ObjectiveTo study the effect of Bufei Tongbi decoction on pulmonary fibrosis in diabetic rats via the transforming growth factor-β₁ （TGF-β₁）/phosphorylated Smad family member 3 （p-Smad3） signaling pathway. MethodsStreptozotocin （60 mg·kg^-1） and bleomycin （24.80 U·kg^-1） were used to prepare the rat model of diabetes with pulmonary fibrosis by intratracheal injection. Sixty rats were randomly assigned into blank， model， low-， medium-， and high-dose （3.98， 7.95， and 15.90 g·kg^-1， respectively） Bufei Tongbi decoction， and pirfenidone （0.36 mg·kg^-1） groups （n=10）. The successfully modeled rats in each group were administrated with corresponding agents once per day for four consecutive weeks. After drug administration， fasting blood glucose and lung function indicators were measured. Chemical immunoassay was employed to determine the serum levels of hydroxyproline （Hyp）， hyaluronic acid （HA）， and laminin （LN）. The lung index was determined by the wet and dry methods. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining， and the degree of fibrosis was detected by Masson staining. The mRNA and protein levels of TGF-β₁， p-Smad3， Smad3， α-smooth muscle actin （α-SMA）， collagen type Ⅰ alpha 1 （Col1A1）， and fibronectin were determined by PCR and Western blotting， respectively. ResultsCompared with the blank group， the model group showed alveolar septa thickening， obvious thickening of the basement membrane of pulmonary blood vessels， severe destruction of the alveolar structure， structural disarrangement of the lung parenchyma， and an increase in the proportion of inflammatory cell infiltration in the lung tissue， together with a large amount of blue collagen deposition and a large amount of collagen fibroplasia in the bronchial wall， vessel wall， interstitium， and alveolar wall， which indicated severe fibrosis. Bufei Tongbi decoction groups and the pirfenidone group showed lower fasting blood glucose level （P<0.05） and higher forced vital capacity （FVC）， cytoplasmic dynein （Cydn）， FEV_0.3/FEV ratio， and lung index （P<0.05） than the model group. Moreover， these groups demonstrated alleviated lung fibrosis， elevated Hyp， HA， and LN levels， down-regulated mRNA levels of α-SMA， Col1A1， and fibronectin， and down-regulated protein levels of TGF-β₁， Smad3， p-Smad3， α-SMA， Col1A1， and fibronectin （P<0.05）. ConclusionBufei Tongbi decoction can inhibit pulmonary fibrosis in diabetic rats by inhibiting the TGF-β₁/p-Smad3 signaling pathway.

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

With advancements in radiology,endoscopic techniques,surgical treatments,cell biology and molecular biology,the un-derstanding of temporomandibular disorders(TMD)has increased.The temporomandibular joint(TMJ)is a complex structure comprising both soft and hard tissues.Within the TMJ,the temporomandibular disc is a soft tissue structure that connects the mandible to the skull,providing cushioning and stability during joint movement.Different imaging techniques have their own advantages and limi-tations in the diagnosis and treatment of TMD.Therefore,using image registration technology to assess the condition and position of the articular disc provides new research perspectives for evaluating TMD,which may contribute to the diagnosis and treatment.This article reviews the latest advancements in TMJ imaging,explores the applications of various image registration techniques,particularly in the context of TMD diagnosis and treatment,and discusses future prospects.Combining the research results of some scholars at home and a-broad with the author’s clinical experience,the article aims to provide valuable insights for clinicians.

Objective To investigate the nutritional status of children with cystic fibrosis(CF)and understand the correlation between malnutrition and clinical characteristics as well as lung function.Methods A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023.Clinical characteristics of CF children with different nutritional statuses were compared,and the correlation between malnutrition and lung function was analyzed.Results A total of 52 CF children were included,comprising 25 boys(48％)and 27 girls(52％),aged between 7 months and 17 years.Respiratory symptoms were the predominant clinical manifestations(96％,50/52).The prevalence of malnutrition was 65％(34/52),with moderate/severe malnutrition being the most common(65％,22/34).The malnutrition group had a longer duration of illness,higher proportion of digestive system symptoms,and lower levels of serum albumin(P＜0.05).Pulmonary function parameters,including forced expiratory volume in one second as a percentage of the predicted value,ratio of forced expiratory volume in one second to forced vital capacity,forced expiratory flow at 25％of forced vital capacity exhaled,forced expiratory flow at 50％of forced vital capacity exhaled,forced expiratory flow at 75％of forced vital capacity exhaled,and maximum mid-expiratory flow as a percentage of the predicted value,were lower in the malnutrition group compared to the normal nutrition group(P＜0.05).Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters(P＜0.05).Conclusions The prevalence of malnutrition is high in CF children and is associated with decreased lung function.CF children with higher body mass index have better lung function.Therefore,screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.[Chinese Journal of Contemporary Pediatrics,2024,26(3):275-281]

Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P＜0.01),and the E2 level was significantly decreased(P＜0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P＞0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P＜0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P＜0.05),had no difference with the blank group(P＞0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P＜0.01),still being lower than the blank group(P＜0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P＞0.05),while the protein expression level of P450arom was lower than that in the model group(P＜0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P＜0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P＜0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P＜0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P＜0.05 or P＜0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L