Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Objective:To investigate the factors influencing the prognosis of critically ill patients and the predictive value of the C-reactive protein-albumin-lymphocyte (CALLY) index.Methods:A retrospective analysis was conducted on the clinical data of 122 critically ill patients admitted to Guoyao Dongfeng General Hospital affiliated with Hubei University of Medicine from June 2022 to December 2023. Patients were divided into a death group and a survival group based on their 28-day prognosis. Clinical data were compared between the two groups to analyze the factors influencing prognosis and assess the predictive value of various indicators. Normally distributed measurement data were expressed as Mean±SD, and intergroup comparisons were performed by independent samples t-test; non-normally distributed measurement data were expressed as M( Q1,Q3), and intergroup comparisons were performed by the Mann-Whitney U test. Counting data were expressed as case (%), and intergroup comparisons were performed by the χ2 test. Multivariate logistic regression was used to analyze factors influencing patient prognosis, and receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of each indicator. Results:The Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate, CRP, and B-type natriuretic peptide levels in the death group were higher than those in the survival group [22 (17, 30) points vs. 17 (14, 22) points, (4.8±1.4) mmol/L vs. (3.3±1.0) mmol/L, 134 (83, 2 381) mg/L vs. 13 (10, 27) mg/L, 259 (111, 592) ng/L vs. 108 (40, 247) ng/L; Z=3.04, P=0.002; t=5.79, P<0.001; Z=8.57, P<0.001; Z=3.28, P=0.001, respectively]. Albumin, neutrophil count, lymphocyte count (LYC), and the CALLY index were lower in the death group than in the survival group [(31±5) g/L vs. (37±6) g/L, (58±9)×10 9/L vs. (63±10)×10 9/L, 0.6 (0.4, 0.8)×10 9/L vs. 1.3 (0.8, 1.7)×10 9/L, 0.03 (0.02, 0.11) vs. 0.26 (0.13, 0.49); t=6.05, P<0.001; t=3.04, P=0.003; Z=5.82, P<0.001; Z=6.52, P<0.001, respectively]. Multivariate logistic regression analysis indicated that the APACHE Ⅱ score and CRP were risk factors for poor prognosis in critically ill patients ( OR=1.349, 95% CI: 1.004-1.821, P=0.048; OR=1.006, 95% CI: 1.003-1.010, P=0.001, respectively), while LYC and the CALLY index were protective factors ( OR=0.297, 95% CI: 0.111-0.795, P=0.016; OR=0.989, 95% CI: 0.955-0.999, P=0.001, respectively). The area under the ROC curve for the CALLY index predicting 28-day mortality in critically ill patients was 0.872 (95% CI: 0.800-0.926), which was higher than that of the APACHE Ⅱ score, LYC, and CRP [0.673 (95% CI: 0.582-0.756), 0.664 (95% CI: 0.573-0.748), 0.576 (95% CI: 0.482-0.665), respectively]. The cut-off values were 0.06, 20 points, 0.8×10 9/L, and 50 mg/L, respectively. When the CALLY index was 0.06, the specificity was 97.65%, the sensitivity was 72.97%, and the Youden index was 0.706. Conclusions:The APACHE Ⅱ score, CRP, LYC, and CALLY index are all factors influencing the prognosis of critically ill patients. The CALLY index has certain predictive value, but its false negative rate is relatively high. Further combination with other indicators is needed to improve its predictive value.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

OBJECTIVE To provide scientific and reasonable recommendations for the identification of Anaerobio-spirillum succiniciproducens in clinical microbiology laboratories by comparing the effectiveness of biochemical methods,matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS),and 16S rRNA gene sequencing.METHODS Methodological evaluation was conducted.A strain of A.succiniciprodu-cens was isolated on Mar.27,2023 from a patient with sepsis caused by a dog bite,who was admitted to Guang-dong Nongken Central Hospital,and analyzed for the morphological characteristics,culture methods,and colony features.The identification of the isolated strain was conducted by the automated microbial identification and anal-ysis system(VITEK 2 Compact 2,bioMerieux),MALDI-TOF MS including VITEK MS,MALDI Biotyper,Au-tof ms 1000,and EX-Accuspec,as well as 16S ribosomal RNA(rRNA)gene sequencing.The performance of each method was evaluated.RESULTSA.succiniciproducens was a strictly anaerobic gram-negative spiral bacteri-um,characterized by slow growth,flat and colorless transparent colonies,and negative oxidase and catalase activ-ity.When using VITEK 2 Compact ANC card,it was not successfully recognized;however,through the identifi-cation by VITEK MS,MALDI Biotyper,Autof ms 1000 and EX-Accuspec,it was all confirmed as A.succinicip-roducens.Additionally,16S rRNA gene sequencing technology also identified it as A.succiniciproducens.CONCLUSIONS Current automated biochemical identification systems are unable to accurately identify A.succi-niciproducens.MALDI-TOF MS and 16S rRNA gene sequencing techniques can reliably confirm A.succinicipro-ducens.Clinical microbiologists should select the appropriate identification method based on their available re-sources.

