenic vein, mesenteric vein and portal vein. Conclusions:The wide detector MDCT target scanning technique can improve the spatial resolution and density resolution of the image, greatly improve the contrast between tumor tissue and peripancreatic tissue and blood vessels, and provide more accurate tumor staging and resectability evaluation information for preoperative evaluation of pancreatic cancer.

Objective:To compare the clinical, pathological features and prognosis of patients who underwent pancreaticoduodenectomy with standard or extended lymph node dissection for pancreatic ductal adenocarcinoma.Methods:A retrospective study was performed on 158 pancreatic head cancer patients who underwent radical resection at the First Affiliated Hospital of Nanjing Medical University from Jul 2017 to Feb 2019. The clinicopathological characteristics and prognosis between the standard dissection group and the extended dissection group were compared. The relationship between the number of examined lymph nodes, positive lymph nodes, and the lymph node ratio, together with their relationship with survival were analyzed.Results:Survival analysis showed no statistical difference in survival between the standard resection group and the extended resection group ( P=0.99). There were statistical differences in gender and age composition between the two group, but no significant differences in operation time, blood loss, or postoperative complications were found. Patients with less examined lymph nodes tended to be of stage N0. examined lymph nodes is positively correlated with positive lymph nodes but is not significantly correlated with lymph node ratio. Positive lymph nodes is strongly correlated with lymph node ratio. The location of lymph node metastasis was not survival-related. Conclusions:There is no prognostic difference between standard lymph node dissection and extended lymph node dissection in pancreatic cancinoma patients after Whipple procedure.