Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.

OBJECTIVE: To investigate the clinical efficacy of unicompartmental knee arthroplasty (UKA) in the treatment of knee osteoarthritis in patients over 75 years old. METHODS: The clinical efficacy of primary fixed platform UKA in patients with osteoarthritis, was retrospectively analyzed from October 2014 to November 2020. Age, body mass index (BMI), range of motion (ROM), preoperative joint function score, the quality of life score and other preoperative indicators were measured by propensity score matching (PSM). The patients were divided into elderly group (≥75 years old) and control group (<75 years old). Oxford knee score(OKS), Western Ontario McMaster Universities osteoarthritis index(WOMAC), Short Form-12 including physical component summary (PCS), mental component summary(MCS), minimal clinically important difference(MCID ) and clinical complications were evaluated preoperatively and postoperatively. RESULTS: A total of 514 patients were analyzed, 428 patients fulfilled the inclusion criteria. A propensity-score matching study was conducted to eliminate confounding factors. After 1∶2 propensity match, there were 84 patients in elderly group (≥75 years), age ranged from 75 to 88 years old, with an average of (78.79±3.08) years old, and 168 patients in control group (<75 years), age ranged from 47 to 74 years old, with an average of (64.10±5.96)years old. The follow-up duration of two groups ranged from 12 to 84 months with an average of (29.35±16.52) months in elderly group, and 12 to 85 months with an average of (31.83±17.34) months in control group. There was only significant difference in age between the elderly and control groups preoperatively (P<0.01). Postoperatively, the elderly group showed significantly higher WOMAC (P<0.01) and lower SF-12 PCS scores (P<0.01) as compared to the control group. There was no significant difference between the elderly group and the control group in knee range of motion, OKS and the proportion of each scoring system reaching the minimum clinical difference value (P>0.05). In the aspect of preperative complications, the elderly group exhibited more surgical site complications and postoperative delirium compared to control group(P<0.05). The differences in other indicators including deep vein thrombosis, acute urinary retention, cardiovascular events, cerebrovascular events and radiolucent lines around prothesis were not statistically significant(P>0.05). CONCLUSION UKA in the treatment of elderly patients over 75 years old with knee osteoarthritis was safe and feasible, and could obtain satisfactory short-term efficacy.
Humans ; Aged ; Aged, 80 and over ; Middle Aged ; Osteoarthritis, Knee/surgery* ; Knee Prosthesis ; Retrospective Studies ; Propensity Score ; Quality of Life ; Knee Joint/surgery* ; Arthroplasty, Replacement, Knee/methods* ; Treatment Outcome

Electronic tongue is one kind of bionic detection technologies, which can objectively reflect the taste of drugs based on electrochemical principle. In this paper, the development histories of electronic tongue both of potential type and voltammetry type were introduced, including their detection principles and key innovation technologies. In order to comprehensively improve the understanding of electronic tongue, its technological progresses, such as the study of dedicated sensors or biosensors for specific tastes, and the development of miniaturized or hybrid devices, were also discussed in detail. And the challenges and countermeasures in the application of electronic tongue were analyzed to provide some suggestions for its further technology promotion.

Azithromycin dry suspension is one of the most commonly used drugs in pediatric clinic, but its taste masking has been difficult to achieve. 5 representative products of azithromycin dry suspension were chose to compare their tastes both using electronic tongue and human sensory evaluation methods, and there existed the differences of bitterness, later bitterness, graininess, and adhesion among these products. Raman micro-imaging was used to determine the difference in taste mainly due to different prescription ingredients and manufacturing techniques. Through mixing the dry suspensions with alkaline mixing solvent, the bad taste of each product was masked after evenly dispersing in the solvent, and their tastes were all close to the taste of the solvent. In the future, it is planned to investigate the stability and bioavailability of the solvent preparations, and then to give the medication suggestion of solvent preparation after ensuring their efficacy.

