Objective To investigate the influence of high copper load on neurobehavior in rats and its possible mechanism of action based on the deacetylase sirtuin 3 （SIRT3）/peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） signaling pathway. Methods A total of 50 adult Sprague-Dawley rats were randomly divided into model group and blank group， with 25 rats in each group. The rats in the model group were fed with 1 g/kg high-copper diet and 0.185% copper sulfate solution （prepared using deionized water） to establish a rat model of high copper load， and after 12 weeks， the shuttle box test and the pole-climbing test were used to observe neurobehavioral changes， while Western blotting and immunofluorescent staining were used to measure the protein expression levels of SIRT3 and PGC-1α in hippocampal tissue. Results The shuttle box test showed that compared with the blank group， the model group had a significant reduction in the number of times of active avoidance reaction after stimulation （P<0.01） and significant increases in the times of active avoidance reaction and passive avoidance reaction （P<0.01）；the pole-climbing test showed that compared with the blank group， the model group had a significant increase in pole-climbing time（P<0.01）. Western blotting and immunofluorescent staining showed that compared with the blank group， the model group had significant reductions in the protein expression levels of SIRT3 and PGC-1α in hippocampal tissue （P<0.05）. Conclusion High copper load has a marked influence on the neurobehavior of rats， possibly by regulating the expression of the SIRT3/PGC-1α signal pathway in hippocampal neurons.

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

Objective To explore the method for establishing a pig left lung orthotopic transplantation model. Methods A total of 4 male Yorkshire pigs weighing (40.0±2.5) kg underwent surgical procedures, including anesthesia, tracheal intubation, donor lung procurement, and recipient lung transplantation. Histological morphology and blood gas analysis of the transplanted lungs were assessed 2 hours after reperfusion to evaluate the histological changes and function of the transplanted lungs. Results The pigs underwent left lung in situ transplantation, effectively simulating conditions relevant to human lung transplantation. Two hours after the transplantation, arterial blood gas analysis showed that arterial partial pressure of oxygen was 155.4-178.6 mm Hg, arterial partial pressure of carbon dioxide was 53.1-62.4 mm Hg, and the oxygenation index was 310.8-357.2 mm Hg. Hematoxylin and eosin staining indicated a low degree of pulmonary edema and minimal cellular infiltration. Conclusion The pig left lung orthotopic transplantation model possesses strong operability and stability. Researchers can replicate this model according to the described methods and further conduct basic research and explore clinical translational applications.

OBJECTIVE To explore the effect and mechanism of berberine in ameliorating asthma in mice by regulating glycolysis via the hypoxia inducible factor-1α （HIF-1α）/pyruvate dehydrogenase kinase-1 （PDHK1） pathway.METHODS Mice were randomly divided into blank control group， model group， low- and high-dose berberine groups （100， 200 mg/kg， intragastric administration）， dimethyloxalylglycine （DMOG， HIF-1α agonist） group （2 mg， intranasal instillation）， and berberine+DMOG group （intragastric administration of 200 mg/kg berberine plus intranasal instillation of 2 mg DMOG）， with 12 mice in each group. Except for the blank control group， mice in the remaining groups were subjected to ovalbumin-induced sensitization and challenge to establish the asthma model. During the challenge period， mice were given corresponding drugs or normal saline once a day for 6 consecutive days. At 24 h after the last challenge， pulmonary function and airway reactivity of mice were determined； the content of ovalbumin-specific immunoglobulin E （OVA-sIgE） in serum was detected； inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted； bronchial inflammation and goblet cell hyperplasia were histologically evaluated； the levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-5， IL-13]， contents of glycolytic products [lactic acid， pyruvic acid， adenosine triphosphate （ATP）]， as well as mRNA and protein expressions related to the HIF-1α/PDHK1 pathway in lung tissue were measured.RESULTS Compared with the model group， the low- and high-dose berberine groups exhibited significantly elevated or increased dynamic lung compliance， peak expiratory flow， forced vital capacity （FVC）， forced expiratory volume in 0.1 second （FEV 0.1 ）， and FEV 0.1 /FVC （ P ＜0.05）， accompanied by significantly decreased airway resistance and enhanced pause value （ P ＜0.05）. Moreover， serum OVA-sIgE content， counts of white blood cell， neutrophil， lymphocyte， monocyte， eosinophil and basophil in BALF， scores for bronchial inflammation and goblet cell hyperplasia， levels of pulmonary inflammatory cytokines and contents of glycolytic products， as well as mRNA and protein expressions of HIF-1α， PDHK1， pyruvate kinase M2 and lactate dehydrogenase A were all significantly reduced （ P ＜0.05）. DMOG pretreatment obviously reversed the protective effects of high-dose berberine in asthmatic mice （ P ＜0.05）.CONCLUSIONS Berberine can inhibit the HIF-1α/PDHK1 pathway to decrease glycolytic level， so as to ameliorate airway inflammation and airway hyperresponsiveness in asthmatic mice.

