LordNet: An efficient neural network for learning to solve parametric partial differential equations without simulated data.

Neural operators, as a powerful approximation to the non-linear operators between infinite-dimensional function spaces, have proved to be promising in accelerating the solution of partial differential equations (PDE). However, it requires a large amount of simulated data, which can be costly to collect. This can be avoided by learning physics from the physics-constrained loss, which we refer to it as mean squared residual (MSR) loss constructed by the discretized PDE. We investigate the physical information in the MSR loss, which we called long-range entanglements, and identify the challenge that the neural network requires the capacity to model the long-range entanglements in the spatial domain of the PDE, whose patterns vary in different PDEs. To tackle the challenge, we propose LordNet, a tunable and efficient neural network for modeling various entanglements. Inspired by the traditional solvers, LordNet models the long-range entanglements with a series of matrix multiplications, which can be seen as the low-rank approximation to the general fully-connected layers and extracts the dominant pattern with reduced computational cost. The experiments on solving Poisson's equation and (2D and 3D) Navier-Stokes equation demonstrate that the long-range entanglements from the MSR loss can be well modeled by the LordNet, yielding better accuracy and generalization ability than other neural networks. The results show that the Lordnet can be 40× faster than traditional PDE solvers. In addition, LordNet outperforms other modern neural network architectures in accuracy and efficiency with the smallest parameter size.

The nutritional roles of zinc for immune system and COVID-19 patients.

Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.

Development of double-layer poly (amino acid) modified electrochemical sensor for sensitive and direct detection of betamethasone in cosmetics.

Screening for illegal use of glucocorticoids (GCs) in cosmetics by electrochemical methods is extremely challenging due to the poor electrochemical activity of GCs. In this study, poly-L-Serine/poly-Taurine modified electrode (P(Tau)/P(L-Ser)/GCE) was prepared for sensitive and direct determination of betamethasone in cosmetics by a simple two-step in situ electropolymerization reaction. The relevant parameters of preparation and electroanalytical conditions were respectively studied, including the concentration of polymerization solution, the number of scanning circles and the scanning rate. The SEM and EDS mapping demonstrated successful preparation of P(Tau)/P(L-Ser)/GCE. The electro-catalytic properties of the obtained electrodes were investigated using cyclic voltammetry and differential pulse voltammetry methods, showing a remarkable improvement of sensitivity for the detection of betamethasone due to the synergic effect of both P(L-Ser) and P(Tau). In addition, we investigated the electrochemical reduction of betamethasone on the surface of modified electrode. It was found that the process was controlled by diffusion effect and involved the transfer of two electrons and two protons. Then the electrochemical sensor method based on P(Tau)/P(L-Ser)/GCE was established and delivered a linear response to betamethasone concentration from 0.5 to 20 µg mL-1 with a limit of detection of 32.2 ng mL-1, with excellent recoveries (98.1%-106.8%) and relative standard deviations (＜4.8%). Furthermore, the established electrochemical sensor method was compared with conventional HPLC method. The results showed that both of them were comparable. Moreover, the established electrochemical sensor method was with the merits of short analysis time, environmentally friendly, low cost and easy to achieve in-site detection.

Asymmetric transmission devices empowered by a cascaded structure of a dielectric metasurface-photonic crystal.

In this Letter, we theoretically propose an all-dielectric quasi-three-dimensional subwavelength structure constructed by a dielectric metasurface cascaded with a multilayer photonic crystal (PC) to achieve a high-performance asymmetric optical transmission (AOT). The desired optical control of the AOT is realized by combining the predetermined anomalous beam steering of a phase gradient metasurface with a unique bandgap as well as transmission characteristics of the multilayered stacked PC. The simulated results demonstrate that the proposed AOT device operating at the center wavelength of 633 nm with a circularly polarized state exhibits a high transmission of up to 62.4% with a contrast ratio exceeding 606. The excellent performance of AOT is achieved by making disassembled transverse magnetic and transverse electric polarized light under the same deflection angle concurrently match with respective high-efficient transmission bands in the multilayer PC. Furthermore, dependence of the performance of the proposed device on structural dimensions is also explored. Fortunately, the designed AOT structure is applicable to any linearly polarized light but is accompanied by double diffraction channels as compared to the circularly polarized light case. Owing to its planar configuration, passive operation, and compelling performance under various polarization states, the proposed strategy for achieving AOT paves a new road for realizing high-performance optical metadevices in compact optical systems.

ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite nuclear localization signal.

ZBTB34 is a novel zinc finger protein with an unknown function. In this study, the gene expression and survival prognosis of ZBTB34 were analyzed across tumors based on the TCGA datasets. According to the bioinformatics analysis and qPCR results, liver hepatocellular carcinomas exhibit a high level of ZBTB34 expression. Additionally, the experiment supported the bioinformatics analysis findings that ZBTB34 expression was regulated by miR-125b-5p and that ZBTB34 affected ZBTB10, POLR1B, and AUH expression in HepG2 cells. Biological software analysis further revealed that ZBTB34 contains a monopartite nuclear localization signal (NLS). Arginine and lysine inside the putative NLS were substituted using the alanine-scanning mutagenesis method. The findings showed that the ability of ZBTB34 to enter the nucleus was abolished by the alanine substitution of the sequence 320RGGRARQKRA329 and the mutation of Lys327 and Arg328 residues. ZBTB34 was co-immunoprecipitated with importin α1, importin α3, importin α4, and importin ß1, according to the results of the co-immunoprecipitation assay. In conclusion, ZBTB34 is a hepatocellular carcinoma-associated protein with a monopartite NLS. The nuclear import of ZBTB34 is mediated by importin α1, importin α3, importin α4, and importin ß1. ZBTB34 performs its biological functions via a putative miR-125b-5p/ZBTB34/(ZBTB10, POLR1B, and AUH) signaling axis in HepG2 cells.

Hepatocyte-targeted delivery using oleanolic acid-loaded liposomes for enhanced hepatocellular carcinoma therapy.

Drug-loaded liposomes have been shown to be effective in the treatment of hepatocellular carcinoma (HCC). However, the systemic non-specific distribution of drug-loaded liposomes in tumor patients is a critical therapeutic challenge. To address this issue, we developed galactosylated chitosan-modified liposomes (GC@Lipo) that could selectively bind to the asialoglycoprotein receptor (ASGPR), which is highly expressed on the membrane surface of HCC cells. Our study demonstrated that the GC@Lipo significantly enhanced the anti-tumor efficacy of oleanolic acid (OA) by enabling targeted drug delivery to hepatocytes. Remarkably, treatment with OA-loaded GC@Lipo inhibited the migration and proliferation of mouse Hepa1-6 cells by upregulating E-cadherin expression and downregulating N-cadherin, vimentin, and AXL expressions, compared to a free OA solution and OA-loaded liposomes. Furthermore, using an axillary tumor xenograft mouse model, we observed that OA-loaded GC@Lipo led to a significant reduction in tumor progression, accompanied by concentrated enrichment in hepatocytes. These findings strongly support the clinical translation of ASGPR-targeted liposomes for the treatment of HCC.

Plasmonic Resonance Coupling of Nanodisk Array/Thin Film on the Optical Fiber Tip for Integrated and Miniaturized Sensing Detection.

Fiber-optic surface plasmon resonance (FOSPR) sensing technology has become an appealing candidate in biochemical sensing applications due to its distinguished capability of remote and point-of-care detection. However, FOSPR sensing devices with a flat plasmonic film on the optical fiber tip are seldom proposed with most reports concentrating on fiber sidewalls. In this paper, we propose and experimentally demonstrate the plasmonic coupled structure of a gold (Au) nanodisk array and a thin film integrated into the fiber facet, enabling the excitation of the plasmon mode on the planar gold film by strong coupling. This plasmonic fiber sensor is fabricated by the ultraviolet (UV) curing adhesive transferring technology from a planar substrate to a fiber facet. The experimental results demonstrate that the fabricated sensing probe has a bulk refractive index sensitivity of 137.28 nm/RIU and exhibits moderate surface sensitivity by measuring the spatial localization of its excited plasmon mode on Au film by layer-by-layer self-assembly technology. Furthermore, the fabricated plasmonic sensing probe enables the detection of bovine serum albumin (BSA) biomolecule with a detection limit of 19.35 µM. The demonstrated fiber probe here provides a potential strategy to integrate plasmonic nanostructure on the fiber facet with excellent sensing performance, which has a unique application prospect in the detection of remote, in situ, and in vivo invasion.

