Protocol for the development of clinical guidelines for the management of chronic primary pain

Introduction Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage.In 2018,the World Health Organization(WHO)revised the International Classification of Diseases,11th Revision(ICD-11)to include chronic pain as an independent disease for the first time(MG30.0).1 At the same time,the ICD-11 also developed new classifications for chronic pain,including chronic primary pain(CPP),chronic cancer-related pain,chronic post-surgical or post-traumatic pain,chronic secondary musculoskeletal pain,chronic secondary visceral pain.

Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: A metaanalysis

Background Pharmacological and conventional nonpharmacological treatments are only moderately effective in treatingeneralised anxiety disorder(GAD).Recently,repetitive transcranial magnetic stimulation(rTMS)has attracted interest because of its potential therapeutic value.Aim To investigate the efficacy and safety of rTMS treatment for GAD.Methods Literature studies published in English or Chinese were screened in 10 electronic databases up to 5 December 2018.The included studies'bias risk was assessed using Cochrane risk of bias assessment tool.Meta-analysis was performed to compute the standardised mean difference(SMD)and risk ratio(RR)along with its 95%Cis through using RevMan V.5.3.Heterogeneity was inspected by I2 and the χ2 test.We performed subgroup analysis and meta-regression to investigate heterogeneity.We used funnel plot to assess publication bias.We used the GRADE approach to assess the whole quality of evidence.Results Twenty-one studies,with a total sample size of 1481,were analysed.The risk of bias in most studies included is moderate,the majority of which are lacking of blinding methods of treatment allocation.The treatment had beneficial effects in the rTMS group compared with the control group in mean anxiety score(SMD=-0.68;95%Cl-0.89 to-0.46).None of the 21 studies included here reported severe adverse events.As for dropout rates,there are no statistically significant differences between the two groups(RR 1.14,95%Cl 0.72 to 1.82)or adverse events(RR 0.95,95%Cl 0.77 to 1.18).No particular influence on the heterogeneity of any variable was observed.The risk of publication bias was low.According to the GRADE approach,the evidence levels of primary outcome(treatment effects)and secondary outcomes(acceptability and safety)were rated as‘medium’.Conclusion The use of rTMS combined with medication treatment may have a significant positive anti-anxiety effect on patients with GAD.However,we should interpret the results cautiously due to the relatively high heterogeneity of the meta-analysis.Future high-quality clinical trials are needed to confirm our results.

Altered heartbeat perception sensitivity associated with brain structural alterations in generalised anxiety disorder

Background Palpitation is a common complaint in generalised anxiety disorder(GAD).Brain imaging studies have Investigated the neural mechanism of heartbeat perception in healthy volunteers.This study explored the neuroanatomical differences of altered heartbeat perception in patients with GAD using structural MRI.Aims Based on the strong somatic-interoceptive symptoms in GAD,we explored the regional structural brain abnormalities involved in heartbeat perception in patients with GAD.Methods This study was applied to the a priori regions using neuroanatomical theories of heartbeat perception,including the insula,anterior cingulate cortex,supplementary motor area and prefrontal cortex.A total of 19 patients with GAD and 19 healthy control subjects were enrolled.We used the FMRIB Software Library voxel-based morphometry software for estimating the grey matter volume of these regions of interest and analysed the correlation between heartbeat perception sensitivity and the volume of abnormal grey matter.Results Patients with GAD showed a significantly decreased volume of grey matter in their left medial prefrontal cortex,right orbital frontal cortex and anterior cingulate cortex.The grey matter volume of the left medial prefrontal cortex negatively correlated with heartbeat perception sensitivity in patients with GAD.Conclusions It should be the first study that shows heartbeat perception is associated with brain structure in GAD.Our findings suggest that the frontal region may play an important role in aberrant heartbeat perception processing in patients with GAD,and this may be an underlying mechanism resulting in the abnormal cardiovascular complaints in GAD.This is hypothesised as a'top-down'deficiency,especially in the medial prefrontal cortex.This will provide the foundation for a more targeted region for neuromodulation intervention in the future.

Abnormal neural oscillations in clinical high risk for psychosis:a magnetoencephalography method study

Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.

