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.

Objective:To evaluate the clinical value of three-dimensional(3D) printing-assisted fenestrated/branched endovascular aortic repair (F/B-TEVAR) for the treatment of endoleak after open surgery for type A aortic dissection.Methods:A multi-center retrospective case series analysis was conducted on 16 patients with anastomotic leakage following Stanford type A aortic dissection open repair, admitted to 12 medical centers between January 2019 and December 2023. All surgeries were led by the vascular surgery team from Department of Vascular Surgery, Nanjing Drum Tower Hospital. The study included 12 males and 4 females, with an age of (58.1±8.2) years (range: 42 to 75 years). Preoperative patient-specific 3D-printed models or 3D parametric surface topological guides were created based on aortic CT angiography data. These models assisted intraoperative external positioning of fenestration sites, combined with stent diameter selection and inner branch techniques to complete endovascular repair. Surgical procedures, complications, and clinical outcomes were evaluated, with follow-up CT imaging to assess efficacy.Results:All patients successfully underwent surgery without conversion to open repair. One patient had distal stent migration from a prior open repair, requiring intraoperative coverage of the main stent window and conversion to an in situ fenestration procedure. The mean operative time was (332.6±111.2)minutes (range: 80 to 460 minutes). No renal failure, paraplegia, or branch artery loss occurred. Postoperative follow-up ( M(IQR)) was 18(18) months(range: 6 to 36 months), with follow-up rates of 16/16 at 6 months, 10/16 at 12 months, 8/16 at 24 months, and 2/16 at 36 months. During follow-up, endoleak occurred in 3 patients, cerebral infarction in 1 patient, and death in 1 patient. The remaining patients demonstrated stable stent positioning, patent branches, and no endoleak. Conclusion:3D technology-guided F/B-TEVAR shows favorable mid-to short-term outcomes in treating anastomotic leakage after open repair of type A aortic dissection.

Objective To summarize and analyze the main clinical characteristics,feature and composition changes of gut microbiota in elderly patients with severe pneumonia,and to further explore the potential correlation between the gut characteristics and the etiology of severe pneumonia in elderly patients.Methods Patients with severe pneu-monia admitted to the respiratory intensive care unit of a tertiary teaching hospital in Changsha were selected as the research subjects.Patients aged ≥65 years were assigned to the elderly severe pneumonia group,while those aged＜65 years were assigned to the non-elderly severe pneumonia group.Based on clinical characteristics and pathogen detection of lower respiratory secretion,the elderly severe pneumonia group was further divided into a pulmonary bacterial infection group and a pulmonary fungal infection group.The pulmonary bacterial infection group was sub-divided into Gram-positive bacteria group and Gram-negative bacteria group based on Gram-staining results.Clinical data of patients were collected,and fecal specimens within 24 hours after admission were obtained for 16S rRNA se-quencing.Differences in gut microbiota characteristics between two groups of patients were compared,and the cor-relation between clinical characteristics of patients in the elderly severe pneumonia group and the abundance of dif-ferential microbiota was analyzed.Subsequently,the gut microbiota characteristics of elderly patients in severe pneumonia group infected by different pathogens were analyzed.Results Gut microbiota analysis showed no signifi-cant statistical differences in α-and β-diversity indicices between patients in the elderly and non-elderly severe pneu-monia groups(both P＞0.05).Linear discriminant analysis effect size(LEFSe)analysis indicated that,compared with patients in the non-elderly severe pneumonia group,the relative abundance of opportunistic pathogens,inclu-ding Pseudomonadales,Moraxellaceae,and Acinetobacter,was significantly higher in patients in the elderly severe pneumonia group(all P＜0.05).Some differential gut microbiota in two groups of patients were correlated with clinical indicators in patients in the elderly severe pneumonia group(all P＜0.05).β-diversity analysis(principal co-ordinate analysis)combined with Anosim analysis revealed that in patients in elderly severe pneumonia group,there was significant differences in gut colony structures between patients in the bacterial and fungal infection groups(R=0.149,P=0.02).Compared with the fungal infection group,patients in bacterial infection group showed a signifi-cantly reduced abundance of probiotics,including Verrucomicrobiales and Collinsella,and opportunistic pathogens such as Akkermansia(all P＜0.05).Conclusion Elderly patients with severe pneumonia have a dysregulated gut microbiota with significantly increased abundance of pathogenic bacteria compared with non-elderly patients.Differ-ential gut microbiota of two groups of patients are correlated with some infection-related and organ function indica-tors in elderly patients with severe pneumonia.Compared with elderly patients with severe fungal pneumonia,those with severe bacterial pneumonia have significant differences in gut colony structures and a notably reduction in probi-otics abundance.

