Polymeric Microneedle Drug Delivery Systems: Mechanisms of Treatment, Material Properties, and Clinical Applications-A Comprehensive Review.

Our comprehensive review plunges into the cutting-edge advancements of polymeric microneedle drug delivery systems, underscoring their transformative potential in the realm of transdermal drug administration. Our scrutiny centers on the substrate materials pivotal for microneedle construction and the core properties that dictate their efficacy. We delve into the distinctive interplay between microneedles and dermal layers, underscoring the mechanisms by which this synergy enhances drug absorption and precision targeting. Moreover, we examine the acupoint-target organ-ganglion nexus, an innovative strategy that steers drug concentration to specific targets, offering a paradigm for precision medicine. A thorough analysis of the clinical applications of polymeric microneedle systems is presented, highlighting their adaptability and impact across a spectrum of therapeutic domains. This review also accentuates the systems' promise to bolster patient compliance, attributed to their minimally invasive and painless mode of drug delivery. We present forward-looking strategies aimed at optimizing stimulation sites to amplify therapeutic benefits. The anticipation is set for the introduction of superior biocompatible materials with advanced mechanical properties, customizing microneedles to cater to specialized clinical demands. In parallel, we deliberate on safety strategies aimed at boosting drug loading capacities and solidifying the efficacy of microneedle-based therapeutics. In summation, this review accentuates the pivotal role of polymeric microneedle technology in contemporary healthcare, charting a course for future investigative endeavors and developmental strides within this burgeoning field.

Enhanced lipid metabolism reprogramming in CHF rats through IL-6-mediated cardiac glial cell modulation by digilanid C and electroacupuncture stimulation combination.

Background: Cardiac lipid metabolism reprogramming is recognized as a critical pathological factor in the progression of chronic heart failure (CHF). The therapeutic potential of digilanid C and electroacupuncture stimulation (ES) in enhancing lipid metabolism and cardiac function has been established. However, the optimal synergistic regulatory strategies of these interventions on cardiac lipid metabolism have yet to be elucidated. Methods: This study aimed to comprehensively evaluate the impact of a digilanid C-ES combination on cardiac steatosis remodeling in CHF. Assessments were conducted across various dimensions, including myocardial oxygen consumption, mitochondrial function, and lipid metabolism. Additionally, we sought to uncover the underlying neuromolecular mechanisms. Results: Our findings, at both molecular and morphological levels, indicated that the synergistic application of digilanid C and ES significantly inhibited myocardial fibrosis and steatosis. This combination therapy facilitated the repair of cardiac neuro-vascular uncoupling and induced a reprogramming of lipid metabolism. Notably, the digilanid C-ES combination ameliorated cardiomyocyte apoptosis and enhanced mitochondrial biogenesis in CHF, leading to a restructured energy supply pattern. Cardiac immunofluorescence analyses revealed the aggregation of cardiac glial cells (CGCs) at sites of abnormal neurovascular coupling, a response to cardiac lipid degeneration. This was accompanied by a marked reduction in the abnormally elevated expression of interleukin 6 (IL-6) and glutamatergic signaling, which correlated with the severity of cardiac steatosis and the aberrant activation of CGCs. The combined therapy was found to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathway, effectively attenuated lipid accumulation and over-recruitment of CGCs and deprivation of glutamatergic nerves. Conclusion: These findings underscore the potential of digilanid C and ES combination therapy as a novel approach to modulate the complex interplay between neurovascular dynamics and metabolic dysregulation in CHF.

A novel nomogram for predicting optimal weight loss response following diet and exercise intervention in patients with obesity.

This study aimed to identify factors associated with optimal weight loss response by analyzing pre-weight loss data from a cohort of 2577 patients with obesity who visited weight management clinics between 2013 and 2022. Out of these, 1276 patients had follow-up data available. Following dietary and exercise interventions, 580 participants achieved optimal weight loss outcomes. Participants were subsequently divided into two groups based on their weight loss outcomes: those who achieved optimal weight loss response and those who did not. Statistical analysis, conducted using RStudio, identified thirteen predictor variables through LASSO and logistic regression, with age emerging as the most influential predictor. A nomogram was developed to predict optimal weight loss response, showing good predictive performance (AUC = 0.807) and clinical applicability, validated by internal validation methods. Decision curve analysis (DCA) further illustrated the nomogram's clinical utility. The developed nomogram prediction model for optimal weight loss response is user-friendly, highly accurate, and demonstrates excellent discriminative and calibration capabilities.

