Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.

Objective: To improve the efficiency of patient treatment in routine, emergency, and mass casualty scenarios (both peacetime and wartime), eliminate reliance on blood type compatibility, and promote the productization of platelet-rich plasma (PRP), this study investigated the optimal mixing ratio for developing a universal PRP formulation. Methods: PRP was prepared from donors with blood types O, A, B, and AB. Samples were mixed in varying proportions, and the optimal ratio was determined based on the trend of anti-A and anti-B antibody titers in the mixed PRP. Concentrations of the growth factors PDGF-AA, PDGF-BB, EGF, TGF-β1, and VEGF were measured by enzyme-linked immunosorbent assay (ELISA) before and after mixing. Results: A mixing ratio of A∶B∶AB=6∶2.5∶24 resulted in no detectable agglutination with either A or B cells in the microcolumn gel system, indicating the absence of immunological reactivity and confirming universal compatibility. Importantly, the levels of all measured growth factors remained unchanged following mixing, suggesting preservation of biological activity. Conclusion: These findings suggest that universal PRP can be prepared by neutralizing blood type antibodies through antigen-antibody reactions.

Objective: To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice. Methods: Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue. Results: Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group. Conclusion Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.

Objective To analyze the risk factors for delayed hemorrhage in patients with early gastric carcinoma(EGC)after endoscopic submucosal dissection(ESD),as well as to explore the predictive value of predictive models.Methods The clinical data of 386 EGC treated with ESD patients from July 2019 to March 2024 were retrospectively analyzed.They were followed up for a short period of time(24 h～30 d postoperatively)after ESD,and were divided into the group of occurrence(50 cases)and the group of non-occurrence(336 cases)according to the occurrence or non-occurrence of delayed hemorrhage.To understand the clinical data of the patients,multivariate Logistic regression was used to analyze the risk factors for delayed hemorrhage in patients with EGC after ESD,and plot receiver operating characteristic curve(ROC curve)to analyze the predicted value.Results The proportions of cardia gastric fundus,lesion diameter ≥ 3 cm,submucosa with fibrosis,coarse blood vessels,and having ulcer or scar in the occurrence group were significantly higher than those in the non-occurrence group,the differences were statistically significant(P＜0.05).The results of multivariate Logistic regression analysis(with an introduction level of 0.05)showed that the lesion location was cardia-gastric fundus(OR=1.088,95％CI:1.040～1.138),the diameter of the lesion was ≥3 cm(OR=1.095,95％CI:1.057～1.135),and fibrosis under the mucosa(OR=1.130,95％CI:1.061～1.203),thick blood vessels under the mucosa(OR=1.177,95％CI:1.116～1.241),and the presence of ulcer or scar(OR=1.082,95％CI:1.057～1.108)were the risk factors for the occurrence of delayed hemorrhage in patients with EGC after ESD(P＜0.05).A prediction model was established:Logit(P)=-9.238+Location of lesion as cardia-gastric fundus × 0.084+Diameter of lesion ≥ 3 cm× 0.091+Submucosal with fibrosis × 0.122+Submucosal with thick blood vessels × 0.163+Ulcer or scar×0.079(P＜0.05),the likelihood ratio test yielded x2=131.09,DF=8,P＜0.05,which indicated that the constructed prediction model was valid.Hosmer-Lemeshow goodness-of-fit test showed a good model fit(P＞0.05).The ROC curve showed an area under the curve(AUC)value of 0.929 at a cutoff value of 12.00,with a sensitivity of 88.00％(95％CI:0.757～0.955)and a specificity of 83.04％(95％CI:0.780～0.869).Conclusion Postoperative delayed hemorrhage in patients with EGC treated with ESD is associated with cardia-gastric fundus,lesion diameter ≥3 cm,submucosal fibrosis,thick blood vessels,and the presence of ulcer or scar,and the prediction value of the prediction model constructed accordingly is good.

