Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Objective:To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD).Methods:Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y ( SRY) gene and azoospermia factor ( AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). Results:Case 1 had a karyotype of 45, X[22]/46, XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+ ), AZFb+ c (-). Case 2 had a karyotype of 45, X[12]/46, X, del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46, XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+ ) and AZFa+ b+ c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46, XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+ ) and AZFa+ b+ c (+ ), and WES revealed a c. 1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+ PP1+ PM2_Supporting). Conclusion:The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.

OBJECTIVE: To explore the clinical characteristics and genetic factors in four patients with Disorder of sex development (DSD). METHODS: Four patients who visited Tianjin Medical University General Hospital between January 2023 and January 2024, presenting with short stature, abnormal external genitalia, or infertility as their chief complaints, were selected as the study subjects. Clinical data were collected, and peripheral or umbilical cord blood samples were obtained for karyotyping analysis and low-depth whole-genome sequencing (CNV-seq). Quantitative fluorescence PCR (QF-PCR) was used to detect the sex-determining region Y (SRY) gene and azoospermia factor (AZF) on the Y chromosome, while fluorescence in situ hybridization (FISH) was employed to determine the location of the SRY gene. Whole exome sequencing (WES) was performed for genetic testing, and Sanger sequencing was used for familial validation of the candidate variants. The study procedure and protocol were approved by the Medical Ethics Committee of Tianjin Medical University General Hospital (Ethics No.: IRB2024-WZ-006). RESULTS: Case 1 had a karyotype of 45,X[22]/46,XY[8], with CNV-seq indicating a mosaic deletion of 7.44 Mb (copy number = 0.2) at Yp11.31-p11.2, a mosaic deletion of 5.32 Mb (copy number = 0.3) at Yq11.1-q11.221, and a deletion of 10.26 Mb (copy number = 0) at Yq11.221-q11.23. Y chromosome microdeletion analysis showed SRY and AZFa (+), AZFb+c (-). Case 2 had a karyotype of 45,X[12]/46,X,del(X)(q26.3)[18], with CNV-seq indicating a mosaic deletion of 132.62 Mb (copy number = 1.4) at Xp22.33-q26.3 and a deletion of 19.62 Mb (copy number = 1) at Xq26.3-q28. Case 3 had a karyotype of 46,XX, with CNV-seq showing two copies of the X chromosome and no Y chromosome. Y chromosome microdeletion analysis showed SRY (+) and AZFa+b+c (-), and FISH confirmed a translocation of the SRY gene to the terminal end of the short arm of the X chromosome. Case 4 had a karyotype of 46,XY, with CNV-seq showing one copy each of the X and Y chromosomes. Y chromosome microdeletion analysis showed SRY(+) and AZFa+b+c (+), and WES revealed a c.1103del variant in the AR gene (maternal origin), which was classified as a pathogenic variant based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) (PVS1+PP1+PM2_Supporting). CONCLUSION The combined application of multiple detection techniques such as chromosomal karyotyping analysis, CNV-seq, QF-PCR, and WES can identify the genetic etiology of DSD patients, providing a basis for clinical consultation and treatment plan formulation.
Humans ; Male ; Female ; Chromosomes, Human, Y/genetics* ; Disorders of Sex Development/genetics* ; Sex-Determining Region Y Protein/genetics* ; Karyotyping ; In Situ Hybridization, Fluorescence ; Exome Sequencing ; Adult ; Child

