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

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Objective:To explore the application value of Oxford nanopore technologies (ONT) in the diagnosis and treatment of periprosthetic joint infection (PJI).Methods:A prospective analysis was conducted on 32 patients with PJI admitted to the joint department of Xi'an Honghui Hospital from October 2021 to March 2023, who met the 2018 PJI diagnostic criteria of the American Skeletal Infection Society (MSIS), including 15 males and 17 females with an average age of 63.93±8.93 years. 32 revision patients who did not meet the 2018 MSIS PJI criteria during the same period were collected as controls (non PJI group), including 13 males and 19 females with an average age of 65.53±8.54 years. All patients underwent joint fluid puncture before or during surgery, and the specimens were tested by ONT, metagenomic next generation sequencing (mNGS), and general microbial culture. The receiver operating characteristic (ROC) curves were drawn for both groups, and the sensitivity, specificity, positive predictive value, negative predictive value, and Youden index of the three detection techniques were calculated and compared to evaluate the detection efficiency of different detection methods in PJI.Results:Among the 32 patients with PJI, 30 were positive for ONT, with a total of 30 pathogenic bacteria detected, and the detection time was 22.37±8.36 h. 31 were positive for mNGS, with a total of 33 bacterial species detected, and the detection time was 46.25±9.36 h. 17 were positive for microbial culture, with a total of 8 bacterial species detected, and the detection time was 96.23±15.62 h. Among the 32 patients with non PJI group, 1 was positive for ONT and 5 were positive for mNGS, with a total of 1 and 3 bacterial species detected, respectively. The results of microbial culture were all negative. The detection time and area under the curve (AUC) of ONT and mNGS were 22.37±8.36 h and 0.953[95% CI (0.901, 1.006)], 46.25±9.36 h and 0.906[95% CI (0.835, 0.977)], respectively, which were better than those of microbial culture 96.23±15.62 h and 0.766[95% CI (0.678, 0.853)], and the difference was statistically significant ( P<0.05). The sensitivity of ONT, mNGS, and microbial culture were 0.938, 0.969, and 0.531, respectively, and the specificity was 0.969, 0.844, and 1.000, respectively. The Jordan index was 0.906, 0.813, and 0.531, respectively. Conclusion:ONT testing has higher diagnostic efficacy than mNGS and microbial culture in the diagnosis of PJI, and also has advantages in detection time. It also suggests that some PJI are not caused by a single microbial infection.

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Objective To evaluate the curative effect ofeliminating flatulence and laxative cream on patients with advanced hepatocellular carcinoma and opioid-associated constipation（OIC）. Methods 120 patients with advanced liver cancer complicated with OIC who were treated at the Third Affiliated Hospital of Naval Medical University from June 2021 to December 2022 were selected as the study subjects. The patients were divided into a control group（lactulose+conventional treatment）and an experimental group（eliminating flatulence and laxative cream + conventional treatment）using a randomized numerical table method. Two groups were compared in terms of defecation, quality of life, and comprehensive post-treatment evaluation（economic cost, number of occurrences of diarrhea, and whether or not there was a change in the dosage of opioids used）. Results After 28 d of intervention, both groups showed better results in relieving OIC（P<0.05）, and the experimental group was significantly better than the control group in terms of the quality of life of patients with advanced hepatocellular carcinoma, the economic cost and the number of diarrhea（P<0.05）. Conclusion In the treatment of OIC in patients with advanced hepatocellular carcinoma, constipation could be relieved by using both topicaleliminating flatulence and laxative cream and oral lactulose solution. Among them, antieliminating flatulence and laxative cream was more acceptable to patients and superior in terms of quality of life and economic cost, which could be a better choice for improving patient satisfaction and safety.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore the clinical efficacy of Xianling Gubao capsules combined with Jintiange capsules in primary osteoporosis and their effects on bone density,bone metabolism,and osteosclerosis protein levels.Methods Patients with primary osteoporosis were randomly divided into control and treatment groups using a random number table.The control group received chewable calcium carbonate with vitamin D3,2 tablets per dose(each containing 600 mg of calcium carbonate),qd;simultaneously,they took Jintiange capsules orally,1.2 g per dose,bid.The treatment group received Xianling Gubao capsules orally,in addition to the treatment received by the control group,1.5 g per dose,bid,for a duration of 6 months.The clinical efficacy,bone density,bone metabolism,and osteosclerosis protein levels before and after treatment were compared between the two groups.Results Four patients dropped out during the trial,and finally,63 patients were included in each of the treatment and control groups.After treatment,the total effective rate in the treatment group were 87.30％(55 cases/63 cases)and in the control group were 71.43％(45 cases/63 cases),with statistically significant difference(P＜0.05).After treatment,the lumbar spine L2-4 density in the treatment and control groups were(0.73±0.09)and(0.96±0.10)g·cm-3;the femoral neck density were(0.68±0.07)and(0.78±0.10)g·cm-3;blood calcium levels were(1.25±0.30)and(1.56±0.41)mmol·L-1;bone calcium levels were(25.51±2.23)and(35.91±5.30)ng·mL-1;alkaline phosphatase levels were(97.54±7.34)and(79.50±6.23)U·L-1;osteosclerosis protein levels were(13.87±4.95)and(10.11±2.99)pg·mL-1,respectively.The comparison of these indicators between the treatment and control groups showed statistically significant differences(all P＜0.05).The main adverse drug reactions in the treatment group were allergic reactions,gastrointestinal reactions,and general fatigue;while in the control group,they were allergic reactions,gastrointestinal reactions,and peripheral edema.The total incidence of adverse drug reactions in the treatment and control groups were 9.52％and 7.94％,respectively,with no statistically significant difference(P＞0.05).Conclusion Xianling Gubao capsules combined with Jintiange capsules can significantly improve the clinical efficacy of patients with primary osteoporosis,increase bone density,and enhance bone metabolism levels.

In July 2024, the National Healthcare Security Administration issued "Notice on Printing and Distributing the 2.0 Edition Grouping Scheme for Diagnosis Related Group(DRG) and Disease-based Payment and Further Advancing Related Work, " marking the official entry of China's DRG payment reform into the 2.0 era. In the 2.0 edition of the DRG grouping scheme, the number of DRGs has increased by six groups, and that of the adjacent DRGs has increased by 33 groups, featuring more scientific and reasonable grouping that aligns better with clinical practice. The National Healthcare Security Administration has also clarified five supporting management mechanisms, including the special case negotiation mechanism, the fund prepayment mechanism, the negotiation and consultation mechanism, the feedback mechanism for opinion collection, and the data disclosure mechanism. These are aimed at optimizing the management of DRG payment reform to ensure a win-win situation for medical institutions, healthcare security departments, and patients. The release of the DRG 2.0 edition provides medical institutions with more refined management tools and a more reasonable paymentmechanism. Medical institutions need to actively embrace this reform, optimize internal management, and improve service quality to achieve cost control and efficiency enhancement, ultimately leading to a win-win situation for patients, healthcare security funds, and medical institutions.

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.