Ulcerative colitis （UC）， a chronic relapsing inflammatory bowel disease， involves multifaceted pathological mechanisms such as intestinal barrier dysfunction， immune dysregulation， and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism， inflammatory regulation， and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine （TCM） prevented and treated UC through the regulation of the AMPK signaling pathway， with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk， alleviating oxidative stress， restoring intestinal immune balance， repairing the intestinal barrier， and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity， TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC， this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.

OBJECTIVE: To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene. METHODS: A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01). RESULTS: Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3). CONCLUSION The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis ; Tubulin/genetics* ; Adult ; Brain/diagnostic imaging* ; Male ; Pedigree ; DNA Copy Number Variations/genetics* ; Exome Sequencing ; Genetic Association Studies ; Magnetic Resonance Imaging

Testicular radiation injury is a structural and functional abnormality of the testes caused directly or indirectly by radiation, which disrupts spermatogenesis and compromises male fertility. The development of effective preventive and therapeutic interventions is essential because of the high prevalence of this condition in clinical settings and its profound effect on patients′ reproductive health and overall well-being. The concept of "the struggle between vital qi and pathogen" is first seen in the Treatise on Cold Pathogenic Diseases. It denotes the dynamic struggle between vital and pathogenic qi. The occurrence, development, and sequelae of all diseases reflect this ongoing conflict. In this context, this study defines the "vital qi" of the testis as its capacity to generate and preserve the essence of reproduction and to resist damage. The pathogenic qi associated with testicular radiation injury is categorized into two types: ionizing poison and retaining evil. The pathogenesis of testicular radiation damage is delineated into three stages by integrating the characteristics of vital and pathogenic qi: the injury, adhesion, and recovery phases. Based on the theoretical framework advanced by this study, the therapeutic approach for testicular radiation injury should adhere to the fundamental principle of strengthening vital qi and eliminating pathogenic factors. Although the primary focus of treatment should be on strengthening vital qi, it should also be complemented by strategies to eliminate pathogenic influences. This paper aims to provide a novel perspective and strategic approach to the traditional Chinese medicine diagnosis, prevention, and treatment of testicular radiation injury. By elucidating the process of testicular radiation injury and its corresponding treatment principles, it seeks to offer valuable insights for clinical practice.

Objective To explore the promoting effect of long-term administration of nicotiflorin on the recovery of neurological function in rats with cerebral ischemia-reperfusion injury （CIRI）. Methods The CIRI model was established and nicotiflorin was injected intraperitoneally after 1 hour of obstruction for 8 weeks. Tail suspension deflection experiment, balance beam experiment and water maze test were performed in the 2nd, 4th and 8th weeks. After 8 weeks, TTC staining was used to observe the volume of infarct atrophy, transcriptome sequencing was employed to screen differential expressed genes （DEGs） and highly enriched pathways were analyzed, Western-bloting and Elisa were used to assess proteins expression related to the pyroptosis pathway and inflammatory cytokines IL-1β and IL-18. Results By long-term administration of nicotiflorin, the contralateral deflection rate was significantly reduced and beam experiment score of CIRI rats was balanced, the number of crossing the platform in water maze test was increased （P<0.05）, the volume of cerebral infarction atrophy was decreased （P<0.01）, which significantly promoted the recovery of neurological