Objective:Autoimmune gastritis (AIG) is characterized by the loss of acid-secreting glands, resulting in hypochlorhydria and hypergastrinemia, conditions that significantly increase the risk of developing gastric neuroendocrine tumors (NETs) and gastric adenocarcinoma. In recent years, AIG has garnered increasing attention in both clinical and research settings. However, comprehensive studies on the clinical and endoscopic characteristics of AIG particularly cases complicated by gastric neoplastic lesions remain limited in China. This study aims to comprehensively summarize the clinical and endoscopic features of AIG and its associated gastric neoplastic lesions.Methods:A retrospective analysis was conducted using medical records from patients with AIG diagnosed at Sichuan Provincial People′s Hospital between 2019 and 2024. Data collected included demographic information, medical history, serological test results, imaging findings, and endoscopic observations. The clinical and endoscopic features of AIG patients with gastric NETs or epithelial-derived tumors were compared to those without gastric neoplastic lesions to identify potential risk factors and diagnostic indicators for tumor development in AIG.Results:A total of 72 patients with AIG were included, of whom 62.5% (45/72) were female, with an age range of 30 to 79 years old (mean age: 57±11 years). Parietal cell antibody (PCA) positivity was observed in 93.1% (67/72), intrinsic factor antibody (IFA) positivity in 45.8% (33/72), and Helicobacter pylori ( H. pylori) co-infection in 48.6% (35/72). Endoscopically, 84.7% (61/72) showed prominent corpus-dominant advanced atrophy; 47.2% (34/72) had sticky adherent mucus; and 41.7% (30/72) displayed residual oxyntic mucosa in the gastric body or fundus. Only 23.6% (17/72) had normal antrum mucosa, and just 16.7% (12/72) showed a circular wrinkle-like pattern. Gastric neoplastic lesions were identified in 35 patients (48.6%), including 15 cases (20.8%) with NETs and 20 cases (27.8%) with epithelial-derived tumors (four adenocarcinomas, three adenomas, and 13 cases of intraepithelial neoplasia). No significant differences were found between tumor and non-tumor groups in terms of age, gender, PCA/IFA positivity, gastrin levels, anemia status, folic acid, or serum iron levels. However, patients with NETs had significantly lower vitamin B 12 levels compared to those without tumors (183±111 ng/L vs. 323±159 ng/L, t=2.47, P=0.042). Additionally, AIG patients with NETs were more likely to be H.pylori-negative compared to both the non-tumor group (66.7% vs. 35.1%, χ2=5.26, P=0.072) and the epithelial-derived tumor group (66.7% vs. 30.0%, χ2=5.80, P=0.055). The incidence of reverse atrophy in the epithelial-derived tumor group was significantly lower than that in the non-tumor group (65.0% vs. 91.9%, χ2=6.49, P=0.011) and the NETs group (65.0% vs. 93.3%, χ2=3.90, P=0.048).? Conclusion:In AIG patients with NETs, serum vitamin B 12 levels are significantly reduced, suggesting that vitamin B 12 deficiency may be a key risk factor or clinical indicator for NET development in AIG. Furthermore, NETs are more frequently observed in AIG patients without H.pylori infection, while epithelial-derived tumors are more commonly associated with H.pylori co-infection.

