Objective: To propose an improved method for constructing the internal quality control (IQC) framework for ELISA assays and validate its efficacy by statistically analyzing IQC data from nine blood center laboratories. Methods: 1) IQC data was collected from nine blood centers and analyzed using a domestic HBsAg ELISA detection kit as an example. 2) Differences between IQC values across batches within Blood Center 1 were assessed. 3) Statistical analyses were performed on batch usage, number of batches used, days of use, number of QC points, batch-specific means, and coefficients of variation (CV) across all nine centers. 4) Using the improved construction method for IQC framework, provisional and permanent frames were established for batches within Blood Center 1 and Blood Center 9, followed by outlier determination. Results: 1) Statistically significant differences were observed in IQC data between batches within Blood Center 1 (P<0.01). It is recommended that both the control material/reagents and the control chart framework be replaced simultaneously. 2) There were substantial differences among 9 blood centers regarding the control material/reagent lot numbers used, the number of QC runs per batch, and the QC values for identical lots. Therefore, individual laboratories should establish their own IQC chart frameworks. 3) The improved IQC framework construction method for ELISA assays is as follows: provisional frames are established via frame-shifting, using the pre-experimental mean and cumulative coefficient of variation (CV) from the preceding batch. For batches used >20 days with >20 QC points, permanent frames are constructed by aggregating in-control data accumulated over ≥20 days with ≥20 points to calculate cumulative mean and standard deviation. The provisional and permanent frames constructed by this method identified all 26 extreme outliers across Blood Centers 1 and 9 as out-of-control. Among the 218 general outliers, 10 were classified as normal by the provisional frames, while the remainder were designated as warnings or out-of-control. This method effectively monitors assay stability. Conclusion: Based on the statistical analysis of IQC practices across blood centers of varying scales, combined with the inherent characteristics of ELISA assays and the batch-to-batch instability of reagents/QC materials, it is recommended to reconstruct QC charts upon lot changes. The proposed method—utilizing frame-shifting for provisional frames and establishing permanent frames based on cumulative data—is applicable to blood center laboratories of differing sizes and effectively monitors the stability of the ELISA assay process.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Chronic pain is a complex condition shaped by long-standing alterations in both physiological and psychological processes. Rather than representing a simple continuation of acute nociceptive signaling, chronic pain is increasingly understood as the outcome of progressive dysregulation within distributed neural systems that govern sensation, affect, motivation, and cognitive control. Neuroimaging and electrophysiological studies indicate that this state is accompanied by extensive plastic changes in deep brain structures and large-scale networks. Beyond well-described central sensitization processes, chronic pain is characterized by disrupted oscillatory rhythms and altered connectivity within large-scale brain networks, including thalamo-cortical circuits and prefrontal-limbic-reward networks. These findings support a conceptual shift from viewing chronic pain as a focal, lesion-driven phenomenon toward recognizing it as a disorder of distributed network pathology. Pharmacological treatments remain central to clinical practice, yet their long-term efficacy is often limited and frequently accompanied by substantial side effects. The ongoing concerns about opioid-related risks and the inadequate therapeutic response in a subset of patients highlight the need for safe, non-pharmacological approaches that can address not only pain but also comorbid disturbances in mood, sleep, and social functioning. Neuromodulation provides a promising path toward mechanism-based and non-pharmacological management of chronic pain by employing physical or chemical stimulation to alter the excitability and synchrony of specific neural populations within central, peripheral, and autonomic systems. While invasive deep brain stimulation demonstrates that targeting deep brain structures can be effective, its clinical application is restricted by surgical risks and cost, highlighting the importance of non-invasive techniques capable of reaching deep targets. Current non-invasive approaches, such as transcranial electric stimulation, are constrained by limited penetration depth and insufficient spatial precision. These limitations hinder reliable engagement of deep regions implicated in pain, including the thalamus and nucleus accumbens, and tend to produce broad, non-specific modulation of cross-network oscillatory activity. Temporal interference (TI) stimulation has emerged as a means of overcoming these obstacles. By delivering interacting high-frequency currents that generate a low-frequency envelope within the head, TI enables focal stimulation of deep targets while minimizing superficial current delivery. Recent multiscale modeling and animal studies indicate that TI exploits the nonlinear rectification properties of neuronal membranes in response to high-frequency carriers, as well as their phase-locked responses to low-frequency envelopes, to generate “peak-focused” electric fields in deep regions under relatively low superficial current loads. Moreover, TI appears to exhibit potential advantages in terms of cell-type selectivity and rhythm-specific engagement, including differential responses across neuronal subtypes and distinct coupling to θ-, β-, and γ-band oscillations. These features suggest a promising avenue for correcting abnormal rhythms and network dynamics that contribute to chronic pain. This review summarizes current knowledge of the neural mechanisms underlying chronic pain and recent advances in TI research. It examines functional disturbances across key pain-related regions and networks, outlines the principles and technical characteristics of TI, and discusses potential deep-brain targets and stimulation strategies relevant to chronic pain. Evidence to date indicates that TI, with its non-invasiveness, tolerability, and capacity for precise deep brain modulation, holds great promise for the management of treatment-resistant chronic pain and may evolve into a new generation of precise and efficient non-pharmacological analgesic strategies.

