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 explore the incidence and risk factors of cardiovascular events in hematological neoplasms patients treated with anthracyclines in the real world. Methods: A total of 408 patients with lymphoma and leukemia, who were treated with anthracyclines during hospitalization in the First Affiliated Hospital of Dalian Medical University from January 1, 2018 to July 31, 2021, were included in this retrospective study. Patients were divided into cardiovascular event group (n=74) and non-cardiovascular event group (n=334). The primary endpoint was cardiovascular events (arrhythmia, heart failure, acute myocardial infarction etc.) after anthracyclines therapy. The secondary endpoint was all-cause mortality, cardiovascular-cause death, discontinued chemotherapy due to cardiovascular events. Multivariate regression analysis was used to investigate the risk factors of cardiovascular events. Kaplan-Meier was performed to calculate the incidence of all-cause mortality. Results: The mean age was (55.6±14.9) years, and there were 227 male patients (55.6%) in this cohort. The median follow-up time was 45 months. During follow-up, cardiovascular adverse events occurred in 74 patients (18.1%), including 45 heart failure (38 were heart failure with preserved ejection fraction), 30 arrhythmia, 4 acute myocardial infarction and 2 myocarditis/pericarditis. Multivariate regression analysis showed age (OR=1.024, 95%CI 1.003-1.045, P=0.027) and history of hypertension over 10 years (OR=2.328, 95%CI 1.055-5.134, P=0.036) were independent risk factors for the cardiovascular events. Kaplan-Meier survival curve showed mortality was significantly higher in cardiovascular event group than in non-cardiovascular event group (47.3% vs. 26.6%, P=0.001). In the cardiovascular event group, chemotherapy was discontinued in 9 cases (12.2%) due to cardiovascular events and cardiovascular death occurred in 7 cases (9.5%). Conclusions: Although heart failure is the main cardiovascular event in lymphoma and leukemia patients post anthracyclines therapy, other cardiovascular events especially arrhythmias are also common. The presence of cardiovascular events is associated with higher risk of all-cause mortality in these patients. Age and long-term hypertension are independent risk factors for cardiovascular events in lymphoma and leukemia patients after anthracyclines treatment.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Child ; Anthracyclines/adverse effects* ; Retrospective Studies ; Risk Factors ; Heart Failure/drug therapy* ; Myocardial Infarction/complications* ; Hematologic Neoplasms/complications* ; Arrhythmias, Cardiac/complications* ; Leukemia/complications* ; Hypertension/complications*

OBJECTIVE: To investigate the molecular mechanism in stable cell strains expressing Mini-hF9 gene with nonsense mutation. METHODS: Mini-hF9 gene and its nonsense mutants were transfected into HeLa cells independently, and stable cell strains were obtained after G418 resistance screening and monoclonal transformation. The altered splicing and protein expression of mRNA in Mini-hF9 gene in stable cell strains were detected by using RT-PCR and Western blot. RESULTS: The wild type and nonsense mutated human coagulation factor IX stable cell strains were constructed successfully, which were named HeLa-F9-WT, HeLa-F9-M1 and HeLa-F9-M2. Only normal splicing Norm was detected in the wild-type cell strain HeLa-F9-WT; Norm and Alt-S1 splicing were detected in HeLa-F9-M1; while Norm, Alt-S1 and Alt-S2 splicing were detected in HeLa-F9-M2. CONCLUSION The nonsense associated altered splicing (NAS) pathway, which generated alternately spliced transcripts, might be triggered in coagulation factor IX gene with nonsense mutation.
Codon, Nonsense ; Factor IX/metabolism* ; HeLa Cells ; Humans ; Mutation ; RNA Splicing ; RNA, Messenger/metabolism*

