Search

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors (TFs) along AK to cSCC progression. Immunohistochemistry (IHC) / immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.

Objective To investigate the effects of different acupuncture manipulations on Deqi sensations and surface myoelectricity, and explore the correlation between Deqi sensations and needling manipulations. Methods Forty-five healthy participants accepted twirling, lifting-thrusting, and twirling plus lifting-thrusting manipulanions at right Zusanli (ST 36), respectively. The acupuncturist's and participants' Deqi sensations were collected by MGH Acupuncture Sensation Scale (MASS). The intensity and occurrence rate of soreness, dull pain, pressure, heaviness, fullness, numbness, sharp pain, warmth, coolness, and throbbing feelings of participants, and tightness, smooth, and tangle feelings of acupuncturist were measured. The correlation between the acupuncturist's and participant's Deqi sensations was analyzed. Surface electromyogram (EMG) were recorded before, during and after needling in 30 participants. The integrated EMG (iEMG), mean power frequency (MPF) and media frequency (MF) were analyzed. Result Both fullness and soreness of participants and tightness of acupuncturist were the most frequently occurred ones. A positive correlation between participants' fullness and acupuncturist's tightness was observed during the three aforementioned needling manipulations (P 1). Almost all the needling sensations measured in the present study could be induced by the three needling manipulations. However, strength of Deqi sensations was exhibited as lifting-thrusting > twirling plus lifting-thrusting > twirling according to MASS index. The iEMG values were increased and MPF, MF values were decreased during needling compaired to those before needling, especially during lifting-thrusting (P Conclusions The intensity and occurrence rate of the different Deqi sensations induced by different needling manipulations were basically similar. The fullness and soreness were both the most frequently induced Deqi sensations. The strongest Deqi sensation could be induced by lifting-thrusting manipulation. There is a positive correlation between participants' fullness and acupuncturist's tightness during the three needling manipulations. The myoelectricity around the acupoint is related to Deqi responses. (Registration No. AMCTR-IOR-20000314).

To investigate the mechanism of electroacupuncture (EA) with the involvement of sarcoplasmic reticulum CaThirty SPF-ranked SD rats were randomly divided into a control group, a model group, an EA group, an aconitine group and an EA plus aconitine group, with 6 rats in each group. The rat model of acute heart failure was established by infusion of high-dose propranolol hydrochloride solution into the right femoral vein. After stabilized for 10 min in the modeled rats, EA was exerted at "Neiguan" (PC 6), with disperse-dense wave, 2 Hz/15 Hz in frequency, 3 mA in intensity, for 30 min in the EA group and the EA plus aconitine group; aconitine solution (10 μg/kg) was injected from the left femoral veins in the rats in the aconitine group and the EA plus aconitine group. Hemodynamic indexes such as the left ventricular systolic pressure (LVSP) and the maximum rate of increase/decrease of left ventricular pressure (±dp/dtCompared with the control group, LVSP and ±dp/dtThe intervention with electroacupuncture achieves the synergism/ attenuation effect of aconitine for the improvements in heart failure probably by up-regulating the expression of SERCA2a and down-regulating the expression of PLB in myocardial tissue.

To investigate the effect of acupuncture in different tissue structures on deqi and the electromyography of acupoint area.Twenty healthy subjects, respectively accepted 4 kinds of needling stimulation, i.e. stimulating skin at Zusanli (ST36), stimulating ST36 with and without skin anesthesia using compound lidocaine cream, and stimulating at Dubi (ST35) without skin anesthesia.Sharp pain and tingling were the main sensations during skin needling at ST36. Fullness, dull pain, soreness and acupuncturist's tightness were the main sensations during needling with or without skin anesthesia at ST36. Fullness was the main sensation during needling at ST35, while the intensity was lower than that during needling at ST36. A positive correlation in the intensity was found between subjects' fullness and acupuncturist's tightness during needling with or without skin anesthesia at ST36. The subjects' fullness appeared earlier about 5 seconds than acupuncturist's tightness. The iEMGs during subjects' fullness and acupuncturist's tightness were 2-3 times of that before needling.Deqi sensations such as subjects' fullness, dull pain, soreness and acupuncturist's tightness are mainly related to the activity of the muscles under the acupoints. Subjects' fullness and acupuncturist's tightness always appear together. Acupuncturist's tightness may be mediated by the muscle stretch reflex induced by needling stimulation.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II – TGF-β1 pathway.

