Frontiers in Medicine最新文献

Janus kinase (JAK) family members, as upstream regulators, phosphorylate not only themselves but also cytokine receptors and signal transducer and activator of transcription (STAT) proteins in the JAK-STAT signaling pathway. The JAK-STAT pathway is associated with various cellular processes, such as cell proliferation, cell death, and immune responses. Considering that the JAK-STAT pathway is involved in immunity, dysfunctional JAKs can cause autoimmune diseases, including rheumatoid arthritis. Therefore, several inhibitors have been developed to inhibit the function of JAKs in the case of abnormal JAK-STAT signaling. Emerging structural data on JAKs highlight the opportunities to design selective inhibitors that can overcome mutation-driven resistance. Therefore, novel JAK inhibitors need to be developed. In this review, we discuss the principal structural features of JAKs, focusing on the active site. In addition, we summarized the updated JAK inhibitors indicated for rheumatoid arthritis that are available in the pharmaceutical market. The binding modes of JAK inhibitors have also been described. Based on the structural analysis of JAKs and their inhibitors, we propose strategies for developing next-generation JAK inhibitors.

Introduction: Medical pipeline programs are one upstream approach to supporting student educational outcomes, a well-documented social determinant of health, through out-of-school time (OST) programming. The Lang Youth Medical Program (LYMP) is a 6-year, hospital-based model designed to immerse students ("Scholars") in a health science and clinical curriculum, fostering interest in health careers and providing educational support for youth in Northern Manhattan. LYMP stands out among other medical pipeline programs for its longitudinal model that targets students in middle school to enable comprehensive academic and career support. This paper aims to describe the structure, implementation, and outcomes of LYMP as a replicable model for improving educational outcomes among underrepresented youth.

Program overview: LYMP draws upon an urban hospital's existing resources and community partnerships to immerse Scholars in academic and clinical exploration. Across 6 years, Scholars receive a body-systems-based curriculum, clinical skills lessons, hospital tours, and annual summer internships, alongside rigorous support for high school and college applications, to prepare them for post-secondary pursuits. Simultaneously, Scholars' families receive parent workshops and connections to wraparound and counseling services as an additional dimension of support.

Outcomes: With a 92.6% retention rate across 16 graduating cohorts, approximately 93% of LYMP alumni pursue undergraduate degrees and one in five have pursued graduate degrees. Among alumni who have graduated college, 26% (n = 30) have returned to work full-time at the hosting hospital. Regardless of their professional or academic pathway, recent LYMP alumni scored 27% higher on standardized tests compared to their peers and report feeling well-equipped with professional and academic skills instrumental in their success.

Discussion: LYMP offers a scalable and replicable blueprint for healthcare institutions seeking to invest in educational equity and workforce development. Its modular curriculum, upstream intervention strategy, and integration within a hospital setting demonstrate how longitudinal, community-rooted programs can effectively support youth in achieving academic success, career readiness, and health literacy. Additionally, LYMP's novel approach has evolved to include socioemotional support and community resources to address the social determinants of health, providing Scholars with a holistic exposure to healthcare while continually meeting its mission to improve educational outcomes among Northern Manhattan youth.

Objective: To develop and validate a clinical prediction model estimating individualized risk of unfavorable treatment outcomes in patients with pulmonary tuberculosis and diabetes mellitus (PTB-DM).

Methods: This retrospective study enrolled 110 inpatients with PTB-DM, categorized into favorable (n = 55) and unfavorable (n = 55) outcome groups. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to select the most relevant predictors from clinical and laboratory data. A multivariate logistic regression model was built based on these predictors to construct a nomogram. The model's performance was evaluated by its discrimination (Area Under the Curve, AUC), calibration (Hosmer-Lemeshow test and calibration curve), and clinical utility (Decision curve analysis). Internal validation was performed using bootstrap resampling (1,000 repetitions).

Results: Four variables were selected by LASSO regression for model construction: Age, Body Mass Index (BMI), pulmonary cavity, and the Glucose-to-Lymphocyte Ratio (GLR). The multivariate model confirmed these as independent risk factors. The nomogram demonstrated excellent discrimination, with an AUC of 0.885 (95% CI: 0.826-0.944) and a bootstrap-corrected AUC of 0.858. Good calibration was indicated by a non-significant Hosmer-Lemeshow test (P = 0.856). Decision curve analysis confirmed the model's clinical net benefit across a wide range of risk thresholds.

Conclusion: We developed and internally validated a nomogram that accurately predicts the risk of unfavorable outcomes in PTB-DM patients by integrating four readily available clinical parameters. This tool shows robust performance and holds promise for aiding clinicians in identifying high-risk individuals for personalized management strategies.

