This study investigated the mechanism by which Jianpi Bushen Yiqi Decoction promotes acetylcholine receptor(AChR) clustering in myasthenia gravis through the Agrin/low-density lipoprotein receptor-related protein 4(LRP4)/muscle-specific receptor tyrosine kinases(MuSK) signaling pathway. A total of 114 female C57BL/6J mice were divided into the normal group, modeling group, and solvent control group. The normal group and the solvent control group were immunized with phosphate-buffered saline(PBS), while the modeling group was established as an experimental autoimmune myasthenia gravis(EAMG) model using the murine-derived AChR-α subunit R97-116 peptide fragment. After successful modeling, the mice were randomly assigned to the model group, the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups, and the prednisone group. After four weeks of continuous treatment, muscle strength was assessed using Lennon scores and grip strength tests. Immunofluorescence staining was conducted on differentiated C2C12 myotubes incubated with a drug-containing serum to observe the number of AChR clusters. The integrity of AChR on myofilaments in mouse gastrocnemius muscles was further assessed by immunofluorescence staining. Hematoxylin-Eosin(HE)staining was applied to examine pathological changes in the gastrocnemius muscles of EAMG mice treated with Jianpi Bushen Yiqi Decoction. Western blot was utilized to detect the expression of key proteins in the Agrin/LRP4/MuSK signaling pathway in both C2C12 myotubes and mouse gastrocnemius muscles. The results demonstrated that compared to the model group, the prednisone group exhibited a significant decrease in the body weights of mice, whereas no significant differences in the body weights of mice were observed among the low-, medium-, and high-dose Jianpi Bushen Yiqi Decoction groups. All treatment groups showed significantly improved grip strength and Lennon scores. Additionally, the formula promoted AChR clustering on myotubes and enhanced AChR integrity in gastrocnemius myofilaments and reduced inflammatory infiltration between muscle tissue and fibrous hyperplasia. Furthermore, Jianpi Bushen Yiqi Decoction upregulated the protein expression of AChRα1, Agrin, and p-MuSK in C2C12 myotubes and increased the protein expression of AChRα1, Agrin, MuSK, p-MuSK, LRP4, and docking protein 7(Dok-7)in gastrocnemius tissue. In conclusion, Jianpi Bushen Yiqi Decoction may promote AChR clustering by targeting key proteins in the Agrin/LRP4/MuSK signaling pathway, thereby improving neuromuscular junction function and enhancing muscle strength.
Animals ; Agrin/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Receptors, Cholinergic/genetics* ; Female ; Mice, Inbred C57BL ; Receptor Protein-Tyrosine Kinases/genetics* ; Neuromuscular Junction/metabolism* ; Myasthenia Gravis, Autoimmune, Experimental/physiopathology* ; Humans ; LDL-Receptor Related Proteins

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

OBJECTIVE: To explore the clinical characteristics, therapeutic responses and prognostic features of E2A-PBX1 fusion gene for childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 837 pediatric patients with ALL who were initially diagnosed in our hospital from July 2010 to November 2017 were retrospectively analyzed, 48 children with positive E2A-PBX1 fusion gene were detected by the real-time quantitative PCR techniques and their data were retrospectively collected for analysis. RESULTS: Among 48 cases with positive E2A-PBX1 fusion gene, there were 26 males and 22 females, with onset ages ranging from 9 months to 13 years old. There were 2 cases (4.2%) in the low-risk group, 32 cases (66.7%) in the intermediate-risk group, and 14 cases (29.1%) in the high-risk group at initial diagnosis. The white blood cell (WBC) counts of 25 cases (53.2%) at initial diagnosis were <50×10⁹/L, 11 cases (23.4%) were (50-100)×10⁹/L, and 11 cases (23.4%) ≥100×10⁹/L. The main immunophenotype was common-B ALL (44 cases, 91.7%). Other leukemia fusion genes such as BCR-ABL1, MLL-AF4, and TEL-AML1 were not observed in this cohort of patients. All patients received the treatment of NPCLC-ALL2008 protocol, and 5 cases (10.4%) occurred poor prednisone response. All the 48 cases achieved complete remission (CR) after the induction treatments. The last follow-up date was April 30, 2023. A total of 5 children relapsed, including 1 case with intermediate risk and 4 cases with high risk. The recurrence rate in the high-risk group was significantly higher than that in the intermediate- and low-risk groups (both P < 0.05). Most relapsed children had elevated WBC counts at initial diagnosis. Among them, WBC counts ≥100×10⁹/L was observed in 4 cases. The recurrence rate among children with WBC counts ≥100×10⁹/L was significantly higher than that with WBC counts <100×10⁹/L (P < 0.01). Four deaths occurred in this cohort, of which 3 died of leukemia recurrence. The 10-year event-free survival rate and 10-year overall survival rate of the 48 children with positive E2A-PBX1 fusion gene were 87.5%±4.8% and 91.7%±4.0%, respectively. CONCLUSION In ALL children with positive E2A-PBX1 fusion gene, those with elevated WBC counts and high risk stratification at initial diagnosis are more likely to experience recurrence. Recurrence is the main cause of death in this group. It is suggested that such kind of children receive more intensive chemotherapy or undergo hematopoietic stem cell transplantation as early as possible to further improve prognosis.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Oncogene Proteins, Fusion/genetics* ; Prognosis ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Retrospective Studies ; Infant ; Homeodomain Proteins