Objective To investigate the influencing factors associated with the risk of positive methylation levels of SHOX2/RASSF1A/PTGER4 genes in patients with pulmonary nodules with TCM susceptibility.Methods Using a cross-sectional study method,totally 165 patients with pulmonary nodules from the Respiratory Department of Wangjing Hospital,China Academy of Chinese Medical Sciences were included from May 2024 to December 2024.Clinical data such as patients'general medical history,nodule imaging reports,lung cancer gene methylation levels,and TCM constitution assessments were organized and statistically analyzed.On the basis of exploring the correlation between various variables and the risk of positive methylation of lung cancer genes through univariate correlation analysis,a binary logistic regression model was used for independent risk factor analysis.Results Univariate correlation analysis showed that age,gender,TCM susceptibility score,diameter of pulmonary nodules and upper lobe of the right lung were correlated with positive methylation levels of the SHOX2/RASSF1A/PTGER4 genes(P=0.03,P=0.02,P=0.01,P<0.01,P=0.03);and binary Logistic regression analysis showed that yang-deficiency quality,qi deficiency,qi depression and phlegm-dampness,the four pulmonary nodules susceptibility body scores were significantly and positively correlated with the risk of SHOX2/RASSF1A/PTGER4 gene methylation positivity.Compared with yang deficiency,phlegm-dampness and qi depression had a higher risk of gene methylation positivity for patients with pulmonary nodules(P=0.04,P=0.02).Conclusion Older age,males,and TCM susceptibility body correlated with the lung cancer gene methylation positive risk are correlated,in which phlegm dampness and qi depression are independent risk factors.

OBJECTIVE To investigate the relationship between 23-site chip genetic screening failures and the results of newborns hearing screening,and to provide clinical reference for the diagnosis and treatment of genetic screening failures.METHODS There were 1 916 newborns born in the Beijing area from November 2022 to May 2024,who did not pass the 23-site chip genetic screening tests and underwent newborn hearing screening with definite initial screening results.Chi-square test was used to analyze the relationship between different mutation types and genotypes and the initial hearing screening results.RESULTS The overall neonatal hearing screening failure rate was 5.27%(101/1 916),with a higher failure rate of 61.54%(56/91)for homozygous and compound heterozygous mutations than the failure rate of 2.54%(45/1 772)for heterozygous mutations,0%(0/34)for digenic gene heterozygous mutations,and 0(0/19)for mtDNA 12S rRNA mutations,with a statistically significant difference(P<0.001).Among the homozygous and compound heterozygous mutations,the failure rates of homozygous and compound heterozygous for GJB2 gene and SLC26A4 gene were 59.76%(49/82)and 77.78%(7/9),respectively,with no statistically significant difference between the two groups(P=0.488).The homozygous and compound heterozygous for GJB2 gene were divided into three groups based on genotype:c.109G>A homozygous mutations,c.109G>A compound heterozygous mutations,and other homozygous and compound heterozygous mutations.The hearing screening failure rates of the three groups,from highest to lowest,were as follow:other homozygous and compound heterozygous mutations(88.89%,8/9),c.109G>A homozygous mutations(65.12%,28/43),and c.109G>A compound heterozygous mutations(43.33%,13/30),with a statistically significant difference(P=0.029).The failure rates of heterozygous for GJB2 gene,SLC26A4 gene and GJB3 gene were 2.86%(40/1 398),1.25%(4/321)and 1.89%(1/53),respectively,with no statistically significant difference among the three groups(P=0.241).The failure rate of hearing screening for individuals with GJB2 heterozygotes of different genotypes and individuals with SLC26A4 heterozygotes of different genotypes did not show statistically significant differences.CONCLUSION The failure rate of newborn hearing screening for homozygous and compound heterozygous mutation of 23-site chip genetic screening is higher than that of other mutation types,verifying the effectiveness of the newborn hearing screening program.Some newborns of homozygous and compound heterozygous mutation can pass the hearing screening,especially those with the c.109G>A homozygous and compound heterozygous mutation,who need clinical follow-up.

In recent years, the incidence of infertility has been steadily increasing. Obesity, recognized as a chronic inflammatory condition, can not only lead to various chronic diseases such as hypertension and diabetes, but also adversely affects female reproductive health,including rare ovulation, anovulation, menstrual irregularities, and even infertility. The reproductive outcomes of overweight/obese women are not optimistic even among people undergoing assisted reproductive technology (ART).However, the mechanisms of overweight and obesity on ART outcomes remain poorly understood. This review aims to summarize current evidence on the impact of overweight and obesity on ART outcomes in women and explore the potential mechanisms.