Prospect of value and application of transcutaneous electrical acupoint stimulation to control blood pressure in proactive healthcare perspective. / 主动健康视域下经皮穴位电刺激调控血压的价值与应用展望.

Hypertension is a global problem threatening human health and life. Although there are many antihypertensive drugs, the low compliance of medication affects its efficacy, and the effect in regulating hypertension has become increasingly prominent. Focusing on the new trend of proactive healthcare management, in the present paper, we made a summary about the status and existing problems of transcutaneous electrical acupoint stimulation (TEAS) in the regulation of blood pressure, and put forward some suggestions, such as selecting acupoints based on classical acupuncture theory to highlight the advantages of TEAS to control blood pressure as a whole, optimizing and screening the parameters of TEAS in the regulation of blood pressure, expanding the research observation indexes etc. We also made a prospect about its future application, hoping to provide new ideas for the proactive regulation, whole-process regulation and integrated regulation of blood pressure.

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes.

BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

Rational synthesis of 1,3,4-thiadiazole based ESIPT-fluorescent probe for detection of Cu2+ and H2S in herbs, wine and fruits.

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.

SLC25A51 decouples the mitochondrial NAD+/NADH ratio to control proliferation of AML cells.

SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix and is required for sustaining cell respiration. We observed elevated expression of SLC25A51 that correlated with poorer outcomes in patients with acute myeloid leukemia (AML), and we sought to determine the role SLC25A51 may serve in this disease. We found that lowering SLC25A51 levels led to increased apoptosis and prolonged survival in orthotopic xenograft models. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from mitochondrial oxidative pathways, notably without increased glycolytic flux. Depletion of SLC25A51 combined with 5-azacytidine treatment limits expansion of AML cells in vivo. Together, the data indicate that AML cells upregulate SLC25A51 to decouple mitochondrial NAD+/NADH for a proliferative advantage by supporting oxidative reactions from a variety of fuels. Thus, SLC25A51 represents a critical regulator that can be exploited by cancer cells and may be a vulnerability for refractory AML.

Quality indicators for epilepsy management in China: The development of a tool to assess care and first three-year report.

OBJECTIVES: Epilepsy care in China has expanded considerably in the last decade but still remains largely unknown; we developed an easy-to-use tool to assess its quality. METHODS: We adapted the Epilepsy Update Quality Measurement, produced by the American Academy of Neurology (AAN) for use in China: The Quality Indicator for Epilepsy Treatment-China National Action (QUIET-CHINA). This tool incorporates a standardized case report form initially for logging quality indicators for people with epilepsy during in-patient stays. Nine quality indicators covered seizures, drugs, diagnostics, screening for co-morbid conditions, counseling for woman of child bearing age, and a composite indicator was further proposed by total number of interventions performed divided by the total number of people eligible in each indicator. The tool also has an electronic reporting and data feedback system. 96 epilepsy centers in 31 jurisdictions in mainland China have been piloted since 2017. RESULTS: Data from 11,600 individuals with epilepsy in the first 3-year study period were analyzed. The median age was 31; 60% were male. The composite indicators were 74%. Seizure freedom rate was less than 25% in all epilepsy types and post-surgical seizure freedom rate was 21%. 90% had seizure type and frequency, antiepileptic drugs recorded, while only 70% with active epilepsy were on regular antiepileptic drugs treatment. Investigations for diagnosis and etiology were performed in around 90% but screening for co-morbid conditions and counseling for women of childbearing potential was 38% and 15% respectively. Severe side effect happened in 2% individuals during the treatment. CONCLUSION: The preliminary results of the national action provided some baseline information. Except for an overall improvement, a significant treatment gap still exists, and psychiatric co-morbidities or issues affecting women are not seen as a priority. QUIET-CHINA will be expanded to more and other levels of hospitals, to help narrow the treatment gap and equalize the comprehensive epilepsy care on the national level.

[Advances in revision surgery after primary total hip arthroplasty for Crowe type â £ developmental dysplasia of the hip].