Hematopoietic stem cell transplantation (HSCT) is a cornerstone therapy for hematological malignancies, frequently complicated by treatment-related oral mucositis (OM). This complication leads to severe pain, nutritional compromise, heightened infection risk, and may result in treatment delays, prolonged hospitalization, and diminished long-term health-related quality of life. While clinical guidelines exist, a significant gap persists between evidence and practice, especially in the systematic and individualized application of preventive strategies. From an evidence-based nursing perspective, this perspective article proposes a comprehensive management framework. This framework integrates evidence synthesis, patient-specific risk assessment, dynamic monitoring, and multidisciplinary collaboration to align standardized interventions with personalized patient needs across all phases of HSCT. By synthesizing current evidence, analyzing practical challenges, and proposing a structured management pathway, this perspective article aims to guide clinical practice, inform future research, and ultimately improve care standards for OM in HSCT patients.

Background: Acute pancreatitis is a common digestive system emergency with heterogeneous clinical courses, and early accurate stratification is crucial for guiding treatment, improving prognosis, and reducing mortality. Existing scoring systems such as the Modified CT Severity Index (MCTSI) primarily rely on imaging features, but alone may not fully reflect inflammatory status, while inflammatory markers like the Lymphocyte-to-Monocyte Ratio (LMR) show potential in predicting disease severity; however, studies combining both are insufficient.

Objective: To investigate the value of integrating LMR with MCTSI to construct a new scoring system (MCTSI-LMR) for early stratification in acute pancreatitis, optimizing clinical predictive efficacy.

Methods: A total of 216 patients with acute pancreatitis admitted to Hefei Third People's Hospital from April 2022 to January 2025 were selected as the study subjects. All patients were divided into mild group (65 cases), moderately severe group (108 cases), and severe group (43 cases) according to the Atlanta classification criteria (2012 revision). All patients underwent abdominal CT scanning and complete blood count within 24 hours of admission to calculate MCTSI scores and LMR values. Using clinical outcomes as the gold standard, inter-group indicator differences and the diagnostic efficacy of the combined score were compared.

Results: Based on disease severity, the severe group had significantly lower LMR values than the mild and moderately severe groups (t = 125.473, P < 0.001) and higher MCTSI scores (t = 298.456, P < 0.001). The incidence of organ failure and mortality showed statistically significant differences between groups (χ² = 98.765, P < 0.001; χ² = 45.678, P < 0.001). Multivariate logistic regression analysis revealed that MCTSI score (Wald = 26.234, P < 0.001) and LMR (Wald = 41.156, P < 0.001) were independent predictors of severe acute pancreatitis. ROC curve analysis indicated that the MCTSI-LMR score had superior predictive performance compared to individual indicators (Z = 3.456-5.678, P < 0.05).

Conclusion: The application of the MCTSI-LMR score in early stratification of acute pancreatitis can significantly enhance predictive efficacy, with notable differences combining imaging and inflammatory markers, providing a reliable tool for clinical early intervention and worthy of promotion and application.

Objective: Although sexual history taking is an essential component of a comprehensive medical history, it is often omitted in practice. To ensure competent assessment, this skill should be taught during medical school. However, interest in the topic-particularly among male students-remains limited. This study therefore aimed (1) to examine the impact of gender on students' motivation to learn sexual history taking and (2) to identify gender-independent factors. The findings are intended to inform teaching innovations that foster motivation in all students and, ultimately, improve the quality of patient care.

Methods: A cross-sectional online survey was conducted in the winter semester 2023/2024 among fifth- to eighth-semester medical students at Friedrich-Alexander University Erlangen-Nuremberg. The questionnaire comprised the Learning Self-Regulation Questionnaire (SRQ-L) and 11 self-developed items addressing potential influences on students' motivation to learn sexual history taking. Data were analyzed using t tests, ANOVA, regression, and mediation analyses.

Results: A total of 318 students participated (86 male, 232 female). Perceived relevance of the topic and the psychiatric clinic as the organizer of the elective course were significant predictors of motivation. Female students showed higher autonomous regulation than males [t (118.68) = -3.48, p < 0.001, d = 0.51] and rated the topic as more relevant [t (121.39) = -3.86, p < 0.001, d = 0.56]. Mediation analysis revealed that the gender effect on autonomous regulation was fully mediated by perceived relevance [indirect effect ab = 0.3231, 95% CI (0.160, 0.4996)].

Conclusion: Gender differences in motivation to attend a voluntary seminar on sexual history taking are explained by perceived relevance rather than biological sex. Relevance plays a central role in fostering autonomous motivation. Therefore, curricular strategies should emphasize the importance of sexual history taking to increase engagement across all genders. Integrating this topic into the compulsory curriculum may compensate for initial gender disparities and contribute to long-term improvements in medical interviewing and patient care.

