Patients with panvascular disease （PVD） often experience bleeding events while receiving standard antithrombotic therapy. Based on the theory of "guarding the channel passages"， the retention of blood stasis is considered as a crucial pathological basis for PVD. The combination of the retention of blood stasis and the failure of the channel passages to contain blood constitutes the core pathogenesis of bleeding events in this condition. According to their pathogenesis and clinical characteristics， bleeding events in PVD are categorized into a bleeding stage and a stable stage. During the bleeding stage， treatment should focus on stanching bleeding and dispersing stasis to restore normal circulation in the channel passages. During the stable stage， treatment should aim to dispel stasis and generate new blood to harmonize the channel passages. In clinical practice， physicians should dynamically weigh the risks of bleeding and ischemia against the intensity of antithrombotic therapy. The ultimate goal is to harmonize qi and blood and ensure that blood remains properly contained within the channel passages， thereby reducing the risk of bleeding events and enhancing overall patient benefit.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

AIM: To investigate the influence of relevant inflammatory markers in peripheral blood on the progression of neovascular glaucoma(NVG)secondary to diabetic retinopathy(DR)patients.METHODS: Retrospective case-control study. Patients were categorized into two groups based on the presence or absence of NVG: those with proliferative diabetic retinopathy(PDR)alone(PDR group, n=148)and those with NVG secondary to PDR(NVG secondary to PDR group, n=142). Peripheral blood inflammatory markers were evaluated, including white blood cell-related indices, neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), monocyte-to-lymphocyte ratio(MLR), and systemic immune-inflammation index(SII). The distinctions in peripheral blood inflammatory markers between the two groups of patients and their relationships with NVG secondary to PDR were analyzed.RESULTS:No statistically significant differences were observed in basic characteristics between the two groups, confirming their comparability. However, significant differences were found in eosinophil percentage and MLR between the PDR group and the NVG secondary to PDR group(all P<0.05), with both values being significantly higher in the NVG secondary to PDR group. Multivariate Logistic regression analysis revealed that the eosinophil percentage and the MLR were factors influencing the development of patients with NVG secondary to PDR.CONCLUSION: Eosinophil percentage and MLR may be associated with the progression of PDR to NVG, and could serve as potential predictive markers for NVG development in PDR patients.