Acupuncture indication knowledge bases: meridian entity recognition and classification based on ACUBERT.

In acupuncture diagnosis and treatment, non-quantitative clinical descriptions have limited the development of standardized treatment methods. This study explores the effectiveness and the reasons for discrepancies in the entity recognition and classification of meridians in acupuncture indication using the Acupuncture Bidirectional Encoder Representations from Transformers (ACUBERT) model. During the research process, we selected 54 593 different entities from 82 acupuncture medical books as the pretraining corpus for medical literature, conducting classification research on Chinese medical literature using the BERT model. Additionally, we employed the support vector machine and Random Forest models as comparative benchmarks and optimized them through parameter tuning, ultimately leading to the development of the ACUBERT model. The results show that the ACUBERT model outperforms other baseline models in classification effectiveness, achieving the best performance at Epoch = 5. The model's "precision," "recall," and F1 scores reached above 0.8. Moreover, our study has a unique feature: it trains the meridian differentiation model based on the eight principles of differentiation and zang-fu differentiation as foundational labels. It establishes an acupuncture-indication knowledge base (ACU-IKD) and ACUBERT model with traditional Chinese medicine characteristics. In summary, the ACUBERT model significantly enhances the classification effectiveness of meridian attribution in the acupuncture indication database and also demonstrates the classification advantages of deep learning methods based on BERT in multi-category, large-scale training sets. Database URL: http://acuai.njucm.edu.cn:8081/#/user/login?tenantUrl=default.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

AIM: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. MATERIALS AND METHODS: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. RESULTS: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. CONCLUSION: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway.

[Quantitative study on the acupoint effects based on complex network analysis: with the examples of the textbook networks formed by Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion].

By extracting the acupoint names and their main indications from cases in Chinese Acupuncture and Moxibustion Therapy and Practical Acupuncture and Moxibustion, the acupoints and their main indications are represented in a reduced dimension, establishing an "acupoint-indication" linkage. Using complex network detection results (node degree values), the specificity of acupoints was assessed. The small-world characteristics of the "acupoint-indication" network are utilized to analyze the consistency of acupoint selection in acupuncture prescriptions and strategies to avoid redundant acupoints. The results show that the "acupoint-indication" network formed by both texts exhibited an approximate "long-tail" distribution, with a large number of node degree values concentrated between 0 and 4 000, while a few nodes have degree values exceeding 10 000. There are significant differences in the number and distribution of nodes with degree values> 10 000 between the two texts. Chinese Acupuncture and Moxibustion Therapy includes 11 acupoints with multiple edges across the body, whereas Practical Acupuncture and Moxibustion contains only 2 such acupoints, located in the lower limbs. Clinically, some acupoints have a broad therapeutic effect and appear in numerous prescriptions. The division of acupoints based on node degree values can coarsely evaluate the body region specificity of acupoints' regulatory effects. The "acupoint-indication" network of Chinese Acupuncture and Moxibustion Therapy has a higher number of edges than that of Practical Acupuncture and Moxibustion, which might be related to the different historical contexts of the two texts. In the future, diagnostic and therapeutic patterns with historical continuity can be utilized to optimize acupuncture prescriptions.

Immune metabolic mechanisms of acupuncture in improving glycolipid metabolic disorders explored through pancreatic adipose tissue. / ä»Žèƒ°è ºè„‚è‚ªç»„ç»‡æŽ¢è®¨é’ˆåˆºæ”¹å–„ç³–è„‚ä»£è°¢ç— çš„å ç–«ä»£è°¢æœºåˆ¶.

Pancreatic adipose tissue serves as a crucial structural basis for the development of glycolipid metabolic disorders. Understanding the mechanisms underlying pancreatic adipose tissue infiltration and regulatory strategies is essential for early intervention in glycolipid metabolic disorders. Pancreatic adipose tissue functions as a significant medium linking systemic immune metabolism, while the pancreatic vascular system emerges as a novel target for sensing pancreatic immune responses and maintaining the body's energy homeostasis, collectively participating in the development of glycolipid metabolic disorders. Acupuncture possesses potential effects in modulating the interaction between resident macrophages and adipocytes in the pancreas, leading to the reversible reduction of excessive pancreatic adipose accumulation, with its action being vascular-dependent.