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

OBJECTIVE: To analyze and compare the effects of leukapheresis on hemostatic function in patients with hyperleukocytic leukemia. METHODS: A total of 139 patients with AML, ALL and CML who underwent leukapheresis from June 2009 to February 2020 and did coagulation test before and after operation were included in this study. The clearance efficiency of each group and the difference among three groups were evaluated, as well as hemostatic function including platelet counts, coagulation indicators, CDSS score and incidence of adverse events. The difference of hemostatic function caused by leukapheresis in different leukemia patients were compared. RESULTS: After leukapheresis, the WBC counts were decreased significantly in the three groups of patients (P<0.001), and the clearance efficiency was highest in ALL patients. However, the platelet counts also were decreased significantly (AML:P＜0.001, ALL: P＜0.001, CML: P＜0.01) in the three groups of patients, particularly for acute leukemia patients with a positive correlation with WBC clearance efficiency(r=0.284). After leukapheresis, fibrinogen decreased, PT and APTT prolonged. For acute leukemia patients, higher CDSS score was related to an elevated incidence of bleeding events (P<0.05). CONCLUSION Leukapheresis is an effective method to decrease the leukemic burden, but it is necessary to monitor the impact on hemostatic function. It is recommended to assess the CDSS socre for acute leukemia patients, in order to identify the predictive value for bleedings.
Acute Disease ; Blood Coagulation ; Blood Coagulation Tests ; Hemorrhage ; Hemostatics ; Humans ; Leukapheresis/methods* ; Leukemia, Myeloid, Acute/therapy*

Objective: To explore the predictive value of the impedance measured during leadless pacemaker Micra implantation on the trend of changes of pacing threshold post implantation. Methods: This is a retrospective cross-sectional study. Patients who received implantation of leadless pacemaker Micra at the Second Xiangya Hospital of Central South University from December 2019 to August 2020 were enrolled. The clinical data and the intraoperative electrical parameters during leadless pacemaker implantation were collected. The impedance and pacing threshold data were analyzed at three time points: immediate release, 5-10 min after release, and after traction test. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to analyze the value of the impedance at immediate release on predicting the trend of changes of pacing threshold post implantation. Results: A total of 21 patients (mean age: (72.2±12.5) years, 12 males) were included. The impedance of 21 patients was (798.1±35.3) Ω immediately after implantation, (800.9±35.6) Ω after 5-10 minutes of release, and (883.6±31.7) Ω after traction test. Impedance was similar between the three time points (P>0.05). The threshold was (0.97±0.11) V/0.24 ms immediately after implantation, (0.95±0.12) V/0.24 ms at 5-10 min after the release, and (0.59±0.06) V/0.24 ms after the traction test. The threshold was significantly lower after the traction test than that immediately after release (P=0.003) and than that at 5-10 minutes after release (P=0.008), suggesting a decreased tendency of the threshold over time. According to the analysis of the ROC curve, the immediate impedance after the release ≥680 Ω could predict the ideal pacing threshold after the traction test (AUC=0.989, 95%CI 0.702-0.964, P<0.001), the prediction sensitivity was 87%, and the specificity was 100%. The pacing threshold would be not ideal with the immediate impedance ≤ 520 Ω (95%CI 0.893-1.000, P<0.001), the sensitivity was 100%, and the specificity was 80%. Conclusions: The impedance immediately after the release has predictive value for the changing trend of threshold post leadless pacemaker Micra implantation. Impedance ≥680 Ω immediately after release is often related with ideal pacing threshold after the traction test. In contrast, the impedance ≤ 520 Ω pacing is often related with unsatisfactory threshold after the traction test, therefore, it is recommended to find a new pacing site to achieve the impedance ≥680 Ω immediately after release during leadless pacemaker Micra implantation.
Aged ; Aged, 80 and over ; Cardiac Pacing, Artificial ; Cross-Sectional Studies ; Electric Impedance ; Humans ; Male ; Middle Aged ; Pacemaker, Artificial ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D. METHODS: A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kg^-1•d^-1) for 7 days. Before and after model establishment, and after intervention, the body mass, 24 h food intake and fecal water content were observed, the visceral sensitivity was detected by abdominal withdrawal reflex (AWR); after intervention, the mental state was evaluated by elevated plus maze (EPM) test, the protein expression of NGF, TrkA and TRPV1 was detected by immunohistochemistry and Western blot in the 4 groups. RESULTS: After model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (P<0.05), first systolic latency of AWR was shortened and number of contraction wave of AWR was increased (P<0.05), and fecal water content was increased (P<0.05) in the model group, the EA group and the western medication group. After intervention, compared with the blank group, open arm residence time ratio (OT%) of EPM was decreased (P<0.05) and protein expression of NGF, TrkA, TRPV1 in colonic tissue was increased in the model group (P<0.05); compared with the model group, the body mass and 24 h food intake were increased (P<0.05), first systolic latency of AWR was lengthened and number of contraction wave of AWR was decreased (P<0.05), the fecal water content was decreased (P<0.05), OT% of EPM was increased (P<0.05), and protein expression of NGF, TrkA, TRPV1 in colonic tissue was decreased (P<0.05) in the EA group and the western medication group. CONCLUSION Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.
Male ; Rats ; Animals ; Receptor Protein-Tyrosine Kinases ; Rats, Sprague-Dawley ; Irritable Bowel Syndrome/therapy* ; Sulfonic Acids ; Nerve Growth Factors ; TRPV Cation Channels/genetics*