Objective:To investigate the clinicopathological characteristics of adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP).Methods:A total of 71 cases craniopharyngioma, included 52 cases of ACP and 19 cases of PCP, diagnosed at the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, China from September 2019 to November 2023 were collected. Clinical pathological data were analyzed, immunohistochemical staining was performed, and mutations in the CTNNB1 and BRAF V600E genes were examined to identify differences between ACP and PCP.Results:The ACP cohort comprised 27 male and 25 female patients, with an age at onset ranging from 6 to 70 years, mean age (42.0±18.3) years. In contrast, the PCP group included 15 males and 4 females, with an age at onset spanning 28 to 74 years, mean age (51.0±13.3) years. The ACP group more commonly showed calcifications on imaging than the PCP group [92.3% (48/52) versus 11/19]. Partial tumor resection and the maximum diameter of the tumor were important factors affecting the recurrence of ACP. Whorled cell clusters, wet keratinization, stellate reticulum, cysts, and calcification were more often seen in ACP than PCP ( P<0.05). Immunohistochemically, all (100%,52/52) of the ACP showed nuclear β-catenin expression, with varying degrees of expression in the nodular whorls, and scattered cytoplasmic β-catenin expression. The BRAF V600E expression was found in the cytoplasm of all (19/19) PCP cases, but only non-specific BRAF V600E nuclear positivity was observed in ACP cases. Molecular testing showed that the mutation rate of the CTNNB1 gene in ACP was 22.7% (5/22), and the mutation rate of the BRAF V600E in PCP was 19/19. Conclusions:ACP and PCP have different age at onset, radiological features, histopathological morphology, and genetic alterations. Proper use and interpretation of immunohistochemical results can help distinguish between ACP and PCP, while molecular testing can be used as an auxiliary diagnostic modality.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of aggressive natural killer-cell leukemia (ANKL).Methods:A retrospective analysis was conducted on 27 ANKL patients treated at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2024. Their clinical data, histomorphology, and immunophenotype were reviewed. Kaplan-Meier analysis was used to evaluate the overall survival (OS), and COX regression analysis was performed to identify prognostic factors affecting OS.Results:Among the 27 patients, 18 were male and 9 were female, with a male-to-female ratio of 2∶1. The age ranged from 15-75 years, with a median age of 42.0 (28.5, 54.5) years. Fever and splenomegaly were the most common signs and symptoms. Most patients presented with pancytopenia, coagulation abnormalities, and liver dysfunction; and all patients had elevated EBV loads. Microscopically, 16 cases showed marked to hypercellular bone marrow proliferation, with predominant interstitial infiltration (15 cases, 55.6%), followed by sinusoidal infiltration (3 cases), diffuse infiltration (6 cases, 22.2%), mixed infiltration (interstitial and focal, 3 cases, 11.1%), focal infiltration (2 cases, 7.4%), and nodular infiltration (1 case, 3.7%). The proportion of tumor cells among nucleated cells ranged from 2% to 80%, with a median of 30%. The tumor cells displayed variable morphology. Hemophagocytosis was observed in 23 cases. Immunohistochemistry revealed that all cases expressed CD56, with mostly expressing cytotoxic molecules (granzyme B, TIA-1). The Ki-67 proliferative index ranged from 50% to 90%. CD56-EBER dual staining showed that NK cells were the primary targets of the virus. Reticulin staining showed increased fibrosis. By flow cytometry, all cases were positive for CD2 but negative for surface CD3 (sCD3), CD4, CD5 and CD57. Among them, 21 cases (95.5%) exhibited a typical phenotype of strong CD56 expression (CD56str+) with CD16 negativity (CD16-), while only one case (4.5%) showed CD16 positivity (CD16+) with dim CD56 expression (CD56dim). In killer-cell immunoglobulin-like receptor (KIR) analysis, 6 out of 17 patients (6/17) demonstrated monoclonal expression, including CD158a (4/6), CD158i (1/6), and CD158e (1/6); the remaining 11 cases (11/17) showed complete absence of KIR expression. All tested cases (17/17) were negative for T-cell receptor (TCR) protein expression. Follow-up period was from 257 days, 1 patient was lost to follow-up, and the remaining 26 patients died. Kaplan-Meier analysis revealed that OS was significantly longer in patients who received chemotherapy compared to those who did not ( P<0.05). Univariate Cox proportional hazards model analysis indicated that age, bone marrow proliferation, proportion of tumor cells among nucleated cells, absolute neutrophil count, platelet count, and triglycerides and bilirubin levels significantly affected OS ( P<0.05). Multivariate COX regression analysis identified triglycerides and bilirubin levels as independent prognostic factors for OS. Conclusion:Aggressive natural killer-cell leukemia is a rare lymphoid malignancy with very poor prognosis. Tumor cells exhibit significant morphological variation, and bone marrow infiltration patterns are diverse. Accurate recognition, early diagnosis, and timely chemotherapy are critical to improving the prognosis of patients with ANKL.

The prevalence of aortic stenosis and regurgitation among the elderly population in China has been increasing year by year.Transcatheter aortic valve implantation(TAVI), as a minimally invasive interventional treatment technique, has become the preferred treatment option for elderly patients with aortic valve disease.It is worth noting that postoperative cognitive dysfunction(POCD), as an important neurocognitive complication after TAVI, is significantly associated with poor prognosis.However, the epidemiological characteristics, pathophysiological mechanisms, and clinical outcomes of POCD remain controversial.This study systematically reviews the existing evidence to elucidate the epidemiological profile, occurrence mechanisms, and relevant clinical risk factors of POCD after TAVI.Furthermore, it explores the neurocognitive assessment methods suitable for this population and critically discusses the clinical application value and research limitations of the current preventive and therapeutic strategies.

Patients with leukemic non-nodal mantle cell lymphoma (nnMCL) typically exhibit an indolent clinical course, and when asymptomatic and without treatment indications, a watchful observation follow-up can be adopted. This article presents a retrospective summary of a case of nnMCL, misdiagnosed as chronic lymphocytic leukemia (CLL) and carrying a TP53 mutation, along with a literature review. The case highlights the importance of differential diagnosis between nnMCL and CLL, and suggests that for nnMCL patients, the presence of high-risk biological markers such as TP53 mutations does not necessarily indicate an immediate need for treatment; rather, a strict watch-and-wait strategy may be a more appropriate option.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.