Acupuncture sensation, as one of the essential signs of

Acupuncture therapy has a positive role in the prevention and treatment of some related diseases by regulating autonomic nervous function. But it has been found in experimental researches that the modulatory effects of acupuncture on autonomic nervous system are not always consistent with each other. Because in the animal studies on the mechanism of acupuncture intervention, the anesthetic agent has to be used and definitely affects the activities of the autonomic nervous system while playing its pharmacological effects. Hence, it is very significant to explore the rational application of anesthetic agents and minimize their unfavorable impacts on the research outcomes. In the present paper, we make a retrospective analysis on (1) the effect of acupuncture intervention on activities of the autonomic nerve in animal models of myocardial ischemia, gastrointestinal mobility, and urinary system; (2) the effect of anesthetics as isoflurane, urethane, pentobarbital sodium, ketamine, α-chloralose, propofolum, etc. on activities of the autonomic nerve system. In terms of different anesthetic modes and various depths of anesthesia by using isoflurane inhalation, mixed solution of urethane and chloralose, etc., some approaches for assessing the state of anesthesia in accordance with the pupillary reflex, righting reflex, footboard reflex, swallowing reflex, heart rate, blood pressure, body temperature, respiration frequency, ventilation volume, oxygen saturation, partial pressure of carbon dioxide, neuromuscular blo-ckade, etc. in combination with the indexes directly and indirectly reflecting functions of the sympathetic and vagus nerves are proposed to analyze the impact of different anesthetic states on the therapeutic effect of acupuncture in various models of dysfunction of the autonomic nerve system. Under the circumstances, it is possible to provide a reference for rational use of anesthetic agents and dosages in the acupuncture research of autonomic nerve regulation.

The measurement of heart rate variability (HRV) has the advantages of noninvasiveness and simple operation and is widely used in clinical trials and scientific research for assessing reactions of the autonomic nervous system. More and more studies on acupuncture also take HRV as an important index. In addition to the definition, origin, analytical methods, and significance of time domain and frequency domain parameters of HRV, we reviewed the situations of application of HRV to acupuncture research in recent years, analyzed the influence of acupuncture and sham acupuncture, different acupuncture methods, and different acupoints on HRV, and confirmed the role of HRV in reflecting the effect of acupuncture on the vagal and sympathetic systems. However, various interference factors for HRV measurement and diverse methods for data analysis may lead to great differences in the experimental results of HRV and the interpretation of parameters. Therefore, careful analysis is needed in future studies on acupuncture with HRV as an observation index.

Objective To examine the effect of electroacupuncture (EA) treatment on abnormal defaecation in a rat model of chronic heterotypic stress (CHS) and investigate the underlying mechanisms. Methods 20 male Sprague-Dawley rats were randomly divided into three groups: normal (n=6), CHS (n=7), and CHS+EA (n=7). Rats in the CHS group and CHS+EA groups received four different types of stressors for 7 days. For rats in the CHS+EA group, EA was applied at ST36 in the bilateral hind legs for 30 min before each stress-loading session. Rats in the normal group did not receive stressors or EA treatment. The faecal pellets of each rat were collected and weighed at a fixed time every day. Protein expression of corticotrophin-releasing factor (CRF) in the hypothalamus and colorectal tissues was measured by Western blotting at the end of the experiment on the 7th day. Results After 7 consecutive days of CHS, the number of faecal pellets, faecal wet weight, and faecal water content were significantly increased in the CHS group compared with the normal group (p=0.035, p=0.008 and p=0.008, respectively). All three parameters were significantly decreased in CHS+EA versus CHS groups (p=0.030, p=0.011 and p=0.006, respectively). Stress significantly increased CRF expression in both the hypothalamus and colorectal tissues. The excessive CRF responses seen following CHS were significantly suppressed by EA treatment. Conclusions EA treatment can ameliorate stress loading induced abnormal defaecation in rats and decrease protein expression of CRF centrally (hypothalamus) and peripherally (colorectal tissues), suggesting a potentially therapeutic role for EA in stress-related responses.

It has been shown that ischemia preconditioning (IPC) can attenuate the myocardial injury induced by ischemic and reperfusion. But it was rarely used in clinic due to its inoperability. Previous studies indicate that electroacupuncture (EA) pretreatment can mimic myocardial ischemia preconditioning (MIPC) to produce cardioprotective effect. The activated adenosine A 2 b receptor has been proven to be involved in mediating the cardioprotection of IPC. In the studies on acupuncture analgesia, it was reported that adenosine receptor was activated by acupuncture stimulation, and acupuncture pretreatment can affect the acti-vities of intracellular A 2 b receptor. Based on those mentioned above, it is highly likely that the A 2 b receptor may also participate in the cardioprotection produced by acupuncture pretreatment. In this paper, we comprehensively reviewed relevant studies regarding 1) the cardioprotective effect of IPC and its limitations, 2) the similar cardioprotection produced by both acupuncture pre-treatment and IPC, 3) the mechanism underlying myocardial ischemic injury and intracellular calcium regulation, 4) the acti-vation of adenosine receptors and effects of acupuncture, 5) the relationship between adenosine receptors and intracellular calcium ion, and 6) the effect of acupuncture on adenosine receptors, so as to provide a novel assumption that A 2 b receptor may be a key factor in mediating the cardioprotection of acupuncture pretreatment. Our future research will systematically explore the me-chanism of acupuncture pretreatment in protecting ischemic myocardium from myocardial cell adenosine A 2 b receptor and intracellular calcium signal transduction related factors.