Objective: To review research advances of revision surgery after primary total hip arthroplasty (THA) for patients with Crowe type Ⅳ developmental dysplasia of the hip (DDH). Methods: The recent literature on revision surgery after primary THA in patients with Crowe type Ⅳ DDH was reviewed. The reasons for revision surgery were analyzed and the difficulties of revision surgery, the management methods, and the related prosthesis choices were summarized. Results: Patients with Crowe type Ⅳ DDH have small anteroposterior diameter of the acetabulum, large variation in acetabular and femoral anteversion angles, severe soft tissue contractures, which make both THA and revision surgery more difficult. There are many reasons for patients undergoing revision surgery after primary THA, mainly due to aseptic loosening of the prosthesis. Therefore, it is necessary to restore anatomical structures in primary THA, as much as possible and reduce the generation of wear particles to avoid postoperative loosening of the prosthesis. Due to the anatomical characteristics of Crowe type Ⅳ DDH, the patients have acetabular and femoral bone defects, and the repair and reconstruction of bone defects become the key to revision surgery. The acetabular side is usually reconstructed with the appropriate acetabular cup or combined metal block, Cage, or custom component depending on the extent of the bone defect, while the femoral side is preferred to the S-ROM prosthesis. In addition, the prosthetic interface should be ceramic-ceramic or ceramic-highly cross-linked polyethylene wherever possible. Conclusion: The reasons leading to revision surgery after primary THA in patients with Crowe type Ⅳ DDH and the surgical difficulties have been clarified, and a large number of clinical studies have proposed corresponding revision modalities based on which good early- and mid-term outcomes have been obtained, but further follow-up is needed to clarify the long-term outcomes. With technological advances and the development of new materials, personalized prostheses for these patients are expected to become a reality.

Magnetic resonance-guided laser interstitial thermal therapy vs. stereoelectroencephalography-guided radiofrequency thermocoagulation in epilepsy patients with focal cortical dysplasia: a systematic review and meta-analysis.

Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) are two effective, minimally invasive treatments for epilepsy with focal cortical dysplasia (FCD). The purpose of this study is to conduct a meta-analysis to evaluate and compare the efficacy and safety of these two therapies in epilepsy patients with FCD. Methods: We searched PubMed, Embase, Cochrane, and other databases for articles published before March 2023. The primary objective was to compare the effectiveness and complications of MRgLiTT and SEEG-RFTC in epilepsy patients with FCD. The second objective was to determine which method provides a better prognosis for specific subgroup patients. Results: According to the inclusion and exclusion criteria, 18 studies were included, comprising 270 FCD patients including 37 patients from 6 MRgLiTT studies and 233 from 12 SEEG-RFTC studies. There were no significant differences between MRgLiTT and SEEG-RFTC groups in the seizure-freedom rate (59%, 95% CI 44-74%; 52%, 95% CI 47-57%, P = 0.86) and the rate of ≥50% seizure-reduction of FCD (90%, 95% CI 80-100%; 90%, 95% CI 86-94%, P = 0.42). Both methods had low complication rates (17.1%, 28/159) and long-term complication (2.5%, 4/159) rate, with no significant difference between them (P = 0.17). Conclusion: Both MRgLiTT and SEEG-RFTC are safe and minimally invasive treatments for patients with FCD. They have comparable performance in terms of postoperative seizure-freedom rates in patients with FCD, and both can be used as treatment options for patients with FCD. Our study found that SEEG-RFTC had a better therapeutic effect in the FCD2b subgroup.

Multifunctional Chiral Chemically-Powered Micropropellers for Cargo Transport and Manipulation.

Practical applications of synthetic self-propelled nano and microparticles for microrobotics, targeted drug delivery, and manipulation at the nanoscale are rapidly expanding. However, fabrication limitations often hinder progress, resulting in relatively simple shapes and limited functionality. Here, taking advantage of 3D nanoscale printing, chiral micropropellers powered by the hydrogen peroxide reduction reaction are fabricated. Due to their chirality, the propellers exhibit multifunctional behavior controlled by an applied magnetic field: spinning in place (loitering), directed migration in the prescribed direction, capture, and transport of polymer cargo particles. Design parameters of the propellers are optimized by computation modeling based on mesoscale molecular dynamics. It is predicted by computer simulations, and confirmed experimentally, that clockwise rotating propellers attract each other and counterclockwise repel. These results shed light on how chirality and shape optimization enhance the functionality of synthetic autonomous micromachines.

Influence of optical surface distortion in a cylindrical Offner stretcher on the far-field signal-to-noise ratio.

