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 investigate the risk factors for depression in middle-aged and elderly Chinese male patients with benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS). METHODS: Based on the data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), we included 8 426 male participants aged ≥ 45 years in this study, and explored the risk factors for depression in patients with BPH/LUTS by logistic regression analysis. RESULTS: Among the total number of participants, there were 1 447 cases of BPH/LUTS, with a prevalence rate of 17.2%, and 36.5% of the patients (529/1 447) were complicated by depression. Logistic regression analysis showed that underlying diseases were the risk factors for depression in patients with BPH/LUTS (OR = 1.29, 95% CI: 1.03－1.62), while the protective factors against the condition included high school education or above (OR = 0.52, 95% CI: 0.36－0.75), urban residence (OR = 0.75, 95% CI: 0.60－0.95), eastern region (OR = 0.61, 95% CI: 0.38－0.97), and 6－9 h/d sleep (OR = 0.52, 95% CI: 0.41－0.66). CONCLUSION Underlying diseases, education level, residential area, geographical region, and sleep duration are influencing factors for depression in middle-aged and elderly male patients with BPH/LUTS in China and deserve the attention of clinicians.
Humans ; Male ; Prostatic Hyperplasia/psychology* ; Risk Factors ; Depression/etiology* ; Aged ; Middle Aged ; Lower Urinary Tract Symptoms/psychology* ; China/epidemiology* ; Logistic Models ; Prevalence ; Longitudinal Studies

Humans ; Immunologic Deficiency Syndromes/genetics*

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

This study aims to explore the core connotation of the compatibility of Aconiti Lateralis Radix Praeparata(Fuzi)-Glycyrrhizae Radix et Rhizoma(Gancao) herb pair under physiological and pathological conditions. The biochemical indicators of serum/myocardial tissue, pathological changes of the myocardial tissue, and serum metabolic profiles of normal rats and heart failure model rats treated with Fuzi Decoction and Fuzi Gancao Decoction were determined. Network pharmacology and metabolomics were employed to establish the metabolite-target-pathway network for Glycyrrhizae Radix et Rhizoma in enhancing the efficacy and reducing the toxicity of Aconiti Lateralis Radix Praeparata, Western blotting was employed to verify the representative pathways in the network. The results showed that both decoctions lowered the levels of creatine kinase and other indicators and mitigate myocardial pathological injury in model rats. However, they caused the abnormal rises in creatine kinase and other indicators and myocardial pathological injury in normal rats. The results indicated that the compatibility reduced the toxicity in normal rats and enhanced the efficacy in model rats. The results of metabolomics showed that Fuzi Gancao Decoction recovered more metabolites in model rats and had weaker effect on interfe-ring with the metabolites in normal rats than Fuzi Decoction. The association analysis showed that the network of Glycyrrhizae Radix et Rhizoma enhancing the efficacy of Aconiti Lateralis Radix Praeparata involved 112 metabolites, 89 targets, and 15 pathways, including calcium and cAMP signaling pathways. The network of Glycyrrhizae Radix et Rhizoma reducing the cardiotoxicity of Aconiti Lateralis Radix Praeparata involved 36 metabolites, 59 targets, and 11 pathways, including adrenergic signaling and tricarboxylic acid cycle in cardiomyocytes. The experimental results of protein expression verified the reliability of the association analysis. This study demonstrated that the core connotation of the herb pair of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma changed under physio-logical and pathological states, and the compatibility results of enhancing efficacy and reducing toxicity were achieved with different metabolic pathways and biological processes.

OBJECTIVE: To compare clinical effect of robot-assisted core decompression and conventional core decompression in treating ARCO Ⅰ stage necrosis of femoral head. METHODS: A retrospective analysis was performed on 60(unilateral operation) patients who underwent core decompression for femoral head necrosis from February 2018 to February 2020. Among them, 30 patients(30 hips) were underwent robot-assisted core decompression (RCD group), including 19 males and 11 females, aged from 17 to 58 years old with an average of(38.50±10.61) years old;30 patients(30 hips) were underwent traditional core decompression surgery (CCD group), including 20 males and 10 females, aged from 20 to 55 years old with an average of (40.63±10.63) years old. Intraoperative fluoroscopy times, intraoperative blood loss and operation time between two groups, and Harris score, visual analogue scale (VAS) before opertaion and 24 months after operation were compared. RESULTS: All patients were followed up, RCD group followed up from 21 to 26 months with an average of(23.40±1.65) months, CCD group followed up from 21 to 26 months with an average of (23.30±1.66) months, and had no difference between two groups(P>0.05). The number of intraoperative X-ray fluoroscopy, intraoperative blood loss and operative time in RCD group were (9.43±1.14) times, (153.80±22.04) ml, (33.40±1.87) min, respectively;while(19.67±1.32) times, (165.04±20.41) ml and (54.75±3.46) min in CCD group respectively;and there were statistical difference between two groups(P<0.05). In addition, there were no statistical difference between two groups in Harris score and VAS at 24 months after operation(P>0.05). CONCLUSION Compared with conventional core decompression, robot-assisted core decompression could reduce the number of intraoperative fluoroscopy, shorten operation time, and reduce risk of surgery.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Case-Control Studies ; Retrospective Studies ; Femur Head Necrosis/surgery* ; Treatment Outcome ; Blood Loss, Surgical ; Robotics ; Bone Transplantation ; Decompression, Surgical ; Femur Head/surgery*