MOTS-c Functionally Prevents Metabolic Disorders.

Mitochondrial-derived peptides are a family of peptides encoded by short open reading frames in the mitochondrial genome, which have regulatory effects on mitochondrial functions, gene expression, and metabolic homeostasis of the body. As a new member of the mitochondrial-derived peptide family, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is regarding a peptide hormone that could reduce insulin resistance, prevent obesity, improve muscle function, promote bone metabolism, enhance immune regulation, and postpone aging. MOTS-c plays these physiological functions mainly through activating the AICAR-AMPK signaling pathways by disrupting the folate-methionine cycle in cells. Recent studies have shown that the above hormonal effect can be achieved through MOTS-c regulating the expression of genes such as GLUT4, STAT3, and IL-10. However, there is a lack of articles summarizing the genes and pathways involved in the physiological activity of MOTS-c. This article aims to summarize and interpret the interesting and updated findings of MOTS-c-associated genes and pathways involved in pathological metabolic processes. Finally, it is expected to develop novel diagnostic markers and treatment approaches with MOTS-c to prevent and treat metabolic disorders in the future.

Is the combination of acupuncture and Western medicine superior to monotherapy in the treatment of patients with Alzheimer's disease: A protocol for systematic review and network meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a common cause of dementia, and there are still a lack of treatment options to reverse or prevent disease progression. Existing evidence shows that acupuncture has advantages in the treatment of AD, but whether the efficacy of acupuncture belongs to the placebo effect remains controversial, and there is no strict systematic review and network meta-analysis to evaluate the efficacy and safety of acupuncture combined with Western medicine in the treatment of AD. METHODS: From the inception to February 2023, the Embase, Latin American and Caribbean Health Sciences Literature, Medline, the Cochrane Collaboration's Controlled Clinical Trials, Scopus, China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure, and Australian Medical Index will be searched using the key phrases "acupuncture," "warm needling," "electroacupuncture," "Alzheimer disease," and "cohort" for all relevant studies. Quality assessment of all studies included in this review will be independently assessed by 2 reviewers using the Cochrane Collaborations tool. When significant heterogeneity is indicated, we will find the source of heterogeneity by subgroup or sensitivity analysis. DISCUSSION: This study will evaluate the efficacy of acupuncture combined with Western medicine in improving cognitive function and activities of daily living in AD patients. The results of this study will verify whether the efficacy of acupuncture in the treatment of AD belongs to the placebo effect, which will also provide a reference for the clinical use of acupuncture combined with Western medicine in the treatment of AD.

Electrically switchable capabilities of conductive polymers-based plasmonic nanodisk arrays.