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Hypertensive nephropathy is one of the common chronic kidney diseases in China,the morbidity and mortality are increasing year by year,which seriously endangers the physical and mental health of patients.Traditional Chinese medicine believes that human is an organic whole,the five viscera and six organs are closely related in physiology and pathology,based on the theory of"holistic concept",the application of Chinese medicine in the treatment of hypertensive nephropathy can effectively improve kidney function and reduce the occurrence of adverse reactions.Therefore,based on the theory of"five viscera in one",this paper summarizes the etiology and pathogenesis of hypertensive nephropathy and the treatment of hypertensive nephropathy from the five aspects of liver,heart,spleen,lung and kidney,aiming to provide new ideas for the prevention and treatment of kidney disease by traditional Chinese medicine.

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway plays a crucial role in the regulation of renal fibrosis by participating in inflammatory response,oxidative stress and autophagy.Paeoniflorin exhibits remarkable efficacy in treating myocardial and liver fibrosis.This article provides a comprehensive review on the research progress of paeoniflora in preventing and treating renal fibrosis through modulation of the PI3K/Akt/mTOR signaling pathway,offering novel insights for traditional Chinese medicine-based approaches to prevent and treat renal fibrosis.

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Pregnancy complicated with acute myeloid leukemia is uncommon,requiring the collaborative management by specialists from departments of hematology,obstetrics,anesthesiology,and neonatology for both the parturient and the neonate.This article reports an anesthesic management process of a parturient woman with acute myeloid leukemia and reviews relevant literature published in recent years to systematically summarize the approach for anesthesia-related perinatal management of such patients.
Humans ; Female ; Pregnancy ; Leukemia, Myeloid, Acute/complications* ; Pregnancy Complications, Neoplastic ; Adult ; Anesthesia, Obstetrical/methods*

Objective To investigate the characteristics of attentional bias towards cancer-related stimuli in breast cancer patients with fear of cancer recurrence(FCR)under subthreshold and suprathreshold stimulus conditions.Methods A total of 94 female breast cancer patients admitted in First Affiliated Hospital of Army Medical University from September 2022 to March 2023 were recruited to complete the Fear of Cancer Recurrence Inventory-Short Form(FCRI-SF)and the dot-probe task.According to the FCRI-SF cut-off score of 13,they were divided into clinical and non-clinical FCR groups,with 47 cases in each group.One-sample t-test and repeated-measures ANOVA were used to statistically analyze the subjects in the 2 groups in terms of attentional bias score,attentional orienting score and attentional disengagement difficulty score.Results The patients in the clinical FCR group showed a significant attentional bias toward cancer-related negative words(P<0.05).Under the subthreshold stimulus condition,its main component was attentional orienting to cancer-related negative words(P<0.05).In the suprathreshold stimulus condition,the main components were attentional orienting to neutral words matched by cancer-related negative words and difficulty in attentional disengagement from cancer-related negative words as well as attentional avoidance for cancer-related positive words(P<0.05).Conclusion Breast cancer patients with clinical FCR have an attentional bias toward cancer-related negative stimuli.Reducing their attention to cancer-related negative stimuli may be an effective measure to reduce FCR level in the patients.