function in rats. Transcriptome sequencing found that the expression of genes in the pyroptosis-related signaling pathways in the brain tissue of rats in the nicotiflorin group was significantly down-regulated （P<0.05）. Western-blot and Elisa experiments showed that nicotiflorin reduced the expression levels of Caspase-1 and GSDMD-N and other pyroptosis-related proteins, and at the same time, the release of inflammatory factors IL-1β and IL-18 was significantly reduced （P<0.05）, indicating that nicotiflorin could inhibit the inflammatory process of pyroptosis. Conclusion Nicotiflorin exhibited a significant long-term promotion effect on the recovery of neurological function in CIRI rats, which potentially attributed from its ability to inhibit pyroptosis.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Objective:To investigate the mechanism of microRNA-597-3p ( miR-579-3p) in improving hypoxic-ischemic encephalopathy (HIE) by regulating the interleukin-1 receptor-associated kinase 1 (IRAK1)/tumor necrosis factor receptor-associated factor 6 (TRAF6)/transforming growth factor-β-activated kinase 1 (TAK1)/nuclear factor-κB (NF-κB) signaling pathway. Methods:Peripheral blood of healthy neonates ( n=5) and HIE newborns ( n=5) from June 2023 to June 2024 in the No.215 Hospital of Shaanxi Nuclear Industry were collected. The differential expression of miRNA in peripheral blood of neonates with HIE was analyzed by next-generation sequencing. The oxygen-glucose deprivation (OGD) method was used to establish the HIE cell model, which was designated as the OGD group, while cells without OGD treatment served as the control group. Rat adrenal pheochromocytoma PC12 cells were transfected with miR-579-3p mimic (mimic), mimic negative control (mimic-NC), miR-579-3p inhibitor (inhibitor), inhibitor negative control (inhibitor-NC), respectively, and divided into the mimic group, mimic-NC group, inhibitor group, inhibitor-NC group. On the basis of mimic group and inhibitor group, IRAK1 overexpression plasmid ( oeIRAK1) and IRAK1 small interfering RNA plasmid ( siIRAK1) were transfected respectively, which were divided into oeIRAK1 group and siIRAK1 group. The relative expression level of mRNA was detected by real-time reverse transcription-PCR. The absorbance ( A) value was detected by cell counting kit-8 assay. The apoptosis rate was detected by Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide double staining. The relative expression of protein was detected by Western blotting. The levels of pro-inflammatory factors and anti-oxidative stress factors were detected by enzyme-linked immunosorbent assay. Bioinformatics analysis was used to predict the binding site between miR-579-3p and IRAK1, and the dual-luciferase reporter assay was performed to validate their targeting relationship. A total of 12 7-day-old SD rats were selected and randomly divided into the HIE group and the sham group by the random number table method. In the HIE group, the right common carotid artery of rats was permanently occluded, followed by hypoxia exposure, whereas rats in the sham group only underwent common carotid artery exposure without ligation or hypoxia treatment. Immunohistochemical staining was used to detect the expression of protein in brain tissue of HIE rats. The least significant difference t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with the healthy neonates, a total of 278 differentially expressed miRNAs were detected in the peripheral blood of neonates with HIE, among which miR-579-3p showed the most significant downregulation. The relative expression level of miR-579-3p in the mimic group (15.78±1.93) was significantly higher than that in the mimic-NC group (1.00±0.14) ( P<0.01), and in the inhibitor group (0.29±0.14) was significantly lower than that in inhibitor-NC group (1.00±0.14) ( P<0.01). The A value in the mimic group (0.89±0.09) was significantly higher than that in the mimic-NC group (0.52±0.08) ( P<0.01), and in the inhibitor group (0.30±0.05 ) was significantly lower than that in the inhibitor-NC group (0.56±0.07) ( P<0.05). The apoptosis rate of mimic group [(7.47±1.53)%] was significantly lower than that in the mimic-NC group [(30.97±3.47)%] ( P<0.05), and in the inhibitor group [(49.05±4.21)%] was significantly lower than that in the inhibitor-NC group [(35.51±3.64)%] ( P<0.01). The relative expression level of cysteine aspartic acid specific protease-3 ( Caspase-3) and B-cell lymphoma-2 (Bcl-2) associated X protein ( Bax) (1.21±0.10, 1.40±0.13), the relative expression of cleaved Caspase-3 and Bax (1.00±0.13, 1.13±0.09), the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α [(45.15±5.14, 38.34±5.69) pg/mg] in the mimic group were significantly lower than those in the mimic-NC group [2.10±0.14, 2.37±0.16, 2.29±0.09, 2.27±0.12, (95.67±9.05, 63.99±5.24) pg/mg] (all P<0.01). The relative expression level of Bcl-2 and Claspin (1.03±0.09, 1.00±0.04), the relative expression of Bcl-2 and Claspin (1.21±0.06, 0.94±0.09), the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) [(67.65±6.86, 58.07±5.20) U/mg] in the mimic group were significantly higher than those in the mimic-NC group [(0.51±0.05, 0.52±0.02, 0.58±0.05, 0.46±0.07, 42.08±5.86, 29.80±4.85) U/mg] ( P<0.05, 0.01). The relative expression level of Caspase-3 and Bax (2.72±0.16, 2.97±0.10), the relative expression of cleaved Caspase-3 and Bax (3.25±0.17, 2.76±0.16), the levels of IL-6 and TNF-α [(122.80±11.59, 92.58±7.56) pg/mg] in the inhibitor group were significantly higher than those in the inhibitor-NC group [(1.86±0.14, 2.12±0.10, 2.35±0.15, 1.82±0.15, (88.13±8.59, 68.61±6.17) pg/mg] ( P<0.05, 0.01). The relative expression levels of Bcl-2 and Claspin mRNA (0.17±0.04, 0.20±0.06), the relative expression of Bcl-2 and Claspin proteins (0.11±0.03, 0.13±0.05), the levels of SOD and GSH-Px [(16.62±3.19, 12.01±1.92) U/mg] in the inhibitor group were significantly lower than those in the inhibitor-NC group [0.54±0.05, 0.54±0.05, 0.53±0.10, 0.45±0.07, (38.09±5.47, 30.90±3.87) U/mg] ( P<0.05, 0.01). IRAK1 was identified as a putative target of miR-579-3p. The relative luciferase activity of wild-type IRAK1 in the mimic group (0.45±0.05) was significantly lower than that in the mimic-NC group (1.00±0.08) ( P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the mimic group (0.96±0.09, 0.96±0.11, 1.34±0.16, 1.74±0.20), the relative expression of IRAK1, TRAF6, TAK1, and phosphorylated NF-κB (p-NF-κB) proteins (0.96±0.20, 1.27±0.19, 1.34±0.18, 1.16±0.19) were all lower than those in the mimic-NC group (1.96±0.17, 1.88±0.24, 2.39±0.23, 2.44±0.20, 2.33±0.22, 2.17±0.24, 2.25±0.28, 2.06±0.28) (all P<0.01). The relative expression levels of IRAK1, TRAF6, TAK1 and NF-κB mRNA in the inhibitor group (2.54±0.15, 2.61±0.13, 2.97±0.15, 2.99±0.20), the relative expression of IRAK1, TRAF6, TAK1 and p-NF-κB proteins (3.73±0.34, 3.17±0.25, 3.68±0.22, 3.29±0.20) were all higher than those in the inhibitor-NC group (1.87±0.18, 1.84±0.19, 2.15±0.24, 2.24±0.26, 2.35±0.23, 1.94±0.25, 2.05±0.27, 2.17±0.29) (all P<0.01). The A value in the oeIRAK1 group (0.66±0.07) was significantly lower than that in the mimic group (0.94±0.10) ( P<0.05), and in the siIRAK1 group (0.51±0.08) was significantly higher than that in the inhibitor group (0.23±0.05) ( P<0.05). The apoptosis rate in the oeIRAK1 group [(23.32±2.40)%] was significantly higher than that in the mimic group [(9.02±1.23)%] ( P<0.05), and in the siIRAK1 group [(28.27±2.57)%] was significantly lower than that in the inhibitor group [(48.96±4.60)%] ( P<0.01). The levels of IL-6 and TNF-α in the oeIRAK1 group [(85.10±6.98, 59.49±5.78) pg/mg] were significantly higher than those in the mimic group [(47.51±8.87, 23.65±3.75) pg/mg], and the levels of SOD and GSH-Px [(49.58±5.63, 41.31±6.21) U/mg] were significantly lower than those in the mimic group [(81.22±6.94, 62.26±5.44) U/mg] ( P<0.05, 0.01). The levels of IL-6 and TNF-α in the siIRAK1 group [(108.25±9.47, 74.87±8.71) pg/mg] were significantly lower than those in the inhibitor group [(142.65±13.88, 104.49±9.18) pg/mg], and the levels of SOD and GSH-Px [(35.87±3.69, 34.89±4.96) U/mg] were significantly higher than those in the inhibitor group [(15.55±3.70, 15.62±3.30) U/mg] ( P<0.05, 0.01). The relative expression level of miR-579-3p in the HIE group (0.47±0.11) was significantly lower than that in the sham group (1.00±0.09) ( P<0.01). The levels of IL-6 and TNF-α in the HIE group [(62.18±6.42, 68.42±4.91) pg/mg] were significantly higher