ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

ObjectiveTo explore the potential mechanisms of kidney-tonifying and blood-activating acupuncture for Alzheimer's disease. MethodsMale SAMP8 mice were randomly divided into a model group， acupuncture group， non-acupoint group， and donepezi group， with 10 mice in each group， and 10 SAMR1 mice as normal group. The acupuncture group received acupuncture at Baihui （GV 20）， Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17）. Xuehai （SP 10）， Shenshu （BL 23）， and Geshu （BL 17） were stimulated on the left side first and then on the right side alternately， once a day. The non-acupoint group received acupuncture at fixed bilateral non-meridian， non-acupoint points under the ribs， once a day. The model and normal groups underwent equivalent handling and restraint stress without acupuncture. The donepezi group received 1 mg/kg donepezil via gastric gavage daily. All groups were treated for 4 weeks. After treatment， Morris water maze tests （to record orientation sailing latency， number of traverses through the platform quadrant） and open field （to record distance travelled） were used to evaluate learning and memory abilities； hippocampal neuronal damage was analyzed via HE and Nissl staining； mitochondrial membrane potential and reactive oxygen species （ROS） were measured using assay kits； Western blot and qRT-PCR were performed to detect silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor gamma coactivator 1-alpha （PGC-1α）， and mRNA expression levels. ResultsCompared with the normal group， mice in the model group and non-acupoint group showed elevated orientation sailing latency and relative multiplicity of ROS in hippocampal tissues， and reduced number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-staining-positive cells in the hippocampal tissues， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1， PGC-1α （P＜0.01）； HE staining showed that the hippocampal tissues of the mice was loosely arranged， with reduced number of neurons and vacuolar degeneration； Nissl staining showed that pyramidal neurons in the hippocampal region were not neatly arranged， and the number of Nissl bodies in the cytoplasm was less and the staining was lighter. Compared with the model group， mice in the acupuncture group and donepezil group had lower orientation sailing latency and relative multiplicity of ROS in the hippocampal tissue， higher number of traverses through the platform quadrant， distance of movement in the open-field experiment， number of Nissl-stained positive cells in the hippocampal tissue， mitochondrial membrane potential， and protein levels and mRNA expression of SIRT1 and PGC-1α （P＜0.01）， and HE staining and Nissl staining showed significant improvement in hippocampal histopathological damage. Compared with the donepezil group， the orientation sailing latency shortened in the acupuncture group of mice （P＜0.01）. ConclusionKidney-tonifying and blood-activating acupuncture method can alleviate the SIRT1/PGC-1α signalling pathway in the hippocampal tissue and improve the mitochondrial function， thus alleviating the neuronal damage， which is one of the possible mechanisms for its treatment of Alzheimer's disease.

