ObjectiveThe study explores the influence of voluntary wheel running on the behavioral abnormalities and the activation state of the hypothalamic-pituitary-adrenal (HPA) axis in autism spectrum disorder (ASD) rats through gut microbiota. MethodsSD female rats were selected and administered either400 mg/kg of valproic acid (VPA) solution or an equivalent volume of saline via intraperitoneal injection on day 12.5 of pregnancy. The resulting offspring were divided into 2 groups: the ASD model group (PASD, n=35) and the normal control group (PCON, n=16). Behavioral assessments, including the three-chamber social test, open field test, and Morris water maze, were conducted on postnatal day 23. After behavioral testing, 8 rats from each group (PCON, PASD) were randomly selected for serum analysis using enzyme-linked immunosorbent assay (ELISA) to measure corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) concentration, to evaluate the functional state of the HPA axis in rats. On postnatal day 28, the remaining 8 rats in the PCON group were designated as the control group (CON, n=8), and the remaining 27 rats in the PASD group were randomly divided into 4 groups: ASD non-intervention group (ASD, n=6), ASD exercise group (ASDE, n=8), ASD fecal microbiota transplantation group (FMT, n=8), and ASD sham fecal microbiota transplantation group (sFMT, n=5). The rats in the ASD group and the CON group were kept under standard conditions, while the rats in the ASDE group performed 6 weeks of voluntary wheel running intervention starting on postnatal day 28. The rats in the FMT group were gavaged daily from postnatal day 42 with 1 ml/100 g fresh fecal suspension from ASDE rats which had undergone exercise for 2 weeks, 5 d per week, continuing for 4 weeks. The sFMT group received an equivalent volume of saline. After the interventions were completed, behavioral assessments and HPA axis markers were measured for all groups. ResultsBefore the intervention, the ASD model group exhibited significantly reduced social ability, social novelty preference, spontaneous activity, and exploratory interest, as well as impaired spatial learning, memory, and navigation abilities compared to the normal control group (P<0.05). Serum concentration of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in the PASD group were significantly higher than those in the PCON group (P<0.05). Following 6 weeks of voluntary wheel running, the ASDE group showed significant improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, spatial learning, memory, and navigation skills compared to the ASD group (P<0.05), with a significant decrease in serum CORT concentration (P<0.05), and a downward trend in CRH and ACTH concentration. After 4 weeks of fecal microbiota transplantation in the exercise group, the FMT group showed marked improvements in social ability, social novelty preference, spontaneous activity, exploratory interest, as well as spatial learning, memory, and navigation abilities compared to both the ASD and sFMT groups (P<0.05). In addition, serum ACTH and CORT concentration were significantly reduced (P<0.05), and CRH concentration also showed a decreasing trend. ConclusionExercise may improve ASD-related behaviors by suppressing the activation of the HPA axis, with the gut microbiota likely playing a crucial role in this process.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

A 71-year-old male presented with esophageal cancer and severe aortic valve regurgitation. Treatment strategies for such patients are controversial. Considering the risks of cardiopulmonary bypass and potential esophageal cancer metastasis, we successfully performed transcatheter aortic valve implantation and minimally invasive three-incision thoracolaparoscopy combined with radical resection of esophageal cancer (McKeown) simultaneously in the elderly patient who did not require neoadjuvant treatment. This dual minimally invasive procedure took 6 hours and the patient recovered smoothly without any surgical complications.

Cryopreservation is the primary technique for in vitro preservation of allogeneic tissue. However, its success is often hindered by factors such as low temperature, ischemia, and hypoxia. This study investigated the potential of Sini Decoction, known for its antioxidant and anti-apoptotic properties, to reduce cryopreservation-induced injury in rats' sciatic nerves. Sini Decoction was prepared according to the Chinese Pharmacopoeia, and its cytotoxicity on Rsc96 cells was assessed by using the CCK-8 method. Sini Decoction at concentrations of 4, 8, and 16 mg·mL~(-1), termed as low-(SL), medium-(SM), and high-(SH) doses group, was used for cryopreservation of rats' sciatic nerves. A normal control(NC) group and a fresh nerve control(fresh) group were set. Flow cytometry and TUNEL staining were used to detect the apoptosis of neural tissue cells after cryopreservation. Western blot was used to detect the expression of apoptosis-related proteins(Bcl-2, Bax, caspase-3, and caspase-8) and nerve regeneration proteins(NGF and BDNF) in vitro after cryopreservation. Oxidative damage of neural tissue after cryopreservation was evaluated by measuring levels of GSH, SOD, MDA, ROS, and ATP. Cryopreserved nerves were then used for allogeneic transplantation. One week after transplantation, CD4~+ and CD8~+ fluorescent double staining assessed inflammatory cell invasion in the transplanted nerve segment, and ELISA evaluated the expression of serum inflammatory factors(IL-1, IFN-γ, and TNF-α) in recipients. Twenty weeks after transplantation, electrophysiology and NF200 neurofilament staining were used to evaluate nerve regeneration. RESULTS:: showed that Sini Decoction at concentrations of below 32 mg·mL~(-1) exhibited no cytotoxicity to Rsc96 cells. During in vitro nerve cryopreservation, Sini Decoction significantly reduced cell apoptosis, ROS, and MDA production compared to the NC group. In the SH group, the protein expression of NGF and BDNF in vitro, as well as ATP, SOD, and GSH production, were significantly increased. In the rejection reaction one week after transplantation, compared to the fresh nerve transplantation group, the SL and SM groups showed reduced CD4~+ and CD8~+ T cell invasion in the transplanted nerve segment and down-regulated IL-1, IFN-γ, and TNF-α expression in recipient serum. Twenty weeks after transplantation, the electrophysiological test results of CMAP, NCV, and NF200 neurofilament protein fluorescent staining in the SM and SH groups were superior to those in the NC and fresh groups. These findings indicate that Sini Decoction offers protective benefits in the cryopreservation of rats' sciatic nerves and holds significant potential for the in vitro preservation of tissue and organs.
Animals ; Apoptosis/drug effects* ; Rats ; Oxidative Stress/drug effects* ; Sciatic Nerve/cytology* ; Cryopreservation ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Protective Agents/pharmacology*