Objective:To explore the correlation between levels of serum cold-inducible RNA-binding protein(CIRBP), cystatin C(CysC) and cognitive impairment in patients with cerebral small vessel disease(CSVD), as well as the diagnostic value of CI in CSVD.Methods:A total of 90 CSVD patients admitted to the Neurology Department of Zhengzhou People's Hospital from January 2024 to December 2024 were consecutively selected. According to the mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA), they were divided into non cognitive impairment group(NCI group, n=47) and cognitive impairment group(CI group, n=43). The general clinical data of patients were collected.Fasting venous blood was collected in the morning on the second day of admission to measure serum CIRBP, CysC, homocysteine(Hcy) and high-sentivity C-reactive protein(hs-CRP) levels.A multiple-factor Logistic regression model was applied to identify independent risk factors for CI in CSVD patients, the predictive performance of the model was evaluated by receiver operating characteristic(ROC) curves, and the area under the curve(AUC) value was calculated to quantify the diagnostic accuracy of the model. Results:The levels of Hcy((13.01±4.22)μmol/L vs (11.44±3.00)μmol/L), hs-CRP((2.84±3.01)mmol/L vs (1.81±1.32)mmol/L), CIRBP((2 412.40±967.78)pg/mL vs (1 715.13±971.98)pg/mL), and CysC((1.93±1.08)mg/L vs (1.24±0.87)mg/L) in the CI group were significantly higher than those in the NCI group(all P<0.05). Multiple Logistic regression analysis showed that both CIRBP( OR=1.001, 95% CI=>1.000-1.002, P=0.011) and CysC( OR=1.833, 95% CI=1.056-3.181, P=0.031) were independently influencing factors of the occurrence of CI in CSVD patients(all P<0.05). ROC curve analysis showed that the optimal cutoff values for serum CIRBP and CysC levels to evaluate CI were 1 875.50 pg/mL and 1.42 mg/L, respectively. The AUC (95% CI) were 0.805(95% CI=0.713-0.897, P<0.001) and 0.716(95% CI=0.607-0.825, P<0.001), respectively.The AUC(95% CI) of combined detection of CIRBP+ CysC was 0.820(95% CI=0.733-0.907, P<0.001), with specificity and sensitivity of 89.4% and 67.4%. Conclusion:The serum CIRBP and CysC levels can serve as independent predictors of CI in CSVD patients. Combined testing can improve the accuracy of patient condition assessment and may assist in the diagnosis and prediction of cognitive impairment in CSVD.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective·To investigate the clinicopathologic features,gene mutation profile,and real-world survival prognosis of diffuse large B-cell lymphoma(DLBCL)with pulmonary involvement.Methods·The clinical data of 110 patients with newly diagnosed,pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between August 2003 and December 2022 were retrospectively collected and analyzed.Evaluation of the efficacy of treatment,survival analyses,and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide,doxorubicin/epirubicine,vincristine,and prednisone(R-CHOP).A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations.Results·Among the 110 patients,72(65.5%)were>60 years old,52(47.3%)were female,92(83.6%)presented with Ann Arbor stage Ⅲ?Ⅳ,20(18.2%)had ECOG scores≥2,75(68.2%)had elevated lactate dehydrogenase(LDH)levels,79(71.8%)had≥2 extranodal involvements,32(31.4%)were classified as germinal center B-cell subtype,22(26.8%)were diagnosed with double expressor lymphoma,and 4(4.6%)with double-hit lymphoma.Among the patients treated with R-CHOP-based first-line regimens,the objective response rate(ORR)was 68.2%,the 5-year progression-free survival(PFS)rate was 43.7%,and the 5-year overall survival(OS)rate was 65.4%.Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS,and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations.Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS(HR=2.47,95%CI 1.28?4.77)and OS(HR=2.71,95%CI 1.21 ? 6.07).Targeted sequencing results showed that PIM1(25.7%),MYD88(24.3%),TP53(18.9%),CD79B(17.6%),KMT2D(17.6%),and TNFAIP3(16.2%)were the high-frequency mutations with mutation rates over 15%.Conclusion·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement.Mutations in PIM1,MYD88,TP53,CD79B,KMT2D,and TNFAIP3 are frequently observed in this population.

Objective:To assess the influencing factors of glycemic control among type 2 diabetes mellitus (T2DM) patients, in particular the correlations between peripheral blood eosinophils and metabolic indicators such as glucose, lipids, and uric acid (UA) in these patients.Methods:T2DM patients who were regularly followed up in the Intensive Diabetes Mellitus Clinic of Peking Union Medical College Hospital from January 2016 to September 2024 were prospectively selected as the research subjects. The clinical data of these patients at their first visit and at the 3rd, 6th, 9th, and 12th months of follow-up were collected. The potential correlations of peripheral blood eosinophils with blood glucose control, lipid metabolism, UA metabolism, and inflammation as well as their influencing factors were analyzed.Results:A total of 161 T2DM patients were included. The glycated hemoglobin A1c (HbA1c) compliance rate was significantly higher during the follow-up visits (3, 6, 9, and 12 months) than baseline (all P<0.05) but showed no significant correlation with the count or percentage of peripheral blood eosinophils. Spearman correlation analysis showed that the percentage of peripheral blood eosinophils was negatively correlated with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ( P=0.049) and high-density lipoprotein cholesterol (HDL-C) ( P=0.002) and positively with serum triglyceride (TG) ( P=0.034) and UA levels ( P<0.001). A further linear regression model analysis of these four variables and the percentage of eosinophils revealed that the percentage of peripheral blood eosinophils was only linearly correlated with serum UA level ( P<0.001). Conclusion:The percentage of peripheral blood eosinophils in T2DM patients is independently correlated with serum UA level, and monitoring serum UA level is important in T2DM management. Early identification and intervention of hyperuricemia can help provide more comprehensive and precise medical interventions for T2DM patients.