than those in the sham group [(20.77±4.68, 31.16±4.95) pg/mg], and the levels of SOD and GSH-Px [(22.63±3.33, 19.07±2.86) U/mg] were significantly lower than those in the sham group [(47.89±4.58, 56.55±4.45) U/mg] (all P<0.01). The relative levels of TLR4, IRAK1, TRAF6, TAK1, NF-κB, and Caspase-3 mRNA, TLR4, IRAK1, TRAF6, TAK1, p-NF-κB, and cleaved Caspase-3 proteins in the HIE group (1.87±0.24, 2.03±0.21, 2.23±0.20, 1.85±0.18, 1.91±0.20, 2.36±0.20, 2.36±0.28, 2.16±0.28, 1.95±0.27, 2.05±0.26, 2.34±0.24, and 2.72±0.23) were all higher than those in the sham group (1.00±0.15, 1.00±0.11, 1.00±0.09, 1.00±0.05, 1.00±0.12, 1.00±0.15, 1.00±0.15, 1.00±0.21, 1.00±0.10, 1.00±0.14, 1.00±0.19, 1.00±0.16) (all P<0.01), which were consistent with the immunohistochemical staining results. Conclusions:miR-579-3p might alleviate HIE-induced neuronal damage by regulating the IRAK1/TRAF6/TAK1/NF-κB signaling pathway.

Objective:To explore the mechanism of Danxing Zhishuang Prescription in the treatment of Parkinson's disease (PD) by combining network pharmacology with animal models.Methods:TCMSP, BATMAN database, Genecards, and OMIM databases were retrieved to obtain the active components and action targets of Danxing Zhishuang Prescription. Venny 2.1.0 was used to intersect drug targets and PD related genes, and a protein interaction network of the intersection targets was constructed using the STRING 12.0 platform. Topology analysis was performed using Cytoscape 3.10.0 software to identify the key targets of Danxing Zhishuang Prescription on PD; GO functional and KEGG pathway enrichment analysis was performed on key targets using the WeChat platform, and molecular docking was validated through AutoDockTools 1.5.7. Using a random number table method, mice were divided into a blank control group, a model group, and a Danxing Zhishuang Prescription group, with 20 mice in each group; except for the blank group, all other groups of mice were orally administered fisetin to prepare PD models; Danxing Zhishuang Prescription group was orally administered with concentrated Danxing Zhishuang Prescription at a dosage of 10.5 g/kg, while the blank group and model group were orally administered with 0.2 ml of physiological saline for 21 days; Western blot was used to detect the expressions of Akt1, Bcl-2, Bax, and α-Syn proteins.Results:359 intersection targets, 69 core targets, and 185 active components were obtained the treatment of PD with Danxing Zhishuang Prescription. The main active components included quercetin, kaempferol, phenylalanine, etc., and the key targets were AKT1, TP53, TNF, ESR1, etc. KEGG analysis revealed several key signaling pathways, such as AGE-RAGE, PI3K-Akt, fluid shear stress and atherosclerosis signaling pathways. The validation experiment results showed that compared with the model group, the expression of Bcl-2 protein was up-regulated ( P<0.01), and the expressions of Bax, Akt1, and α-Syn proteins were down-regulated in the Danxing Zhishuang Prescription group ( P<0.01). Conclusions:Danxing Zhishuang Prescription has the advantages of multi target and multi pathway treatment for PD. Its mechanism may be related to down-regulating the expressions of Bax, Akt1, and α-Syn proteins, improving brain blood supply, regulating neurotransmitter balance, inhibiting oxidative stress response, and promoting nerve regeneration.

The pricing and reimbursement of orphan drugs are related to the accessibility of patients,and are of great significance to the prevention and guarantee of rare diseases.European countries have formed special standards and paths for health technology evaluation,and established special payment funds and diversified risk-sharing agreements,which have effectively improved the accessibility of orphan drugs.Based on this,it selected typical European countries to compare the orphan drug pricing and reimbursement methods.Then,it put forward some suggestions"building orphan drug health technology evaluation accelerated program,exploring the health of orphan drug classification security mechanism,and attaining supply incentives and development incentives through orphan drug pricing and adjustment",to optimize the basis for the orphan drug market access mechanism to provide reference.