OBJECTIVE: To observe change in serum growth differentiation factor 11 (GDF11) and killer cell lectin-like receptor B1 (KLRB1), to construct a nomogram model for 28-day death in patients with septic shock, and to explore its predictive value. METHODS: A prospective observational study was conducted. The patients with septic shock admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from September 2023 to March 2025 were selected as the septic shock group, the patients with sepsis admitted to the emergency general ward during the same period were selected as the sepsis group, and healthy individuals undergoing physical examination during the same period were selected as the control group. On the day of hospital admission or physical examination for the research subjects, the levels of serum GDF11 and KLRB1 were detected by enzyme-linked immunosorbent assay (ELISA). The patients with septic shock were divided into survival and death groups based on their 28-day survival status. The patients' gender, age, past medical history, infection site, severity of illness, mechanical ventilation, blood purification, infection indicators, biochemical indicators, coagulation function indicators, and blood lactic acid (Lac) were collected. The clinical data of the patients with septic shock between the two groups with different prognoses were compared. Multivariate Logistic regression analysis was used to screen the risk factors for 28-day death in patients with septic shock, and bivariate Pearson correlation analysis was conducted. A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. The discrimination and calibration of the nomogram model were evaluated using the receiver operator characteristic curve (ROC curve), Hosmer-Lemeshow goodness-of-fit test, and calibration curve. The clinical utility of the model was evaluated using clinical decision curve analysis (DCA). RESULTS: A total of 168 patients in the emergency ICU were enrolled in the septic shock group, 40 patients in the emergency general ward were enrolled in the sepsis group, and 40 healthy individuals were enrolled in the control group. Compared with the healthy control group, the serum GDF11 levels in the sepsis and septic shock groups were significantly increased (μg/L: 13.09±3.51, 19.28±5.36 vs. 4.17±0.92, both P < 0.05), and the serum KLRB1 levels were significantly decreased (ng/L: 57.36±11.28, 45.52±9.07 vs. 84.19±17.16, both P < 0.05), with more significant changes in the septic shock group (both P < 0.05). Among the 168 patients with septic shock, 96 survived and 72 died within 28 days. Compared with the survival group, the serum GDF11 level in the death group was significantly increased (μg/L: 24.24±4.81 vs. 15.56±4.62, P < 0.05), and the serum KLRB1 level was significantly decreased (ng/L: 28.53±8.69 vs. 58.26±9.45, P < 0.05). There were also statistically significant differences in sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), activated partial thromboplastin time (APTT), D-dimer, and Lac between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.96, 95% confidence interval (95%CI) was 1.38-3.65), Lac (OR = 1.38, 95%CI was 1.09-2.01), GDF11 (OR = 1.54, 95%CI was 1.21-2.33) and KLRB1 (OR = 0.64, 95%CI was 0.41-0.78) were independent risk factors for 28-day death in patients with septic shock (all P < 0.05). Bivariate Pearson correlation analysis showed that SOFA score was significantly positively correlated with Lac and GDF11 (r value was 0.37 and 0.58, respectively, both P < 0.05), and significantly negatively correlated with KLRB1 (r = -0.72, P < 0.05). A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. ROC curve analysis showed that the area under the ROC curve (AUC) of the nomogram model for predicting 28-day death in patients with septic shock was 0.963 (95%CI was 0.929-0.990), indicating that the model had good discrimination and predictive ability. The Hosmer-Lemeshow goodness-of-fit test (χ ² = 9.578, P = 0.295) and calibration curve indicated that the predicted values of the model were in good agreement with the actual values. DCA indicated that the model provided a high net benefit for clinical decision-making. CONCLUSIONS The serum GDF11 level was significantly increased and the KLRB1 level was significantly decreased in patients with septic shock. The nomogram model based on GDF11 and KLRB1 could more accurately evaluate the 28-day death of patients with septic shock.
Humans ; Shock, Septic/blood* ; Nomograms ; Prospective Studies ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Spontaneous coronary artery dissection is a non-atherosclerotic cause of acute coronary syndrome, particularly among young women. A 46-year-old female without a family history of cardiac disease and traditional atherosclerotic risk factors presented to hospital with non-ST-segment elevation myocardial infarction. Diagnostic coronary angiography revealed moderate stenosis of the left main coronary artery and the left anterior descending artery with blood flow thrombolysis in myocardial infarction grade 3. The left circumflex artery was observed hypoplastic without significant stenosis. Intravascular ultrasound revealed an extensive intramural hematoma from the middle of the left anterior descending branch to the left main trunk and a compressed lumen with intact intima. The patient underwent conservative treatment and remained asymptomatic 11 months after discharge. Repeat coronary computed tomography angiography showed haematoma absorption with stenosis relief. Spontaneous coronary artery dissection of the left main coronary artery is relatively rare. Its management is based on the patient’s clinical condition and lesion characteristics.