Education and training of acupuncture-moxibustion professionals from the perspective of medicine-engineering interdiscipline: case analysis of China's higher education reform and transformation under the background of "emerging medical education". / åŒ»å·¥ç»“åˆè§†è§’ä¸‹é’ˆç¸ä¸“ä¸šäººæ‰çš„æ•™è‚²ä¸ŽåŸ¹å ».

A sustainable training system for acupuncture-moxibustion and tuina professionals, integrating "medicine, industry, education and research" is established, under the main framework of the medicine-engineering interdiscipline, and with the consideration of the issues of medicine, the application of engineering technology, the thinking approaches of sciences, and the collaboration of business studies. It is the potential power to support the development of traditional medicine. Through analyzing the difficulties of the medicine-engineering interdiscipline of acupuncture specialty, and in association with the experiences of the early-stage development of the collaboration between medicine and engineering, the paper presents the cases of China's higher education reform and transformation under the background of "emerging medical education" so as to explore a replicable personnel training mode.

Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.

Gut-targeted therapies for type 2 diabetes mellitus: A review.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.

Electroacupuncture stimulation ameliorates cognitive impairment induced by long-term high-fat diet by regulating microglial BDNF.

Long-term high-fat diet (HFD) in adolescents leads to impaired hippocampal function and increases the risk of cognitive impairment. Studies have shown that HFD activates hippocampal microglia and induces hippocampal inflammation, which is an important factor for cognitive impairment. Electroacupuncture stimulation (ES), a nerve stimulation therapy, is anti-inflammatory. This study explored its therapeutic potential and mechanism of action in obesity-related cognitive impairment. 4-week-old C57 mice were given either normal or HFD for 22 weeks. At 19 weeks, some of the HFD mice were treated with ES and nigericin sodium salt. The cognitive behavior was assessed through Morris water maze test at 23 weeks. Western blotting was used to detect the expression levels of pro-inflammatory molecules IL-1ß and IL-1R, synaptic plasticity related proteins synaptophysin and Postsynaptic Density-95 (PSD-95), and apoptotic molecules (Caspase-3 and Bcl-2), in the hippocampus. The number, morphology, and status of microglia, along with the brain-derived neurotrophic factor（BDNF） content, were analyzed using immunofluorescence. ES treatment improved cognitive deficits in HFD model mice, and decreased the expressions of microglial activation marker, CD68, and microglial BDNF. Inhibition of proinflammatory cytokine, IL-1ß, and IL-1R promoted PSD-95 and synaptophysin expressions. Peripheral NLRP3 inflammasome agonist injections exacerbated the cognitive deficits in HFD mice and promoted the expressions of IL-1ß and IL-1R in the hippocampus. The microglia showed obvious morphological damage and apoptosis. Collectively, our findings suggest that ES inhibits inflammation, regulates microglial BDNF, and causes remodeling of hippocampal function in mice to counteract obesity-like induced cognitive impairment. Overexcitation of peripheral inflammasome complexes induces hippocampal microglia apoptosis, which hinders the effects of ES.

Electroacupuncture alleviates intrauterine adhesion through regulating autophagy in rats.

Autophagy is a well-conserved metabolic system that maintains homeostasis by relying on lysosomal breakdown. The endometrium of patients with intrauterine adhesion (IUA) and an animal model exhibits impaired autophagy. Autophagy is negatively correlated with inflammation. Activation of autophagy can inhibit the inflammatory response, while defects in autophagy will activate the inflammatory response. Here, we studied whether electroacupuncture (EA) inhibits inflammation and promotes endometrial injury repair by activating endometrial autophagy. The IUA animal model was established by mechanical injury plus lipopolysaccharide infection. EA stimulation was applied to the acupoints Guanyuan (CV4), bilateral Sanyinjiao (SP6), and Zusanli (ST36). The results indicated that EA could improve endometrial morphology, attenuate endometrial fibers, and enhance endometrial receptivity in the rat. EA could increase the autophagosomes of endometrial epithelial cells, increase the levels of LC3 and Beclin1, and decrease the level of p62. Additionally, EA may also suppress the nuclear factor kappa-B (NF-κB) signaling pathway and reduce the release of inflammatory factors. Additionally, the effect of EA was comparable to that of the autophagy agonist rapamycin, and the autophagy inhibitor 3-methyladenine reversed the therapeutic effect of EA. Therefore, we assume that EA may facilitate endometrial healing by activating autophagy and reducing NF-κB signal pathway-mediated inflammation.

