The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

Objective To construct a morphological brain network in patients with cerebral small vessel disease(CSVD)and predict it application for cognitive function.Methods A total of 64 eld-erly CSVD patients admitted in our hospital from January 2020 to February 2024 were retrospec-tively recruited.Cognitive function was assessed with Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Their clinical data,and results of cognitive function and multi-modal MRI scanning were collected and analyzed.3D T1-weighted imaging based on Kullback-Leibler divergence similarity was used to construct individual morphological brain net-work,and the connectome-based predictive model was employed to construct a cognitive predic-tion model.Results The network,which is significantly and positively correlated with the MMSE and MoCA scores,was mainly located in the default mode network,and could effectively predict individual MMSE and MoCA scores(r=0.795,P=4.436×10-15;r=0.794,P=4.974×10-15,P＜0.01).The connections,which were significantly negatively correlated with MMSE or MoCA scores,were mainly located between the salience/ventral attention network and other networks,and could also effectively predict individual MMSE and MoCA scores(r=0.766,P=1.679× 10-13;r=0.850,P=6.915×10-19,P＜0.01).Combined positive correlation and negative correla-tion networks,the model showed further improved predictive performance(r=0.849,P=7.603 × 10-19;r=0.888,P=1.445 × 10-22,P＜0.01).Conclusion Individual morphological brain network can effectively predict cognitive function in elderly CSVD patients,and can be used as a convenient tool for early warning of cognitive impairment related to CSVD.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

Improving the reproducibility of biomedical research results is a major challenge.Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at https://arriveguidelines.org). The fourth part of the article includes the items 1-5 of ARRIVE 2.0 Recommended 11 section, which covers "Abstract" "Background" "Objectives" "Ethical statement" and "Housing and husbandry". Its aim is to promote the full understanding and use of the ARRIVE 2.0 guidelines by domestic researchers, enhance the standardization of experimental animal research and reporting, and promote the high-quality development of experimental animal technology and comparative medicine research in China.

Objective:To explore the differences of resting-state spontaneous neural activity between migraine without aura (MwoA) patients with response or nonresponse to non-steroidal anti-inflammatory drugs (NSAIDs), and its correlation with migraine-related features.Methods:From February 2021 to April 2022, thirty MwoA patients with response to NSAIDs, 30 MwoA patients with nonresponse to NSAIDs, and 30 healthy controls were recruited in the Affiliated Jiangning Hospital of Nanjing Medical University.All subjects were scanned with a 3.0 T resting-state functional magnetic resonance imaging scanner.The percent amplitude of fluctuation (perAF) approach was used to calculate the differences of the resting state brain functional activities among the three groups (Bonferroni multiple comparison correction). SPSS 24.0 software and RESTplus software were used for statistical analysis.Analysis of variance was used for the perAF values of three groups.Correlation analysis was performed between perAF values of brain regions with significant differences and migraine-related features.Results:The brain areas showing significant differences of perAF among the three groups located in the left anterior cingulate cortex (ACC)( x, y, z = -6, 9, -3), left middle frontal gyrus (MFG)( x, y, z =-39, 48, 9) and left middle temporal gyrus (MTG)( x, y, z = -57, -30, -15)(all P<0.05, Bonferroni correction). Compared with nonresponse group, the perAF in response group showed significant decreased in the left ACC, MFG and MTG.There was positive correlation between the perAF of left ACC and disease duration ( r=0.506, P=0.007). Compared with healthy controls, the perAF of nonresponse group showed increased in the left ACC, which was negatively correlated with frequency ( r=-0.414, P=0.032). Conclusion:The neural activity of prefrontal cortex and ACC may be the neuropathological basis underlying response to NSAIDs in MwoA treatment.Moreover, the ACC has certain correlations with migraine-related characteristics, which may serve as a potential neuroimaging biomarker to evaluate the efficacy of NSAIDs.

Post-stroke seizures and epilepsy are common complications of stroke, and its risk factors include age, stroke location, lesion size, stroke type, degree of neurological deficit, reperfusion therapy, use of statins. This article reviews the risk factors for post-stroke seizures and epilepsy, as well as commonly used predictive models.

Background: Crawling-type gastric adenocarcinoma is a rare subtype of gastric cancer, however, the understanding on this special entity of gastric cancer is still lacking. Aims: To investigate the clinical, endoscopic and pathological characteristics of crawling-type early gastric adenocarcinoma. Methods: Patients diagnosed as crawling-type early gastric adenocarcinoma in Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were recruited consecutively in a retrospective study. The clinical data were reviewed, the pathological specimens were collected for immunohistochemical staining, and a telephone follow-up was conducted for prognosis analysis. Results: Fourteen patients with crawling-type early gastric adenocarcinoma and fulfilling the inclusion criteria were enrolled in the study, of them, 9 were male, 5 were female, and the mean age was 65.9 years old. No family history of gastric cancer was reported. The clinical manifestations were not specific. All patients were positive for Helicobacter pylori (Hp) infection. Tumors were more likely to occur in the middle and lower thirds of the stomach, with marked atrophic background mucosa. Macroscopically, 11 lesions were superficial-depressed (0-IIc) and 3 were superficial-flat type (0-IIb+ IIc). The color of the lesions was red. Lesions with indistinct border were observed endoscopically in 10 cases. Complete resection was achieved in all 14 patients after endoscopic submucosal dissection n=10 or surgical treatment n=4. Three submucosal and 11 intramucosal infiltration were observed pathologically. Immunohistochemical results of gastric (MUC5AC and MUC6) and intestinal (MUC2, CD10 and CDX-2) markers showed that most of the patients were mixed immunophenotype; the Ki-67 index ranged mostly between 30% and 70%. In a mean follow-up time of 38 months, all 14 patients were survived. Two patients with heterochronous early gastric cancer were found by follow-up endoscopy. Conclusions: When a superficial-depressed or superficial-flat type tumor with reddish color change and atrophic background mucosa is observed endoscopically in an Hp-positive patient, the possibility of crawling-type early gastric adenocarcinoma should be considered. Adequate preoperative evaluation should be carried out to judge the extent and depth of tumor invasion, which may guide the decision of treatment strategy. Postoperative endoscopic surveillance is recommended.

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.
Aged ; Aged, 80 and over ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Critical Illness ; Immunity ; Retrospective Studies ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects* ; Viral Vaccines/adverse effects*