The electrically dynamic regulation of plasmonic nanostructures provides a promising technology for integrated and miniaturized electro-optical devices. In this work, we systematically investigate the electrical regulation of optical properties of plasmonic Au nanodisk (AuND) arrays integrated with different conductive polymers, polypyrrole (PPy), polyaniline (PANI), and poly(3,4-ethylenedioxythiophene) (PEDOT), which show their respective superiority of electrical modulation by applying the appropriate low voltages. For the hybrid structure of polymer-coated AuND arrays, its reflection spectrum and corresponding structural color are dynamically modulated by altering the complex dielectric function of the covering nanometer-thick conductive polymers based on the electrically controlled redox reaction. Due to the distinct refractive index responses of different polymers on the external voltage, polymer-coated AuND arrays exhibit different spectral variations, response time, and cycle stability. As a result, the reflection intensity of PPy-coated AuND arrays is mainly tailored by increasing optical absorption of the PPy polymer over a broad spectral range, which is distinguished from the wavelength shift of the resonance modes of AuND arrays induced by the other two polymers. Additionally, AuND arrays integrated with both PANI and PEDOT polymers exhibit a rapid switching time of less than 50 ms, which is 5 times smaller than the case of the PPy polymer. Most importantly, PPy-coated AuND arrays exhibit excellent cycle stability over 50 cycles compared to the other two polymers integrated devices. This work demonstrates a valuable technique strategy to realize high-performance polymer-coated dynamically tunable nanoscale electro-optical devices, which has especially significance for smart windows or dynamic display applications.

The effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in critically ill patients with acute kidney injury: An observational study using the MIMIC database.

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia. Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia. Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27-0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39-0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40-0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45-0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55-2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96-1.51). Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.

Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length.

Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.

Hydrogel Loaded with VEGF/TFEB-Engineered Extracellular Vesicles for Rescuing Critical Limb Ischemia by a Dual-Pathway Activation Strategy.

Critical limb ischemia (CLI) is the most severe clinical manifestation of peripheral arterial disease, which causes many amputations and deaths. Conventional treatment strategies for CLI (e.g., stent implantation and vascular surgery) bring surgical risk, which are not suitable for each patient. Extracellular vesicles (EVs) can be a potential solution for CLI. Herein, vascular endothelial growth factor (VEGF; i.e., a crucial molecule related to angiogenesis) and transcription factor EB (TFEB; i.e., a pivotal regulator of autophagy) are chosen as the target gene to improve the bioactivity of EVs derived from endothelial cells. The VEGF/TFEB-engineered EVs (Engineered-EVs) are fabricated by genetically engineering the parent cells, and their versatile functions are confirmed using three cell models (human umbilical vein endothelial cells, myoblast, and monocytes). Injectable thermal-responsive hydrogel are then combined with Engineered-EVs to combat CLI. These results reveal that the hydrogel can enhance the stability of Engineered-EVs in vivo and release EVs at different temperatures. Moreover, the results of animal studies indicate that Engineered-EV/Hydrogel can significantly improve neovascularization, attenuate muscle injury, and recover limb function after CLI. Finally, mechanistic studies shed light on the therapeutic effect of Engineered-EV/Hydrogel due to the activated VEGF/VEGFR pathway and autophagy-lysosomal pathway.

Gold embedded chitosan nanoparticles with cell membrane mimetic polymer coating for pH-sensitive controlled drug release and cellular fluorescence imaging.

In this work, gold embedded chitosan nanoparticles (Au@CS NPs) were fabricated by a one-pot method. The benzaldehyde-terminated poly[(2-methacryloyloxy) ethyl phosphorylcholine] (PMPC) was applied to modification of the gold doped chitosan nanoparticles. The obtained Au@CS-PMPC NPs had the diameter of 135 nm with a narrow distribution. The size of the Au@CS-PMPC NPs, as well as the size of the embedded gold NPs, might be well-controlled by adjusting the feeding ratio between chitosan and HAuCl4. Furthermore, the Au@CS-PMPC NPs showed increased colloidal stability, high drug loading content, pH-responsive drug release, excellent biocompatibility and bright fluorescence emission. The results demonstrated that Au@CS-PMPC NPs showed a great potential for tumor therapy via the combination advantages of pH-sensitive controlled drug release and cellular fluorescence imaging.

Ultrastretchable, Tough, Antifreezing, and Conductive Cellulose Hydrogel for Wearable Strain Sensor.