Objective To investigate the effect of acupuncture at Hegu(LI4)on neural activity in the visual cortex of healthy volunteers using functional near-infrared spectroscopy(fNIRS).Methods Each healthy volunteer underwent three sets of trials in a resting state:the LI4 group received acupuncture stimulation at the right Hegu(LI4)acupoint;the negative control was the sham acupoint group(SHAM group);and the positive control was the visual stimulation group(VISUAL group).fNIRS was used to simultaneously monitor changes in oxygenated hemoglobin(Oxy-Hb)levels in the vis-ual cortex during various stages of acupuncture or visual tasks,thereby reflecting the activation level of the visual cortex.The entire acupuncture procedure was performed with the subjects' eyes closed.fNIRS recorded the raw optical density values of hemodynamics in the region of interest(ROI)of the visual cortex during each task phase.The relative coefficientβ value for oxygenated hemoglobin was obtained via Matlab analysis,and the coefficient difference Δβ value between the task period and the baseline period was calculated,representing the degree of change in oxygenated hemoglobin content in-duced by the stimulus,which reflected the change in activation level of the visual cortex after acupuncture or visual stimu-lation.A larger Δβ value indicates a higher degree of visual cortex activation.Generalized estimating equations(GEE)were applied to analyze the differences in visual cortex activation levels among the LI4,SHAM,and VISUAL groups.Results In channels 15 and 17 of the striate area and channels 10 and 13 of the extrastriate area,the Δβ values of sub-jects in the LI4 group during the needle manipulation and withdrawal phases were significantly higher than those in the SHAM group(all P＜0.01).When comparing the Δβ values of the LI4 group during the needle manipulation and withdrawal phases with those of the VISUAL group,under the current sample size,the differences were not statistically significant(all P＞0.05).The Δβ values in both the striate and extrastriate areas of the LI4 group peaked during the needle manipulation phase.Conclusion Acupuncture at Hegu(LI4)can effectively activate the visual cortex in healthy volunteers,with the most significant increase in activation observed during the needle manipulation phase.

Blood transfusion can transmit various pathogenic microorganisms, including parasites, spirochetes, bacteria, and viruses, leading to transfusion-transmitted infectious diseases as well as numerous clinical transfusion-related adverse reactions. To ensure blood safety, multiple strategies have been implemented, including assessing donor health status, blood screening, and preparation, processing, storage, and supply of blood components. However, there is still room for improvement in preventing various transfusion-related infectious diseases and adverse reactions due to objective factors such as donor health consultation, the threats and prevention costs associated with emerging infectious disease pathogens, and the limitations of blood screening in terms of scope and sensitivity. This article aims to review the research progress on the preparation, storage, and supply of blood components.

Spontaneous coronary artery dissection is a non-atherosclerotic cause of acute coronary syndrome, particularly among young women. A 46-year-old female without a family history of cardiac disease and traditional atherosclerotic risk factors presented to hospital with non-ST-segment elevation myocardial infarction. Diagnostic coronary angiography revealed moderate stenosis of the left main coronary artery and the left anterior descending artery with blood flow thrombolysis in myocardial infarction grade 3. The left circumflex artery was observed hypoplastic without significant stenosis. Intravascular ultrasound revealed an extensive intramural hematoma from the middle of the left anterior descending branch to the left main trunk and a compressed lumen with intact intima. The patient underwent conservative treatment and remained asymptomatic 11 months after discharge. Repeat coronary computed tomography angiography showed haematoma absorption with stenosis relief. Spontaneous coronary artery dissection of the left main coronary artery is relatively rare. Its management is based on the patient’s clinical condition and lesion characteristics.

Objective To investigate the effect of acupuncture at Hegu(LI4)on neural activity in the visual cortex of healthy volunteers using functional near-infrared spectroscopy(fNIRS).Methods Each healthy volunteer underwent three sets of trials in a resting state:the LI4 group received acupuncture stimulation at the right Hegu(LI4)acupoint;the negative control was the sham acupoint group(SHAM group);and the positive control was the visual stimulation group(VISUAL group).fNIRS was used to simultaneously monitor changes in oxygenated hemoglobin(Oxy-Hb)levels in the vis-ual cortex during various stages of acupuncture or visual tasks,thereby reflecting the activation level of the visual cortex.The entire acupuncture procedure was performed with the subjects' eyes closed.fNIRS recorded the raw optical density values of hemodynamics in the region of interest(ROI)of the visual cortex during each task phase.The relative coefficientβ value for oxygenated hemoglobin was obtained via Matlab analysis,and the coefficient difference Δβ value between the task period and the baseline period was calculated,representing the degree of change in oxygenated hemoglobin content in-duced by the stimulus,which reflected the change in activation level of the visual cortex after acupuncture or visual stimu-lation.A larger Δβ value indicates a higher degree of visual cortex activation.Generalized estimating equations(GEE)were applied to analyze the differences in visual cortex activation levels among the LI4,SHAM,and VISUAL groups.Results In channels 15 and 17 of the striate area and channels 10 and 13 of the extrastriate area,the Δβ values of sub-jects in the LI4 group during the needle manipulation and withdrawal phases were significantly higher than those in the SHAM group(all P＜0.01).When comparing the Δβ values of the LI4 group during the needle manipulation and withdrawal phases with those of the VISUAL group,under the current sample size,the differences were not statistically significant(all P＞0.05).The Δβ values in both the striate and extrastriate areas of the LI4 group peaked during the needle manipulation phase.Conclusion Acupuncture at Hegu(LI4)can effectively activate the visual cortex in healthy volunteers,with the most significant increase in activation observed during the needle manipulation phase.