A recombinant adenovirus(rAd)for expression of Mycobacterium tuberculosis(M.tb)c-di-AMP phosphodiesterase CnpB was constructed,and its induced humoral immune response was detected.The codon-optimized gene of M.tb CnpB was cloned into the adenoviral plasmid pcADV.The recombinant plasmid pcADV-CnpB was transfected into HEK293T cells,and expression was detected with Western blot.The recombinant plasmid pcADV-CnpB and the backbone plasmid were co-transfected into HEK293T cells to obtain the recombinant adenovirus rAd-CnpB.rAd-CnpB was amplified in HEK293T cells,and the target protein expression of rAd-CnpB was detected with Western blot and immunofluorescence.Mice were immunized with rAd-CnpB intranasally,and their sera and bronchoalveolar lavage fluid(BALF)were collected.ELISA was used to detect levels of antigen-specific antibodies.Restriction enzyme digestion and sequencing indicated that the recombinant plasmid pcADV-CnpB was successfully constructed and led to protein expression in eukaryotic cells.rAd-CnpB was packaged and produced in HEK293T cells.After amplification and purification,rAd-CnpB with a titer of 5.53×1010 PFU/mL was obtained.rAd-CnpB led to CnpB expression in HEK293T cells.Intranasal immunization with rAd-CnpB increased levels of IgG and secretory IgA in BALF and led to high levels of IgG in sera.rAd-CnpB,the recombinant adenovirus for expression of c-di-AMP phosphodiesterase CnpB was successfully constructed,and was found to induce antigen-specific humoral and mucosal immune responses through mucosal immunization.Thus,rAd-CnpB may be used in further research on new TB vaccine strategies.

The new era imposes heightened demands on medical professionals,who must not only possess a solid theoretical foundation but also exhibit strong practical skills and innovative capabilities.The quality of medical func-tional laboratory construction is crucial for cultivating high-caliber medical talents.In light of the current developmental status and trends regarding functional experiment teaching within Chinese higher education institutions,particularly the disparities in development across various regions and institutions,the Functional Experiment Teaching Committee of the Chinese Pathophysiology Society has developed an expert consensus on laboratory construction standards.This consensus was established through comprehensive investigations,research,and extensive discussions to provide a reference for di-verse institutions to continuously enhance their levels of laboratory construction.

Objective To explore the correlation between serum G protein signaling modulator 2(GPSM2),adapter related protein complex 3 subunit mu2(AP3 M2)with clinical pathological features and postoperative prognosis of early colorectal cancer(CRC)patients.Methods From January 2020 to December 2021,142 early CRC patients(CRC group)and 96 colorectal polyp patients(benign lesion group)treated in our hospital were included,and 80 healthy volunteers(control group)were also included.RT-qPCR was used to detect serum GPSM2 and AP3M2.Kaplan-Meier survival curve was performed to analyze the relationship between serum GPSM2 and AP3M2 with the prognosis of CRC.Cox regression was performed to analyze the risk factors affecting the prognosis of CRC.ROC curve was used to explore the forecast value of serum GPSM2 and AP3M2 for the prognosis of CRC.Results The benign lesion group and CRC group had manifestly higher serum GPSM2 and AP3M2 than the control group,and with the CRC group being higher than the benign lesion group(P＜0.05).Serum GPSM2 and AP3M2 in CRC patients were related to their differentiation degree(P＜0.05).The 3-year survival rate of patients with low GPSM2 and AP3M2 was higher than that of patients with high GPSM2 and AP3M2(85.29％、87.14％vs 67.57％、65.28％)(Log Rank x2=7.205,10.800,P＜0.05).Low differentiation degree and elevated serum GPSM2 and AP3M2 were risk factors affecting the prognosis of CRC(P＜0.05).The AUC of serum GPSM2 and AP3M2 combined to predict the prognosis of CRC patients was 0.903(Zjoint-GPSM2=2.882,Zjoint-AP3M2=3.322,P＜0.05),the sensitivity is 88.24％,and the specificity is 82.41％.Conclusion The serum GPSM2 and AP3M2 in CRC patients are elevated and closely related to differentiation degree and prognosis.The joint of the two has high clinical value in forecasting the prognosis of CRC.