INCloud:integrated neuroimaging cloud for data collection,management,analysis and clinical translations

Background Neuroimaging techniques provide rich and accurate measures of brain structure and function,and have become one of the most popular methods in mental health and neuroscience research.Rapidly growing neuroimaging research generates massive amounts of data,bringing new challenges in data collection,large-scale data management,efficient computing requirements and data mining and analyses.Aims To tackle the challenges and promote the application of neuroimaging technology in clinical practice,we developed an integrated neuroimaging cloud(INCloud).INCloud provides a full-stack solution for the entire process of large-scale neuroimaging data collection,management,analysis and clinical applications.Methods INCloud consists of data acquisition systems,a data warehouse,automatic multimodal image quality check and processing systems,a brain feature library,a high-performance computing cluster and computer-aided diagnosis systems(CADS)for mental disorders.A unique design of INCloud is the brain feature library that converts the unit of data management from image to image features such as hippocampal volume.Connecting the CADS to the scientific database,INCloud allows the accumulation of scientific data to continuously improve the accuracy of objective diagnosis of mental disorders.Results Users can manage and analyze neuroimaging data on INCloud,without the need to download them to the local device.INCloud users can query,manage,analyze and share image features based on customized criteria.Several examples of'mega-analyses'based on the brain feature library are shown.Conclusions Compared with traditional neuroimaging acquisition and analysis workflow,INCloud features safe and convenient data management and sharing,reduced technical requirements for researchers,high-efficiency computing and data mining,and straightforward translations to clinical service.The design and implementation of the system are also applicable to imaging research platforms in other fields.

The China Alzheimer Report 2022

China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

Meta-analysis of cognitive function in Chinese first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) profile of impairment

Background Compromised neurocognition is a core feature of schizophrenia. With increasing studies researching cognitive function of Chinese patients with first-episode schizophrenia (FES) using MATRICS Consensus Cognitive Battery (MCCB), it is not clear about the level and pattern of cognitive impairment among this population. Aim To provide a meta-analysis systematically analysing studies of neurocognitive function using MCCB in Chinese patients with FES. Methods An independent literature search of both Chinese and English databases up to 13 March 2019 was conducted by two reviewers. Standardised mean difference (SMD) was calculated using the random effects model to evaluate the effect size. Results 56 studies (FES=3167, healthy controls (HC)=3017) were included and analysed. No study was rated as 'high quality' according to Strengthening the Reporting of Observational Studies in Epidemiology. Compared with HCs, Chinese patients with FES showed impairment with large effect size in overall cognition (SMD=-1.60,95% Cl -1.82 to -1.38,厂=67%) and all seven cognitive domains, with the SMD ranging from -0.87 to -1.41. In nine MCCB subtests, patients with FES showed significant difference in Symbol Coding (SMD=-1.90), Trail Making Test (TMT)(SMD=-1.36), Continuous Performance Test-Identical Pairs (SMD=-1.33), Hopkins Verbal Learning Test (SMD=-1.24), Brief Visuospatial Memory Test (SMD=-1.18), Mazes (SMD=-1.16), Category Fluency (SMD=-1.01), Spatial Span (SMD=-0.69) and Mayer-Salovey-Caruso Emotional Intelligence Test (SMD=-0.38). Conclusions Our meta-analysis demonstrates that Chinese patients with FES show neurocognitive deficits across all seven MCCB cognitive domains and all nine subtests, particularly in two neurocognitive domains: speed of processing and attention/vigilance, with the least impairment shown in social cognition. Symbol Coding and TMT may be the most sensitive tests to detect cognitive deficit in Chinese patients with FES.

