ObjectiveTo observe the clinical effectiveness and safety of Dingchan Granule （定颤颗粒） for paroxysmal atrial fibrillation with syndrome of qi stagnation and blood stasis. MethodsUsing a randomised， double-blind， placebo controlled study method， 90 patients with paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome were divided into 45 cases each in the treatment group and the control group. Both groups were given conventional western medicine treatment， and the treatment group was additionally treated with Dingchan Granule， while the control group was treated with Dingchan Granule placebo， both of which were taken orally for 8 g each time twice a day. Both groups were treated for 8 weeks. We compared the clinical effectiveness， the improvement of traditional Chinese medicine （TCM） symptoms and the recovery rate of atrial fibrillation between the two groups. We compared the number and duration of atrial fibrillation episodes， TCM symptoms score， atrial fibrillation symptom classification， 24-hour average ventricular rate， Pittsburgh Sleep Quality Index （PSQI）， anxiety index， depression index before and after treatment， and evaluated the safety of the two groups. ResultsThe total clinical effectiveness rate in the treatment group was 82.22% （37/45）， which was better than 60.00% （27/45） in the control group （P＜0.05）. The total effective rate of TCM syndrome effectiveness in the treatment group was 88.89% （40/45）， which was better than 66.67% （30/45） in the control group （P＜0.05）； and the rate of atrial fibrillation regression in the treatment group was 26.67% （12/45）， better than 6.67% （3/45） in the control group （P＜0.05）. The number and duration of atrial fibrillation episodes in both groups were significantly decreased （P＜0.01）， and the number and duration of atrial fibrillation episodes in the treatment group were lower than those in the control group （P＜0.01）. The TCM syndrome scores of both groups after treatment were significantly lower than before treatment （P＜0.01）， and the scores of the treatment group was lower than those of the control group （P＜0.05）. The severity of atrial fibrillation symptoms and the grading of atrial fibrillation symptoms in both groups after treatment were improved （P＜0.01）， and the degree of symptom improvement in the treatment group was better than that in the control group （P＜0.01）. The 24-hour average ventricular rate of both groups after treatment was significantly lower （P＜0.01）. The PSQI， anxiety index and depression index of the treatment group were all lower than before treatment （P＜0.01）， while the PSQI and anxiety index of the control group were both lower than before treatment （P＜0.01 or P＜0.05）， the PSQI， anxiety index and depression index of the treatment group being lower than those of the control group （P＜0.05 or P＜0.01）. No adverse events occurred in both groups， and no abnormalities were observed in blood， urine， stool routine， liver and kidney function， and coagulation function indexes. ConclusionDingchan Granule for paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome can alleviate clinical symptom， improve TCM symptom scores， increase atrial fibrillation recovery rate， stabilise the average ventricular rate， and significantly improve the quality of sleep， alleviate the anxiety and depression， with a good safety profile.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

AIM To investigate the effects of volatile oil from Acorus tatarinowii Schott(A.tatarinowii)on neuroinflammation in a rat model of tic disorders.METHODS The SD rats were randomly divided into the blank group(8 rats)and the model group(40 rats).The rat models of tic disorders established successfully by intraperitoneal injection of iminodiapropionitrile(IDPN)were further divided into the model group,the tiapride group and the high-dose,moderate-dose and low-dose A.tatarinowii volatile oil groups,with 8 rats in each group.The 4-week intragastric treatment of respective drug was initiated the next day after the completion of modeling,and normal saline was dosed upon the blank group and the model group,during which the rats' behavioral changes were assessed by stereotyped behavior and motor behavior score every week.After the administration,the rats had their morphological changes of striatal neurons observed by Nissl staining;their levels of TGF-β,IL-10,TNF-αand IL-1β in serum and striatum detected by ELISA;their striatal protein expressions of CX3CL1 and CX3CR1 detected by Western blot and immunohistochemistry;and their striatal expressions of M1,M2 microglia marker proteins CD86,CD206,SYN and PSD-95 detected by immunofluorescence co-staining.RESULTS Compared with the model group,the A.tatarinowii volatile oil groups demonstrated improved twitch-like behavior;decreased scores of motor behavior and rigid behavior(P＜0.01);alleviated damage of Nissl bodies in neurons;increased serum and striatum levels of TGF-β and IL-10(P＜0.05,P＜0.01);decreased levels of TNF-α and IL-1β(P＜0.01);decreased striatal protein expressions of CX3CL1 and CX3CR1(P＜0.01);increased protein expressions of PSD95 and SYN(P＜0.05,P＜0.01);and decreased CD86/Iba1(P＜0.01)and increased CD206/Iba1(P＜0.01)in terms of the fluorescence intensity.CONCLUSION A.tatarinowii volatile oil contributes an anti-tic effect and improves the neuroinflammation in the brain of the rat model of tic disorders by promoting the transformation of microglia into M2 type via CX3CL1/CX3CR1 signal axis.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.

