Objective:To discuss the clinical characteristics of the patients with hypertrophic cardiomyopathy(HCM)complicated with microcirculatory dysfunction(CMD),and to analyze the impact of concurrent CMD on the prognosis of the HCM patients.Methods:A total of 211 patients diagnosed with HCM and having complete cardiac magnetic resonance imaging(CMR)examination results from January 1,2019 to September 30,2023 were collected.They were divided into HCM complicated with CMD group(68 cases)and HCM complicated without CMD group(143 cases)based on CMR assessment.The clinical data such as age,gender,admission symptoms,and past medical history,blood test data such as troponin,electrocardiogram,echocardiography,and CMR data including abnormal Q wave,ST segment depression,inverted T wave,PR interval,QRS wavelength,corrected QT interval,ejection fraction(EF),left atrial diameter(LAD),left and right ventricular end-diastolic diameters,cardiac output,E peak,A peak,and maximum wall thickness(MWT)of the patients were compared between two groups.Logistic regression was used to analyze the clinical characteristics of the HCM patients complicated with CMD;multivariate modified Poisson regression was used to analyze the risk factors for major adverse cardiovascular events(MACE)in the HCM patients.Results:Compared with HCM complicated without CMD group,the percentage of palpitation patients in HCM complicated with CMD group was significantly increased(P<0.05),the percentage of tachycardia episode patients was significantly increased(P<0.05),the troponin level was significantly increased(P<0.05),and the percentage with a history of hypertension patients was significantly decreased(P<0.05).Compared with HCM complicated without CMD group,the percentage of abnormal Q wave on electrocardiogram in the patients in HCM complicated with CMD group were significantly increased(P<0.05),the percentage of inverted T wave and the EF of the patients was significantly decreased(P<0.05),the LAD was significantly increased(P<0.05),and the MWT was significantly increased(P<0.05).The multivariate Logistic regression analysis results showed that increased LAD(OR=1.05,95％CI:1.00-1.11,P=0.048)and increased MWT(OR=1.11,95％CI:1.03-1.19,P=0.007)were the risk factors for concurrent CMD in the HCM patients;history of hypertension(OR=0.40,95％CI:0.20-0.80,P=0.010)was a protective factor for concurrent CMD in the HCM patients.The average follow-up time in this study was 20.5 months.A total of 27 patients experienced MACE,with an overall incidence of 12.80％,including 12 patients in HCM complicated with CMD group and 15 patients in HCM complicated without CMD group.The multivariate modified Poisson regression analysis results showed that history of diabetes(RR=2.34,95％CI:1.09-5.06,P=0.030),history of arrhythmia(RR)=4.00,95％CI:1.82-8.83,P=0.001),and decreased ejection fraction(RR=0.96,95％CI:0.94-0.99,P=0.001)were risk factors for MACE in the HCM patients.Conclusion:The HCM patients complicated with CMD have unique clinical characteristics,including higher symptom burden,left atrial enlargement,myocardial hypertrophy,and increased troponin levels.Concurrent CMD does not increase the short-term risk of adverse events;diabetes,arrhythmia,and decreased EF are key risk factors for prognosis;early intervention and complication management for HCM complicated with CMD patients may improve the long-term prognosis of the HCM patients.

Objective To evaluate the efficacy and safety of dupilumab combined with 2％cleboride ointment in the treatment of moderate to severe atopic dermatitis,as well as its impact on serological indica-tors.Methods A retrospective analysis was conducted on the clinical data of 67 patients with moderate to se-vere atopic dermatitis(AD)admitted to the Department of Dermatology of Shaoxing University Affiliated Hospital from March 2021 to December 2024.The study subjects were divided into an experimental group(n=35)and a control group(n=32)according to the treatment method.The experimental group was treated with Dupilumab injection and 2％Cleboride ointment,while the control group was treated with ebastine tab-lets and 2％cleboride ointment.Clinical and related serological indicators of patients after 16 weeks of treat-ment were collected,and the itch digital scale score,eczema area and severity(EASI)score,IL-4,IL-13 levels,and incidence of local skin adverse reactions were analyzed before and after treatment in both groups.Results The total effective rate of the experimental group after treatment was 94.29％(33/35),which was higher than the control group[53.13％(17/32)],and the difference was statistically significant(x2=12.862,P＜0.001).There was no statistically significant difference in symptom scores,IL-4,and IL-13 levels between the two groups before treatment(P＞0.05).After treatment,the symptom scores of the experimental group were lower than those of the control group,and the difference was statistically significant(P＜0.05).The lev-els of IL-4 and IL-13 in the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.05).The incidence of adverse reactions in the experimental group was 2.86％(1/35),significantly lower than the 34.38％(11/32)in the control group,and the difference was sta-tistically significant(x2=9.252,P=0.002).Conclusion The combination of dupilumab injection and 2％cleboride ointment is effective in relieving skin symptoms,regulating cellular immune function,reducing in-flammatory reactions,and minimizing local skin adverse reactions in patients with moderate to severe AD.It is worthy of clinical promotion and use.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

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.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.