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.

Objective:To explore the effects of Zishui Qinggan Decoction on the PTEN-induced putative kinase protein 1 (PINK1)/Parkin and cyclic GMP-AMP (cGAS)/ stimulator of interferon genes (STING) signaling pathways; To reveal the anti-inflammatory mechanism of Zishui Qinggan Decoction in treating depression.Methods:Totally 60 rats were randomly divided into control group, model group, and Zishui Qinggan Decoction low-, medium-, and high-dosage groups using a random number table method ( n=12 in each group) . All rats except for the rats in control group were prepared with CUMS induced depression models. The rats in the Zishui Qinggan Decoction low-, medium-, and high-dosage groups were orally administered with 12, 24, and 48 g/kg of Zishui Qinggan Decoction for gavage, respectively. The control group and model group were orally administered with distilled water of equal volume for gavage, once a day for 4 weeks. Forced swimming test (FST), the open field test (OFT) and the sucrose preference test (SPT) were used to detect behavioral changes in rats in each group. Hematoxylin eosin (HE) staining was used to observe the cell structure of the medial prefrontal cortex. The levels of IL-1 β, IL-6, TNF-α and Interferon-γ (IFN-γ) were detected using ELISA. Western blot was used to detect the expressions of Pink1, Parkin, cGAS and STING. Results:Behavioral testing results showed that, compared with the model group, the incubation period for rats in Zishui Qinggan Decoction low-, medium-, and high-dosage groups to enter the first immobility state in FST was significantly prolonged ( P<0.05), and the immobility time was significantly shortened ( P<0.05); the time spent in the central area was significantly increased ( P<0.05), and the incubation period for entering the central area was significantly shortened in ( P<0.05); the percentage of sugar water consumption significantly increased in ( P<0.05). HE staining revealed that the aggregation of prefrontal cortex nuclei decreased, the number of neurons increased, and the distribution of neurons was uniform in Zishui Qinggan Decoction low-, medium-, and high-dosage groups. Compared with the model group, the levels of IL-1β, IL-6, TNF-α and IFN-γ in the Zishui Qinggan Decoction groups significantly decreased ( P<0.05). The protein expressions of PINK1 and Parkin in the prefrontal cortex in Zishui Qinggan Decoction groups significantly increased ( P<0.05), while the protein expression levels of cGAS and STING significantly decreased ( P<0.05). Conclusion:Zishui Qinggan Decoction can significantly improve the depressive behavior, neuronal damage, and neuroinflammatory response in CUMS rats. Its mechanism may be related to up-regulating the PINK1/Parkin signaling pathway and inhibiting the cGAS/STING signaling pathway.

Frailty is a clinical syndrome characterized by the gradual decline of multiple organ func-tion and the emergence of vulnerable phenotype.Patients with frailty exhibit diminished resistance to stress,which often leads to unfavorable outcomes following surgery,including cognitive decline,prolonged hospital-ization,and increased rates of complications and mortality.Given that frailty is a dynamic and reversible process,it is recommended to implement appropriate optimization measures during the perioperative period in order to improve patient outcomes.Recent studies have revealed that abnormal energy metabolism plays a crucial role in the development and occurrence of frailty.This article will primarily focus on abnormalities in glucose metabolism,lipid metabolism,and amino acid metabolism among frail patients,and emphasize the significance of correcting these metabolic irregularities during the perioperative period in order to reduce complications and improving surgical safety.

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Humans ; Mice ; Animals ; Psilocybin/metabolism* ; Fear ; Extinction, Psychological ; Brain-Derived Neurotrophic Factor/metabolism* ; Bromodeoxyuridine/pharmacology* ; Hippocampus/metabolism* ; Neuronal Plasticity ; TOR Serine-Threonine Kinases/metabolism*

Background Both domestic and foreign studies on the diet quality of patients with thyroid nodules are rare at present, and the relationship between thyroid nodules and diet quality is still unclear. Objective This study aims to evaluate the diet quality of thyroid nodules with the China Healthy Diet Index (CHDI) and to explore the relationship between diet quality and thyroid nodules. Methods We conducted a hospital-based case-control study in which 387 patients with thyroid nodules were matched individually (1∶1) by gender and age (±3 years) to the controls who ordered a routine physical examine and with negative thyroid nodules reported by B-ultrasound in the same hospital. A structured questionnaire was applied to collect data on general characteristics and diet. CHDI was employed to evaluate the diet quality of the two groups. CHDI is based on the Dietary Guidelines for Chinese Residents and the recommended food intake in the balanced diet pagoda, combined with the dietary nutritional status of Chinese population. The index contains 13 scoring components, and the highest total score is 100, with a higher score representing better dietary quality. CHDI scores < 60, 60-<80, and ≥80 are recognized as unqualified, qualified, and good diet quality, respectively. Results The scores of the thyroid nodule cases were lower than the scores of the controls in total vegetables, dark vegetables, fruits, and fish/shrimps (all Ps<0.05). The nonparametric test results found that there were significant differences in the distributions of scores in total vegetables, dark vegetables, fruits, soybeans, and fish/shrimps between the case and the control groups (all Ps<0.05). The percentages reaching the full scores in food variety, meat and eggs, and empty calories in both groups exceeded 60%, while the percentages reaching the full scores in whole grains/beans/tubers, dairy, soybeans, and sodium were lower than 30% in the two groups. The median CHDI scores of the thyroid nodule cases and the controls were 69.1 and 72.9, respectively; the cases' CHDI score was lower than the controls' (P<0.05). The proportions of unqualified diet in the case and the control groups accounted for 23.0% and 13.7% respectively (P=0.001). After being adjusted for education level, marital status, occupation, monthly household income per capita, body mass index, hypertension/diabetes, energy, and iodine intake, the results of logistic regression analysis showed that the risk for thyroid nodules was negatively associated with CHDI score (CHDI qualified group vs. CHDI unqualified group, OR=0.484, 95%CI: 0.291-0.804; CHDI good dietary quality group vs. CHDI unqualified group, OR=0.414, 95%CI: 0.230−0.746). Conclusion The diet quality of patients with thyroid nodules is lower than that of the control group, as the former reported lower consumptions of total vegetables, dark vegetables, fruits, and fish/shrimps. Those who have good or qualified diet quality show a reduced risk of thyroid nodules than those with unqualified dietary quality.