Objective To investigate the longitudinal clinical manifestations of acute radiation dermatitis(ARD)induced by particle therapy in nasopharyngeal carcinoma patients and to analyze associated risk factors.Methods A longitudinal study design was employed,encompassing nasopharyngeal carcinoma patients who underwent particle therapy at the Shanghai Proton and Heavy Ion Center from Mar to Sept 2023.Participants were assessed weekly(1-12 weeks)following the commencement of radiotherapy and at baseline,prior to the start of treatment.Data collection included the patient demographic questionnaire,the Radiation Therapy Oncology Group(RTOG)grading criteria for acute radiation injury,and the radiation-induced skin reaction assessment scale(RISRAS).Photographic documentation was utilized to capture changes in the irradiated skin area.The enrolled patients with nasopharyngeal carcinoma were grouped according to different particle therapy regimens.Survival data were analyzed by Log-rank and Cox regression methods,while a linear mixed-effects model was applied to repeated measures data.Results A total of 119 patients with nasopharyngeal carcinoma were enrolled.The overall incidence of ARD was 89.1%,which included 39.5%of grade 1,45.4%of grade 2 and 4.2%of grade 3.With the extension of time,the severity of ARD peaked at week 7(RISRAS=13.26±4.512),then began to decrease,ultimately reaching a lower level.Multiple Cox proportional hazards models were constructed,revealing that proton/heavy ion radiotherapy was associated with a lower risk of ARD compared to photon/proton plus heavy ion radiotherapy(HR=0.19,95%CI:0.04-0.92,P=0.039).Additionally,concurrent cisplatin/nedaplatin chemotherapy was identified as a risk factor for the development of ARD.Least squares(LS)mean differences were calculated at different time points,and the results demonstrated that the RISRAS scores of the photon/proton plus heavy ion group were consistently and significantly higher from week 5 to week 7 compared with the proton plus heavy ion group,and despite a decrease by week 8,statistical differences remained(week 5:LS mean difference 3.35,95%CI:0.94-5.76,P=0.007;week 6:LS mean difference 5.23,95%CI:2.20-8.26,P=0.001;week 7:LS mean difference 7.13,95%CI:3.67-10.59,P<0.001;week 8:LS mean difference 4.04,95%CI:0.74-7.34,P=0.017).Patients undergoing concurrent cisplatin chemotherapy had higher RISRAS scores from week 7 to week 8 of radiotherapy compared with those not receiving chemotherapy[week 7:adjusted mean difference(Adj.MD)4.20,95%CI:1.96-6.57,P=0.006;week 8:Adj.MD 2.79,95%CI 0.55-5.03,P=0.015].Similarly,patients on concurrent nedaplatin chemotherapy had higher RISRAS scores from weeks 6 to 7 compared with those not on chemotherapy(week 6:Adj.MD 3.75,95%CI:1.54-5.96,P=0.001;week 7:Adj.MD 4.41,95%CI:2.12-6.70,P<0.001).Skin care measures during treatment and accompanying symptoms such as weight loss were not statistically associated with the development of ARD.Conclusion Proton/heavy ion radiotherapy has a lower risk of ARD,while concurrent cisplatin/nedaplatin chemotherapy is a risk factor for ARD.

BACKGROUND:The asymmetrical biomechanical environment of adolescent idiopathic scoliosis can lead to further wedge deformation of the vertebral body,which may affect cardiopulmonary function and compress nerves in severe cases.Adolescent idiopathic scoliosis with different degrees of scoliosis should be treated with exercise,bracing,and surgery.However,the mechanical mechanism of selecting an orthopedic approach remains unclear due to the individual variability of patients.OBJECTIVE:To investigate the biomechanical mechanism of different orthopedic modalities for the treatment of adolescent idiopathic scoliosis to provide a basis for clinical selection of treatment modalities based on the spine model of adolescent idiopathic scoliosis patients.METHODS:Based on the CT images of an adolescent idiopathic scoliosis patient,a scoliosis model(C7-L5)was reconstructed in Mimics software in three dimensions,and lateral thrust force was applied at the T8/T9 thorax and vertical distraction force was applied over the C7 vertebra with the magnitude of 20,40,60,80,100,and 120 N.The intervertebral disc stress and vertebral displacement in concave and convex sides,and Cobb angle of the spine were analyzed under two orthopedic modalities.RESULTS AND CONCLUSION:(1)With lateral thrust,there was no significant change in the C7T1-T7T8 intervertebral disc.The concave and convex stress of T7T8-L4L5 segment decreased first and then increased with the increase of lateral thrust force.The correction effect of lateral thrust on the segment near T8T9 was obvious and weakened with the extension of the segment to the cephalic and caudal ends.At 120 N of lateral thrust,the thoracic Cobb angle changed from 53.2° to 32.5° and the lumbar Cobb angle changed from 50.2° to 43.9°.(2)With the vertical distraction,the thoracic intervertebral disc stresses first decreased and then increased,and all the lumbar disc stresses decreased.The C7 displacement was the most obvious,and the correction effect gradually diminished with the segment extended to the caudal end.At a vertical distraction force of 120 N,the thoracic Cobb angle changed from 53.2° to 39.4° and the lumbar Cobb angle changed from 50.2° to 47.6°.(3)It is concluded that both orthopedic modalities provide improvement in the degree of scoliosis,with the thoracic correction being greater than the lumbar correction.Also,the asymmetric stress distribution on the concave and convex sides is improved,which contributes to normal bone growth.A vertical distraction approach is appropriate for larger Cobb angles,and a lateral thrust approach is appropriate for smaller Cobb angles.The results of this study help to understand the mechanism of spinal orthosis and provide a theoretical basis for the choice of orthopedic approach.

This paper reports a death due to septic shock caused by Shewanella algae bloodstream infection and Epstein-Barr virus(EBV)co-infection in an elderly male patient who had no history of seawater exposure.She-wanella algae was identified in blood culture.Antimicrobial susceptibility testing showed that the strain was sus-ceptible to meropenem while resistance to ceftriaxone.EBV sequence was detected by metagenomic next-generation sequencing(mNGS)of blood specimen.Despite meropenem combined with antiviral and anti-shock treatment,the patient still rapidly progressed to multiple organ failure and died.This case suggests that Shewanella algae infec-tion relevant to freshwater environment exposure should be alerted,co-infection with EBV can exacerbate the severi-ty of sepsis,and potential risk of treatment failure should be paid attention in clinical practice despite carbapenems susceptibility confirmed by testing.