Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

Intraflagellar transport (IFT) is a core mechanism for ciliary assembly, length maintenance, ciliary proteome homeostasis and signal transduction. Most proteins required for ciliary structure and function are synthesized in the cytoplasm. Because the ciliary compartment is separated from the cell body by the selective barrier of the transition zone, these proteins cannot freely equilibrate between the cytoplasm and the cilium. Consequently, axonemal components, membrane proteins and signaling molecules must be actively imported into cilia, retrieved from the ciliary compartment, and recycled or degraded through highly ordered transport and sorting pathways. The IFT system is mainly composed of the IFT-A complex, IFT-B complex, kinesin-2, dynein-2 and the Bardet-Biedl syndrome protein complex (BBSome). Through coordinated anterograde and retrograde transport, these modules mediate the dynamic trafficking of different classes of ciliary cargoes. Anterograde transport delivers structural and membrane-associated components from the ciliary base toward the ciliary tip, whereas retrograde transport retrieves IFT components and selected cargoes back toward the ciliary base and cytoplasm. In this way, IFT not only supports the construction of the axoneme but also contributes to the maintenance of ciliary composition and the regulation of ciliary signaling activity. In recent years, advances in cryo-electron microscopy, in situ cryo-electron tomography and single-molecule imaging have greatly improved our understanding of the molecular mechanisms underlying IFT. These approaches have revealed how IFT trains are assembled at the ciliary base, how they move along axonemal microtubule tracks, how they undergo directional switching at the ciliary tip, and how cargoes are retrieved and recycled. Among the IFT modules, IFT-B acts as the major scaffold of IFT trains. It participates in cargo loading, motor coupling and initiation of anterograde transport. IFT-A is involved in retrograde transport, membrane protein adaptor function and train remodeling. The BBSome, through reversible association with the IFT system, regulates ciliary membrane protein sorting, signaling receptor clearance and renewal of the ciliary proteome. These functions indicate that the IFT machinery is not a simple linear transport pathway, but rather a dynamic and reconfigurable transport system. The conversion of transport direction is a key step in the IFT cycle. This process is closely associated with disassembly of anterograde trains, dissociation of kinesin-2, activation of dynein-2 at the ciliary tip and reassembly of retrograde trains. In terms of pathogenic mechanisms, IFT abnormalities may cause ciliopathies through four major pathways: defects in ciliary assembly and structure, abnormal localization of ciliary cargoes, dysregulation of signaling pathways, and impaired cargo unloading and retrieval. These defects can affect multiple organ systems, including the retina, kidney, skeleton, respiratory tract, reproductive system, and neuro-metabolic system. Current therapeutic strategies are still mainly based on symptomatic support and maintenance of organ function. Overall, IFT is a dynamic transport system jointly regulated by axonemal structure, motor activity, cargo selection and cellular signaling. It links ciliary architecture with protein turnover and signaling regulation, thereby playing a fundamental role in both ciliary homeostasis and ciliopathy pathogenesis. Further elucidation of IFT regulatory mechanisms and their relationships with disease phenotypes will help promote mechanism-based classification, genetic diagnosis and precision intervention for ciliopathies.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Objective To investigate the relationship between ST-segment elevation myocardial infarction(STEMI)treatment time nodes and coronary microcirculation dysfunction(CMD)after primary percutaneous coronary intervention(PCI)and its prognosis,providing evidence for early identification of high-risk patients,further optimization of treatment system,shortening treatment time and improving prognosis.Methods This study selected 150 STEMI patients who received primary PCI at the 920th Hospital of the Joint Logistic Support Force of the People's Liberation Army of China from March 2023 to September 2023 as the CMD group after PCI(89 cases),with a microcirculation resistance index(caIMR)of≥40 U based on coronary angiography.caIMR＜40 U was classified as the non-CMD group(61 cases).The clinical data,various examination indicators and imaging data of the two groups of patients were collected,and the occurrence of major adverse cardiovascular events(MACE)within half a year after direct PCI of the patients was followed up.The correlation between the two variables was analyzed using Spearman.Multivariate Logistic regression was used to analyze the relationship between each treatment time point and the occurrence of CMD after direct PCI.Using receiver operating characteristic(ROC)curve analysis to predict the occurrence of CMD after direct PCI.The survival curves between the two groups were plotted using the Kaplan-Meier method.Results The levels of symptom onset-to-balloon(S-to-B),symptom onset-to-first medical contact(S-to-FMC),first medical contact-to-balloon(FMC-to-B),symptom onset-to-door(S-to-D)and first medical contact-to-door(FMC-to-D)in the CMD group were significantly higher than those in the non-CMD group(all P＜0.05).Correlation analysis showed that S-to-D,S-to-FMC,the time from FMC-to-B,and the time from FMC-to-D were all positively correlated with the time from S-to-B(r=0.996,P＜0.001;r=0.937,P＜0.001;r=0.431,P＜0.001;r=0.441,P＜0.001).Multivariate Logistic regression analysis indicated that the duration of S-to-D(OR 2.165,95％CI 1.655-2.830,P＜0.001)was a significant influencing factor for CMD.Moreover,S-to-D has a relatively high predictive value for the occurrence of CMD after direct PCI.The area under the ROC curve is 0.898(95％CI 0.850-0.946,P＜0.001),the optimal cut-off value is 231 min,the sensitivity is 82.0％,and the specificity is 88.5％.Kaplan-Meier curve analysis showed that the cumulative survival rate of MACE outcomes in the CMD group was significantly lower than that in the non-CMD group(Log-rank P=0.009).Conclusions Shortening the S-to-D time can reduce the occurrence of CMD after PCI,thereby reducing the incidence of MACE and improving prognosis.