Prevalence and dynamic features of psychological issues among Chinese healthcare workers during the COVID-19 pandemic:a systematic review and cumulative meta-analysis

Background The COVID-19 pandemic has placed tremendous pressure on healthcare workers who are at the frontline in the battle against it,causing various forms of psychological distress.Aims To outline the prevalence and dynamic changing features of medical workers’psychological issues and to review the related national policies during the COVID-19 pandemic in China.Methods We systematically searched for studies on the psychological states of Chinese medical staff from 1 January 2020 to 8 May 2020.The aggregate prevalence of each psychological issue was calculated and plotted to observe the changes over time.Policies on psychological support for medical staff during the pandemic were reviewed to explore their link to the prevalence of psychological problems.Results In total,26 studies were included in this study.A total of 22062 medical workers were surveyed from 31 January to 27 February 2020.Medical staff exhibited a substantial prevalence of anxiety symptoms,depression symptoms,stress-related symptoms and sleep problems during the survey period,with aggregate prevalence rates of 27.0%,26.2%,42.1%and 34.5%,respectively.Cumulative meta-analyses revealed that the prevalence of psychological distress peaked at the beginning of the pandemic and subsequently exhibited a slow downward trend.Conclusion Chinese medical staff displayed significant psychological disturbance during the outbreak of the COVID-19 pandemic,which was especially severe at the early stage.Implementing supportive policies may help alleviate ongoing psychological problems in healthcare workers.

Massachusetts General Hospital and the Shanghai Mental Health Center:the past,present and future of a psychiatric research partnership

INTRODUCTION There are many obstacles to developing,maintaining and strengthening international research collaborations,whether they are posed by geography,culture or,most recently,global economics and politics.It is critically important to overcome these obstacles,especially when it comes to fostering the types of breakthrough biomedical science that benefit from diverse perspectives,methodologies and data sets.Moreover,the research underlying these breakthroughs unfolds over the course of years,and even decades.For these reasons,and more,the Department of Psychiatry at Massachusetts General Hospital(Mass General)and the Shanghai Mental Health Center(SMHC)are taking the long view:exploring and implementing numerous collaborative research and training projects that are leading to better care and treatments for patients,both in the USA and China,who suffer from a range of psychiatric disorders.

Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study

Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037).The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia(r=−0.46,p=0.004).Conclusions These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia.The ratio of initial attentive orienting was associated with negative symptoms in female patients.

Correlation of hair risperidone concentration and serum level among patients with schizophrenia

Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.

Speech databases for mental disorders: A systematic review

Background The employment of clinical databases in the study of mental disorders is essential to the diagnosis and treatment of patients with mental illness. While text corpora obtain merely limited information of content, speech corpora capture tones, emotions, rhythms and many other signals beyond content. Hence, the design and development of speech corpora for patients with mental disorders is increasingly important. Aim This review aims to extract the existing speech corpora for mental disorders from online databases and peer-reviewed journals in order to demonstrate both achievements and challenges in this area. Methods The review first covers publications or resources worldwide, and then leads to the reports from China, followed by a comparison between Chinese and nonChinese regions. Results Most of the speech databases were recorded in Europe or the United States by audio or video. Some were even supplemented by brain images and Event- Related Potential (ERP) statistics. The corpora were mostly developed for patients with neurocognitive disorders like stutter and aphasia, and mental illness like dementia, while other types of mental illness such as bipolar disorder, anxiety, d即ression and autism were scarce in number in database development. Strengths and limitations The results demonstrated that database development of neurocognitive disorders in China is much scarcer than that in some European countries, but the existing databases pave an instructive road for psychiatric problems. Also, the methods and applications of databases from the leading countries are inspiring for Chinese scholars, who are searchi ng methods for developing a comprehensive resource for clinical studies.

Effect of Heat Treatment on Microstructure and Mechanical Behavior of Cu-Bearing 316L Stainless Steel Produced by Selective Laser Melting

Cu-bearing stainless steels(SSs)with high strength,excellent plasticity,and effective antimicrobial properties hold significant potential for applications in the marine industry.In this study,Cu-bearing SSs with copper ranging from 0 to 6.0 wt%were successfully prepared using selective laser melting(SLM)technology.For the Cu-bearing SSs with different copper contents,the effect of heat treatment on the microstructural and mechanical behaviors was studied systematically.Microstructural observations revealed that the subgrain size of Cu-bearing SSs increased with heat treatment at 500℃ and 700℃ for 6 h.Furthermore,the tensile strength and elongation increased after the heat treatment temperature due to the combined effect of dislocations,twins,andε-Cu precipitated phases.Notably,after heat treatment at 700℃,the SLM4.5Cu sample exhibited an abnormal rise in tensile strength and elongation.This finding suggests that the diffusion strengthening caused byε-Cu precipitates exceeded the stacking fault energy.Consequently,the tensile strength and elongation reached 693.32 MPa and 56.94%,respectively.This work provides an efficient approach for preparing Cu-bearing SSs with exceptional strength and plasticity.