In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.

Screening single-cell trajectories via continuity assessments for cell transition potential.

Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Stormwater and flood simulation of sponge city and LID mitigation benefit assessment.

In the context of global climate change and the influence of human activities, the concept of "sponge city" is put forward to realize the purification, collection, and reuse of rainwater. The effective evaluation of LID facilities in sponge cities is of great guiding significance for the promotion and construction of sponge cities. IFMS (Integrated Flood Modeling System) Urban was selected to construct the rainstorm simulation. LID parameters were added to simulate the improvement of urban waterlogging after the construction of sponge city. A reasonable disaster loss assessment method was used to calculate the disaster mitigation benefit brought by the construction of sponge city. Through the comparison of the inundation situation before and after LID facilities' construction, it can be concluded that the mitigation effect of LID facilities on the overall inundation area of the city decreases with the increase of rainfall recurrence period, with the maximum reduction rate reaching 13.63% in the 5-year recurrence period and the minimum reduction rate of 11.06% in the 50-year recurrence period. LID facilities have a better disaster reduction effect for rainfall events with a small recurrence period than for rainfall events with a large recurrence period.

Dynamics of SLC25A51 reveal preference for oxidized NAD+ and substrate led transport.

SLC25A51 is a member of the mitochondrial carrier family (MCF) but lacks key residues that contribute to the mechanism of other nucleotide MCF transporters. Thus, how SLC25A51 transports NAD+ across the inner mitochondrial membrane remains unclear. To elucidate its mechanism, we use Molecular Dynamics simulations to reconstitute SLC25A51 homology models into lipid bilayers and to generate hypotheses to test. We observe spontaneous binding of cardiolipin phospholipids to three distinct sites on the exterior of SLC25A51's central pore and find that mutation of these sites impairs cardiolipin binding and transporter activity. We also observe that stable formation of the required matrix gate is controlled by a single salt bridge. We identify binding sites in SLC25A51 for NAD+ and show that its selectivity for NAD+ is guided by an electrostatic interaction between the charged nicotinamide ring in the ligand and a negatively charged patch in the pore. In turn, interaction of NAD+ with interior residue E132 guides the ligand to dynamically engage and weaken the salt bridge gate, representing a ligand-induced initiation of transport.

Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study.

BACKGROUND: Most physicians consider molars with chronic apical periodontitis (CAP) lesions as contraindications for immediate implant placement. At the patient's request, we perform immediate implant placement of the mandibular molars with CAP in clinical practice. AIM: To retrospectively analyze and compare the 5-year outcomes of immediate implant placement of the mandibular molars with CAP and those without obvious inflammation. METHODS: The clinical data of patients with immediate implant placement of the mandibular molars in the Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Qingdao University, from June 2015 to June 2017 were collected. The patients were divided into CAP (n = 52) and no-CAP (n = 45) groups. Changes in bone mineral density and bone mass around implants were analyzed 5 years after implant restoration. RESULTS: At 5 years after implantation, the peri-implant bone mineral density was 528.2 ± 78.8 Hounsfield unit (HU) in the CAP group and 562.6 ± 82.9 HU in the no-CAP group (P = 0.126). Marginal bone resorption around implants did not differ significantly between the two groups, including buccal (P = 0.268) or lingual (P = 0.526) resorption in the vertical direction or buccal (P = 0.428) or lingual (P = 0.560) resorption in the horizontal direction. Changes in the peri-implant jump space did not differ significantly between the two groups, including the buccal (P = 0.247) or lingual (P = 0.604) space in the vertical direction or buccal (P = 0.527) or lingual (P = 0.707) space in the horizontal direction. The gray value of cone-beam computed tomography measured using Image J software can reflect the bone mineral density. In the CAP area, the gray values of the bone tissue immediately and 5 years after implant placement differed significantly from those of the surrounding bone tissue (P < 0.01). CONCLUSION: The results of this study suggest that immediate implant placement of the mandibular molars with CAP can achieve satisfactory 5-year clinical results, without significant differences in the complications, survival rate, or bone tissue condition from the no-CAP mandibular molars.

Extracellular Matrix Stiffness Regulates Microvascular Stability by Controlling Endothelial Paracrine Signaling to Determine Pericyte Fate.