Objective Focused cardiac ultrasound (FCU) and lung ultrasound (LU) are increasingly being used in critically ill patients. This study aimed to investigate the effect of FCU in combination with LU on these patients and to determine if the timing of ultrasound examination was associated with treatment change. Methods This is a multicenter cross-sectional observational study. Consecutive patients admitted to the intensive care unit (ICU) were screened for enrollment. FCU and LU were performed within the first 24 h, and treatment change was proposed by the performer based on the ultrasound results and other clinical conditions. Results Among the 992 patients included, 502 were examined within 6 h of ICU admission (early phase group), and 490 were examined after 6 h of admission (later phase group). The early phase group and the later phase group had similar proportions of treatment change (48.8%
Critical Illness ; Cross-Sectional Studies ; Echocardiography ; Humans ; Intensive Care Units ; Lung/diagnostic imaging* ; Retrospective Studies

Objective To explore the characteristics of medical sexual orientation, sexual behavior and acquired immunodeficiency syndrome(AIDS) related knowledge changing with grade. Methods A group of 876 undergraduate students of 2015 in a medical university were selected to conduct an anonymous survey once a year and a total of four times using self-compiled questionnaires on AIDS-related knowledge, sexual orientation and behavior of college students. Descriptive epidemiological methods were adopted for statistical description. Results The distribution of sexual orientation among medical students with different survey batches was statistically significant ( 2=26.223, P=0.036). The proportion of openly gay people in the total number of homosexuals showed an increasing trend ( 2trend=4.150, P=0.042). Follow-up study of Chinese medicine students on AIDS related knowledge of the overall rate of increased ( 2trend=23.462, P<0.001). The incidence of general sexual behavior and male homosexual sex among medical students in the past six months showed an increasing trend with grade growth ( 2trend=4.450, P=0.035; 2trend=6.738，P=0.009). At the second and third follow-ups, the proportion of men who used condoms occasionally and never used condoms increased, and the difference was statistically significant ( 2=7.935, P=0.047). Conclusions Due to the weak awareness of medical sexual safety protection, the school should continue to strengthen the AIDS publicity and prevention education of medical students in all grades, and improve the school sexual health education mechanism.

OBJECTIVETo analyze the relation of HBV infection with clinical characteristics and prognosis in NHL patients, so as to explore the significance of HBV detection.

METHODSSixty-eight NHL patients from December 2013 to December 2016 were enrolled in NHL group and 136 patients with other malignancies were chosen in control group, the detectable rate of HBV was compared between 2 groups. The correlation of HBV infection with sex, age, stage, cell origin, expression of P53 and BCL-2 in NHL patients was analyzed. The prognosis-related factors in NHL patients were also analyzed.

RESULTSThe infection rate of HBV in NHL group was 51.47%(35/68), that in control group was 15.44% (21/136), and the difference was statistically significant(χ=27.768,P<0.05). HBV infection correlated with cell origins and expression of BCL-2 in NHL patients(P<0.05). The prognosis of NHL patients demonstrated no correlation with sex, age, cell origins and HBV infection (P>0.05), while the prognosis was significantly related with stage, expression of P53 and BCL-2(P<0.05).

CONCLUSIONHBV infection correlates with BCL-2 expression level of NHL patients, and shows influence on the prognosis of patients.

Objective: To observe the effect of poloxamer 188 (P188) on megakaryocyte cultivation and induction from cord blood mononuclear cells in order to obtain more megakaryocyte progenitor cells (MPC). Methods: The cord blood mononuclear cells were isolated and inoculated in cell culture bag or cell culture flask respectively. The WIGGENS shaker and cell culture bags were used to mimick WAVE Bioreactor for three-dimensional (3D) cell culture, and the P188 was added to induction medium, The cells were detected for morphology, surface marker, viability, and number on day 14. Results: In the two-dimensional (2D) culture, CD41(+), CD41(+)/CD61(+), CD61(+) megakaryocytic numbers increased significantly after adding P188 (all P<0.01). And in the 3D culture of adding P188, the cell volume became larger and the nuclear shape was irregular, the cytoplasm appeared magenta granules, and the megakaryocyte cells became more mature. By 3D culture, the expression of CD41/CD61 was (36.30±1.27)% vs (23.95±1.34)%, hence the differentiation for MPC was significantly higher than that in the 2D group (P<0.01). Furthermore, adding P188 in 3D culture resulted in highest differentiation efficiency for MPC [(59.45±1.20)%]. There were no significantly differences in terms of cell viability and cell number among 3D culture containing P188, 2D and 3D culture groups (all P>0.05). Conclusion: 3D culture was beneficial for the differentiation of MPC, but the cell viability was lower than 2D group; However, the satisfied cell growth and better induction efficiency were obtained by adding of P188, which might provide a new method of megakaryocytes production for clinical application.
Bioreactors ; Cell Differentiation ; Cells, Cultured ; Fetal Blood ; Megakaryocytes ; Poloxamer