Updated Review on the Clinical Use of Repetitive Transcranial Magnetic Stimulation in Psychiatric Disorders

With the ability to modulate cortical activity,repetitive transcranial magnetic stimulation（r TMS） is becoming increasingly important in clinical applications for psychiatric disorders. Previous studies have demonstrated its promising efficacy in depression and schizophrenia, and emerging evidence has also been found in patients with anxiety disorder, obsessive–compulsive disorder, and substance or food craving. However, the overall literature features some conflicting results, varied quality of studies,and a lack of consensus on optimal r TMS parameters.Besides, the efficacy of r TMS in patients with medicationresistant symptoms has drawn most attention from clinicians. Here we review multi-site studies and double-blind randomized controlled trials（RCTs） in single sites, as well as meta-analyses of RCTs in the last three years, in order to update evidence on efficacy and the optimal protocol of r TMS in psychiatric disorders, especially for medicationresistant symptoms.

Transient fault identification method for bipolar short-circuit fault on MMC‐HVDC overhead lines based on hybrid HVDC breaker

A bipolar short‐circuit transient fault identification method for overhead transmission lines in modular multi‐level converter‐based high voltage direct current(MMC‐HVDC)grid based on the hybrid HVDC breaker is proposed.The circuit breakers on both sides of the positive and negative overhead transmission lines will trip after a bipolar short‐circuit fault in the MMC‐HVDC grid.In order to identify whether the fault is a transient fault,the isolating switch of the DC breaker on one line side is reclosed first,and the voltage change on this line side in the case of transient and permanent faults is analysed.By comparing the electrical characteristics of the voltage on the line side under transient and permanent faults,a transient fault identification method is proposed,and the calculation method of the setting value of the criterion is obtained.Finally,by building the MMC‐HVDC system model for simulation in power systems computer aided design,the accuracy and effectiveness of the proposed method for transient fault identification are verified.

Single-cell transcriptomics provides insights into the origin and immune microenvironment of cervical precancerous lesions

Dear editors,Despite efforts to implement vaccination and screening programs,cervical cancer(CC)remains a public health problem[1].Over 90%of cases are associated with persistent human papillomavirus(HPV)infections.HPV integrates its DNA into the basal cells of the transformation zone,the region where the epithelium transitions from the columnar epithelial cells of the endocervix to the stratified squamous epithelium cells of the ectocervix,leading to the production of proteins(E6 and E7)that eventually cause dysplasia[2,3].Squamous cell carcinoma(SCC)and cervical adenocarcinoma(AD)are the two most common types of HPV-related CC[4].SCC and AD have a longterm stage of preinvasive(PRE)lesion,which are named high-grade squamous intraepithelial lesion(HSIL)or adenocarcinoma in situ(AIS),respectively[5].However,no studies were conducted to determine why some individuals with HPV infections develop HSIL while others develop AIS.

Segregation between the parietal memory network and the default mode network： effects of spatial smoothing and model order in ICA

Abstract A brain network consisting of two key parietal nodes, the precuneus and the posterior cingulate cortex, has emerged from recent fMRI studies. Though it is anatomically adjacent to and spatially overlaps with the default mode network （DMN）, its function has been associated with memory processing, and it has been referred to as the parietal memory network （PMN）. Independent component analysis （ICA） is the most common data-driven method used to extract PMN and DMN simultaneously. However, the effects of data preprocessing and parameter determi- nation in ICA on PMN-DMN segregation are completely unknown. Here, we employ three typical algorithms of group ICA to assess how spatial smoothing and model order influence the degree of PMN-DMN segregation. Our findings indicate that PMN and DMN can only be stably separated using a combination of low-level spatial smoothing and high model order across the three ICA algorithms. We thus argue for more considerations on parametric settings for interpreting DMN data.