FAPbBr3@PbBr(OH) phosphor with high stability for anti-counterfeiting application via water induction.

Organic-inorganic hybrid perovskite nanocrystals have become a very widely used as semiconductor light-emitting materials. However, perovskite nanocrystals face stability challenges, which is a key factor hindering their application. In this paper, by introducing water into the synthesis of formamidinium lead bromide (FAPbBr3) perovskite, ultra-stable FAPbBr3@PbBr(OH) fluorescent material was prepared. The photoluminescence intensity of the material after the addition of water increased 2.9 times compared with that before the addition of water. The excellent green fluorescence emission was still maintained after four cycles of wash-dry treatment. Meanwhile, it also exhibits good ultraviolet and thermal stability. The above enhanced performance of FAPbBr3nanocrystals is attributed the protection of PbBr(OH). In addition, the prepared material can be used in anti-counterfeit patterns. The anti-counterfeit patterns have good color rendering and the luminous color has a high dependence on temperature. Both of these features make it very valuable for various fluorescent anti-counterfeiting labels.

[Feasibility analysis of puncture robot technology for the application of acupuncture robot].

The difficulties such as how to accurately locate acupoints and safely insert needles are presented in acupuncture robot. The puncture robot with high technological similarity to acupuncture robot is getting mature, and a large number of human trials and animal experiments have been conducted for the development of puncture robot. Through comparing the similarities and differences between puncture robot and acupuncture robot in the aspects of through-skin puncture, needle insertion and needle removal, the valuable technology of puncture robot is analyzed for the development of acupuncture robot, and the crucial direction of technology migration is determined. ①Integrating the mechanical feedback and medical imaging technology and utilizing the multi-modal perception to achieve the safety of acupuncture operation. ②Emphasizing the integration of the existing designs of chest puncture robot to realize the acupuncture operation with inhalation and exhalation involved. ③Focusing on the development of relevant technology of automatic needle removal through conducting the actual scenario of treatment with acupuncture robot in patients under non-anaesthetic condition.

In vitro comparative study of multimodal imaging nano-assembled microspheres with two clinical drug-eluting beads loaded with doxorubicin.

DC Beads and CalliSpheres are commonly used microspheres in clinical transcatheter arterial chemoembolization, but these microspheres cannot be visualized by themselves. Therefore, in our previous study, we developed multimodal imaging nano-assembled microspheres (NAMs), which are visualized under CT/MR and the location of embolic microspheres can be determined during postoperative review, facilitating the evaluation of embolic areas and guiding subsequent treatment. Moreover, the NAMs can be carried with positively and negatively charged drugs, increasing the choice of drugs. Systematic comparative analysis of the pharmacokinetics of NAMs with commercially available DC Bead and CalliSpheres microspheres is important for evaluating the clinical application of NAMs. In our study, we compared the similarities and differences between NAMs and two drug-eluting beads (DEBs) in respect to drug loading capacity, drug release profiles, diameter variation and morphological characteristics. The results indicate that NAMs had good drug delivery and release characteristics as well as DC Bead and CalliSpheres in vitro experimental stage. Therefore, NAMs have a good application prospect in transcatheter arterial chemoembolization treatment of hepatocellular carcinoma.

Correction to: A nomogram model for the risk prediction of type 2 diabetes in healthy eastern China residents: a 14­year retrospective cohort study from 15,166 participants.

[This corrects the article DOI: 10.1007/s13167-022-00295-0.].

Neuromechanical Dimorphism of Hypoglycemic Effect of Electroacupuncture.

INTRODUCTION: Electroacupuncture (EA) has a favorable impact on blood glucose stability. Blood glucose homeostasis is linked to sexual dimorphism. The majority of research has, however, focused on male participants, and sex differences have not been adequately taken into account. METHODS: Here, we investigated how EA intervention affected pancreatic metabolic stress and explored if there were any sex-related changes in the maintenance of pancreatic function following intraperitoneal injection of a 10 g/kg glucose solution. RESULTS: The transient receptor potential vanilloid 1 (TRPV1) calcitonin gene-related peptide (CGRP)-ß cell pathway of the male pancreas is vital to maintain glucose metabolism in mice. In contrast, there is a sex bias in TRPV1, which implies that female mice have additional routes for preserving glucose homeostasis. EA is ineffective on Trpv1-/- male mice. It also revealed that TRPV1 in male mice served as a crucial mediator for the EA control of blood glucose. Meanwhile, the sympathetic marker tyrosine hydroxylase showed higher expression in the male pancreas, while the cholinergic marker choline acetyltransferase is expressed predominantly in female mice. Injecting γ-aminobutyric acid into the paraventricular nucleus of male mice caused a disruption in blood glucose and a lack of response to EA. It verified that male mice had a more pronounced sympathetic innervation of the pancreas than female mice. CONCLUSION: Our research has demonstrated that the TRPV1 sensory afferent nerve and sympathetic efferent nerve are capable of maintaining glucose homeostasis, exhibiting a distinct sexual dimorphism. Furthermore, this regulation is contingent on the EA effect.