Japanese spotted fever(JSF)is an infectious disease caused by Rickettsia japonica,with nonspecific clinical symptoms and a high risk of misdiagnosis.We reported a case of JSF,in which Rickettsia japonica was detected in blood cells by metagenomic next-generation sequencing.The patient recovered after treatment with doxycycline.This report provides a reference for the clinical diagnosis and treatment of JSF.
Humans ; High-Throughput Nucleotide Sequencing ; Metagenomics ; Rickettsia/isolation & purification* ; Spotted Fever Group Rickettsiosis/microbiology*

Objective To explore the physical function indicators of elderly women with fall experiences,so as to provide more data reference for fall prevention,risk assessment,and solving of aging-related health problems in elderly women.Methods The fall history of 167 elderly women in communities in Tianjin was investigated by a questionnaire.The participants were assigned into a fall group(more than 2 falls in the last 1 year)and a non-fall group according to the number of falls.Body composition was tested by an Inbody 770 Body Composition Analyzer,and the calcaneus bone mineral density was measured by a UBD2002A Ultrasound Bone Densitometer.The muscle strength and proprioception of knee and ankle joints of lower limbs were measured by a PRIMUS BTE Isokinetic Tester.The muscle strength of lower limbs was evaluated by the number of 30-second sitting-rising.The visual sensitivity was examined by two-contrast near point reading cards(with a small number of strokes).The dynamic and static balance abilities were determined by a Korebalance Tester,and the static balance ability was tested by one-leg standing with eyes closed.The dynamic and static balance was assessed based on the Berg balance scale,and walking gait characteristics were studied by a BTS three-dimensional motion capture system.Results The skeletal muscle content(P<0.001),strength of non-dominant knee flexor muscle(P=0.002),number of 30-second sitting-rising(P=0.006),and average walking speed(P=0.013)in the fall group were lower than those in the non-fall group.The visual acuity at 10% grayscale(P=0.001),active knee joint position sense(P<0.001),strength of non-dominant ankle flexor muscle(P<0.001),and one-leg standing time with eyes closed(P<0.001)in the fall group were lower than those in the non-fall group.The fall group outperformed the non-fall group in right-left balance rate(P=0.031)and forward-backward balance rate(P=0.028)during static and dynamic balance tests.Conclusion The ankle angle,proprioception,muscle strength,and skeletal muscle content of lower limbs,visual sensitivity,dynamic and static balance abilities,and walking ability of elderly women with fall experiences were lower than those without fall experiences.