Isomers are widely distributed in Chinese herbal medicines,and can be discriminated by energy-resolved mass spectrometry( ER-MS). However,ER-MS was performed through direct injection of reference compounds with syringe pump,which encountered a significant technical barrier for high-throughput and automated measurements. Herein,online ER-MS was conducted using LC-MS platform,and a pair of isomers,kaempferol vs luteolin,were employed as a case study to illustrate and assess the utility of online ER-MS for isomeric discrimination. High-resolution tandem mass spectrometry data of both flavonoids were acquired on LC-QE-Orbitrap-MS,and the fragmentation pathways responsible for the primary fragment ions were proposed. The primary signal in MS1 occurred at m/z 285( [M-H]-),and the primary signals of either compound generated by retro-Diels-Alder fragmentation were observed at m/z 151 and 133. The spectral information was subsequently transferred onto LC-Qtrap-MS platform to carry out online ER-MS. Two precursor-to-product ion transition candidates were constructed as m/z 285>151 and 285>133,and either afterward derived a set of pseudo-ion transitions( PITs) and so forth,exactly corresponding to a series of progressive collision energies( eg-5,-8,-11 e V,and so on). All PITs were typed into the monitoring list of multiple reaction monitoring program to generate the peak area datasets. Either dataset was normalized using the highest values in the set and imported into Graph Pad Prism software to plot the Gaus-sian-shaped curve that was termed as the break-down graph. The apex of the regressive curve was termed as optimal collision energy( OCE). The OCE values corresponding to m/z 285>151 were calculated as-29. 06 e V and-35. 71 e V for kaempferol and luteolin,respectively. In the case of m/z 285>133,the OCEs were yielded as-44. 15 e V for kaempferol and-49. 01 e V for luteolin. With re-ference to their chemical structures,the location of hydroxyl group was regarded to be responsible for the differences of either m/z 285>151 or 285>133 between the isomers,attributing to their different bond properties. Above all,online ER-MS offers an eligible tool for isomeric discrimination,and provides meaningful information for the accurate chemical composition characterization based on LC-MS,which is not limited to Chinese herbal medicines.
Chromatography, Liquid ; Flavonoids ; Kaempferols ; Luteolin ; Tandem Mass Spectrometry

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/drug therapy* ; Drugs, Chinese Herbal ; Insulin Resistance ; Podocytes ; Pyroptosis ; Rats