Objective To investigate the prevalence of Schistosoma japonicum infections in wild rodents in schistosomiasis-endemic areas of China, so as to provide insights into formulation of technical guidelines for monitoring of and the precise control strategy for S. japonicum infections in wild rodents during the elimination phase. Methods Two administrative villages where schistosomiasis was historically highly prevalent were selected each from Dongzhi County, Anhui Province, and Duchang County, Jiangxi Province as study villages. Wild rodents were captured from study villages with baited traps or cages at night in June and September, 2021. The number of rodents captured was recorded, and the rodent species was characterized based on morphologi-cal characteristics. Liver tissues were sampled from captured rodents for macroscopical observation of the presence of egg granu- lomas, and S. japonicum infection was detected simultaneously using liver tissue homogenate microscopy, examinations of mesenteric tissues for parasites, and modified Kato-Katz thick smear technique (Kato-Katz technique). A positive S. japonicum infection was defined as detection of S. japonicum eggs or adult worms by any of these methods. The rate of wild rodent capture and prevalence of S. japonicum infections in wild rodents were compared in different study villages and at different time periods, and the detection of S. japonicum infections in wild rodents was compared by different assays. Results The overall rate of wild ro- dent capture was 8.28% (237/2 861) in Dongzhi County, and the wild rodent capture rates were 9.24% (133/1 439) and 7.31% (104/1 422) in two study villages (χ² = 3.503, P = 0.061), and were 8.59% (121/1 409) and 7.99% (116/1 452) in June and September, 2021, respectively (χ² = 0.337, P = 0.561). The overall rate of wild rodent capture was 3.72% (77/2 072) in Duchang County, and the wild rodent capture rates were 6.91% (67/970) and 0.91% (10/1 102) in two study villages (χ² = 51.901, P < 0.001), and were 4.13% (39/945) and 3.37% (38/1 127) in June and September, 2021, respectively (χ² = 0.815, P = 0.365). Rattus norvegicus was the predominant rodent species captured in both counties, accounting for 70.04% (166/237) of all captured wild rodents in Dongzhi County and 88.31% (68/77) in Duchang County. No S. japonicum infection was detected in wild rodents captured in Duchang County. Nevertheless, the overall prevalence of S. japonicum infections was 51.05% (121/237) in wild rodents captured in Dongzhi County, with prevalence rates of 50.38% (67/133) and 51.92% (54/104) in two study villages (χ² = 0.098, P = 0.755), and 54.31% (63/116) and 47.93% (58/121) in September and June, 2021, respectively (χ² = 0.964, P = 0.326). Of 237 wild rodents captured in Dongzhi County, there were 140 (59.07%) rodents with visible hepatic egg granulomas, 117 (49.47%) tested positive for S. japonicum eggs by liver tissue homogenate microscopy, 34 (14.35%) tested positive for S. japonicum eggs with Kato-Katz technique; however, no adult S. japonicum worms were detected in mesenteric tissues. In addition, hepatic egg granulomas were found in all wild rodents tested positive for S. japonicum eggs with liver tissue homogenate microscopy. Conclusions The rate of wild rodent capture and prevalence of S. japonicum infection in wild rodents vary greatly in schistosomiasis-endemic areas of China, and the prevalence of S. japonicum infection is slightly higher in wild rodents captured in autumn than in summer. Liver tissue is recommended as the preferred sample for surveillance of S. japonicum infection in wild rodents, and a combination of macroscopical observation of hepatic egg granulomas and liver tissue homogenate microscopy may be a standard method for surveillance of S. japonicum infection in wild rodents.

In June 1958, the first specialized acupuncture hospital, the Affiliated Acupuncture Experimental Hospital of Jiangsu Provincial School of TCM, was established in Nanjing. This hospital was founded under the initiative of Mr. CHENG Dan'an, the founder of the Chengjiang School of Acupuncture. Centered on clinical acupuncture, the hospital also carried out research and teaching, forming an integrated development model of medical care, education, and research. Its development experience, including a clear hospital-running philosophy, orientation toward solving clinical needs, and deep integration of medical care, education, and research, provides important historical references for the construction of modern specialized acupuncture hospitals.
China ; History, 20th Century ; Acupuncture Therapy/history* ; Humans ; Acupuncture/education* ; Hospitals, Special/history*

