Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

OBJECTIVE To systematically review the key regulatory requirements for pharmacy compounding drug products in the United States， and to provide references for improving the management framework of pharmacy compounding drug products in China， thereby ensuring the safety and accessibility of medication use. METHODS A literature revi ew was conducted to summarize the regulatory requirements and practical characteristics of pharmacy compounding drug products under Section 503A of the United States Federal Food， Drug， and Cosmetic Act . Based on regulatory experience of the United States， current status and existing deficiencies in pharmacy compounding drug products in China were analyzed， and targeted recommendations were proposed. RESULTS &CONCLUSIONS The United States has established a systematic regulatory framework for pharmacy compounding drug products under Section 503A， covering prescription management， active pharmaceutical ingredient management， list management of withdrawn or removed drugs and drugs that present demonstrable difficulties for compounding， recordkeeping management， interstate distribution and so on. Through standardized regulation of the entire compounding process and collaborative governance with expert advisory committees， this framework effectively balances individualized medication needs with drug quality and safety. In contrast， pharmacy compounding drug products in China remain largely confined to traditional Chinese medicine and face several challenges， including the lack of legal and regulatory support， inadequate quality control， lagging development of industry standards， and shortages of specialized personnel. It is recommended that China should establish a tiered regulatory system， develop comprehensive technical standards， build a localized regulatory framework， promote technological innovation， and strengthen professional talent cultivation to better balance the legitimate rights and interests of public medication use with drug safety and efficacy， thereby enhancing public health.

Objective: To explore the diagnosis, treatment and prognosis of primary prostatic signet ring cell carcinoma (SRCC), so as to provide reference for the clinical diagnosis and treatment. Methods: A retrospective analysis was conducted on the clinical data of 6 patients with primary prostatic SRCC treated in Nanjing Drum Tower Hospital during Nov.2020 and Sep.2024.The clinical manifestations, imaging features, treatment methods, histological characteristics and prognosis were summarized. Results: The average age of the patients was (72.00±4.28) years.Varying degrees of dysuria occurred in 4 patients. All patients underwent multi-parametric magnetic resonance imaging (mpMRI) examination before surgery, and the results indicated typical prostate cancer.Preoperative biopsies showed high-grade (Gleason 8-10) prostate acinar adenocarcinoma.Postoperative pathological diagnoses were mixed types of prostate acinar adenocarcinoma and SRCC, and no metastasis was found in the pelvic lymph nodes.All patients were followed up for 1 to 46 months after surgery and are currently alive.Robot-assisted laparoscopic radical prostatectomy only was performed in 3 cases; apalutamide and leuprolide/triptorelin was administered after surgery in 2 cases; bicalutamide + goserelin was administered after surgery in 1 case, who developed bladder metastasis of prostate cancer 24 months later, and the serum prostate-specific antigen (PSA) concentration decreased to a safe level (<0.2 ng/mL) after the use of darolutamide with radiotherapy.No recurrence or metastasis was found in the remaining patients. Conclusion: Primary prostatic SRCC is a rare and highly aggressive malignant tumor of the prostate.The diagnosis depends on pathological examinations due to lack of specific imaging features and clinical manifestations.The prognosis is poor, and there is currently no standardized treatment.The combined use of surgery, hormonotherapy and radiotherapy can help improve the survival rate of patients.

OBJECTIVES: To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. METHODS: We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. RESULTS: TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. CONCLUSIONS High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Prognosis ; Cell Proliferation ; Parathyroid Hormone-Related Protein/genetics* ; Cell Line, Tumor ; Cell Movement ; Disease Progression ; Signal Transduction ; Male ; RNA, Messenger/genetics* ; Female

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

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.