OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

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 gender differences in the causal relationship between testosterone-related hormones and type 2 diabetes mellitus(T2DM), and to analyze the mediating role of blood lipids in this relationship.Methods:Using two-sample Mendelian randomization(TSMR) and two-step Mendelian randomization(MR) methods, we explored the causal associations between testosterone-related hormones, T2DM, and blood lipids in different genders. The potential mediating role of blood lipids between testosterone-related hormones and T2DM was quantitatively assessed using multivariate Mendelian Randomization(MVMR).Results:In males, each standard deviation( SD) increase in genetically predicted total testosterone(TT) was associated with lower odds of T2DM( OR=0.90, 95% CI 0.82-0.97, P=0.009) and higher high-density lipoprotein-cholesterol(HDL-C) level( β=0.08 SD, 95% CI 0.03-0.13, P=0.002). In women, each SD rise in genetically predicted bioavailable testosterone(Bio-T) was associated with higher odds of T2DM( OR=1.24, 95% CI 1.10-1.40, P<0.001), lower HDL-C level( β=-0.13 SD, 95% CI -0.21--0.05, P<0.001). Mediation analysis revealed that HDL-C played a mediating role(7.83%) between Bio-T and T2DM in women. However, HDL-C showed no mediating effect between SHBG and TT levels on T2DM, and low-density lipoprotein-cholesterol(LDL-C) showed no mediating effect between TT levels on T2DM in men. Conclusions:Lower levels of TT and SHBG in men, and high levels of Bio-T in women may increase the risk of T2DM. In women, regulating HDL-C levels may offer a potential strategy for the prevention and treatment of T2DM related to Bio-T disorders.

Objective:To explore the high-risk factors affecting the severity of neonatal necrotizing enterocolitis (NEC).Methods:This study involved 153 NEC patients admitted to the Neonatology Department of the Children's Hospital of Soochow University from January 1, 2017, to December 30, 2023. Based on the severity of NEC determined by Bell's criteria, these patients were divided into two groups: mild group (Bell stage Ⅱ, n=70) and severe group (Bell stage Ⅲ, n=83). Clinical data including general conditions, clinical treatment and disease status before the onset of NEC, laboratory test results, and perinatal conditions of the mothers were retrospectively collected. Univariate analysis (rank-sum test and Chi-square test) and multivariate analysis (logistic regression analysis) were used to explore the risk factors affecting the severity of NEC. Results:The proportion of infants with gestational age<37 weeks or birth weight<1 500 g, the rate of antibiotic usage, sepsis or shock were higher in the severe group than in the mild group [91.6% (76/83) vs. 75.7% (53/70); 55.4% (46/83) vs. 34.3% (24/70); 85.5% (71/83) vs. 71.4% (50/70); 55.4% (46/83) vs. 17.1% (12/70); 30.1% (25/83) vs. 8.6% (6/70); with χ 2 values of 7.22, 6.84, 4.57, 23.64, and 10.91, respectively, all P<0.05]. Furthermore, the severe group had a late initiation of breastfeeding and longer durations of peripherally inserted central catheter (PICC) placement and parenteral nutrition [2.00 d (1.00-2.00 d) vs. 1.00 d (1.00-2.00 d); 0.00 d (0.00-18.00 d) vs. 0.00 d (0.00-7.50 d); 14.00 d (5.00-21.00 d) vs. 10.50 d (0.00-18.25 d), with Z values of -2.90, -1.98, and -2.09, respectively, all P<0.05]. (2) Within 48 h before the onset, the severe group had higher proportions of infants with decreased white blood cell count, decreased platelet count, electrolyte imbalance, and metabolic acidosis than the mild group [53.0% (44/83) vs. 14.3% (10/70); 49.4% (41/83) vs. 10.0% (7/70); 38.6% (32/83) vs. 14.3% (10/70); 37.3% (31/83) vs. 14.3% (10/70), with χ2 values of 24.94, 27.38, 11.23, and 10.30, respectively, all P<0.05]. Besides, the levels of procalcitonin and C-reactive protein were higher in the severe group than in the mild group [2.31 ng/ml (0.26-11.71 ng/ml) vs. 0.22 ng/ml (0.00-2.19 ng/ml); 58.50 mg/L (14.34-125.25 mg/L) vs. 8.20 mg/L (0.23-34.56 mg/L), with Z values of -3.88 and -5.02, respectively, both P<0.05]. (3) Multivariate logistic regression analysis showed that prolonged duration of PICC placement, decreased platelet count, electrolyte imbalance, metabolic acidosis, and concurrent sepsis were independent risk factors affecting the severity of NEC [ OR (95% CI) values were 1.104 (1.020-1.196), 5.364 (1.667-17.253), 4.047 (1.171-13.986), 4.333 (1.290-14.556), and 3.290 (1.005-10.774), respectively, with all P<0.05]. Conclusions:Prolonged duration of PICC placement, concurrent sepsis, decreased platelet count, electrolyte imbalance, and metabolic acidosis in NEC patients are more likely to lead to severe cases. In clinical practice, attention should be paid to relevant indicators, and abnormal changes should be identified and intervened in a timely manner to reduce the occurrence of severe NEC.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To evaluate the long-term outcomes and predictors of coronary atherosclerotic lesions deemed functionally non-ischemic (quantitative flow ratio(QFR)>0.80) and deferred from intervention.Methods:This study is a post-hoc analysis of the FAVOR Ⅲ China trial, which enrolled 3 825 patients with stable or unstable angina pectoris or with myocardial infarction occurring at least 72 hours prior to screening, between December 5, 2018 and January 9, 2020 from 26 research centers in China. Coronary vessels with QFR>0.80 and without interventional treatment were analyzed in this study. The primary endpoint was 3-year target vessel revascularization. Vessels with revascularization (revascularized group) during follow-up were matched 1∶1 using propensity score matching to comparable vessels without revascularization (non-revascularized group). Multivariate Cox regression analysis was used to identify the risk factors for target vessel revascularization (TVR).Results:A total of 6 212 functionally negative vessels with deferred intervention were included in the final analysis, among which 153 vessels (2.5%) underwent TVR during a 3-year follow-up. Prior to propensity score matching, 6 059 vessels comprised the non-revascularized group. At the vessel level, compared to the non-revascularized group, the revascularized group exhibited a significantly higher proportion of males (79.1% (121/153) vs. 70.2% (4 253/6 059), P=0.018), higher body mass index ((25.6±4.0) kg/m2 vs. (24.3±5.2) kg/m2, P=0.003), and a higher prevalence of hypertension (73.9% (113/153) vs. 65.1% (3 944/6 059), P=0.025). And 152 pairs of vessels were successfully matched. Multivariate Cox regression analysis identified in-stent restenosis lesions ( HR=2.59, 95% CI 1.28-5.23, P=0.008) as an independent risk factor for target vessel revascularization. Conclusions:Coronary lesions classified as functionally non-ischemic at baseline are not entirely stable and may progress to lesions that requiring revascularization over time. In-stent restenosis emerges as a critical independent predictor of revascularization.