Objective:To explore the correlation between levels of serum cold-inducible RNA-binding protein(CIRBP), cystatin C(CysC) and cognitive impairment in patients with cerebral small vessel disease(CSVD), as well as the diagnostic value of CI in CSVD.Methods:A total of 90 CSVD patients admitted to the Neurology Department of Zhengzhou People's Hospital from January 2024 to December 2024 were consecutively selected. According to the mini-mental state examination(MMSE) and Montreal cognitive assessment(MoCA), they were divided into non cognitive impairment group(NCI group, n=47) and cognitive impairment group(CI group, n=43). The general clinical data of patients were collected.Fasting venous blood was collected in the morning on the second day of admission to measure serum CIRBP, CysC, homocysteine(Hcy) and high-sentivity C-reactive protein(hs-CRP) levels.A multiple-factor Logistic regression model was applied to identify independent risk factors for CI in CSVD patients, the predictive performance of the model was evaluated by receiver operating characteristic(ROC) curves, and the area under the curve(AUC) value was calculated to quantify the diagnostic accuracy of the model. Results:The levels of Hcy((13.01±4.22)μmol/L vs (11.44±3.00)μmol/L), hs-CRP((2.84±3.01)mmol/L vs (1.81±1.32)mmol/L), CIRBP((2 412.40±967.78)pg/mL vs (1 715.13±971.98)pg/mL), and CysC((1.93±1.08)mg/L vs (1.24±0.87)mg/L) in the CI group were significantly higher than those in the NCI group(all P<0.05). Multiple Logistic regression analysis showed that both CIRBP( OR=1.001, 95% CI=>1.000-1.002, P=0.011) and CysC( OR=1.833, 95% CI=1.056-3.181, P=0.031) were independently influencing factors of the occurrence of CI in CSVD patients(all P<0.05). ROC curve analysis showed that the optimal cutoff values for serum CIRBP and CysC levels to evaluate CI were 1 875.50 pg/mL and 1.42 mg/L, respectively. The AUC (95% CI) were 0.805(95% CI=0.713-0.897, P<0.001) and 0.716(95% CI=0.607-0.825, P<0.001), respectively.The AUC(95% CI) of combined detection of CIRBP+ CysC was 0.820(95% CI=0.733-0.907, P<0.001), with specificity and sensitivity of 89.4% and 67.4%. Conclusion:The serum CIRBP and CysC levels can serve as independent predictors of CI in CSVD patients. Combined testing can improve the accuracy of patient condition assessment and may assist in the diagnosis and prediction of cognitive impairment in CSVD.

A 36-year-old male developed unconsciousness and no response to voice stimuli after taking approximately 2 050 mg felodipine (the specific time was unknown). Two hours later, he was sent to the department of emergency by his family and admitted to the hospital. His vital signs showed body temperature 35.1 ℃, pulse 148 times/min, respiration 32 times/min, and blood pressure 65/34 mmHg. Acute drug poisoning, acute toxic cardiomyopathy, acute toxic shock, acute type Ⅱ respiratory failure, acute toxic encephalopathy, and acute renal failure were diagnosed based on the patient′s clinical manifestations combined with laboratory tests results, cardiac ultrasound, chest and abdominal CT scans. Endotracheal intubation connected to a ventilator for invasive assisted ventilation, pressure boosting, and fluid resuscitation were given. At the same time, repeated gastric lavage and enema were performed to remove toxins. Blood perfusion was intermittently and repeatedly administered, and continuous renal replacement therapy was used. The blood concentration of felodipine was 1 298 μg/L at 2 hours after admission, and cardiac arrest occurred at 4 hours. Venous-arterial extracorporeal membrane oxygenation (V-A ECMO) treatment was administered immediately. After 48 hours of ECMO operation, sedatives were discontinued and the patient′s consciousness was improved after 4 hours. On the 5th day of ECMO treatment, his heart rate was 72 beats per minute, and blood pressure was 127/65 mmHg. The blood concentration of felodipine decreased to 2 μg/L. The patient′s vital signs were significantly improved and ECMO supportive treatment was withdrawn. After 26 days of hospitalization, the patient recovered and was discharged.

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.