Glucose ; Humans ; Hypothalamo-Hypophyseal System ; Lycium ; Pituitary-Adrenal System ; Resistance Training

Objective:To observe the clinical efficacy of Yishen Tongluofang in treating oligosperm type male infertility with kidney deficiency and blood stasis syndrome and explore its effect on serum sex hormones and seminal plasma microenviro. Method:One hundred and four patients were randomly divided into observation group and control group with 52 cases each. Patients in control group took compound Xuanju capsules orally， 3 capsules/time， 3 times/day. Patients in observation group took Yishen Tongluofang， 1 dose/day. Treatment courses continued three months and followed up for three months in both groups. The pregnancy situations of spouses within six months were recorded. Examination of semen parameters before and after treatment and score of kidney deficiency and blood stasis syndrome were conducted. The levels of seminal plasma zinc， fructose， elastase， acid phosphatase and α-glucosidase， serum follicle stimulating hormone （FSH）， luteinizing hormone （LH）， prolactin （PRT） and testosterone （T） were detected before and after treatment. Result:During the observation period of six months， the pregnancy rate of spouses in the observation group was 22.00%， higher than 10.00% in the control group， but the difference was not statistically significant （χ²=2.678，P>0.05）. The clinical efficacy in the observation group was better than that of the control group （Z=2.326，P<0.01）. Sperm concentration， sperm motility， sperm motility， normal morphological sperm and linear movement speed of the observation group were all superior to those of the control group （P<0.01）. The levels of zinc and fructose in seminal plasma of the observation group were higher than those of the control group （P<0.01）， and the score of kidney deficiency and blood stasis syndrome was lower than that of the control group （P<0.01）. Serum FSH， LH and PRT levels in the observation group were lower than those in the control group （P<0.01）， and the T level was higher than that in the control group （P<0.01）. The seminal plasma elastase of the observation group was lower than that of the control group， while the levels of acid phosphatase and α-glucosidase were higher than those of the control group （P<0.01）. Conclusion:Yishen Tongluofang can significantly improve sperm parameters， regulate the level of sex hormones and seminal plasma environment in patients with oligosperm type male infertility， and improve the tendency of spouse pregnancy. Its clinical efficacy is better，so it is worthy of further research and application.

Background: Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship. Methods: Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, , etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. drug release and skin permeation experiments and pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs. Results: Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength. Conclusion From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

Objective Few reports are seen comparing esophageal stent placement (ESP) and the endoscopic incision method (EIM) in the treatment refractory esophageal anastomotic strictures (EAS) following esophageal carcinoma resection (ECR). This study was to evaluate the effect ESP versus that of EIM in the treatment of refractory EAS after ECR. Methods We retrospectively analyzed the clinical data on 50 cases of post-ECR refractory EAS treated by ESP (n = 32) or EIM (n = 18) in our Center of Digestive Medicine between January 2012 and December 2018. We recorded and compared the pre- and post-operative dysphagia scores, post-operative complications and follow-up results between the two groups of patients. Results Compared with the EIM group, the patients of the ESP group had a remarkably lower dysphagia score post-operatively (1.4±0.5 vs 1.0±0.0, P<0.01), a smaller diameter of the dilated esophagus ([19.9±1.8] vs [11.0±1.9] mm, P<0.01), higher incidence rates mild and severe chest pain (P=0.022), and a higher rate of relief of esophageal stricture at 12 months after surgery (P<0.05). Conclusion EIM can rapidly relieve the symptoms of esophageal anastomotic stricture, while ESP may achieve a longer duration of relief. Both of the procedures are safe for patients with refractory esophageal anastomotic stricture.