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 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 analyze the innate circuit qi endowment of patients with seasonal allergic rhinitis(SAR)in Renyin year(Ren-Yin stem-branch year of Chinese lunar calendar).Methods A retrospective study was conducted in 8 918 SAR patients who were treated in the Department of Otorhinolaryngology of Xiyuan Hospital,China Academy of Chinese Medical Sciences in pollen seasons of the spring and autumn(i.e.,the period of March 5 to May 21,and the period of August 7 to September 23)in 2022(Renyin year).The characteristics of circuit qi at birth date of the SAR patient were analyzed.Results The occurrence of SAR in Renyin year was related to the suiyun(yearly circuit phase),sitian(the first half of the alterable yearly circuit qi),dominant qi,and circuit qi combination.The two-factor model analysis showed that the occurrence of SAR in Renyin year was closely related with suiyun-sitian and dominant qi-guest qi.High morbidity of SAR was shown in the patients born in the year of heavenly-stem Ren and earthly-branch Xu,and with the circuit qi features of five circuits being wood circuit,Suiyun being excessive wood circuit,sitian of yangming dryness-gold,zaiquan(the second half of the alterable yearly circuit qi)of shaoyin monarch-fire,dominant qi being yangming dryness-gold,and circuit qi combination being disharmony.The two-factor model analysis showed that the morbidity of SAR was increased in the year with the circuit qi features of suiyun-sitian being excessive wood circuit and taiyang cold-water,and the combination of dominant qi and guest qi being yangming dryness-gold and taiyang cold-water.Conclusion Among the innate circuit qi factors,suiyun,sitian,dominant qi,and circuit qi combination have an impact on the occurrence of SAR.The interaction between innate circuit qi and circuit qi at onset may be one of the important mechanisms leading to the occurrence of SAR.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Enterogenic Candida albicans(C.albicans)infection refers to the translocation of intestinal colonized C.albicans under certain conditions,breaking through the intestinal tract,causing tissue infection or even invasive C.albicans infection.As the first contact point of Candida,the intestinal mucosa is the first line defending coloni-zation or invasion of C.albicans,often inhibiting infection by physical barrier and activating host immunity.As an-other defense mechanism,the intestinal microbiota jointly resists the invasive infection of C.albican through regula-ting pH,secreting antimicrobial peptides,and competing for adhesion points.This review summarizes the roles of three key factors,namely intestinal mucosa,intestinal immunity and microbiota,in enterogenic C.albicans infec-tion,providing new ideas for scientific research on invasive candidiasis caused by intestinal colonization.

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 develop a rapid and accurate Monte Carlo program(simplified code for dosimetry of carbon ions,SPEEDO)for carbon ion therapy.Methods For electromagnetic process,type Ⅱ condensed history simulation scheme and continuous slowing down approximation were used to simulate energy straggling,range straggling,multiple scattering,and ionization processes.For nuclear interaction,5 types of target nuclei were considered,including hydrogen,carbon,nitrogen,oxygen,and calcium.The produced secondary charged particles followed the same condensed history framework.The study simulated the transport of carbon ions in 4 materials(water,soft tissues,lung,and bone),and the calculated doses were validated against TOPAS(a Monte Carlo simulation software for radiotherapy physics),followed by a comparison with dose measurements in a water phantom from the HIMM-WW(a medical heavy-ion accelerator facility in Wuwei).Results SPEEDO's simulation results showed good consistency with TOPAS.For each material,in the voxel region where the physical dose was greater than 10％of the maximum dose point,the relative maximum dose error of both was less than 2％.At treatment energy of 400 MeV/u,SPEEDO's computation time was significantly less than that of TOPAS(13.8 min vs 105.0 min).SPEEDO's calculation results also showed good agreement with HIMM-WW measurements in terms of lateral dose distribution and integrated dose depth curve.Conclusion SPEEDO program can accurately and rapidly perform Monte Carlo dose calculations for carbon-ion therapy.

Objective:To observe the clinical efficacy and action mechanism of Jujing Decoction(JJD)in the treatment of as-thenoteratozoospermia(ATZ)by comparing JJD with combined administration of the antioxidant stress drug and sperm energy metabo-lism agent.Methods:According to the inclusion criteria,we enrolled 67 male patients with ATZ in this randomized controlled clini-cal study and treated them by oral administration of JJD(the JJD group,n=34)or natural vitamin E combined with L-carnitine solu-tion(the positive control group,n=33),both for 12 weeks.We collected the semen parameters,sperm DNA fragmentation index(DFI),sperm mitochondrial membrane potential(MMP),seminal plasma reactive oxygen species(ROS)and superoxide dismutase(SOD)levels from the patients,observed the ultrastructure of sperm mitochondria under the transmission electron microscope(TEM)before and after treatment,and analyzed the clinical efficacy and action mechanism of JJD by comparing the data obtained between the two groups.Results:Treatment and follow-up were completed in 60 of the cases,30 in the JJD and 30 in the positive control group.The total rate of clinical effectiveness was significantly higher in the JJD than in the positive control group(76.8％vs 43.3％,P＜0.05).Compared with the baseline,the percentages of progressively motile sperm(PMS)and morphologically normal sperm(MNS),DFI and MMP were significantly improved(P＜0.05),the level of seminal plasma ROS decreased(P＞0.05),and that of SOD re-markably increased(P＜0.05)after treatment with JJD;PMS,MNS,DFI and MMP were also improved(P＞0.05),seminal plas-ma ROS decreased(P＞0.05)and SOD increased(P＜0.05)in the positive controls after medication.In comparison with the posi-tive controls,the patients treated with JJD showed even more significant improvement in PMS([29.37±14.56]％vs[42.68±15.86]％,P＜0.05),MNS([1.84±1.32]％vs[3.66±1.72％]％,P＜0.05),DFI([32.66±5.23]％vs[16.61±4.20]％,P＜0.05)and MMP([46.47±9.48]％vs[61.79±8.61]％,P＜0.05),ROS([7.08±0.51]vs[5.06±0.52]μmol/L,P＞0.05),and SOD([100.65±10.59]vs[139.05±14.71]U/ml,P＜0.05).TEM revealed significantly improved ultrastructure of sperm mitochondria after treatment with JJD.No serious adverse reactions were observed in either group dur-ing follow-up.Conclusion:JJD,superior to natural vitamin E and L-carnitine oral solution,can safely and effectively increase the percentages of PMS and MNS,MMP and the level of seminal plasma SOD,reduce sperm DFI and seminal plasma ROS,and improve the ultrastructure of sperm mitochondria in patients with ATZ.The underlying mechanism of action may be related to its ability of im-proving the structure and function of sperm mitochondria via antioxidant stress.

Objective: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.