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 investigate the status quo of training and domestic use of 707 clinical nutrition support specialty nurses from 21 provinces,cities,and autonomous regions in China. And to analyze their influencing factors and provide reference for improving the training system of clinical nutrition support specialty nurses,selection and development of specialist nurses in clinical nutrition support. Methods:From October to November 2023,a cross-sectional survey was conducted on 707 clinical nutrition support specialty nurses from 21 provinces,cities,and autonomous regions across China was conducted using a convenience sampling method based on a questionnaire about the training and home use of clinical nutrition support nurses. Univariate and multiple linear regression analysis was used to examine the use status and application of clinical nutrition support specialty nurses in five aspects:clinical nursing practice,nursing education,nursing management,coordination,nursing research and consultation. Results:The use of specialist clinical nutrition support nurses is not ideal,with 75.67％ of specialist nurses scoring less than 208 points (i.e. less than 80％ of the total score). Among the use of different dimensions,the clinical nursing practice dimension received the highest score (54.17±10.26),followed by the nursing education dimension (36.98±8.00). The results of multiple linear regression analysis show that hospital level and professional title are independent influencing factors influencing the use and development of specialist nurses. Conclusion:There is a need to further improve the utilisation of clinical nutrition support nurses. It is recommended that links and cooperation between hospitals at all levels,communities,and families be strengthened. For specialist nurses with higher professional titles,encourage them to fully play their roles,strengthen training in weak areas,continuously optimize the professional ability of clinical nutrition support nursing teams,comprehensively improve the quality of clinical nutrition support specialist nursing,and promote their high-level development.

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22β,25-expoxy-26-[(O-β-D-glucopyranosyl)oxy]-1β,3β-dihydroxyfurosta-5-en(1), β-sitosterol myristate(2), β-sitosterol lactate(3), β-sitosterol 3-O-β-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 μmol·L~(-1).
Helleborus/chemistry* ; Molecular Structure ; Plant Roots/chemistry* ; Rhizome/chemistry* ; Magnetic Resonance Spectroscopy

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*

Humans ; Comorbidity ; Diabetes Mellitus/genetics* ; East Asian People ; Hypertension/genetics* ; Hypertriglyceridemia/genetics* ; Obesity/genetics* ; Receptors, Calcitriol/genetics*

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Fibrosis/prevention & control* ; Hyperglycemia/prevention & control* ; Hypoglycemic Agents/pharmacology* ; Inflammation/prevention & control* ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes/pharmacology*

Objective To explore the influence of muscle and fat distribution on sit-up ability of female college students. Methods A total of 1560 female students majoring in non-physical education in a Guangxi University were randomly selected. Body composition was measured by the bioresistance antibody component meter. According to the National Physical Health Test Standard, the height, weight and sit-ups of female college students were measured. The students were divided into four groups according to the score of sit-ups:<60 points, 60-69 points, 70-79 points, ≥80 points. SPSS 22.0 statistical software was used to analyze the data. Results There were statistically significant differences in body fat rate, total fat mass, trunk fat mass, trunk fat rate, visceral fat area, visceral fat mass and subcutaneous fat mass in different sit-ups (F value were 3.414, 2.914, 2.881, 3.347, 3.064, 3.235, 2.766, P<0.05). That was, the fat parameters in the 60-69 group were the highest and ≥80 the lowest. However, there was no significant difference between total muscle mass and trunk muscle mass in each score segment. After correcting for age, height, and weight factors, except for visceral fat area and visceral fat mass, the correlation between other fat parameters and sit-up score were negatively correlated, which were statistically significant (r<0, P<0.05). There was a positive correlation between each muscle parameter and sit-up performance (r>0, P<0.05). Compared with other parameters, the correlation coefficient between trunk muscle mass and sit-ups was the largest. Conclusion The distribution of fat and muscle has different effects on sit-up ability. Female college students' sit-up ability is greatly affected by subcutaneous fat and trunk muscle, and has nothing to do with visceral fat.

Objective To study the mechanism of bone marrow mesenchymal stem cell (BMSC)-mediated alleviation of pulmonary alveolitis in mice exposed to silica dust. Methods Thirty mice were randomly divided into 3 groups:control group, and two silica groups with or without BMSCs transplantation.Through the tracheal tube clearance, mice in control group received a single injection 20.0 μL of 0.90% sodium chloride solution by one time.Mice from in silica group and silica/BMSCs transplantation group first received a single injection of 20.0 μL silica dust suspension (mass concentration 250 g/L); followed by either 500.0 μL of 0.90% sodium chloride solution or by 500.0 μL of BMSCs suspension (cell density 1×10⁹/L) through tail vein infusion 6 hours later.Mice were euthanized on the 3th day of the experiments.The levels of NALP3 inflammasome in lungs was determined by Western blot.Transwell system was used for co-culture of BMDM (in upper-chamber) and BMSC (in lower-chamber) co-culture.The level of cytokines IL-1β in BMDM cultural supernatant was detected by enzyme linked immunosorbent assay after stimulated by SiO₂ stimulation.The levels of NALP3 inflammasome of in BMDM was determined by Western blot. Results The levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in lungs of silica/BMSCs transplantation group were lower than that in silica group (P < 0.01).In the experiment in vitro, the concentrations of IL-1β in SiO₂ exposed BMSC/BMDM co-culture group were lower than the SiO₂ exposure only groups (P < 0.05).Meanwhile, the levels of pro-IL-1β, IL-1β, pro-caspase-1, caspase-1 in BMDM was lower than that in silica group (P < 0.01).The level of these proteins didn′t change while when the cell-free supernatant of BMSC culture was directly added. Conclusion The BMSC could inhibit NALP3 inflammasome of macrophages stimulated by SiO₂.