BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

BACKGROUND:In vitro construction of tissue-engineered intestinal models plays an important role in intestinal regeneration and intestinal disease research.The interaction of intestinal nervous system and intestinal epithelial barrier to maintain body homeostasis is a hot topic in the bionic construction of tissue-engineered intestinal tract.OBJECTIVE:To construct a bionic model that can mimic the enteric nervous system in vivo.METHODS:Using fibroin protein with villus structure as scaffold,human induced neural stem cells solidified with collagen were added to intestinal epithelial cells(Caco-2 and HT29-MTX-E12)for 3-day culture to construct a co-culture system of intestinal epithelial cells and nerve cells(co-culture group).Human induced neural stem cells or intestinal epithelial cells cultured alone that were inoculated with fibroin scaffolds were set as controls.Cell morphology was observed by scanning electron microscopy and hematoxylin-eosin staining.Cell activity was detected by Live/Dead cell staining.Human induced neural stem cell differentiation was detected by β-microtubulin immunofluorescence staining.Intestinal epithelial histological properties and barrier function were detected by microvillin,sucrase-isomaltase,tight junction protein 1,E-calmodulin,and mucin-2 immunofluorescence staining.The function of mucus secretion from intestinal epithelial cells was detected by Alcian blue staining.Alkaline phosphatase staining was performed to detect differentiation of intestinal epithelial cells,at the same time,sucrase-isomaltase,tight junction protein 1,and alkaline phosphatase mRNAs were detected by RT-qRCR.RESULTS AND CONCLUSION:The neuralized intestinal mucosal co-culture model with villi structure was successfully constructed,and neural stem cells and intestinal epithelial cells on the fibroin scaffold showed good cellular activities.After neuralization,the activity of alkaline phosphatase and sucrase-isomaltase in intestinal epithelial cells was enhanced,while the expression level of tight junction protein 1 was up-regulated.To conclude,the neuralized bionic intestinal epithelial model is beneficial to the maturation of intestinal mucosal epithelial cells and the formation of barrier function.

Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

Alacrima-achalasia-mental retardation syndrome(AAMR) is an extremely rare autosomal recessive genetic disorder caused by mutation in the GMPPA gene. Its pathogenesis is associated with congenital disorders of glycosylation. The clinical manifestations involve multiple system impairments, with alacrima, achalasia, and mental retardation as the core features. This article reports the diagnosis, treatment process and long-term follow-up outcomes after deep brain stimulation in one patient with AAMR complicated with dystonia, aiming to improve clinicians' understanding of this disease.

OBJECTIVE To upgrade and perfect the quality standard of Psidii Guajavae Folium. METHODS A total of 24 batches of Psidii Guajavae Folium samples were adopted in this study. The macroscopic traits and powder microscopic features of the medicinal materials were observed， and thin-layer chromatography （TLC） identification was carried out. In accordance with corresponding methods documented in Volume Ⅳ of the 2025 edition of the Chinese Pharmacopoeia， multiple indexes were determined， including foreign matter， moisture， total ash， acid-insoluble ash， water-soluble extractives， heavy metals （lead， cadmium， copper， arsenic， mercury） as well as residues of 47 prohibited pesticides. A high-performance liquid chromatography （HPLC） method was established to quantify guaijaverin in Psidii Guajavae Folium. Meanwhile， the HPLC fingerprint of the herb was constructed， followed by similarity evaluation and cluster analysis of all samples. RESULTS The macroscopic traits of Psidii Guajavae Folium complied with relevant specifications of quality standards. Distinct microscopic characteristics were observed in medicinal powder， including non-glandular hairs， calcium oxalate crystals， vessels and stomata. TLC results revealed identical fluorescent spots at positions corresponding to the guaijaverin reference substance on chromatograms of test samples. Among the 24 batches of samples， the detection ranges were 0.3%-2.8% for foreign matter， 5.1%-10.7% for moisture， 5.3%-7.2% for total ash， 0.4%-1.8% for acid-insoluble ash， and 11.8%-26.3% for water-soluble extractives. The test results of heavy metals， harmful elements and prohibited pesticide residues all satisfied the Chinese Pharmacopoeia limit criteria. Methodological validation of content determination and fingerprint analysis met relevant validation requirements. The guaijaverin content of the 24 batches ranged from 0.14% to 0.28%. The HPLC fingerprint similarity values of all samples fluctuated between 0.828 and 0.997； fifteen common peaks were calibrated， six of which were chemically identified. The 24 batches were divided into two major clusters， and cluster classification showed high consistency with sample origins. CONCLUSIONS This research optimizes the TLC identification protocol of Psidii Guajavae Folium and supplements new quality control items including quantitative assay and chromatographic fingerprint. Tentative quality limits are proposed as follows： moisture ≤12.0%， total ash ≤8.0%， water-soluble extractives ≥10.0%， and guaijaverin content ≥0.14% （calculated based on dry products）.

BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）. ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］

ObjectiveTo explore the relationship between triglyceride high-density cholesterol-glucose body index （TyHGB） and gestational diabetes mellitus （GDM）. MethodsThis single-center retrospective cohort study was conducted. A total of 723 singleton pregnant women who received prenatal care and delivered at Lingnan Hospital， the Third Affiliated Hospital of Sun Yat-sen University， from May 2024 to July 2024 were enrolled. Clinical baseline data and laboratory test results in the first trimester （before 13⁺⁶ weeks of gestation） were collected. Based on the tertiles of the TyHGB index were equally divided into 3 groups. Clinical baseline data， and GDM risk were compared among the three groups. ResultsCompared with the control group， the GDM group had older maternal age， higher Pre-pregnancy BMI， FPG， TG， and higher values of 75 g OGTT fasting plasma glucose， 1 h plasma glucose， and 2 h plasma glucose. The early-pregnancy TyHGB index， andincidence of macrosomiawere all higher in the GDM group than in the control group （ all P<0.05）， whereas gestational weight gain （GWG） was lower than that of the control group （P<0.05）. The individuals were divided into three groups according to the tertiles of the TyHGB index. Significantly differences were identified among TyHGB index tertiles in maternal age， parity， Pre-BMI， FPG， TC， TG， HDL-C， LDLL-C， Ur， 75 g OGTT fasting plasma glucose， 1 h plasma glucose， 2 h plasma glucose， GWG， neonatal birth weight， GDM， GH， macrosomia incidence， and cesarean section rate（all P<0.05）. Further trend test analysis found that matenal age， parity， Pre-BMI， FPG， TC， TG， LDL-C， 75 g OGTT_FPG， 75 g OGTT_1 h PG and 75 g OGTT_2 h PG level， neonatal birth weight， GDM， GH， incidence of macrosomia and cesarean section rate all showed an upward trend. The multivariate Logistic regression models revealed that there was an independent positive correlation between TyHGB index and the risk of GDM. Curve fitting by restricted cubic splines （RCS） were used to assess linearity between TyHGB and GDM， and there was a linear dose-response relationship between TyHGB and GDM （P _{nonlinear test} = 0.597）. The threshold value for early pregnancy TyHGB index to predict GDM was 6.449 ， with an area under the curve （AUC） of 0.644 （95% CI： 0.597-0.691）， sensitivity of 0.480 ， and specificity of 0.779. After adjusting for maternal age， Pre-BMI， family history of diabetes， and history of GDM， the AUC for the early pregnancy TyHGB index to predict GDM was 0.672 （95% CI： 0.626-0.718）. ConclusionThe early-pregnancy TyHGB index is independently associated with GDM risk， and exhibits a linear dose-response relationship with GDM. It may serve as an early screening and monitoring tool for pregnant women at high risk of GDM. However， its predictive value for GDM requires further validation.

Clear aligner treatment is a novel technique in current orthodontic practice. Distinct from traditional fixed orthodontic appliances, clear aligners have different material features and biomechanical characteristics and treatment efficiencies, presenting new clinical challenges. Therefore, a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique. This expert consensus discusses case selection and grading of treatment difficulty, principle of clear aligner therapy, clinical procedures and potential complications, which are crucial to the clinical success of clear aligner treatment.
Humans ; Consensus ; Orthodontic Appliance Design ; Orthodontic Appliances, Removable ; Tooth Movement Techniques/methods* ; Malocclusion/therapy* ; Orthodontics, Corrective/instrumentation*

OBJECTIVE: In order to enhance the efficacy of anti-breast cancer, paclitaxel nanoparticles (PTX NPs) and polypyrrole nanoparticles (PPy NPs) were combined with photothermal therapy and chemotherapy. At the same time, the two dosage forms of PTX NPs and PTX NPs gel were compared. METHODS: PTX NPs were prepared by self-assembly method, and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium (MTT) and other methods, and the efficacy and side effects in vivo were further investigated. RESULTS: The average hydrated diameter, PDI and electric potential of PTX NPs were (210.20 ± 1.57) nm, (0.081 ± 0.003) mV and (15.80 ± 0.35) mV, respectively. MTT results showed that the IC₅₀ value of PTX NPs on 4 T1 cells was 0.490 μg/mL, while that of PTX injection was 1.737 μg/mL. The cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX injection. The tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%, respectively. Together with local photothermal stimulation, the tumor inhibition rate of the PTX NPs reached 91.05%, surpassing that of the gel under the same conditions (48.98%), moreover, the organ index and H&E staining results of PTX NPs showed a decrease in toxicity. CONCLUSION This combination therapy can significantly enhance the effect of anti-breast cancer, and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

Bacterial infection is a major threat to global public health, and can cause serious diseases such as bacterial skin infection and foodborne diseases. It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time. In this work, we developed a 4-mercaptophenylboronic acid gold nanoparticles (4-MPBA-AuNPs)-functionalized hydrogel microneedle (MPBA-H-MN) for bacteria detection in skin interstitial fluid. MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min. Surface enhanced Raman spectroscopy (SERS) detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria. Overall, the capture efficiency of this method exceeded 50%. In the concentration range of 1 × 10⁷ to 1 × 10¹⁰ colony-forming units/mL (CFU/mL), the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration. Using random forest (RF)-based machine learning, bacteria were effectively distinguished with an accuracy of 97.87%. In addition, the harmless disposal of used MNs by photothermal ablation was convenient, environmentally friendly, and inexpensive. This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.