Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective:This study sought to examine the clinicopathological features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and to discuss its differential diagnosis.Methods:A total of 36 MEITL cases, collected between June 2015 and January 2024 from the Fourth Affiliated Hospital of Soochow University and the First Affiliated Hospital, College of Medicine, Zhejiang University, were analyzed. Patients underwent immunohistochemistry, in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER), and T-cell receptor (TCR) gene rearrangement testing. Clinical data, laboratory results, and follow-up information were collected for correlation analysis.Results:The cohort included 36 patients (20 males and 16 females) aged 17-76 years (median: 57 years). Tumors outside the intestine were observed in 22 cases (61%). A total of 32 patients (89%) underwent surgical intervention and/or chemotherapy, and one patient received auto-HSCT. The median follow-up duration was 11.5 months (range: 8-73 months), with a median overall survival of 6 months (range: 1-67 months) ; 34 patients died during the follow-up period. Morphologically, nine cases (25%) exhibited significant pleomorphism. Immunohistochemical analysis revealed that high expression levels of both P53 and c-Myc were correlated with atypical morphology ( P=0.003 and P=0.016, respectively). Notably, patients with high P53 expression had significantly shorter survival times than those with low P53 expression ( χ2=4.922, P=0.027), whereas survival did not differ significantly based on c-Myc expression levels ( χ2=0.034, P=0.854). Furthermore, a PD-L1 CPS score ≥10 was observed in 22 cases (68.8%). Scattered EBER positivity in background cells was identified in four cases. All tested cases (17/17, 100.0%) showed clonal TCR gene rearrangements. Conclusions:MEITL is a rare but highly aggressive lymphoma with distinct clinical and pathological features. A subset of cases may exhibit atypical morphological patterns, complicating the diagnostic process. Improving awareness of this neoplasm is helpful for early and precise diagnosis as well as the estabolishment of novel therapy regimen.

Uric acid (UA) is the final metabolite of purines in the human body. An imbalance in UA production and excretion that disrupts homeostasis leads to elevated blood UA levels and the development of hyperuricemia (HUA). Approximately one-third of UA is excreted through the intestinal tract. As a crucial component of the intestinal microenvironment, the gut microbiota plays a pivotal role in regulating blood UA levels. Alterations or imbalances in gut microbiota composition are linked to the onset of HUA, which implies the potential of gut microbiota as a novel target for the prevention and treatment of HUA. This review introduces the occurrence mechanism and damage of hyperuricemia, examines the association between HUA and the gut microbiota and their metabolites, and explores the molecular mechanisms underlying gut microbiota-targeted therapies for HUA. Furthermore, it discusses the potential applications of probiotics, prebiotics, and traditional Chinese medicine (including both single herbs and compound formulas) with UA-lowering effects, along with cutting-edge technologies such as fecal microbiota transplantation and machine learning in HUA treatment. This review provides valuable perspectives and strategies for improving the prevention and treatment of HUA.
Hyperuricemia/microbiology* ; Humans ; Gastrointestinal Microbiome/physiology* ; Probiotics/therapeutic use* ; Uric Acid/blood* ; Fecal Microbiota Transplantation ; Prebiotics ; Medicine, Chinese Traditional

Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Objective:This study sought to examine the clinicopathological features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and to discuss its differential diagnosis.Methods:A total of 36 MEITL cases, collected between June 2015 and January 2024 from the Fourth Affiliated Hospital of Soochow University and the First Affiliated Hospital, College of Medicine, Zhejiang University, were analyzed. Patients underwent immunohistochemistry, in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER), and T-cell receptor (TCR) gene rearrangement testing. Clinical data, laboratory results, and follow-up information were collected for correlation analysis.Results:The cohort included 36 patients (20 males and 16 females) aged 17-76 years (median: 57 years). Tumors outside the intestine were observed in 22 cases (61%). A total of 32 patients (89%) underwent surgical intervention and/or chemotherapy, and one patient received auto-HSCT. The median follow-up duration was 11.5 months (range: 8-73 months), with a median overall survival of 6 months (range: 1-67 months) ; 34 patients died during the follow-up period. Morphologically, nine cases (25%) exhibited significant pleomorphism. Immunohistochemical analysis revealed that high expression levels of both P53 and c-Myc were correlated with atypical morphology ( P=0.003 and P=0.016, respectively). Notably, patients with high P53 expression had significantly shorter survival times than those with low P53 expression ( χ2=4.922, P=0.027), whereas survival did not differ significantly based on c-Myc expression levels ( χ2=0.034, P=0.854). Furthermore, a PD-L1 CPS score ≥10 was observed in 22 cases (68.8%). Scattered EBER positivity in background cells was identified in four cases. All tested cases (17/17, 100.0%) showed clonal TCR gene rearrangements. Conclusions:MEITL is a rare but highly aggressive lymphoma with distinct clinical and pathological features. A subset of cases may exhibit atypical morphological patterns, complicating the diagnostic process. Improving awareness of this neoplasm is helpful for early and precise diagnosis as well as the estabolishment of novel therapy regimen.

Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using next-generation sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

OBJECTIVE To evaluate the clinical efficacy and safety of XELOX chemotherapy （oxaliplatin+capecitabine） combined with antiangiogenic agent （apatinib） and immunotherapy （camrelizumab） in patients with inoperable metastatic colorectal cancer （CRC）of microsatellite stable （MSS） type. METHODS Clinical medical records of 40 patients with inoperable metastatic CRC of MSS type treated in Lishui People’s Hospital from January 2020 to January 2021 were retrospectively collected. According to the treatment plan， the patients were divided into control group （20 cases） and observation group （20 cases）. Control group was given XELOX+apatinib regimen， while observation group was given XELOX+apatinib+camrelizumab regimen. Every 3 weeks was a treatment cycle， and the treatment lasted for 2 consecutive cycles. The objective response rate （ORR）， disease control rate （DCR）， progression-free survival （PFS）， overall survival （OS） and adverse events （AEs） were recorded for all patients. RESULTS The ORR and DCR of observation group were 65.0% and 85.0%， respectively； and the ORR and DCR of control group were 35.0% and 75.0%， respectively， with no statistical significance between 2 groups （P＞0.05）. The median PFS of observation group and control groups were 16.0 months and 8.0 months， respectively； and the median OS were 19.0 months and 12.5 months， respectively， with statistical significance between 2 groups （P＜0.05）. Each patient in both groups had at least one AEs， and the incidences of reactive skin capillary hyperplasia and hyperthyroidism in observation group （40.0%， 20.0%） were significantly higher than those in control group （both were 0） （P＜0.05）. The incidence of nausea and vomiting in control group （90%） was significantly higher than observation group （10%） （P＜0.05）. There were 14 cases （70.0%） of patients with grade 3 or above AEs in observation group， and only 5 cases （25.0%） in control group， with statistical significance between 2 groups （P＜0.05）. However， no severe AEs that could not be tolerated or fatal occurred in the two groups， which could be alleviated after drug withdrawal or treatment. CONCLUSIONS The efficacy of XELOX chemotherapy combined with apatinib and camrelizumab in inoperable metastatic CRC patients of MSS type is comparable to that of XELOX chemotherapy combined with apatinib， but it has certain advantages in ORR， PFS and OS， and controllable safety.

Objective:To investigate the reference value of ultrasonography (US) image features, elastography and serum thyroid stimulating hormone (TSH) levels in preoperative diagnosis of differentiated thyroid carcinoma (DTC).Methods:Retrospective analysis was conducted to collect clinical data of patients undergoing thyroid surgery in the Fourth Affiliated Hospital of Harbin Medical University from September 2018 to January 2020. All patients underwent conventional ultrasound, elastography examination and serum TSH level measurement before surgery; patients were divided into benign group and DTC group according to the results of pathological results of the operation, and the US image features and elasticity score were analyzed by chi-square test and multivariate logistic regression to evaluate the causes of DTC; a multivariate logistic regression model was established and the receiver operating characteristic curve (ROC) was drawn with the regression model, by analyzing the area under the ROC curve (AUC), sensitivity, specificity and accuracy, the reference value of US image features, elastography and serum TSH levels in the preoperative diagnosis of DTC were judged.Results:Clinical data of 81 patients were collected, including 17 men and 64 women, aged (48.72 ± 10.58) years. In benign group, there were 37 cases, including 10 men and 27 women, with age of (53.24 ± 9.59) years; there were 44 patients in DTC group, including 7 men and 37 women, with age of (44.91 ± 9.95) years old, the age difference between benign group and DTC group was significant ( t = 3.822, P < 0.05), while the gender difference was not statistically significant (χ 2 = 1.498, P > 0.05). There were significant differences in the number, size, echo level, microcalcification, aspect ratio and elasticity score between benign group and DTC group (χ 2 = 49.000, 4.457, 32.111, 5.444, 4.457, 49.926, P < 0.05); multivariate logistic analysis showed that hypoecho, microcalcification, aspect ratio > 1 and elasticity score were risk factors for DTC ( OR = 8.042, 4.787, 4.160, 2.380, P < 0.05), the ROC curve of the multivariate logistic regression model showed that the AUC was 0.841 (95% CI = 0.743 - 0.939), sensitivity was 90.91%, specificity was 72.97%, and accuracy was 82.72%; the AUC of serum TSH level prediction of DTC showed that the AUC was 0.721 ( P < 0.05), sensitivity was 72.70%, specificity was 64.90%, accuracy was 54.30%, and TSH best cut-off value was 2.215 μU/ml. Conclusion:In the preoperative diagnosis of DTC, US image features, elastography and serum TSH levels are of important clinical reference value for diagnosis of DTC, and the establishment of multivariate logistic regression model is conducive in improving the clinicians prediction of the occurrence of DTC.

