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.

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.

Objective To investigate the efficacy of combined prediction of postpartum hypertension using 24-h urinary protein quantification(24-hUP),hematocrit and plasma albumin difference(HCT-ALB),and brain natriuretic peptide(BNP)in patients with severe preeclampsia at the end of pregnancy.Methods A retrospective study was conducted using cluster sampling to select 540 patients with severe preeclampsia from the University City Hospital affiliated to Chongqing Medical University between January 2018 and December 2022.Patients were divided into a hypertension group(n=98)and a non-hypertension group(n=442)based on the occurrence of postpartum hypertension.Clinical data[age,body mass index(BMI),maternal type,abortion history,family history of hypertension,smoking history,total cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG),systolic blood pressure(SBP),diastolic blood pressure(DBP)]and levels of 24-hour urinary protein excretion(UP),hematocrit-albumin(HCT-ALB),and BNP in the third trimester of pregnancy were compared between the two groups to analyze the predictive value of these indicators for postpartum hypertension.Results The levels of BMI,family history of hypertension,TC,TG,FBG,SBP and DBP in hypertensive group were higher than those in non-hypertensive group[(25.63±1.37)kg/m2 vs(23.05±1.23)kg/m2,70.41%vs 30.54%].(5.32±1.14)mmol/L vs(3.91±0.95)mmol/L,(3.48±0.82)mmol/L vs(1.66±0.43)mmol/L,(7.24±1.60)mmol/L vs(4.83±1.22)mmol/L,(148.27±13.29)mmHg vs(127.65±10.71)mmHg,(92.36±5.17)mmHg vs(84.20±4.35)mmHg],the difference was statistically significant(P<0.05).The levels of urinary protein,HCT,HCT-ALB and BNP at 24 h at the end of pregnancy in hypertension group were also higher than those in non-hypertension group[(7.82±2.18)g/24 h vs(6.15±1.26)g/24 h,(34.22±3.15)%vs(32.80±1.77)%].(6.19±2.01)vs(3.46±0.90),(646.43±170.59)pg/mL vs(523.81±134.62)pg/mL],while ALB level was lower than that of the non-hypertension group[(28.03±1.13)g/L vs(29.34±1.44)g/L],with statistically significant differences(P<0.05).There was a positive correlation between 24-hUP,HCT,HCT-ALB,BNP and SBP,DBP,while ALB was negatively correlated with SBP and DBP,the difference was statistically significant(P<0.05).24-hUP,HCT-ALB and BNP at the end of pregnancy were independent risk factors for postpartum hypertension,with a combined prediction AUC of 0.930(95%CI:0.905～0.950),a Jordon index of 0.719,sensitivity of 85.71%,the specificity of 86.20%.The AUC of the combined prediction was significantly greater than that of each individual predictor,with statistically significant differences(P<0.05).Conclusion 24-hUP,HCT-ALB,and BNP at the end of pregnancy are independent risk factors for postpartum hypertension.Their combined predictive efficacy is significantly superior to that of individual indicators and can be used as an optimal clinical method for predicting whether patients with severe preeclampsia will develop postpartum hypertension.

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

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.

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

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.

Continuous inflammatory response and repeated tissue damage lead to a chronic inflammatory state that is an important pathological feature of chronic refractory wounds, and plays an important pathogenic role in the occurrence and development of chronic refractory wounds. Multiple types of programmed cell death can release damage-associated molecular patterns, and trigger or induce sustained inflammatory responses, leading to dysregulated tissue repair. This review will outline the known role of programmed cell death in the inflammatory response of chronic refractory wounds from the perspective of generating damage-associated molecular patterns, and explore possible research directions on the role and mechanism of programmed cell death in chronic refractory wounds.

Diffusion weighted imaging is an important imaging technique for diagnosing and evaluating the effectiveness of disease treatment,mainly focusing on the overall diffusion behavior of water molecules but ignoring the microscopic movement of water molecules and the details of tissue microstructures.Combining oscillatory gradient spin-echo and pulsed gradient spin echo sequences,time-dependent diffusion MRI(td-dMRI)captured diffusion MRI signals at varying time,in order to obtain information of different microstructures,which had recently emerged into clinical application with the advancements of hardware.The principles of td-dMRI technology and its application progresses in tumors were reviewed in this article.