Conductive hydrogels have shown great potential in the field of flexible strain sensors. However, their application is greatly limited due to the low conductivity and poor mechanical properties at subzero temperatures. Herein, an ultrastretchable, tough, antifreezing, and conductive cellulose hydrogel was fabricated by grafting acrylonitrile and acrylamide copolymers onto the cellulose chains in the presence of zinc chloride using ceric ammonium nitrate as the initiator. The resulting hydrogel exhibited ultrastretchability (1730%), excellent tensile strength (160 kPa), high elasticity (90%), good toughness (1074.7 kJ/m3), and fatigue resistance property due to the existence of dipole-dipole and multiple hydrogen-bonding interactions on the hydrogel network. In addition, the introduced zinc chloride endowed the cellulose-based hydrogel with remarkable electric conductivity (1.54 S/m) and excellent antifreezing performance (-33 °C). Finally, the hydrogel showed high sensitivity and stability to monitor human activities. In summary, this work presented a facile strategy to construct conductive hydrogel with excellent antifreezing and mechanical properties simultaneously, which showed great potential for wearable strain sensors.

[Acupuncture at acupoints along the meridians for primary insomnia: a multi-center randomized controlled trial].

OBJECTIVE: To compare the clinical effect differences among different acupoint selection methods for primary insomnia. METHODS: A total of 333 patients with primary insomnia were recruited from 3 study centers and randomly divided into a group A (111 cases, 7 cases dropped off), a group B (111 cases, 5 cases dropped off) and a group C (111 cases, 2 cases dropped off). The patients in the group A were treated with acupuncture at Shenmen (HT 7) and Baihui (GV 20), the patients in the group B were treated with acupuncture at Sanyinjiao (SP 6) and Baihui (GV 20), and the patients in the group C were treated with acupuncture at non-acupoint and Baihui (GV 20). All the treatment was given once a day, 30 min each time; 5 treatments were taken as a course and 5 courses of treatment were given. The Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS) scores were evaluated before and after treatment as well as 4 weeks after treatment. The encephalofluctuograph technology (ET) was observed before and after treatment. RESULTS: Compared before treatment, the PSQI scores after treatment and at follow-up were significantly decreased in three groups (P<0.01), and the decrease in the group A and the group B was greater than that in the group C (P<0.01). Compared before treatment, the AIS scores after treatment and at follow-up was significantly decreased in three groups (P<0.01), and the decrease in the group A was greater than that in the group C (P<0.05). The interclass and between-groups ET before and after treatment had no significant difference (P>0.05). CONCLUSION: The acupuncture at acupoints along the meridians could improve the sleep quality in patients with primary insomnia, and the therapeutic effect of acupoint along the meridians is better than that of non-acupoint.

Cell membrane mimetic copolymer coated polydopamine nanoparticles for combined pH-sensitive drug release and near-infrared photothermal therapeutic.

In this study, we modified the well-known photothermal polydopamine nanoparticles with the poly[(2-methacryloyloxy)ethyl phosphorylcholine-b-(2-dimethylamino)ethyl methacrylate] (PMPC-b-PDMAEMA) diblock copolymers, containing both biocompatible cell membrane phosphorylcholine zwitterions segments and pH-responsive dimethylaminoethyl units on the polymer chains, to achieve both the photothermal property and pH-responsive release behavior. The results showed that the obtained nanoparticles had a narrow size distribution with the diameter about 220 nm. Besides, the modified polydopamine nanoparticles showed enhanced colloidal stability, pH-sensitive drug release behavior, excellent biocompatibility and remarkable near-infrared photothermal property. Thus, it is highly anticipated that PMPC-b-PDMAEMA modified polydopamine nanoparticles can serve as a powerful drug delivery system for combined pH-sensitive drug release and near-infrared photothermal therapeutic.

[Manual Acupuncture Stimulation of Paired Acupoints Can Relieve Sleep Disorder Possibly by Upregulating Pineal Melatonin Protein and Its Receptor mRNA Levels in the Suprachiasmatic Nucleus in Insomnia Rats].