Objective:To investigate the adult thyroid structural abnormalities and epidemiological characteristics in different regions of Heilongjiang Province.Methods:From December 2017 to November 2018, 30 survey sites were selected in 13 prefecture-level cities under the jurisdiction of Heilongjiang Province by the population probability sampling (PPS) method, and 120 local residents aged 20 to 70 who lived for more than 1 year in the local area were selected from each survey site for thyroid ultrasound examination. The occurrence of thyroid structural abnormalities in different genders, ages and regions were analyzed.Results:A total of 3 870 residents were investigated, including 1 248 males and 2 622 females, aged (48.3 ± 12.6) years; 2 075 urban residents and 1 795 rural residents. A total of 2 144 cases of thyroid structural abnormalities were detected, with a total detection rate of 55.40% (2 144/3 870); among them, 1 476 cases of thyroid focal nodular lesions, 359 cases of diffuse lesions, and 309 cases of diffuse lesions with focal nodules, the detection rates were 38.14%, 9.28%, and 7.98%, respectively. The detection rate of thyroid structural abnormalities was 61.25% (1 606/2 622) in women and 43.11% (538/1 248) in men, the difference was statistically significant (χ 2=111.899, P < 0.01). There was significant difference in the total detection rate of thyroid structural abnormalities among different age groups (χ 2=185.959, P < 0.01); and with the increase of age, the total detection rate of thyroid structural abnormalities showed an upward trend (χ 2trend=173.576, P < 0.01). There was significant difference in the total detection rate of thyroid structural abnormalities in adults among different prefecture-level cities (χ 2=108.487, P < 0.01); but there was no significant difference in the total detection rate of thyroid structural abnormalities between urban and rural (χ 2=0.103, P > 0.05). Conclusions:The main thyroid structural abnormalities in Heilongjiang Province are focal nodular lesions. The detection rate of women is higher than that of men, and the older the age, the higher the detection rate. There are differences in the detection rate of thyroid structural abnormalities in adults of different prefecture-level cities, but there is no significant difference between urban and rural.

Objective To study the relationship of microRNA-145(miR-145) and CD44 in the hepatocellular carcinoma(HCC).Methods 13 clinical samples of HCC tissues and corresponding normal liver tissues were collected at department of General Surgery,Second Affiliated Hospital of Fujian Medical University from October 2015 to June 2016.The patients with positive expression of CD44 were studied.The expression levels of miR-145 and CD44 in HCC tissues and corresponding normal tissues were detected by real-time quantitative PCR.Western blot was performed to detect the expression of CD44 in HCC cells Hep G2 and SNU423.Biological information methods predicted whether miR-145 and CD44 have a targeted relationship.CD44 expression levels were detected after high expression of miR-145 in HCC cell line with positive expression of CD44.The vector and luciferase reporter genes were constructed to verify the interaction between miR-145 and CD44.The effects of miR-145 on proliferation in HCC cell lines with positive and negative CD44 expression were examined by tetramethylazoazole salt (MTT) assay.Results 8 of the 13 patients showed positive CD44 expression in HCC tissues.Compared with normal liver tissues,the relative expression of miR-145 in HCC tissues was significantly lower (0.998±0.010 vs.0.503±0.046,P＜0.05),and the relative expression of CD44 was higher (0.996±0.005 vs.1.878±0.108,P＜0.05).Bioinformatics suggested that miR-145 had a targeted relationship with CD44.High expression of miR-145 can significantly reduce the expression level of CD44 mRNA in HCC cell SNU423 (0.941±0.010 vs.0.515±0.021,P＜0.05) and down-regulate the expression of CD44 protein.Confirmed by luciferase reporter assay,CD44 is the target gene of miR-145.After transfection with miR-145 mimics,the proliferation of CD44 positive cell SNU423 was significantly inhibited (P＜0.05).Conclusions miR-145 can affect the proliferation of CD44 positive HCC cells by regulating the expression of CD44,which may be one of the pathogenesis of HCC.