Chitosan is a partially deacetylated polymer of acetyl glucosamine obtained byalkaline deacetylation of chitin. It displays interesting properties such as biocompatibility, biodegradability as its degradation products are non-toxic, non-immunogenic, and non-carcinogenic. It can be modified chemically for the presence of amino and hydroxyl groups to prepare functional derivatives of chitosan. Chitosan and its derivatives have good adsorption ability for metal ions due to theirs high percentage of nitrogen, amino and hydroxyl groups on their chemical structure act as chelation sites for metal ions. This article reviews the developments of the studies on coordination between chitosan, derivatives and metal ions, as well as the applications of chitosan-based complexes in many fields such as antibacterial effect, the catalysts, metal recovery and detection, and agriculture.

The aim of this work is to investigate the effect of electroacupuncture (EA) at PC6 on the hypertension and myocardial hypertrophy in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA group with WKY rats as normal control. EA was applied once a day in 8 consecutive weeks. The blood pressure (BP), cardiac function, and hypertrophy as well as the underlying mechanisms were investigated. After EA treatment, the enhanced BP in SHR + EA group was significantly lower compared to both the period before EA and model group. Echocardiographic, morphological studies showed that the enhanced left ventricular anterior and posterior wall end-diastolic (LVAWd and LVPWd) thickness, diameters and cross-sectional area (CSA) of cardiac myocyte, as well as the ratio of heart weight to body weight (HW/BW), were markedly diminished in SHR + EA group, while the reduced left ventricular ejection fraction, left ventricular short axis fraction shortening, and E/A ratio were significantly ameliorated. The levels of Angiotensin-converting enzyme (ACE) and Angiotensin II Type 1 and 2 receptors (AT1R, AT2R) in SHRs were also significantly attenuated by EA. The results suggest that EA at bilateral PC6 could arrest the hypertension development and ameliorate the cardiac hypertrophy and malfunction in SHRs, which might be mediated by the regulation of ACE, AT1R, and AT2R.

Long-lasting hypertension results in ventricular remodeling characteristic of myocardial hypertrophy including myocyte hypertrophy and myocardial fibrosis, a pathological process failed to be blocked by the current biomedical means and could eventually lead to heart failure. It has been shown that acupuncture can excite the parasympathetic nerve to counter the overtonic activity of sympathetic nerve, elicit antihypertensive effect and produce cardioprotection via the regulation of calcium signaling-related proteins in myocytes, suggesting its potential role in the management of these disorders. In this paper, the authors review relevant studies and propose, with respect to the autonomic nerve, endocrine system, cytokines and intracellular calcium signaling pathways, several novel ideas concerning the treatment of hypertensive myocardial hypertrophy and cardiac malfunction by acupuncture.

Background The previous study showed that the cardiac arrhythmias induced by myocardial ischemia and reperfusion were attenuated by the pretreatment of acupuncture; however, the related mechanism is not understood. The present study was therefore designed to determine whether intracellular Ca2+ ([Ca2+]i) and connexin 43 (Cx43) are involved in the mediation of the anti-arrhythmic effect of electro-acupuncture (EA) pretreatment in the rats subjected to simulative global ischemia and reperfusion (SGIR). Methods SGIR was made in the isolated heart by a low flow perfusion followed by a flow restoration. Four groups of animals are involved in the present study, including normal control group, SGIR group, EA group and EA plus 18 beta-glycyrrhetinic acid (EAG) group. For EA pretreatment, bilateral Neiguan acupoints (PC6) of the rats were stimulated for 30 min once a day in 3 consecutive days. Cx43 antagonist was given to the rats in EAG group 30 minutes before the EA pretreatment. The resting [Ca2+]i concentration, calcium oscillation, the contents of total Cx43 and non-phosphrylated Cx43 and arrhythmia score were compared among different groups. Results In EA group, the arrhythmic score, the resting [Ca2+]i concentration and the number of [Ca2+]i oscillations were all significantly less than those in SGIR group (all P

Darier’s disease (DD, MIM 124200) is an autosomal dominant inherited skin disease. Mutations in the ATP2A2 gene, which encoded the sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase isoform 2 (SERCA2), are responsible for this skin disorder. Here we report the clinical, genetic, and molecular characterization of a large Chinese family with DD. We identified mutation c.632G>A (p.G211D) in the ATP2A2 gene in this family. Genotype– phenotype correlation in available family members provided helpful genetic counseling information for mutation carriers.