Myasthenia gravis(MG)is an autoimmune disease characterized primarily by skeletal muscle weakness and,in severe cases,respiratory involvement.Western medical treatment predominantly relies on immunosuppressants,but long-term administration often leads to notable side effects.In contrast,traditional Chinese medicine(TCM)offers the advantage of multi-target interventions.However,the pathogenesis of MG has not been fully elucidated,and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development.This paper systematically reviews the etiology and pathogenesis,diagnostic criteria,and progress of animal model research for MG from both Chinese and Western medicine perspectives.In Western medicine,the pathogenesis of MG is closely related to genetic susceptibility,environmental factors,and autoantibody-mediated postsynaptic membrane damage.In TCM,MG is classified under the category of"flaccidity syndrome",attributed to congenital deficiencies and acquired malnourishment.Western diagnostic criteria involve a combination of clinical symptoms,fatigue testing,serum antibody assays,and electrophysiological evaluation.In contrast,TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation.Currently available animal models mainly include experimental autoimmune myasthenia gravis(EAMG)and passive transfer myasthenia gravis(PTMG).The Toredo acetylcholine receptor(AChR)induced EAMG model aligns well with Western diagnostic criteria,but poorly matches secondary symptoms in TCM.The synthetic AChR peptide model is widely used,but shows low conformity with TCM syndromes.Models induced by muscle-specific tyrosine kinase(MuSK),low-density lipoprotein receptor-related protein 4(LRP4),and transgenic models demonstrate high innovation but exhibit low clinical conformity.Evaluation of these models requires integration of behavioral,electrophysiological,and immunological indicators.However,a systematic framework for modelling TCM syndromes is still lacking.Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models.Additionally,it is crucial to establish a TCM syndrome evaluation system based on"validation by prescription",as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies.This review provides a theoretical foundation for optimizing MG animal model design,advancing the research on the combination of Chinese and Western medicine,and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

To study the immunoregulatory effects of lycorine on mice infected with Toxoplasma gondii(T.gondii),BALB/c mice were treated with 20 mg/kg lycorine solution after peritoneal in-fection with T.gondii RH strain.The serum and spleen of mice were collected at the 1st,3rd,5th and 7th day,respectively,and the spleen index of mice was calculated.The proportion of T lympho-cyte subtypes and NK cells were detected in mice by flow cytometry,and the changes of cytokine levels in mice were measured using ELISA kit,so as to evaluate the immunomodulatory effect of lycorine on mice infected with T.gondii.At the same time,the heart,liver,spleen,lungs,and kid-neys of mice were collected at the 7th day,and the pathological changes of the mouse organs were observed through pathological tissue sections,and the amount of the parasite in the liver,lung,kid-ney,and brain of the mice was detected by fluorescence quantitative PCR.The results showed that the survival time of the mice treated with lycorine was significantly extended,and the survival rate reached 80％.The spleen index of mice treated with lycorine was lower than that of the control group.Lycorine up-regulates the ratio of the CD4+T lymphocytes and NK cells in the spleen of mice infected with T.gondii,and helps to improve the ability of mice to resist T.gondii infection.Lycorine can up-regulate the levels of anti-inflammatory cytokine IL-4 and down-regulate the lev-els of pro-inflammatory factors IFN-γ,IL-1β,and IL-9 in serum of mice infected with T.gondii,which is conducive to reducing the damage of inflammatory response and enhancing the ability of anti-T.gondii infection.In addition,lycorine can alleviate the pathological damage of T.gondii to the liver,lungs,spleen,and kidneys of mice,and significantly reduce the amount of the parasite in the lung of mice.The results showed that lycorine could up-regulate the proportion of immune cells CD4+T lymphocytes and NK cells,inhibit the inflammatory response of mice infected with T.gondii,reduce the pathological damage of mice organs,and enhance the ability of mice to resist T.gondii infection,which is expected to become a novel anti-T.gondii drug.

Objective:To analyze the genetic mutation characteristics of the first reported case of DNA ligase Ⅳ syndrome primarily presenting as eczematous dermatitis and purpura in China.Methods:Clinical data were collected from a child with DNA ligase Ⅳ syndrome, and whole-exome sequencing was performed to identify genetic mutations.Results:The patient presented with generalized eczematous dermatitis and purpura, accompanied by pancytopenia, growth retardation, and immunodeficiency. Genetic testing revealed compound heterozygous mutations at three sites in the DNA ligase Ⅳ gene, namely c.467C>T (p.A156V) , c.833G>T (p.R278L) , and c.1271-c.1275del (p.K424fs*20) , among which c.467C>T (p.A156V) had not been previously reported.Conclusion:Children with DNA ligase Ⅳ syndrome may present with eczematous dermatitis and purpura, and compound heterozygous mutations in the DNA ligase Ⅳ gene may represent the genetic cause of this condition.

