Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

To describe the history, current status and development trend of clinical pharmacist training in China.

This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

The writing of pharmacist-managed clinics documents （hereinafter referred to as “outpatient medication record”） is a necessary part of pharmacist-managed clinics service. Outpatient medication record is an important carrier to reflect the quality of pharmacist-managed clinics service. The Chinese Hospital Association Pharmaceutical Specialized Committee was entrusted by the Pharmaceutical Administration Department of the National Health Commission to lead the formulation of the Guidelines for the Pharmacist-managed Clinics Service and Document Writing and Usage （Reference） （hereinafter referred to as Guidelines） according to the compilation method of group standards and the technical route of “documentation combing→framework establishment→draft writing→opinion collection→Guidelines formation”. The Guidelines standardizes the basic requirements of pharmacist-managed clinics record management and the basic content of record， and provides a general template and two specialized templates including pregnant and lactating pharmacist-managed clinics record template and cough and asthma pharmacist-managed clinics record template， which provides a reference for medical institutions to write pharmacist-managed clinics record. This paper introduces the formulation process of Guidelines and analyzes the key contents of Guidelines， which is helpful for the application practice of Guidelines and further improves the quality of pharmacist-managed clinics work.

BACKGROUND: Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS: RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS: SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Animals ; NF-E2-Related Factor 2/metabolism* ; Mice ; Macrophages/immunology* ; Sepsis/metabolism* ; Kelch-Like ECH-Associated Protein 1/genetics* ; T-Lymphocytes/immunology* ; Humans ; Signal Transduction/physiology* ; RAW 264.7 Cells ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Flow Cytometry ; T-Cell Exhaustion

Objective: To investigate whether syndecan-2(SDC2) can affect the proliferation, invasion and migration of cervical cancer cells by regulating ferroptosis and its possible mechanism. Methods : Normal cervical epithelial cells H8 and cervical squamous carcinoma cells C33A were cultured and divided into H8 group and C33A group. C33A cells were cultured and divided into control group, low SDC2 expression group, SDC2+ferroptosis inhibitor(ferrostation-1) group and SDC2 + ferroptosis inducer(erastin) group. Western blot was used to detect the protein levels of SDC2, solute carrier family 7 member 11(SLC7A11) and glutathione peroxidase 4(GPX4). RT-qPCR was used to detect the SDC2 mRNA level in C33A cells. ELISA kits were used to detect the levels of reactive oxygen species(ROS), glutathione(GSH) and ferrous ion(Fe2+) in C33A cells. The cloning ability of C33A cells was detected by plate cloning. The migration ability of C33A cells was detected by scratch test. Transwell assay was used to detect the invasion ability of C33A cells. Results : Compared with H8 group, the protein and mRNA expressions of SDC2, SLC7A11 and GPX4 in C33A group increased(P<0.05). Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells in the low SDC2 group decreased(P<0.05), the protein and mRNA expressions of SLC7A11 and GPX4 in C33A cells decreased(P<0.05), and the GSH level decreased. ROS and Fe2+levels increased(P<0.05). Compared with the low SDC2 group, the protein and mRNA expressions of SLC7A11 and GPX4 increased(P<0.05), the GSH level increased, and the ROS and Fe2+levels decreased(P<0.05) in the low SDC2+ferrostation-1 group. Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells with low SDC2+erastin expression decreased(P<0.05). Conclusion The expression of SDC2 increases in C33A cervical cancer cells. Low expression of SDC2 can activate SLC7A11/GPX4 pathway mediated ferroptosis, thereby reducing the proliferation, invasion and migration of C33A cells.

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Objective:To study the distribution of TCM constitutions in maintenance hemodialysis (MHD) patients.Methods:This is a multicenter cross-sectional study. The general clinical data, dialysis-related parameters and physical and chemical examination data of MHD patients from 6 dialysis centers in Sichuan were collected. At the same time, DS01-A tongue and facial pulse information collection system was used for TCM constitution discrimination.Results:A total of 232 MHD patients were enrolled , and 417 kinds of TCM constitutions were detected, including 59 patients (25.43%) with moderate constitution and 173 patients (74.57%) with biased constitution. Phlegm-dampness was the most common type of solid constitution 47 patients (20.26%). The most common deficiency constitution was qi deficiency 86 patients (37.07%). There were certain differences in the physical distribution of patients with different gender, age, dialysis age, BMI, and whether they had diabetes, hypertension or anemia.Conclusions:The TCM constitutions of MHD patients are mainly biased constitution. Gender, age, BMI, diabetes or hypertension have a certain impact on the distribution of TCM constitutions. At the same time, different constitutions may have an impact on the anemia of MHD patients. The intervention of TCM constitutions on MHD patients may be beneficial to the prognosis of MHD patients.

Objective:To construct an objective and scientific core competence training system for intensive care unit (ICU) specialized nurses in Yunnan Province, and to provide references for formulating a homogeneous and standardized ICU specialized nurse training strategy and assessment.Methods:Based on the theoretical basis of the nurse-patient safety competency framework, the relevant literature of nursing job competence was consulted, the core competency training system of ICU specialized nurses in Yunnan Province was constructed, and the expert letter questionnaire was designed through theoretical analysis. From January to May 2020, 15 experts of critical care medicine from Yunnan Province were consulted by Delphi method to establish a core competency training system for ICU specialized nurses in Yunnan Province. SPSS 21.0 was used to input and analyze the data.Results:A total of 2 rounds of Delphi expert consultation were carried out. The final core competency indicators for ICU specialized nurses included effective communication, teamwork, safety risk management, nursing quality improvement and professionalism, including 5 first-level indicators, 14 second-level indicators and 59 third-level indicators. The effective recovery rates of the two rounds of Delphi expert consultation questionnaires were 100.00% (15/15) and 86.67% (13/15), the expert authority coefficient values were 0.863 and 0.881 respectively, the Kendall harmony coefficients of the first-level index, the second-level index and the third-level index were 0.381, 0.299 and 0.250, and χ2 value was 22.86, 58.22 and 217.30, with statistically significant differences ( P<0.001). The 5 first-level indicators were safety risk management (0.360), professionalism (0.280), teamwork (0.200), nursing quality improvement (0.120), and effective communication (0.040) in descending order. Conclusions:The established core competence training system for ICU specialized nurses in Yunnan Province based on patient safety is reliable and scientific, which can provide objective basis for the on-the-job training, evaluation and development of patient safety education courses for ICU specialized nurses in Yunnan Province.