Multimodal imaging of nano-assembled microspheres loaded with doxorubicin and Cisplatin for liver tumor therapy.

Currently, clinically available drug-loaded embolic microspheres have some shortcomings, such as being invisible with standard medical imaging modalities and only being able to carry positively charged drugs. The visualization of drug-loaded microspheres is very important for real-time monitoring of embolic position to improve the therapeutic effect. Meanwhile, the visualization of microspheres can enable postoperative reexamination, which is helpful for evaluating the embolization area and guiding the subsequent treatment. In addition, microspheres capable of loading different charged drugs can increase the choice of chemotherapeutic drugs and provide more possibilities for treatment. Therefore, it is of great importance to explore drug-loaded microspheres capable of multimodal imaging and loading drugs with different charges for transarterial chemoembolization (TACE) treatment of liver tumors. In our study, we designed a kind of nano-assembled microspheres (NAMs) that can realize computer X-ray tomography (CT)/magnetic resonance imaging (MRI)/Raman multimodal imaging, be loaded with positively and negatively charged drugs and test their imaging ability, drug loading and biological safety. The microspheres have strong attenuation performance for CT, high T2 relaxation for MRI and good sensitivity for surface enhanced Raman spectroscopy (SERS). At the same time, our microspheres can also load the positively charged drug, doxorubicin (DOX), and negatively charged drug Cisplatin. One gram of NAMs can hold 168 mg DOX or 126 mg Cisplatin, which has good drug loading and sustained-release capacity. Cell experiments also showed that the nano-assembled microspheres had good biocompatibility. Therefore, as multimodal developed drug loaded microspheres, nano assembled microspheres have great potential in TACE treatment of liver cancer.

[Effect of electroacupuncture at "Tianshu" (ST25) on the regulation of nitrergic neurons in different intestinal segments in streptozotocin induced type 2 diabetic rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST25) on nitrergic neurons in jejunum and distal colon in type 2 diabetic rats, so as to explore its mechanism of regulating different intestinal segments. METHODS: Twenty-four SD rats were randomly divided into control, model and EA groups (n=8 in each group). The diabetes model was established by intraperitoneal injection of streptozotocin (35 mg/kg) and high-sugar and high-fat diet for 2 weeks. EA (2 Hz/15 Hz, 2 mA) was applied to bilateral ST25 for 20 min, once a day, 6 days a week for 4 weeks. The intestinal motility was evaluated by observing the first red stool excretion time and the distal colon bead excretion time. HE staining was used to observe the histological changes of jejunum and distal colon. The positive expression and protein expression of intestinal total neuronal marker protein gene product 9.5（PGP9.5） and neuronal nitric oxide synthase (nNOS) in jejunum and distal colon were detected by immunofluorescence staining and Western blot, respectively. RESULTS: After modeling, the blood glucose was significantly increased (P<0.01), the first red stool excretion time and the distal colon bead excretion time were shortened (P<0.01), the expression levels of PGP9.5 and nNOS in jejunum and distal colon were decreased (P<0.01) in the model group relevant to the control group. After treatment, compared with the model group, the blood glucose was decreased (P<0.01), the first red stool excretion time and the distal colon bead excretion time were prolonged (P<0.01, P<0.05), and the expression levels of PGP9.5 and nNOS in jejunum and distal colon were increased (P<0.05, P<0.01) in the EA group. HE staining showed disordered structure in intestinal mucosa of the jejunum and distal colon, and reduction of the number of goblet cells in the model group, which was relatively milder in the EA group. CONCLUSION: EA can effectively improve the intestinal mucosal damage and restore intestinal motor function in type 2 diabetic rats, which may be related to its function in regulating the number of nitrergic neurons in the intestinal nervous system.