Objective :To evaluate therapeutic effect of allisartan isoproxil tablet on carotid atherosclerosis (CAS) le‐sion in patients with mild to moderate essential hypertension (EH).Methods :A total of 120 patients with mild to moderate EH complicated CAS treated in our hospital were enrolled .They were randomly divided into valsartan group (n＝60 ,received valsartan 80mg／d) and allisartan isoproxil group (n＝60 ,received allisartan isoproxil tablet 240mg／d) ,both groups received measure by carotid vascular ultrasound before treatment ,24 weeks and 48 weeks af‐ter treatment and its result were compared between two groups .Results :Compared with before treatment ,there were significant reductions in IMT ,size ,thickness and number of carotid atherosclerotic plaques on 24 weeks and 48 weeks after treatment in two groups ,and above indexes of 48 weeks were significantly lower than those of 24 weeks , P＜0.05 or ＜0.01. The decreased value of IMT in allisartan isoproxil group was significantly higher than that of valsartan group ,and there were no significant difference between two groups in time point of size ,thickness and number of carotid atherosclerotic plaques , P＞0.05 all.Conclusion :Therapeutic effect of two drugs on size ,thick‐ness and number of carotid atherosclerotic plaques are similar ;but therapeutic effect of allisartan isoproxil tablet on IMT is significantly better than that of valsartan .

Diabetic retinopathy (DR) is one of the most common causes of visual impairment and blindness in diabetic patients.It is particularly important to set up simpler,safer,non-invasive and highly effective methods for diagnosis as well as monitoring DR.A variety of new fundus imaging techniques show great advantages in early diagnosis,treatment and monitoring of DR in recent years,The main characteristics of wide-field scanning laser imaging system is achieving a large range of retinal image in a single photograph and without mydriasis.It provides several options for color images,FFA and FAF,which satisfy to detect the retina,choroid and vascular structure.Multi spectral fundus imaging system is suitable for DR screening,because it is able to recognize the typical characteristics of DR,such as microaneurysms,hemorrhage and exudation,and is non-invasive and convenient.OCT angiography is a quantitative examination that provides foveal avascular zone area,macular blood flow density,which provides strong evidence for DR diagnosis.The improvement of these new techniques will help us to build up a personalized evaluation system of DR.

Objective To establish reference values for blood pressure in cynomolgus monkeys in different ages.Methods The blood pressures and blood lipids indexes were detected in 521 cynomolgus monkeys using an American BECKMAN-CX4 automatic biochemical analyzer and a wrist electronic blood pressure monitor.Statistical tests were performed to analyze the data.Results Significant differences were found in blood pressure values of cynomolgus monkeys in different ages.Blood pressure values in the elderly group were higher than those of other groups.The morbidity of hypertension in the elderly group was higher than those of the other groups.Body mass index (BMI) in the hypertension group was higher than that of normal group in the same age.The incidence of hypertension in the elderly group with hyperlipemia was higher than that of other groups.Logistic regression analysis showed that age, BMI and hyperlipidemia in the hypertensive group were 1.435, 1.218, and 2.337 times higher than those of the normal group when predicting the risk of hypertension.Conclusions We have initially established reference values of blood pressure in cynomolgus monkeys in different ages.Age, BMI and hyperlipidemia are risk factors of spontaneous hypertension in cynomolgus monkeys, and the measurement of blood pressure may provide a basis for the screening of cynomolgus monkey model of spontaneous hypertensive and related research.

Parkinson's disease (PD) was the second most common neurodegenerative disorder after Alzheimer's disease. Incidence of PD was ascending year by year. The etiology of PD is poorly understood, involving aging, genetic and environmental factors. Recently, environmental compound had attracted more and more research interest. Studies and extrapolation from epidemiology, animal experiments and cell culture suggested that environmental compound had involved in the molecular mechanisms including mitochondrial dysfunction, oxidative stress, microglia activation,abnormal aggregation of α-synuclein and autophagy damage,which seemed to increase PD risk.