Objective:To explore the effect and safety profile of psycho-cardiology model combined with phased re-habilitation exercise on psychological state,cardiac function,sleep quality,cognitive function and quality of life of patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This ran-domized controlled study enrolled 150 CHD patients with anxiety and sleep disorder who underwent PCI in the Psy-cho-cardiology Medical Center of Beijing Anzhen Hospital,Capital Medical University between January 2023 and April 2023.Patients were randomly divided into control group(n=75)and intervention group(n=75).Patients in the control group received routine management mode intervention after PCI,comparing to those in the intervention group receiving psycho-cardiology model combined with phased rehabilitation exercise intervention after PCI.Both groups were intervened for 2 months and followed up for 6 months.Mental state,heart function,sleep quality,cog-nitive function,quality of life and incidence of adverse events were compared between two groups.Results:Com-pared to those in control group,patients in intervention group had significant lower scores of generalized anxiety dis-order-7(GAD-7)[(5.16±1.19)points vs.(7.53±1.68)points],patient health questionaire-9(PHQ-9)[(7.63±1.03)points vs.(10.41±1.54)points],Athens insomnia scale(AIS)[(3.69±1.35)points vs.(6.43±2.11)points]and left ventricular end diastolic diameter(LVEDd)[(44.50±2.86)mm vs.(54.11±3.46)mm](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(60.06±3.05)％vs.(53.90±3.05)％],scores of Seattle angina questionnaire(SAQ)[(83.31±6.59)points vs.(52.75±5.66)points]and mini-mental state examination(MMSE)[(26.44±4.68)points vs.(23.23±4.01)points](P＜0.001 all).We detec-ted significant lower incidence of adverse events in intervention group compared to control group(4.29％vs.16.44％,P=0.018).Conclusion:Psycho-cardiology model combined with phased rehabilitation exercise may im-prove psychological state,heart function,sleep quality,cognitive function and quality of life in CHD patients with anxiety and sleep disorder after PCI with considerable safety.