OBJECTIVE: To observe the effect of manual acupuncture stimulation of paired "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non-acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) mRNAs in insomnia rats, so as to explore their action difference and the underlying mechanism in improving insomnia. METHODS: Male SD rats were randomly divided into normal control (n=12), mo-del (n=8), GV 20+HT 7(n=12), GV 20+SP 6(n=11), and GV 20+ non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of Para-chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days. The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the midpoint between the elbow-tip and armpit on the medial side of the upper-arm) were punctured with filiform needles and manipulated by rotating the needle for about 1 min which was repeated once again every 10 min during 30 minutes' needle-retaining. The treatment was conducted once daily for 7 days. The expression levels of MT immunoactivity in the conarium tissue, and MT1 and MT2 mRNAs of the suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and fluorescence quantitative real time-PCR, respectively. RESULTS: After modeling, the expression levels of pineal MT (an increase of gray value means a decrease of immunoactivity), SCN MT1 and MT2 mRNAs were notably down-regulated in the model group relevant to the normal control group (P<0.05, P<0.01). Following the treatment, the down-regulated expression levels of MT protein, and MT1 and MT2 mRNAs were obviously reversed in the GV 20 + HT 7, GV 20 + SP 6 groups relevant to the model group (P<0.05, P<0.01). The therapeutic effect of GV 20+ HT 7 was superior to that of GV 20+ non-acupoint in up-regulating the expression of MT1 mRNA (P<0.01), and markedly superior to that of GV 20+ SP 6 and GV 20+ non-acupoint in increasing the sleep duration and in up-regulating the expression of MT2 mRNA (P<0.01). No significant differences were found among the 3 treatment groups in up-regulating the expression of MT (P>0.05). CONCLUSION: Manual acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep disorder in insomnia rats, which may be related to its effects in increasing the levels of pineal MT protein, and MT1 and MT2 mRNAs in hypothalamic SCN.

[Effect of Different Stimulating Strength of Electroacupuncture on Gastrointestinal Motility and RhoA/ROCK Signaling in Gastric Antral Smooth Muscle in Diabetic Gastroparesis Rats].

OBJECTIVE: To observe the effect of different strength of electroacupuncture (EA) stimulation on gastrointestinal motility and Ras homolog gene family member (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) signaling in diabetic gastroparesis (DGP) rats, so as to reveal the underlying mechanisms of EA for improving DGP. METHODS: Sixty SD rats were randomly and equally divided into blank control, DGP model, weak EA, medium EA, and strong EA groups (n＝12 rats in each). The DGP model was established by intraperitoneal injection of streptozotocin (STZ, 55 mmol/kg, 2%) and high-sugar and high-fat fodder feeding for 8 weeks. EA (0.12, 0.24, 0.36 mA, 20 Hz/100 Hz) was applied to "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and "Liangmen" (ST 21) for 20 min, once daily for 15 successive days. Blood glucose levels were measured weekly with blood glucose meter and blood glucose test paper. Fecal phenol red excretion method was used to display gastric emptying and small intestinal propulsion function. The expression of RhoA protein in the gastric antral smooth muscle tissue was detected by immunohistochemistry and Western blot (WB), separately, and that of ROCK, myosin phosphatase target subunit 1 (MYPT 1) and phosphorylated (p)-MYPT 1 proteins in gastric antrum detected by WB. RESULTS: Compared with the blank control group, the gastric emptying rate and small intestine propulsion rate of the model group were significantly decreased (P<0.05), and the blood glucose level was remarkably increased (P<0.05). Moreover, the expression levels of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins in the gastric antrum were significantly down-regulated relevant to the control group (P<0.05). After administration of EA, the decreased gastric emptying rate and intestinal propulsion rate, and the down-regulated expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins were significantly increased in the strong, medium and weak EA stimulation groups (P<0.05). Comparison among the 3 EA groups showed that the strong stimulation was significantly superior to weak stimulation in up-regulating the expression of RhoA, ROCK, MYPT 1 and p-MYPT 1 proteins, and obviously superior to the medium stimulation in up-regulating RhoA and MYPT 1 protein levels (P<0.05), while the medium stimulation was significantly stronger than the weak stimulation in up-regulating the expression of ROCK, MYPT 1 and p-MYPT 1 proteins (P<0.05). There were no significant differences among the 3 EA groups in up-regulating the gastric emptying rate and small intestinal propulsion rate, and between the strong stimulation and medium stimulation in the expression levels of ROCK and p-MYPT 1 proteins (P>0.05). CONCLUSION: Electroacupuncture stimulation of ST 36-SP 6-ST 21 at 0.12, 0.24 and 0.36 mA can promote the gastrointestinal motility in DGP rats, which may be associated with its effects in enhancing RhoA/ROCK signaling in the gastric antral smooth muscle at different degrees.