Humans ; Accidental Falls ; Aged ; Female ; Postural Balance ; Muscle Strength ; Body Composition ; Bone Density ; Surveys and Questionnaires ; Gait

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:This study aims to investigate sex-specific abnormalities?? in gray matter volume (GMV) in Children with autism spectrum disorder (ASD) and their associations with gene expression.Methods:T 1-weighted brain MRI data were collected at the MRI Center of the University of Electronic Science and Technology of China between 2022 and 2023 from 100 children with ASD and 90 typically developing (TD) children. Voxel-based morphometry (VBM) was used to explore GMV differences between ASD boys and TD boys, and between ASD girls and TD girls. Partial least squares regression (PLSR) was performed based on the Allen Human Brain Atlas to identify genes associated with GMV alterations, followed by enrichment analyses. Cell-type-specific expression analyses were used to examine associations across developmental stages and brain structures. Protein-protein interaction (PPI) networks were constructed to identify hub proteins. Results:Compared to TD boys, ASD boys showed increased GMV in the right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, temporal pole, parahippocampal gyrus, fusiform gyrus, cuneus, and precuneus, as well as in the bilateral orbital part of the superior frontal gyrus and the gyrus rectus. Decreased GMV was observed in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 635 genes were associated with these GMV alterations, enriched in pathways related to DNA-templated transcription, RNA metabolism and biogenesis, and ion binding. Developmental analysis indicated strong associations with the cerebellum during early, middle-to-late childhood, and adolescence, and with the cerebral cortex in early adulthood. Protein-protein interaction (PPI) network analysis highlighted NOB1, GNL3L, ESF1, TFB2M, and WDR75 as specific hub proteins. Compared to TD girls, ASD girls exhibited increased GMV in the right middle and inferior temporal gyri, temporal pole, and fusiform gyrus, and decreased GMV in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 765 genes were associated, enriched in pathways related to ion channel activity, signal transduction, and regulation of membrane potential. These genes showed strong associations with the amygdala during mid-to-late fetal development, middle-to-late childhood, adolescence, and early adulthood; with the cerebellum during late infancy, early childhood, and early adulthood; with the cerebral cortex during the mid-to-late fetal development, early neonatal period, and adolescence; with the hippocampus during middle-to-late childhood and adolescence; with the striatum during adolescence and early adulthood; and with the thalamus during early-to-mid fetal development, early neonatal period, and early adulthood. PPI network analysis identified ANK3, ANK1, SCN4B, NFKB1, and PXN as specific hub proteins. Conclusion:Both ASD boys and ASD girls exhibit GMV abnormalities compared with TD controls. The specific genes associated with GMV alterations are enriched in distinct biological pathways in boys and girls. Cell-type-specific expression analyses further revealed sex-dependent differences in developmental timing and brain structural correlations, and distinct PPI networks were constructed for each group.

Objective:To understand the molecular evolutionary characteristics of the recombinant strain GII.3[P12] of norovirus acute gastroenteritis outbreaks and aggregated outbreaks in China from 2022 to 2023.Methods:Epidemiological information, case information, clinical samples, as well as detection and genotyping information of norovirus outbreaks and aggregated outbreaks from 2022 to 2023 were collected; positive samples of the GII.3[P12] recombinant strain were subjected to nucleic acid extraction, whole-genome amplification, and sequence analysis; and homology simulation method were used to construct a three-dimensional structure and predict antigenic epitopes.Results:From January 2022 to December 2023, a total of 1 136 norovirus outbreaks and aggregated outbreaks were reported in China′s norovirus outbreak surveillance network, and genotyping result were successfully obtained for 942 outbreaks, with GII dominating, accounting for 76.0% (716/942), and the proportion of GI and mixed genotypes being 15.8% (149/942) and 8.2% (77/942). Norovirus outbreaks caused by GII were dominated by GII.3[P12] (22.5%, 161/716), while other major genotypes included GII.17[P17] (18.7%, 134/716), GII.4_Sydney 2012[P16] (11.6%, 83/716) and GII.6[P7] ( 11.3%, 81/716). 2022-2023 Outbreaks caused by GII.3[P12] were concentrated in February-March (54.0%, 87/161), with the main outbreaks occurring in nursery and primary schools (87.5%), the mode of transmission was mainly human-to-human (68.9%), and the main susceptible population was children aged 3-7 years (93.3%). In this study, the genome sequences of 25 GII.3[P12] recombinant strains were obtained, and according to the phylogenetic analysis, it was shown that the GII.3[P12] recombinant strains in China in 2022-2023 belonged to the Cluster IV cluster of sublineage b (7 strains) and sublineage c (18 strains). A total of 11 linear and 8 conformational epitopes were predicted by epitope prediction analysis, and the predicted linear and conformational epitopes had overlapping positions, and each conformational epitope was part of the predicted linear epitope with conserved potential antigen-binding and receptor-binding sites.Conclusions:The recombinant strain GII.3[P12] is one of the epidemic strains that will cause outbreaks and clusters of norovirus in China in 2022-2023, and its genome did not undergo significant mutation.