Objectives: To explore the clinical feathers and prognosis of primary malignant pericardial mesothelioma (PPM) reported in inland China. Methods: We searched Chinese data bases and collected medical records of PPM from 1981 to 2015 for patients' clinical, imaging, pathological, diagnostic and therapeutic information to explore the possible impact factors for prognosis. Results: A total of 186 patients were enrolled including 122 (65.6％) male, the mean age was (40.9±14.5) years at the range of (2-79) years. There were 108/166 (65.1％) patients suffered from dyspnea which was the most common symptom, 17 (10.2％) were complicated with cardiac tamponade and 48 (28.9％) complicated with constrictive pericarditis. 65 patients were misdiagnosed and 40 (61.5％) of them were diagnosed for tubercular pericarditis. 94 patients died and 30 (31.9％) of them died during hospitalization. 86 patients were discharged and received the follow-up study at the median of 6 months, 64 (74.4％) of them died. Multivariate Cox regression analysis did not find the meaningful clinical, imaging or pathological parameters to predict patients' mortality. Conclusion: PPM is a rare and highly aggressive pericardial malignant tumor, mainly involving middle-age males. Pathological combining immunohistochemical examinations are helpful for PPM diagnosis. Effective therapy has been lacking and comprehensive individualized therapy may improve the patients' prognosis.

In order to establish the quality standard of Berberidis Cortex and improve its quality control level, water, total ash, acid-insoluble ash and alcohol-soluble extract were determined according to procedures recorded in the Chinese Pharmacopoeia (2010 edition). The qualitative and quantitative analyses were performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) methods. The results showed that TLC identification had a good resolution with clear spots. The water content was 8.39%-12.23%; total ash was 4.50%-9.96%; acid-insoluble ash was 0.10%-0.69%, and the alcohol-soluble extraction was 20.62%-37.13%. The average contents of magnoflorine, jatrorrhizine, palmatine, and berberine in Berberidis Cortex were 5.98%, 0.63%, 0.30%, 2.50%, respectively. It was concluded that the developed method was accurate and good in specificity, which can be used for quality control of Berberidis Cortex in the future.

Wildlife tending and artificial cultivation is an important way to protect the wild resources of Rhodiola crenulata. It is a study hotspot at present. The distribution information of R. crenulata was collected by query data and field survey, the ecological suitability regionalization was conducted based on maximum entropy model combine with ecological factors, including climate, soil and altitude. To provide the reference for production layout, suitable planting area and the selection of artificial planting base by studying the ecological suitability regionalization of R. crenulata. The potential distribution areas mainly concentrated in the easen Tibet, western Sichuan, southern Qinghai, and Gansu Gannan Tibetan Autonomous Prefecture, Yunnan Diqing Tibetan Autonomous Prefecture. There were 5 major environmental factors to have obvious influence on ecology suitability distributions of R. crenulata, including altitude (contribution rate of 61.8%), precipitation of warmest quarter (contribution rate of 19%), the coefficient of variation of precipitation seasonality (contribution rate of 4.7%), the SD of temperature seasonality (contribution rate of 4%), mean temperature of driest quarter (contribution rate of 2.5%). The AUCs of ROC curve were both above 0.9, indicating that the predictive results with the Maxent model were highly precise. The study of the ecological suitability regionalization of R. crenulata based on Maxent can provide a scientific basis for the selection of artificial planting base.