BACKGROUND: The differentiation of pericytes into myofibroblasts causes microvascular degeneration, ECM (extracellular matrix) accumulation, and tissue stiffening, characteristics of fibrotic diseases. It is unclear how pericyte-myofibroblast differentiation is regulated in the microvascular environment. Our previous study established a novel 2-dimensional platform for coculturing microvascular endothelial cells (ECs) and pericytes derived from the same tissue. This study investigated how ECM stiffness regulated microvascular ECs, pericytes, and their interactions. METHODS: Primary microvessels were cultured in the TGM2D medium (tubular microvascular growth medium on 2-dimensional substrates). Stiff ECM was prepared by incubating ECM solution in regular culture dishes for 1 hour followed by PBS wash. Soft ECM with Young modulus of ≈6 kPa was used unless otherwise noted. Bone grafts were prepared from the rat skull. Immunostaining, RNA sequencing, RT-qPCR (real-time quantitative polymerase chain reaction), Western blotting, and knockdown experiments were performed on the cells. RESULTS: Primary microvascular pericytes differentiated into myofibroblasts (NG2+αSMA+) on stiff ECM, even with the TGFß (transforming growth factor beta) signaling inhibitor A83-01. Soft ECM and A83-01 cooperatively maintained microvascular stability while inhibiting pericyte-myofibroblast differentiation (NG2+αSMA-/low). We thus defined 2 pericyte subpopulations: primary (NG2+αSMA-/low) and activated (NG2+αSMA+) pericytes. Soft ECM promoted microvascular regeneration and inhibited fibrosis in bone graft transplantation in vivo. As integrins are the major mechanosensor, we performed RT-qPCR screening of integrin family members and found Itgb1 (integrin ß1) was the major subunit downregulated by soft ECM and A83-01 treatment. Knocking down Itgb1 suppressed myofibroblast differentiation on stiff ECM. Interestingly, ITGB1 phosphorylation (Y783) was mainly located on microvascular ECs on stiff ECM, which promoted EC secretion of paracrine factors, including CTGF (connective tissue growth factor), to induce pericyte-myofibroblast differentiation. CTGF knockdown or monoclonal antibody treatment partially reduced myofibroblast differentiation, implying the participation of multiple pathways in fibrosis formation. CONCLUSIONS: ECM stiffness and TGFß signaling cooperatively regulate microvascular stability and pericyte-myofibroblast differentiation. Stiff ECM promotes EC ITGB1 phosphorylation (Y783) and CTGF secretion, which induces pericyte-myofibroblast differentiation.

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19.

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics. Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship. Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01-1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87-0.97, p = 0.002). Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.

Transgenerational Epigenetic Inheritance of MHC Class I Gene Expression is Regulated by the CCAAT Promoter Element.

Transgenerational epigenetic inheritance is defined as the transmission of traits or gene expression patterns across multiple generations that do not derive from DNA alterations. The effect of multiple stress factors or metabolic changes resulting in such inheritance have been documented in plants, worms and flies and mammals. The molecular basis for epigenetic inheritance has been linked to histone and DNA modifications and non-coding RNA. In this study, we show that mutation of a promoter element, the CCAAT box, disrupts stable expression of an MHC Class I transgene, resulting in variegated expression among progeny for at least 4 generations in multiple independently derived transgenic lines. Histone modifications and RNA polII binding correlate with expression, whereas DNA methylation and nucleosome occupancy do not. Mutation of the CCAAT box abrogates NF-Y binding and results in changes to CTCF binding and DNA looping patterns across the gene that correlate with expression status from one generation to the next. These studies identify the CCAAT promoter element as a regulator of stable transgenerational epigenetic inheritance. Considering that the CCAAT box is present in 30% of eukaryotic promoters, this study could provide important insights into how fidelity of gene expression patterns is maintained through multiple generations.

Biofeedback physical regulation of hypertension based on acupoints: A clinical trial.