Background: Acute myeloid leukemia (AML) is a malignant disorder originating from myeloid hematopoietic stem and progenitor cells. Despite the availability of current treatment options, a significant number of patients fail to achieve complete remission after initial chemotherapy. CD33, a transmembrane protein highly expressed on AML cells, serves as a promising therapeutic target. This study aimed to develop and evaluate chimeric antigen receptor T cells (CAR-T) and antibody-drug conjugates (ADC) based on humanized antibodies, specifically targeting CD33, to assess their potential efficacy against AML.

Methods: Monoclonal antibodies specific to human CD33 were generated by immunizing mice and then humanized. These humanized antibodies were then used to construct CAR-T cells and ADCs, and their cytotoxic properties were evaluated both in vitro and in vivo. In the in vivo experiments, mice bearing Molm13-Luciferase tumor cells were assigned to different treatment groups and were administered with saline, Gemtuzumab-MMAE, or Clone3HM-MMAE.

Results: The in vitro experiments revealed that several antibody clones, including Clone2HM, Clone3HM, Clone5HM, Clone6HM, and Clone7HM, displayed strong cytotoxic effects against Molm13-Luciferase tumor cells when conjugated with MMAE, outperforming the positive control antibody Gemtuzumab-MMAE. In the in vivo studies, mice treated with Clone3HM-MMAE showed a significant reduction in tumor signals, which nearly disappeared in the latter stages of the experiment. This led to a substantially longer survival time compared to other groups. Additionally, the body weight of mice in all treatment groups remained stable throughout the treatment period, indicating a favorable safety profile.

Conclusion: The CAR-T cells and ADCs developed in this study, based on humanized antibodies, showed significant anti-tumor efficacy in the AML model. Clone3HM-MMAE, in particular, demonstrated excellent anti-tumor activity along with a strong safety profile. These results strongly support the further development of targeted therapeutic strategies for AML.

Vibrio vulnificus infection is characterized by rapid progression and poor prognosis, which can lead to disability or death without timely intervention. In some cities or countries where the incidence of V. vulnificus infection is not high, it is easy to cause misdiagnosis and delay the treatment of the disease. This case showed a 42-year-old man from a non-coastal area in China who accidentally stabbed his right hand while handling seafood 1 day earlier. He developed significant local redness, swelling, pain, and systemic symptoms. When the patient visits the doctor, the doctor makes an accurate initial diagnosis based on the patient's medical history and clinical manifestations. Effective antibiotic combination treatment is given before the feedback of bacterial culture results. Fasciotomy is immediately performed when there are signs of progression of osteofascial compartment syndrome. Finally, the patient's right hand and right forearm were preserved.

Background: We previously developed a novel score derived from the Sequential Organ Failure Assessment score and demonstrated its ability to predict delayed cerebral ischemia-associated infarctions following spontaneous subarachnoid hemorrhage. In the current study, we investigated whether the new score (ICCTUS score) can predict neurological outcome.

Methods: We retrospectively evaluated all SAH patients in our neurosurgical ICU during a 10-year period. Patients were included if clinical data were available to determine SOFA and ICCTUS scores. Outcome was objectified by the modified Rankin Scale (mRS) after 6 months. Every parameter of the SOFA score was graded for its predictive value and combinations were tested using ROC analysis.

Results: 430 patients fulfilled the inclusion criteria (68.14% female, mean age: 56.8 ± 12.5 years). Median SOFA and ICCTUS scores were 5. The SOFA score had an AUC of 0.76 for prediction of unfavorable outcome. In comparison, the WFNS achieved an AUC of 0.71, and the HH an AUC of 0.64. For the ICCTUS score, which is based exclusively on the subscores rating the central nervous system, the cardiovascular system, and the respiratory system the AUC was at 0.8 with a sensitivity of 0.74, a specificity of 0.74, a PPV of 0.83 and a NPV of 0.62. The Youden index was 0.48 (cut-off ≥3 points).

Conclusion: The ICCTUS score was at least equal or superior to the established scores in predicting unfavorable outcome after SAH. The score could be implemented as an additional tool in multimodal diagnostics to identify patients at high risk.

Introduction: Hemifacial spasm (HFS) is a neurological disorder characterized by involuntary, paroxysmal twitching of facial muscles, primarily presenting as sudden and recurrent contractions on one side of the face. This case report described the therapeutic effect of electroacupuncture (EA) in a cervical cancer patient who developed HFS following chemotherapy.

Case description: A 60-year-old female patient with cervical cancer developed severe involuntary twitching of the right facial muscles following chemotherapy, which significantly impaired her daily activities. The patient was diagnosed with HFS and was introduced to the acupuncture department to receive EA treatment. Following 15 sessions of EA treatment, the patient's HFS symptoms improved significantly, with complete resolution of facial muscle twitching.

Conclusion: The case suggests that EA may be an effective alternative treatment for chemotherapy-induced HFS.