Background and aims Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism. Methods A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs. Results Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423). Conclusions M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer. Graphical abstract

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion: The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.
Adolescent ; Adult ; Child ; Child, Preschool ; Chimerism ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo evaluate the effect of promoting male circumcision among the general population in the high HIV prevalence areas of Guangxi Province.

METHODSWe interviewed 590 male residents from Hezhou and Qinzhou areas of Guangxi Province and conducted intervention using male circumcision promotion materials and various methods. If the subjects were willing and had no contraindication, they were referred to the appointed hospitals to receive circumcision. We conducted follow-up visits at 6 and 9 months after intervention for the changes in the subjects' knowledge, attitude and practice related to male circumcision.

RESULTSThe male circumcision knowledge, willingness and operation rate were significantly improved after intervention (P < 0.05), but with no significant difference between the two follow-up visits (P > 0.05). The number of those who knew that phimosis and redundant prepuce were the reasons for circumcision increased from 66.1% at baseline to 81.9% and 79.8% at the two follow-up visits; those who knew that circumcision could prevent AIDS and sexually transmitted diseases increased from 28.0% to 77.4% and 78.6%; those who knew that surgical complications could be pain, bleeding and infection increased from 29.5%, 19.3% and 39.3% to 72.5%, 58.2% and 59.4% at the first follow-up and 75.0%, 57.0% and 63.0% at the second; those who were willing to receive circumcision increased from 35.3% at baseline to 59.6% and 61.3% at the two follow-up visits; and the rate of surgery increased from zero to 12.7% and 16.1%.

CONCLUSIONThe promotion of male circumcision among the general population in the high HIV prevalence areas of Guangxi Province significantly improved their knowledge, attitude and practice related to AIDS prevention. And the promotion activities should focus on the publicity of AIDS knowledge, risks of phimosis and redundant prepuce, and safety of circumcision.

Acquired Immunodeficiency Syndrome ; prevention & control ; Adult ; China ; Circumcision, Male ; psychology ; Health Education ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Phimosis ; surgery ; Prevalence ; Surveys and Questionnaires

OBJECTIVESTo detect the loss of heterozygosity (LOH) of circulating DNA in the plasma of patients with hepatocellular carcinoma (HCC), and to assess its potential as a clinical predictive marker.

METHODSThree high-polymorphic microsatellite markers D8S277, D8S298 and D8S1771 located at chromosome 8p were selected to detect LOH in plasma DNA of 62 HCC patients. The associations between LOH and its clinicopathological features, including HBsAg, liver cirrhosis, serum AFP level, tumor size, tumor cell differentiation, and intrahepatic metastasis were also examined.

RESULTSIn plasma DNA of the 62 HCC patients, LOH was found at one or several loci in 36 (58.1%), and heterozygosity at D8S277, D8S298, and D8S1771 loci was 74.2% (46/62), 75.8% (47/62), and 69.4% (43/62), respectively. LOH frequency at D8S277, D8S298 and D8S1771 was 32.6% (15/46), 44.7% (21/47), and 46.5% (20/43), respectively. LOH in plasma DNA was more frequently detected in the patients with intrahepatic cancer metastasis than those without metastasis (62.5 percent vs. 26.1 percent, P < 0.05); however, no statistically significant correlations were observed between LOH at these loci and other clinicopathological features analyzed in this study.

CONCLUSIONSLOH at D8S298 in plasma DNA may be a potential predictive marker of intrahepatic metastatic recurrence after surgical resection of the HCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; blood ; genetics ; Chromosomes, Human, Pair 8 ; DNA ; blood ; Female ; Humans ; Liver Neoplasms ; genetics ; Loss of Heterozygosity ; Male ; Middle Aged

OBJECTIVETo discuss the diagnosis and treatment of primary hepatic carcinoid tumor (PHCT).

METHODSReport one case of huge PHCT treated in February 2004, and search the other 19 cases which were published from January 1994 to December 2006 in the Chinese biological and medical literature database. The clinical manifestation, pathological findings, diagnosis and treatment of these 20 PHCT patients were analyzed retrospectively.

RESULTSThe main symptoms were abdominal pain or discomfort (8 cases) and abdominal mass (7 cases), cases with typical carcinoid syndrome were rare (3 cases). Immunohistochemical staining was positive for neuron-specific enolase, chromogranin A and synaptophysin in most cases. Sixteen cases received operation, among which there were 13 removed completely, other 4 cases were treated by transcatheter arterial chemoembolization (TACE).

CONCLUSIONSThe definite diagnosis of PHCT depends on pathological and histochemical findings. Complete surgical resection is the best treatment for PHCT with favourable prognosis. TACE is also effective for nonoperative cases.

Antigens, CD34 ; analysis ; Carcinoid Tumor ; diagnosis ; metabolism ; therapy ; Chromogranin A ; analysis ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Liver Neoplasms ; diagnosis ; metabolism ; therapy ; Male ; Middle Aged