Objective To investigate the effect of triglyceride-glucose index(TyG)on the short-term prognosis of patients with initial acute ischemic stroke.Methods A total of 391 patients with initial acute ischemic stroke who were hospitalized in Kunshan Second People's Hospital and The Affiliated Suzhou Hospital of Nanjing Medical University from Jun.2020 to Jun.2023 were retrospectively included.According to the modified Rankin scale(mRS)scores at 90 d follow-up,they were assigned to good prognosis group(286 cases)or poor prognosis group(105 cases).Logistic regression and receiver operating characteristic(ROC)curve were used to evaluate the effect of TyG on the short-term prognosis of patients with initial acute ischemic stroke.Results Compared with the good prognosis group,the patients of poor prognosis group had older age,higher proportion of atrial fibrillation,higher levels of homocysteine,triglyceride,total cholesterol,low-density lipoprotein,and TyG,and higher National Institutes of Health stroke scale(NIHSS)score(all P＜0.05).Multivariate logistic regression analysis showed that age,homocysteine,TyG and NIHSS score were independent risk factors for poor prognosis in patients with initial acute ischemic stroke(all P＜0.05).ROC curve analysis showed that TyG combined with NIHSS score had good predictive value for poor prognosis of patients with initial acute ischemic stroke,and the area under curve value was 0.795.Conclusion The combination of TyG and NIHSS score is an independent influencing factor for poor short-term prognosis in patients with initial acute ischemic stroke.

Objective:To investigate the current situation of nuclear medicine practices, determine the number of nuclear medicine staff, conduct internal exposure monitoring and dose estimation for nuclear mecidine staff engaged in 131I treatment in Zhejiang province. Methods:A survey was conducted over all the 22 hospitals involved in 131I treatment in the province. The 131I activity in thyroid of 96 stafff in 131I treatment workplaces were measured by means of direct method. At the same time, the effective doses from internal exposure were estimated and the influencing factors were analyzed. Results:131I activity in thyroids was found to be above the detection limit for 49 staff (51.04%) in nineteen hospitals. The maximum value of 131I activity was 629.18 Bq. There was no statistically significant difference in 131I detection rate in thyroid of 131I treatment staff between different positions, different genders and different levels of hospitals ( P>0.05). Comparisons of 131I activity of thyroid of nuclear medicine staff for theatment of thyroid cancers had shown that the highest was for nurses, followed by technicians and doctors, and the lowest was for cleaning staff ( H=6.39, P<0.05). The estimated committed effective dose to the nuclear medicine staff ranged from 0.05 to 2.37 mSv, with those below 1 mSv accounting for 93.88% of the total. Logistic regression analysis showed that nursing position was the risk factor contributing to the committed effective dose ( OR=2.805, 95% CI 1.076-7.314). Conclusions:In Zhejiang province, the committed effective dose to thyroid of nuclear medicine staff from 131I internal exposure was not in excess of the dose limit. However, the staff performing iodine therapy still need to strengthen protection against internal exposure and take scientific and effective protective measures to reduce the risk of health hazards from internal exposure.

Urolithiasis represents a prevalent clinical challenge marked by high recurrence rates and morbidity，with existing preventive strategies struggling to effectively curb its epidemic trajectory，thereby posing a significant threat to public health. The etiology of this condition is intricate，involving a complex network of interactions spanning classical supersaturation-crystallization theory，Randall’s plaque theory，and multifactorial elements such as cellular injury，inflammatory responses，metabolic derangements，the gut-kidney axis，immune dysregulation，and genetic predisposition. However，the critical mechanisms initiating stone formation and the early pathophysiological processes remain incompletely elucidated，constituting the core impasse in current preventive strategies. This review systematically synthesizes classical theories and cutting-edge advancements in urolithiasis etiology research，emphasizing the urgent need to integrate emerging technologies，including high-dimensional omics，advanced imaging modalities，and artificial intelligence，to dissect pivotal pathological nodes in early stone formation. Such interdisciplinary efforts are essential to overcome cognitive bottlenecks and ultimately achieve personalized，precision-based prevention strategies.