Icariin is a pure compound derived from Epimedium brevicornu Maxim, and it helps the regulation of male reproduction. Nevertheless, the role and underlying mechanisms of Icariin in mediating male germ cell development remain to be clarified. Here, we have demonstrated that Icariin promoted proliferation and DNA synthesis of mouse spermatogonial stem cells (SSCs). Furthermore, surface plasmon resonance iron (SPRi) and molecular docking (MOE) assays revealed that phosphodiesterase 5A (PDE5A) was an important target of Icariin in mouse SSCs. Mechanically, Icariin decreased the expression level of PDE5A. Interestingly, hydrogen peroxides (H 2 O 2 ) enhanced the expression level of phosphorylation H2A.X (p-H2A.X), whereas Icariin diminished the expression level of p-H2A.X and DNA damage caused by H 2 O 2 in mouse SSCs. Finally, our in vivo animal study indicated that Icariin protected male reproduction. Collectively, these results implicate that Icariin targets PDE5A to regulate mouse SSC viability and DNA damage and improves male reproductive capacity. This study thus sheds new insights into molecular mechanisms underlying the fate decisions of mammalian SSCs and offers a scientific basis for the clinical application of Icariin in male reproduction.
Male ; Animals ; Flavonoids/pharmacology* ; Mice ; Cyclic Nucleotide Phosphodiesterases, Type 5/drug effects* ; DNA Damage/drug effects* ; Cell Survival/drug effects* ; Cell Proliferation/drug effects* ; Spermatogonia/drug effects* ; Reproduction/drug effects* ; Adult Germline Stem Cells/metabolism* ; DNA Replication/drug effects*

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

OBJECTIVES: To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study. METHODS: The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP. RESULTS: The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001). CONCLUSIONS Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans ; Helicobacter Infections/complications* ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Child ; Male ; Female ; Helicobacter pylori ; Prognosis ; Child, Preschool ; Logistic Models ; Retrospective Studies ; Risk Factors ; Polymorphism, Single Nucleotide ; Adolescent ; Infant

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To investigate the Wnt signaling pathway and miRNAs mechanism of extracts of Plastrum Testudinis (PT) in the treatment of osteoporosis (OP). METHODS: Thirty female Sprague Dawley rats were randomly divided into 5 groups by random number table method, including sham group, ovariectomized group (OVX), ovariectomized groups treated with high-, medium-, and low-dose PT (160, 80, 40 mg/kg per day, respectively), with 6 rats in each group. Except for the sham group, the other rats underwent bilateral ovariectomy to simulate OP and received PT by oral gavage for 10 consecutive weeks. After treatment, bone mineral density was measured by dual-energy X-ray absorptiometry; bone microstructure was analyzed by micro-computed tomography and hematoxylin and eosin staining; and the expressions of osteogenic differentiation-related factors were detected by immunochemistry, Western blot, and quantitative polymerase chain reaction. In addition, Dickkopf-1 (Dkk-1) was used to inhibit the Wnt signaling pathway in bone marrow mesenchymal stem cells (BMSCs) and miRNA overexpression was used to evaluate the effect of miR-214 on the osteogenic differentiation of BMSCs. Subsequently, PT extract was used to rescue the effects of Dkk-1 and miR-214, and its impacts on the osteogenic differentiation-related factors of BMSCs were evaluated. RESULTS: PT-M and PT-L significantly reduced the weight gain in OVX rats (P<0.05). PT also regulated the bone mass and bone microarchitecture of the femur in OVX rats, and increased the expressions of bone formation-related factors including alkaline phosphatase, bone morphogenetic protein type 2, collagen type I alpha 1, and runt-related transcription factor 2 when compared with the OVX group (P<0.05 or P<0.01). Meanwhile, different doses of PT significantly rescued the inhibition of Wnt signaling pathway-related factors in OVX rats, and increased the mRNA or protein expressions of Wnt3a, β-catenin, glycogen synthase kinase-3β, and low-density lipoprotein receptor-related protein 5 (P<0.05 or P<0.01). PT stimulated the osteogenic differentiation of BMSCs inhibited by Dkk-1 and activated the Wnt signaling pathway. In addition, the expression of miR-214 was decreased in OVX rats (P<0.01), and it was negatively correlated with the osteogenic differentiation of BMSCs (P<0.01). MiR-214 mimic inhibited Wnt signaling pathway in BMSCs (P<0.05 or P<0.01). Conversely, PT effectively counteracted the effect of miR-214 mimic, thereby activating the Wnt signaling pathway and stimulating osteogenic differentiation in BMSCs (P<0.05 or P<0.01). CONCLUSION PT stimulates bone formation in OVX rats through β-catenin-mediated Wnt signaling pathway, which may be related to inhibiting miR-214 in BMSCs.
Animals ; MicroRNAs/genetics* ; Female ; Rats, Sprague-Dawley ; Wnt Signaling Pathway/genetics* ; Osteogenesis/genetics* ; Mesenchymal Stem Cells/cytology* ; Cell Differentiation/drug effects* ; Bone Density/drug effects* ; Ovariectomy ; Osteoporosis/drug therapy* ; beta Catenin/metabolism* ; Rats ; Intercellular Signaling Peptides and Proteins/metabolism* ; Drugs, Chinese Herbal/pharmacology*