Objective:To explore the relationship between visceral adipose tissue (VAT) and the severity and prognosis of obese patients with acute pancreatitis (AP).Methods:The clinical data of 224 obese patients with AP admitted to The Third Affiliated Hospital of Chongqing Medical University and Chongqing Dongnan Hospital from January 2020 to December 2023 were collected, retrospectively. According to the severity of AP, they were divided into mild AP group (MAP group), moderately severe AP group (MSAP group), and severe AP group (SAP group). According to the in-hospital treatment outcomes of the patients, they were divided into the survival group and death group (death within 7-30 days after admission). The basic information of AP patients, the severity score of AP and laboratory indicators were collected. The visceral adiposity index (VAI) was calculated through the values of waist circumference, body mass index, triglycerides and high-density lipoprotein cholesterol; and the VAT area was measured by CT scan. The Spearman rank correlation analysis method was used to evaluate the correlation between the VAT area and the AP severity index as well as other indicators. Multivariate logistic regression analysis was used to analyze the influencing factors of in-hospital mortality in obese patients with AP. The receiver operating characteristic curve (ROC) was drawn, and the area under curve (AUC), cut-off value, sensitivity and specificity were calculated to evaluate the predictive value of VAT area for SAP, as well as the predictive value of VAT area for in-hospital mortality in obese AP patients.Results:The VAI of MAP group, MSAP group and SAP group were 1.63(1.21, 2.74), 2.30(1.28, 3.36) and 3.01(2.17, 3.86), respectively, and the VAT area were 138.90(121.30, 155.10)cm 2, 149.90(135.10, 166.70)cm 2 and 192.30(168.80, 223.80)cm 2, respectively. There were significant differences in VAI and VAT area among the three groups (all P values <0.05). Compared with MAP group, the area of VAI and VAT area in MSAP group and SAP group were significantly increased ( P<0.05), and the area of VAT in SAP group was further increased than that in MSAP group, the differences were statistically significant (all P values <0.05). Spearman analysis showed that the VAT area was significantly positively correlated with acute physiology and chronic health evaluationⅡ scoring system (APACHEⅡ) score, modified CT severity index (MCTSI), and Balthazar CT grading score (all P values <0.05). It was also significantly positively correlated with body mass index, serum glycated hemoglobin, triglycerides, low-density lipoprotein cholesterol and VAI (all P values <0.05). ROC analysis showed that the AUC value of VAI in identifying SAP was 0.641 (95% CI 0.562-0.720), the corresponding cut-off value was 2.75, the sensitivity was 57.6%, and the specificity was 69.0%; The AUC value of VAT area in identifying SAP was 0.869 (95% CI 0.813-0.924), the corresponding cut-off value was 165.85 cm 2, the sensitivity was 78.8%, and the specificity was 84.8%, and the predictive value of VAT area was significantly better than that of VAI ( P<0.001). The APACHEⅡ, MCTSI, Balthazar CT grading score, VAI and VAT area in the death group were significantly higher than those in the survival group, and the differences were statistically significant (all P values <0.05). Multivariate logistic regression analysis showed that VAT area was an independent predictor of in-hospital mortality in obese AP patients ( P<0.05), with an AUC value of 0.831 (95% CI 0.756-0.907), a cutoff value of 173.70 cm 2, a sensitivity of 77.8%, and a specificity of 85.5%. Conclusions:The VAT area is significantly associated with the aggravation of AP and the increased risk of in-hospital mortality in obese patients, and is expected to serve as a reliable indicator for predicting the severity and prognosis of obese patients with AP.

Although the COVID-19 pandemic has subsided, the risk of the outbreak of new emerging infectious diseases remained constantly present. As such an outbreak can have devastating consequences to the society and economy, development of warning strategies before it takes place is a critical and urgent research task. However, there are currently no validated methods that are both effective and practically feasible for giving pre-outbreak alerts. As such, timely identification and rapid response after an outbreak takes place is still a feasible and effective method for responding to new emerging infectious diseases. The speed and efficiency of the response are largely contingent upon preparedness during the inter-epidemic periods. This paper aims to outline our thinking about the framework for infectious disease early warning and propose some recommendations. Implementation of such a strategy in practice necessitates the establishment of pilot initiatives to test the early warning system according to our proposed principles. These pilots may use severe influenza or hypothetical outbreak scenarios as examples, define warning signals, develop the mechanisms for epidemiological investigation, reporting and response so as to conduct feasibility assessments.