Objective:To explore the high-risk factors affecting the severity of neonatal necrotizing enterocolitis (NEC).Methods:This study involved 153 NEC patients admitted to the Neonatology Department of the Children's Hospital of Soochow University from January 1, 2017, to December 30, 2023. Based on the severity of NEC determined by Bell's criteria, these patients were divided into two groups: mild group (Bell stage Ⅱ, n=70) and severe group (Bell stage Ⅲ, n=83). Clinical data including general conditions, clinical treatment and disease status before the onset of NEC, laboratory test results, and perinatal conditions of the mothers were retrospectively collected. Univariate analysis (rank-sum test and Chi-square test) and multivariate analysis (logistic regression analysis) were used to explore the risk factors affecting the severity of NEC. Results:The proportion of infants with gestational age<37 weeks or birth weight<1 500 g, the rate of antibiotic usage, sepsis or shock were higher in the severe group than in the mild group [91.6% (76/83) vs. 75.7% (53/70); 55.4% (46/83) vs. 34.3% (24/70); 85.5% (71/83) vs. 71.4% (50/70); 55.4% (46/83) vs. 17.1% (12/70); 30.1% (25/83) vs. 8.6% (6/70); with χ 2 values of 7.22, 6.84, 4.57, 23.64, and 10.91, respectively, all P<0.05]. Furthermore, the severe group had a late initiation of breastfeeding and longer durations of peripherally inserted central catheter (PICC) placement and parenteral nutrition [2.00 d (1.00-2.00 d) vs. 1.00 d (1.00-2.00 d); 0.00 d (0.00-18.00 d) vs. 0.00 d (0.00-7.50 d); 14.00 d (5.00-21.00 d) vs. 10.50 d (0.00-18.25 d), with Z values of -2.90, -1.98, and -2.09, respectively, all P<0.05]. (2) Within 48 h before the onset, the severe group had higher proportions of infants with decreased white blood cell count, decreased platelet count, electrolyte imbalance, and metabolic acidosis than the mild group [53.0% (44/83) vs. 14.3% (10/70); 49.4% (41/83) vs. 10.0% (7/70); 38.6% (32/83) vs. 14.3% (10/70); 37.3% (31/83) vs. 14.3% (10/70), with χ2 values of 24.94, 27.38, 11.23, and 10.30, respectively, all P<0.05]. Besides, the levels of procalcitonin and C-reactive protein were higher in the severe group than in the mild group [2.31 ng/ml (0.26-11.71 ng/ml) vs. 0.22 ng/ml (0.00-2.19 ng/ml); 58.50 mg/L (14.34-125.25 mg/L) vs. 8.20 mg/L (0.23-34.56 mg/L), with Z values of -3.88 and -5.02, respectively, both P<0.05]. (3) Multivariate logistic regression analysis showed that prolonged duration of PICC placement, decreased platelet count, electrolyte imbalance, metabolic acidosis, and concurrent sepsis were independent risk factors affecting the severity of NEC [ OR (95% CI) values were 1.104 (1.020-1.196), 5.364 (1.667-17.253), 4.047 (1.171-13.986), 4.333 (1.290-14.556), and 3.290 (1.005-10.774), respectively, with all P<0.05]. Conclusions:Prolonged duration of PICC placement, concurrent sepsis, decreased platelet count, electrolyte imbalance, and metabolic acidosis in NEC patients are more likely to lead to severe cases. In clinical practice, attention should be paid to relevant indicators, and abnormal changes should be identified and intervened in a timely manner to reduce the occurrence of severe NEC.

Skin is an organ with complex structure and function. Extensive skin defects and chronic non-healing wounds cause serious problems for patients and clinicians, while traditional repair methods are still not able to completely reconstruct the structure and function of skin. To achieve complete reconstruction of skin structure and function is a great challenge that needs to be solved in the field of wound repair. Induced pluripotent stem cells, which have the potential to differentiate into any human cells, are widely used in the field of regenerative medicine research. In recent years, skin organoids constructed through in vitro cultivation of stem cells contain epidermis, dermis, and multiple skin appendages, which overcomes the limitations of traditional skin substitute and opens new avenues for wound repair and its basic research. This review outlines the status of the research and application of skin organoids and discusses their current challenges in clinical translation and prospects for development.