Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

It has gradually become a consensus in the industry that the traditional Chinese medicine gypsum should be decocted first, but the understanding of decocting method is not completely unified in the works of doctors since ancient times, and there are occasional disputes about whether it is necessary to decocting first. In this study, the phase determination, physical and chemical characterization, qualitative and quantitative analysis of inorganic and organic components of the decoctions of herbal pairs and the whole prescription Maxingshigan decoction with gypsum as the center, and the pre-decoctions and co-decoctions of them were carried out to explore the scientific connotation of the pre-decoctions of gypsum. Results show that decoction phases were different between the co-decoctions and pre-decoctions of licorice-gypsum (Gancao-Shigao, GC-SG), ephedra-gypsum (Mahuang-Shigao, MH-SG) and almond-gypsum (Xingren-Shigao, XR-SG). The results of the micromorphology, particle size and zeta potential of herbal pairs and prescription (Quanfang, QF) showed that the supramolecular particles in pre-decoctions were smaller, more uniform and more stable than the co-decoctions. The results of organic components analysis showed that different cooking methods did not change the organic composition and content. ICP-OES results showed that the content of inorganic components in pre-decoctions was higher than in co-decoctions for the same boiling time of gypsum. The IR results showed that the pre-decoctions had stronger chemical functional group effect than the co-decoctions. To sum up, compared with the co-decoction, the pre-decoction of gypsum has different phase state and chemical composition interaction, and the difference of inorganic composition is an important material basis affecting the change of phase state compared with the co-decoction. It indicates that the material basis of traditional Chinese medicine decoction is indeed different whether gypsum is decocted first or not, which can provide a basis for the clinical application of decocted gypsum.

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Objective:To develop an Oral Frailty Assessment Scale for Elderly Inpatients and test its reliability and validity.Methods:Through literature review, qualitative interview, expert consultations and pre-investigation, the preliminary draft of Oral Frailty Assessment Scale for Elderly Inpatients was formed. Using the convenient sampling method, a total of 300 elderly patients who were hospitalized in Geriatrics Department of Zhongnan Hospital of Wuhan University from April to June 2023 were selected as the research subjects. The reliability and validity of the scale were tested using item analysis, exploratory factor analysis, confirmatory factor analysis and reliability analysis.Results:A total of 300 questionnaires were distributed in this study, and 274 valid questionnaires were collected, with an effective response rate of 91.33% (274/300). The Oral Frailty Assessment Scale for Elderly Inpatients included four dimensions of teeth, dry mouth, swallowing and chewing, with a total of 11 items. The exploratory factor analysis extracted four common factors, and the cumulative variance contribution rate was 69.059%. The Cronbach's α coefficient for the scale was 0.76, the split-half reliability coefficient was 0.67, and the retest reliability coefficient was 0.98.Conclusions:The Oral Frailty Assessment Scale for Elderly Inpatients has good reliability and validity, which is suitable for evaluating oral frailty in elderly inpatients.

Objective: To examine the safety and effectiveness of inflatable video-assisted mediastinoscopic transhiatal esophagectomy (IVMTE). Methods: Totally 269 patients admitted to the Anhui Provincial Hospital of Anhui Medical University who underwent IVMTE (IVMTE group, n=47) or thoracoscopy combined with minimally invasive Mckeown esophageal cancer resection (MIME group, n=222) from September 2017 to December 2021 were analyzed retrospectively. There were 31 males and 16 females in IVMTE group, aged (68.6±7.5) years (range: 54 to 87 years). There were 159 males and 63 females in MIME group, aged (66.8±8.8) years (range: 42 to 93 years). A 1∶1 match was performed on both groups by propensity score matching, with 38 cases in each group. The intraoperative conditions and postoperative complication rates of the two groups were compared by t test, Wilcoxon rank, χ² test, or Fisher exact probability method. Results: Patients in IVMTE group had less intraoperative bleeding ((96.0±39.2) ml vs. (123.8±49.3) ml, t=-2.627, P=0.011), shorter operation time ((239.1±47.3) minutes vs. (264.2±57.2) minutes, t=-2.086, P=0.040), and less drainage 3 days after surgery (85(89) ml vs. 675(573) ml, Z=-7.575, P<0.01) compared with that of MIME group. There were no statistically significant differences between the two groups in terms of drainage tube-belt time, postoperative hospital stay, and lymph node dissection stations and numbers (all P>0.05). The incidence of Clavien-Dindo grade 1 to 2 pulmonary infection (7.9%(3/38) vs. 31.6%(12/38), χ²=6.728, P=0.009), total complications (21.1%(8/38) vs. 47.4%(18/38), χ²=5.846, P=0.016) and total lung complications (13.2%(5/38) vs. 42.1%(16/38), χ²=7.962, P=0.005) in the IVMTE group were significantly lower. Conclusion: Inflatable video-assisted mediastinoscopic transhiatal esophagectomy combined with laparoscopic esophagectomy is safe and feasible, which can reach the same range of oncology as thoracoscopic surgery.
Male ; Female ; Humans ; Retrospective Studies ; Esophagectomy/methods* ; Treatment Outcome ; Laparoscopy ; Thoracoscopy ; Lymph Node Excision/methods* ; Esophageal Neoplasms/surgery* ; Postoperative Complications

Aim To prepare the sea cucumber enzy¬molysis fermentation liquid (SCEFL) by enzymatic hydrolysis of protease and fermentation of probiotics and to investigate the effect of SCEFL on the immunosup-pression induced by cyclophosphamide in mice and to explore its mechanism by metabomic method. Methods The immunosuppressive model was induced by in-traperitoneal injection of cyclophosphamide. C57BL/6J mice were randomly divided into normal group, model group, Levamisole group, SCEFL groups (at low, medium and high doses). The pathological changes of spleen were observed by HE staining. The proportion of CD4

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acupuncture Therapy ; Reperfusion Injury/therapy* ; Brain Ischemia/therapy* ; Cerebral Infarction/therapy* ; NLR Proteins

The overdiagnosis of prostate cancer (PCa) caused by nonspecific elevation serum prostate-specific antigen (PSA) and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently. We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies. In this retrospective study, clinical data of 1807 patients from three Chinese hospitals were used. The final model was built using stepwise logistic regression analysis. The apparent performance of the model was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. Finally, a risk stratification system of clinically significant prostate cancer (csPCa) was created, and diagnosis-free survival analyses were performed. Following multivariable screening and evaluation of the diagnostic performances, a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System (PI-RADS) score was established. Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration. Finally, we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values. The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7% and 99.4%, respectively, for patients with a risk threshold below 0.05 after the initial negative prostate biopsy, which was significantly better than patients with higher risk. Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa. It provides a standardized tool for Chinese patients and physicians when considering the necessity of prostate biopsy.

Humans ; Aneurysm, False/etiology* ; Heart Aneurysm/complications* ; Heart Ventricles/surgery*