Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To investigate the prevalence and risk factors of overweight and obesity among Chinese children aged 3-18 years from 11 provinces, antonomous regions, or municipalities.Methods:This national cross-sectional community health survey utilized a multistage stratified cluster-random sampling method to recruit 193 997 nationally representative participants from 11 provinces, autonomous regions, or municipalities between January 2017 and December 2019. All participants underwent physical examinations, and their caregivers completed questionnaires assessing participants′ dietary, lifestyle, familial, and perinatal information. Multilevel multinomial logistic regression models were employed to identify the potential risk factors.Results:The cohort comprised 193 997 children (102 178 boys, 91 819 girls),aged (10±4) years. Overall prevalence rates were 30 574(15.8%)overweight children and 17 217(8.9%) obesity children. Boys exhibited higher overweight and obesity rates than girls (17.0% (17 368/102 178) vs. 14.4% (13 206/102 178), 11.3% (11 553/91 819) vs. 6.2% (5 664/91 819), χ2=249.12,1 578.69,both P<0.001). The detection rates of obesity in Tanner stage 2 and 3 were the highest in boys and girls, with 13.4%(2 231/16 665) and 8.6%(880/10 221) respectively. Risk factors for obesity included parental overweight (paternal OR=2.34 and maternal OR=2.29), annual household income of 100 000-200 000 yuan (compared with<100 000 yuan, OR=1.04), higher paternal education (compared with below high school,high school and a college education OR=1.09,1.14), birth weight >4.0 kg (≤5 and>5 years old OR=1.74, 1.44,respectively), and western food consumption≥1 time/month (compared with<1, 1-2, 3-4,>4 times/month OR=1.36, 1.30, 1.67(≤5 years), 1.19, 1.16, 1.15 (>5 years), respectively) (all P<0.05). Conversely, coarse grain intake≥1 times/week (compared with<1 times/week, every day, 3-4, 1-2 times/week OR=0.74, 0.80, 0.71 (≤5 years), 0.75, 0.87, 0.90(>5 years), respectively, all P<0.05) was associated with reduced obesity risk. Conclusions:Obesity epidemiology in children demonstrates significant heterogeneity across age, gender, geographic regions, and pubertal stages. It is necessary to establish a personalized prevention and control strategy.

Objective:Exploring the effect of radiofrequency ablation treatment to restore sinus rhythm on the improvement of functional mitral regurgitation (FMR) and cardiac structure in patients with atrial fibrillation combined with moderate or severe FMR, compared with drug therapy alone.Methods:This retrospective cohort study consecutively enrolled patients diagnosed with persistent atrial fibrillation and moderate or severe FMR who were admitted to the Third Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2021. Forty-eight patients who were treated with radiofrequency ablation and maintained sinus rhythm were enrolled in the ablation group, and 63 patients who were treated with medication alone during the same period were in the medicine group. Patients in the ablation group and medicine group were matched in a 1∶1 ratio using a propensity score, and 41 patients were finally included in each of the 2 groups. All patients reexamined echocardiography after 3-month of treatment. The proportion of patients with FMR improvement and the differences in changes of cardiac structural and functional parameters were compared between groups.Results:After propensity score matching, the ablation group was aged (69.3±7.1) years with 21 males (51.2%) and the medicine group was aged (71.3±9.4) years with 21 males (51.2%). The echocardiography after 3-month of treatment showed the rate of FMR improvement was significantly higher in the ablation group than in the medicine group (19 (46.3%) vs. 33 (80.5%), P<0.001), and patients in the ablation group showed a significant decrease in FMR extent (Δmitral regurgitation area: (-1.30±2.64) cm 2 vs. (-3.55±2.50) cm 2, P<0.001), left atrial size (Δleft atrial diameter: (-0.17±3.78) mm vs. (-2.46±4.01) mm, P=0.009) and E/e′ (ΔE/e′:-2.54±7.34 vs.-6.34±7.08, P=0.021) compared with the medicine group. There was also a significant decrease in left ventricular size (Δleft ventricular end diastolic diameter: (-3.12±6.62) mm vs. (-0.73±3.62) mm, P=0.046) and significant increase in left ventricular ejection fraction (Δleft ventricular ejection fraction: (2.73±9.69) % vs. (-0.93±5.41) %, P=0.038) in ablation group. Conclusion:Performing radiofrequency ablation to restore sinus rhythm can effectively reduce the severity of mitral regurgitation and improve left atrial and left ventricular remodeling and cardiac function in patients with atrial fibrillation and FMR.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Glutaricacidemia type 1(GA1) is an autosomal recessive disease caused by reduced or missing glutaryl-CoA dehydrogenase activity which hamps metabolism of lysine, hydroxylysine and tryptophan. The catabolic products of glutarylcarnitine and glutaric acid are abnormally accumulated in the body, resulting in metabolic disorders which primarily lead to damage to the nervous system. Clinical manifestations of patients include macrocephaly, dystonia, dyskinesia, and developmental retardation. Acute encephalopathy may be induced in infants and young children due to infection, vaccination and surgery. For GA1 is a rare disease and its clinical manifestations are similar to other neurological diseases, it may be easily missed or misdiagnosed. To facilitate early diagnosis and treatment and improve the prognosis, this consensus was formulated by pediatric experts from the fields of endocrinology and genetic metabolism through full discussion and reference to the latest literature and guidelines home and abroad.