OBJECTIVE: To investigate the effect of piperlongumine(PL) on the proliferation and ferroptosis of human adriamycin-resistant chronic myeloid leukemia K562/ADR cells, and to explore its possible molecular mechanism. METHODS: CCK-8 assay was used to detect the effect of PL on the survival rate of K562/ADR cells and to screen the appropriate drug concentration. After K562/ADR cells were treated with low, medium and high concentrations of PL(2, 4, and 6 μmol/L), EdU proliferation assay and plate colony formation assay were used to detect cell proliferation and colony formation ability. CCK-8 assay was used to detect the effects of different inhibitors (Fer-1, Z-VAD, Nec-1) combined with PL on cell proliferation. The intracellular Fe²⁺, ROS, malondialdehyde(MDA) and glutathine(GSH) contents were respectively detected by iron ion colorimetry, DCFH-DA fluorescent probe, MDA and GSH kits. RT-qPCR and Western blot were respectively used to detect the expression level of GPX4 mRNA and protein in cells. Bioinformatics websites predicted miRNA that could target and regulate GPX4 . RT-qPCR was used to detect the effects of different concentrations of PL on the expression levels of the predicted miRNA. Dual luciferase gene reporter assay was used to verify the targeting relationship between miR-214-3p and GPX4 . After treating cells with PL or PL+miR-214-3p inhibitor, the Fe²⁺, ROS, MDA, GSH centents and GPX4 protein expression levels in cells were detected. RESULTS: PL inhibited K562/ADR cell proliferation in a concentration-dependent manner（r =0.979）. Compared with the blank control group, the survival rate, EdU positive cells rate in low, medium and high concentration PL groups were significantly decreased (P < 0.01). Compared with the PL group alone, the survival rate of cells in the Z-VAD+PL group was increased slightly (P < 0.05). The cell survival rate was significantly increased in medium or high concentration PL+Fer-1 group (P < 0.01). Compared with blank control group, ROS expression level in low concentration PL group was slightly increased (P < 0.05), and GSH content was slightly decreased (P < 0.05). In medium and high concentration PL groups, the contents of Fe²⁺, ROS and MDA were significantly increased (P < 0.01), while the contents of GSH, expression of GPX4 mRNA and protein were significantly decreased(P < 0.01). Bioinformatics prediction and double luciferase reporter gene experiment confirmed the targeting relationship between GPX4 and miR-214-3p. Compared with the blank control group, the expression level of miR-214-3p in cells of medium and high concentration PL groups was significantly increased (P < 0.01). Compared with PL group alone, the intracellular Fe²⁺, ROS and MDA contents in PL+miR-214-3p inhibitor group were all decreased (P < 0.01), while GSH content and GPX4 protein expression levels were significantly increased (P < 0.01). CONCLUSION Medium and high concentrations of PL can inhibit the proliferation of K562/ADR cells by inducing ferroptosis, which is related to the regulation of miR-214-3p pathway.
Humans ; Ferroptosis/drug effects* ; MicroRNAs/metabolism* ; Dioxolanes/pharmacology* ; Cell Proliferation/drug effects* ; K562 Cells ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Reactive Oxygen Species ; Doxorubicin/pharmacology* ; Signal Transduction ; Piperidones

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

OBJECTIVE: Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. METHODS: A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. RESULTS: Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. CONCLUSION Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals ; Nerve Regeneration/drug effects* ; Mice ; Peripheral Nerve Injuries/physiopathology* ; Male ; Ganglia, Spinal/enzymology* ; Axons/physiology* ; Peroxidase/antagonists & inhibitors* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology* ; Disease Models, Animal ; Strychnine/pharmacology*

Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

Objective:To investigate the epidemiological characteristics of pneumonia and the related factors of the length of hospitalization of pneumonia in the elderly aged 60 years and older in Ningbo in 2019.Methods:Data on hospitalized cases of pneumonia in the elderly aged 60 years and older in Ningbo in 2019 were collected through the regional health information platform, and the population data of Ningbo in 2019 were obtained through the Zhejiang Provincial Bureau of Statistics. A descriptive epidemiological analysis was conducted on hospitalized cases of pneumonia in the elderly population, and factors related to the length of hospitalization were explored.Results:A total of 15 956 hospitalized cases of pneumonia aged 60 years and older were reported in Ningbo in 2019, and the incidence of pneumonia requiring hospitalization was 1.02% (15 956/1 571 431). The incidence was 1.13% (8 613/760 357) in males and 0.83% (6 759/811 074) in females, and the ratio of male to female cases was 1.27∶1. The highest incidence was found in the ≥80 age group (2.52%), and the lowest incidence was found in the 60-69 age group (0.58%). March, February, and January were the peak period of pneumonia hospitalization. The main types of pneumonia diagnosed were not specified (65.12%), followed by bacterial pneumonia (34.60%). The M( Q1, Q3) of hospitalized patients with pneumonia was 9 (7, 13) days. The results of multivariate logistic regression analysis showed that gender (female: OR=0.911, 95% CI: 0.849-0.978) and older age (70-79 years old: OR=1.211, 95% CI: 1.111-1.321; ≥80 years old group: OR=1.486, 95% CI: 1.365-1.617), settlement method (self-payment: OR=0.567, 95% CI: 0.464-0.691), higher level of hospitals (Grade Ⅱ: OR=1.902,95% CI:1.723-2.100; Grade Ⅲ: OR=1.546,95% CI:1.407-1.698) were associated with the length of hospitalization for pneumonia in people aged 60 years and older in Ningbo. Conclusions:Hospitalization with pneumonia in people aged 60 years and older was high in winter and spring, men and older adults were in high-risk groups in Ningbo in 2019. Gender, age, billing method, and level of hospitals may be related factors to the length of hospitalization for pneumonia.