[Effect of Acupuncture Stimulation of Different Acupoint Combinations on Sleep and Expression of Circadian Clock and Bmal 1 Genes in Hypothalamus of Insomnia Rats].

OBJECTIVE: To observe the effect of manual acupuncture stimulation (MAS) of "Baihui"(GV 20)-"Shenmen"(HT 7)or GV 20-"Sanyinjiao"(SP 6) on sleep and expression of circadian rhythm genes (Clock and Bmal 1) in the hypothalamus in insomnia rats, so as to select a better acupoint group for insomnia. METHODS: A total of 53 SD rats were randomly divided into normal control (n=12),insomnia model (n=8), GV 20-HT 7(n=12), GV 20-SP 6(n=11),and GV 20-non-acupoint (n=10) groups. The insomnia model was established by intraperitoneal injection of p-chlorophenylalanine (PCPA,500 mg/kg,100 mg/mL) once daily for 2 days. The MAS (uniform reinforcing-reducing needling) was applied to GV 20-HT 7, GV 20-SP 6 or GV 20-non-acupoint for 30 min,once daily for 7 days. The sleep onset latency and sleep duration were gauged after intraperitoneal injection of pentobarbital sodium (35 mg/kg). The expression levels of Clock mRNA and Bmal 1 mRNA in the hypothalamic tissues containing ventrolateral preoptic area (VLPO) and suprachiasmatic nucleus (SCN) region were detected by fluorescence quantitative real-time PCR. RESULTS: Following administration of pentobarbital sodium,the sleep latency was significantly prolonged and the sleep duration was considerably shortened in rats of the model group(P<0.05). After the treatment, the increased sleep latencies in the GV 20-HT 7, GV 20-SP 6 and GV 20-non-acupoints were all significantly down-regulated (P<0.05), and the decreased sleep duration was significantly increased only in the GV 20-HT 7 group relevant to the model group (P<0.05), but not in the GV 20-SP 6 and GV 20-non-acupoint groups (P<0.05). There were no significant differences in the sleep latency among the 3 treatment groups (P<0.05). The sleep duration was obviously prolonged in the GV 20-HT 7 group than in the GV 20-SP 6 and GV 20-non-acupoint groups (P<0.05). After modeling, the expression levels of Clock mRNA and Bmal 1 mRNA in hypothalamic VLPO and SCN regions were significantly down-regulated relevant to the normal control group (P<0.01). Following the treatment, the expression levels of Clock mRNA in the VLPO and SCN regions of the GV 20-SP 6 and GV 20-HT 7 groups, and those of Bmal 1 mRNA in the VLPO and SCN regions of the 3 treatment groups were considerably increased relevant to the model group (P<0.05, P<0.01). The effects of GV 20-HT 7 were significantly superior to those of GV 20-SP 6 and GV 20-non-acupoint (and also the action of GV 20-SP 6 was evidently superior to that of GV 20-non-acupoint) in up-regulating the expression of Clock mRNA and Bmal 1 mRNA in both VLPO and SCN regions (P<0.05, P<0.01). CONCLUSIONS: Manual acupuncture stimulation of GV 20-HT 7 can improve the sleep latency and duration in insomnia rats,which may be associated with its effects in up-regulating the expression levels of circadian Clock mRNA and Bmal 1 mRNA in hypothalamic VLPO and SCN regions, and the efficacy of GV 20-HT 7 is obviously better than that of GV 20-SP 6 and GV 20-non-acupoint.