BACKGROUND: Hypertension is a predominant risk factor for cardiovascular disease and has imposed a global disease burden. Poor medication compliance is the major obstacle to antihypertensive drug therapy, and negative mood status is also detrimental to blood pressure (BP) management. While transcutaneous electrical acupoint stimulation (TEAS), as an electrical stimulation modality for biofeedback physical regulation based on acupoints, offers a such nondrug alternative option that is noninvasive, safe, and effective with high adherence. However, the optimal stimulation parameters of TEAS for hypertension remain unclear, especially the frequency, which needs further exploration. OBJECTIVE: The study aims to investigate the efficacy of TEAS for hypertension, and to screen the optimal electrical stimulation frequency. METHODS: This is an 8-week, randomized, controlled pilot trial with 3 parallel groups. In a ratio of 1:1:1, 120 patients with stage 1 hypertension will be divided into the TEAS-2Hz group, TEAS-10Hz group, or usual care group. All patients will receive the usual care for hypertension including lifestyle education, etc. Additionally, the 2 TEAS groups will receive 12 sessions of TEAS interventions at 2 Hz or 10 Hz, 3 times weekly for 30 minutes each, with 4 weeks of follow-up. The main outcome will be the change from baseline to week 4 in systolic BP among the groups. Secondary outcomes consist of changes in diastolic BP, mean arterial pressure, heart rate, heart rate variability, medication adherence, and quality of life. The safety outcomes will be any adverse event during the treatment. DISCUSSION: As a pre-study for the next large clinical trial of TEAS for hypertension, this study will offer references for optimized frequency of biofeedback electrical devices and promote more consciousness of the benefits of body-mind holistic regulation of BP, thereby achieving proactive and overall process management of BP.

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects.

A set of 22 analogs of licochalcone A was designed and synthesized to explore their potentials as dipeptidyl peptidase 4 (DPP4) inhibitors with anti-inflammatory effects. The anti-DPP4 effects of these analogs were evaluated using the fluorescent substrate Gly-Pro-N-butyl-4-amino-1,8-naphthalimide (GP-BAN). The nitro-substituted analogue 27 exhibited the most potent activity (Ki = 0.96 µM). A structure-activity relationship investigation revealed that 4-hydroxyl and 5-chloro substituents are essential for DPP4 inhibition, while the 3'-nitro substituent improved both DPP4 inhibition and microsomal stability. Furthermore, compound 27 demonstrated good selectivity for DPP4 over other proteases, including dipeptidyl peptidase 9 (DPP9), thrombin, prolyl endopeptidase (PREP), and fibroblast activation protein (FAP). The cytotoxic effect of 27 was evaluated in cancer cell lines HepG-2 and Caco-2 and in somatic RAW264.7 cells and RPTECs. Compound 27 showed no toxicity to normal cells and weak toxicity to cancer cells. In a living cell imaging assay, 27 blocked the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells. This compound also dose-dependently suppressed the expression levels of the chemokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß).

Genetic predisposition to subjective well-being, depression, and suicide in relation to COVID-19 susceptibility and severity.

BACKGROUND: Epidemiological studies have reported associations between subjective well-being (SWB), depression, and suicide with COVID-19 illness, but the causality has not been established. We performed a two-sample Mendelian randomization (MR) analysis to investigate the causal link between SWB, depression, suicide and COVID-19 susceptibility and severity. METHODS: Summary statistics for SWB (298,420 cases), depression (113,769 cases) and suicide (52,208 cases) were obtained from three large-scale GWAS. Data on the associations between the Single Nucleotide Polymorphisms (SNPs) and COVID-19 (159,840 cases), hospitalized COVID-19 (44,986 cases), and severe COVID-19 (18,152 cases) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by the Inverse Variance Weighted, MR Egger and Weighted Median methods. Sensitivity tests were used to evaluate the validity of the causal relationship. RESULTS: Our results showed that genetically predicted SWB (OR = 0.98, 95 % CI: 0.86-1.10, P = 0.69), depression (OR = 0.76, 95 % CI: 0.54-1.06, P = 0.11), and suicide (OR = 0.99, 95 % CI: 0.96-1.02, P = 0.56) were not causally related to COVID-19 susceptibility. Similarly, we did not find a potential causal relationship between SWB, depression, suicide and COVID-19 severity. CONCLUSIONS: This indicated that positive or negative emotions would not make COVID-19 better or worse, and strategies that attempted to use positive emotions to improve COVID-19 symptoms may be useless. Improving knowledge about the SARS-CoV-2 and timely medical intervention to reduce panic during a pandemic is one of the effective measures to deal with the current decrease in well-being and increase in depression and suicide rates.