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To investigate the use of apolipoprotein B (ApoB) diagnostic algorithm for hyperlipidemia typing combined with whole exome sequencing in the precise diagnosis of familial hyperlipidemia.Methods:A retrospective observational study was conducted by collecting clinical information on all patients who attended our hospital, and had their lipid levels tested from January 2023 to May 2024, including 440 patients with low-density lipoprotein cholesterol (LDL-C)>4.10 mmol/L. Family history, current lipid levels, medication use, and comorbidities were collected by telephone follow-ups. Among them, 10 patients had a family history of hyperlipidemia. Peripheral venous blood samples were collected from patients with a family history of hyperlipidemia, and whole exome sequencing was performed.Results:According to the Fredrickson typing of WHO, 10 patients (P1 to P10) could be categorized into two groups, of which only type Ⅱa could be excluded in 6 cases, and the typing could not be determined in 4 cases. The ApoB diagnostic algorithm of hyperlipidemia typing could classify patients P1 and P2 as type Ⅱa, patients P3 to P7, P9 and P10 as type Ⅱb, and patient P8 as type Ⅴ, respectively. Whole exome sequencing detected mutations in LDLR, PCSK9, C5AR2, KIF12, ALMS1, ABCG5, COL4A3, and MTTP genes.Conclusion:The ApoB diagnostic algorithm for hyperlipidemia can be used for accurate typing of hyperlipidemia, and ApoB could be recommended as a routine lipid testing parameter. The ApoB diagnostic algorithm for hyperlipidemia combined with whole exome sequencing could be used for the accurate typing of patients with familial hyperlipidemia and defining the underlying gene mutations.

Objectives:To investigate the epidemiological characteristics and ethnic differences of cardiovascular-kidney-metabolic syndrome(CKM)among the Hani,Dai,Bai,and Lisu populations in Yunnan Province,and to provide evidence for developing effective prevention and control strategies for CKM.Methods:A cross-sectional survey was conducted among four ethnic minority groups.A total of 3 906 permanent residents aged 18 years and older were enrolled using a multistage cluster random sampling method.CKM stages(0-4)were defined based on the 2023 American Heart Association criteria,stages 3-4 were classified as advanced CKM.Descriptive statistics and chi-square tests were used to compare the prevalence of CKM stages across ethnic groups.Modified Poisson regression was applied to estimate relative risk(RR)and 95%confidence intervals(CI)for factors associated with advanced CKM.Results:The prevalence rates of CKM stage 1 and above among the Hani,Dai,Bai and Lisu ethnic groups were 80.1%,87.3%,84.8%and 67.8%,respectively.The prevalence of CKM was generally higher in males than in females,and the prevalence of CKM increased significantly with age.The Dai ethnic group had the highest prevalence of advanced CKM(24.7%,95%CI:22.1%-27.4%),while the Lisu ethnic group had the lowest prevalence of advanced CKM(13.7%,95%CI:11.5%-15.9%).Modified Poisson regression analysis showed that older age and higher body mass index were common risk factors for advanced CKM across all four ethnic groups.Additionally,except for the Lisu ethnic group,the other three ethnic groups had specific individual risk factors:among the Hani ethnic group,low educational attainment(RR=2.18,95%CI:1.12-4.25)and low income(RR=1.47,95%CI:1.00-2.18)were the primary risk factors of CKM.Among the Dai ethnic group,smoking(RR=1.60,95%CI:1.07-2.37)and a family history of cardiovascular disease(RR=1.61,95%CI:1.14-2.27)are the primary risk factors of CKM.Among the Bai ethnic group,male gender(RR=0.48,95%CI:0.29-0.79)was the primary risk factor of CKM.Conclusions:The prevalence of CKM stage 1 or higher is relatively high among the four minority ethnic groups in Yunnan province.There are significant differences in staging characteristics and primary risk factors across ethnic groups,necessitating the development of stratified,differentiated intervention strategies to achieve precise prevention and control and ethnic health equity in terms of CKM.

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals