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 association between serum levels of thyroglobulin (Tg), thyroid stimulating hormone (TSH) and antibodies and lymph node metastasis (LNM) in papillary thyroid cancer (PTC) .Methods:A total of 1 502 patients with PTC who were admitted to the Department of Breast and Thyroid Surgery of the First Affiliated Hospital of Chongqing Medical University from Jan. 2019 to Jan. 2022 were retrospectively enrolled, including males ( n=431), females ( n=1 071), aged < 55 years ( n=1 271), and ≥ 55 years old ( n=231). All patients were pathologically confirmed to have PTC after surgery. Univariate analysis was performed on the general data of patients and the indexes in the postoperative pathology report and the LNM group, and the data of P<0.05 in the analysis were included in the regression analysis to determine the independent risk factors of cervical LNM in PTC patients. Patients were divided into 8 subgroups according to the different statuses of the three thyroid antibodies (TGAb, TPOAb, TRAb) : [ (+) indicates positive; (-) indicates negative]. According to the order of TGAb, TPOAb, and TRAb, there are the following 8 states, 1 (+++) ; 2 (---) ; 3 (++-) ; 4 (+--) ; 5 (+-+) ; 6 (-+-) ; 7 (-++) ; 8 (--+). The differences in general clinical information, Tg and TSH between the two groups were compared, and the receiver operating characteristic curve (ROC) curve of Tg in the diagnosis of PTC lymph node metastasis was constructed, and regression analysis was used to explore the diagnostic value of serological indicators in the diagnosis of cervical LNM in PTC. Results:In this study, compared with the non-metastasis group, there were 308 males (33.2%) and 225 patients (24.3%) with bilateral PTC in metastasis group. The mean serum Tg value was (25.5±2.1) ng/mL and the TSH level was significantly increased ( P<0.05), and the results of binary logistic regression analysis showed that males ( OR=1.57, P<0.001), bilateral PTC ( OR=1.448, P<0.001), non-papillary carcinoma (>10 mm) ( OR=1.745, P<0.001) and increased Tg level ( OR=1.007, P=0.002) were independent risk factors for cervical lymph node metastasis in PTC patients, and the area under the ROC curve of Tg in the evaluation of cervical lymph node metastasis was 0.634 [95% CI (0.636, 0.691), P<0.05], while the TSH status was 0.56-1.39 ( OR=0.375, P=0.013). 1.40-2.29 ( OR=0.422, P=0.003) ; 2.30-5.91 ( OR=0.466, P=0.004) ; ≥5.91 ( OR=0.41, P=0.001) was not a risk factor. Conclusion:Male sex, bilateral thyroid cancer, non-papillary carcinoma (>10 mm), and preoperative serum Tg>29.8 ng/mL are the influencing factors of LNM in PTC patients.

Objective:To analyze the application value of 18F-FDG PET in the preoperative evaluation of patients with extratemporal lobe epilepsy (ETLE) and explore improved methods to enhance its localization accuracy. Methods:A total of 41 patients (25 males, 16 females, age (22.7±7.5) years) who underwent surgery and ultimately confirmed ETLE in Peking Union Medical College Hospital between January 2006 and November 2022 were enrolled. The accuracy of preoperative independent 18F-FDG PET imaging and the combined application of 18F-FDG PET and MRI in detecting epileptogenic foci and their impacts on treatment decisions were retrospectively analyzed by using visual and semi-quantitative methods. Fisher′s exact test was used to analyze the data. Results:In all 41 patients, 40 cases were found metabolic abnormalities in extratemporal lobe by independent 18F-FDG PET based on visual analysis. Among them, 26 showed unifocal metabolic abnormalities, which were localized as epileptogenic foci. Fourteen patients showed multifocal metabolic abnormalities, and the epileptogenic foci were further verified in 8 cases through semi-quantitative analysis. In 1 case with negative PET visual analysis, a micro-metabolism focus was found at the abnormal MRI signal area. Among 13 patients with negative independent MRI, 9 were found microstructures abnormalities in brain regions with hypometabolism. 18F-FDG PET improved clinical decision-making in 18 patients (43.9%, 18/41). There were 30 patients (73.2%, 30/41) with seizure-free postsurgery, and the prognosis was not significantly different between patients with unifocal 18F-FDG PET metabolic pattern and those with multifocal ones (73.1%(19/26) vs 10/14, P=1.000). Conclusions:18F-FDG PET can be a useful diagnostic tool for patients with ETLE. Semi-quantitative analysis helps to detect more epileptogenic foci with multifocal metabolic abnormalities. The combined evaluation of 18F-FDG PET and MRI can improve the accuracy in localizing epileptogenic foci outside the temporal lobe.

Purpose: The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB). Materials and Methods: We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB. Results: With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival. Conclusion After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.
Humans ; Metformin/pharmacokinetics* ; Diabetes Mellitus, Type 2/metabolism* ; Hypoglycemic Agents/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Aging

Objective:To summarize the prognosis of medullary thyroid carcinoma (MTC) patients with biochemical recurrence (the increase of postoperative calcitonin and no abnormal imaging) and to investigate the optimal cut-off value of calcitonin for postoperative structural recurrence (with imaging abnormality).Methods:Literature retrieval was conducted for PubMed, CNKI, EMbase, Web of Science, Cochrane and other databases, and literatures related to the increase of calcitonin after MTC surgery were included. Review Manager 5.4 software was used for Meta-analysis of the recurrence and death. SPSS 23.0 software was used and receiving operating characteristic (ROC) curve was used to analyze the rising folds of postoperative calcitonin level in comparison with the maximum value of experiment detection, and to predict the outcome of biochemical recurrence transforming to structural recurrence, and then the optimal cut-off value could be worked out.Results:A total of 7 studies including 1 005 MTC patients (276 cases of biochemical recurrence and 542 cases of biochemical cure). Meta-analysis showed that structural recurrence rate in postoperative biochemical recurrence group [40.6% (112/276) vs. 2.2% (12/542); OR = 27.99, 95% CI 14.57-53.78, P < 0.001] and mortality [10.0% (19/190) vs. 0.96% (3/312); OR = 7.26, 95% CI 2.42-21.84, P < 0.001] were higher than those in the biochemical cure group (normal postoperative calcitonin level and no disease state). The data of 89 MTC patients with biochemical recurrence were collected in another 4 studies. ROC curve analysis showed that area under the curve of the rising folds of postoperative calcitonin level in predicting structural recurrence was 0.825; according to the cut-off value at all sections, the optimal cut-off value of the increased postoperative calcitonin was 50 times, the sensitivity was 66. 7%, the specificity was 88.6%. Conclusions:MTC patients with postoperative biochemical recurrence have higher structural recurrence rate and mortality compared with patients with normal postoperative calcitonin. The postoperative elevation of calcitonin more than 50 times the maximum value of the laboratory detection can be taken as the critical diagnostic value, when more than 50 times is prone to structural recurrence.

Objective:To identify the risk factors for chronic postsurgical pain (CPSP) after craniotomy.Methods:This was a single-center retrospective cohort study.The patients who underwent craniotomy in Beijing Tiantan Hospital, Capital Medical University from December 2019 to May 2020 were enrolled.The occurrence of CPSP, anxiety, depression and quality of life were determined by telephone follow-up with Short-form McGill Pain Questionnaire-2, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-Item, a five-level EuroQol five-dimensional questionnaire.The patients were divided into CPSP group ( n=106) and non-CPSP group ( n=252) according to the results of investigation.Then univariate analysis and logistic regression analysis were performed to identify the risk factors for CPSP. Results:There was significant difference in age, a history of preoperative pain, a history of alcohol addiction, transoccipital approach and degree of lesion resection between the two groups ( P<0.05). The results of logistic regression analysis showed that age ≥ 60 yr was a protective factor for CPSP after craniotomy; a history of preoperative pain ≥3 months, a history of alcohol addiction, transoccipital approach and partial resection of the lesion were independent risk factors for CPSP after craniotomy. Conclusion:Age≥60 yr is a protective factor for CPSP after craniotomy; a history of preoperative pain (≥3 months), a history of alcohol addiction, transoccipital approach and partial resection of the lesion are independent risk factors for CPSP after craniotomy.

Objective:To analyze the clinical manifestations and laboratory features in patients with myeloid neoplasms complicated with clonal T large granular lymphocyte (T-LGL) proliferation.Methods:The clinical data of 5 patients with myeloid neoplasms complicated with clonal T-LGL proliferation from November 2017 to November 2018 in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed retrospectively.Results:The median age was 60 years old. All patients had a history of abnormal peripheral blood cell counts for over 6 months. The absolute lymphocyte count in peripheral blood was less than 1.0×10 9/L. In addition to the typical T-LGL phenotype, the immunophenotype was heterogenous including CD4 +CD8 - in 2 patients, the other 3 CD4 -CD8 +. Four patients were αβ type T cells, the other one was γδ type. STAT3 mutation was detected in 1 patient by next-generation sequencing, the other 4 cases were negative. Conclusions:Clonal T-LGL proliferation with myeloid neoplasm develops in an indolent manner, mainly in elderly patients. Hemocytopenia is the most common manifestation. The diagnosis of T-LGL proliferation does not have specific criteria, that it should be differentiated from other T cell proliferative disorders, such as T-cell clones of undetermined significance. STAT3 or STAT5b mutation may help distinguish.

For the researches relating to the biomedical fields such as preparation of drug micro-particulates and biomedical materials coating, according to the modular design concept and combing the piezoelectric micro-jetting technology with electromechanical engineering and automatic control technology, the drug micro-jetting multifunctional system was designed, which included the spraying support subsystem, - motion platform, -axis subsystem and rapid installation subsystem. The drug micro-jetting multifunctional system was run and adjusted. The versatility, rationality and feasibility of this system were validated by the experiments of amoxicillin microcapsule preparation, titanium alloy drug-loaded coating preparation and balloon electrode coating preparation. It was shown that the system can be used as basic platform in multi-disciplinary cross technology research such as biomedical engineering, pharmaceutical engineering and so on.
Alloys ; Drug Delivery Systems ; Electrodes ; Titanium

Objective To explore the correlation between extratemporal hypometabolism on preoperative 18F-FDG PET imaging and the outcome after temporal lobectomy in temporal lobe epilepsy (TLE)patients.Methods A total of 96 patients with intractable TLE who underwent temporal lobectomy were recruited.The outcome was evaluated according to International League Against Epilepsy (ILAE) 2001 outcome classification (OC) criteria:OC 1-3 was considered as good outcome and OC4-6 as poor outcome.The follow-up period was more than 2 years.The 18F-FDG PET brain images were retrospectively analyzed.The preoperative extratemporal cortical hypometabolism and extratemporal subcortical hypometabolism occurred in basal ganglia and thalamus were taken as independent exposure factors of poor outcome and the odds ratios (OR) were calculated respectively.Results Thirteen of 96 cases had poor outcome.Extratemporal cortical hypometabolism was found in 12 of 83(14.5％) cases with good outcome and in 11 of 13 cases with poor outcome.Extratemporal subcortical hypometabolism was found in 25 of 83 (30.1％) cases with good outcome and in 10 of 13 cases with poor outcome.The occurrence of extratemporal hypometabolism was significantly higher in poor outcome group than that in good surgical outcome group (cortical:x2 =26.63 ;subcortical:x2 =8.70; both P＜0.05).The OR of extratemporal cortical hypometabolism was 32.54,with 95％ CI of 6.40-165.44,and that of extratemporal subcortical hypometabolism was 7.73,with 95％ CI of 1.96-30.52.Conclusion Extratemporal cortical hypometabolism and subcortical hypometabolism in TLE patients are associated with poor outcome of temporal lobectomy in TLE patients.