Primordial dwarfism (PD) refers to a group of monogenic genetic disorders characterized by intrauterine growth restriction (IUGR) and severe, persistent postnatal growth retardation. These diseases have been associated with variants of multiple genes whose products are mainly involved in critical cellular biological processes such as maintenance of genomic stability, DNA damage repair, mRNA splicing regulation, and centrosome function. Variants of such genes can directly impair cell proliferation and developmental potential. With the widespread application of molecular genetic technologies such as high-throughput sequencing, significant progress has been made in the research of PD. This article focuses on the major subtypes of PD, including Seckel syndrome, Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, MOPD type II, and Meier-Gorlin syndrome. It has systematically summarized the advances in their clinical phenotypic characteristics, pathogenic genes, and molecular mechanisms, with an aim to deepen the understanding of the essence of growth disorders associated with PD.
Humans ; Dwarfism/genetics* ; Microcephaly/genetics* ; Phenotype ; Fetal Growth Retardation/genetics* ; Osteochondrodysplasias/genetics* ; Growth Disorders ; Micrognathism ; Patella/abnormalities* ; Congenital Microtia

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.

ObjectiveTo evaluate the methodological quality and reporting quality of published guidelines/consensuses on traditional Chinese medicine （TCM）/integrated traditional Chinese and Western medicine diagnosis and treatment of nonalcoholic fatty liver disease （NAFLD）， and to provide a basis for formulating guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD in the future. MethodsDatabases including PubMed， Embase， Web of Science， CNKI， Wanfang Data， and CBM and the websites of China Association of Chinese Medicine and China Association of Integrative Medicine were searched for related articles published up to September 1， 2024. Two clinical researchers independently assessed the methodological quality and reporting quality of the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD by using Appraisal of Guidelines for Research and Evaluation Ⅱ （AGREE Ⅱ） and Reporting Items for Practice Guidelines in Healthcare （RIGHT）. ResultsA total of nine guidelines/consensuses were included after literature screening， with four guidelines and five expert consensuses. The scores of different domains assessed by AGREE Ⅱ for the nine guidelines/consensuses were as follows： scope and purpose （47.1%）， stakeholder involvement （41.0%）， rigor of development （21.6%）， clarity of presentation （40.2%）， applicability （19.0%）， and editorial independence （19.6%）. The recommendation level of the articles was B level （recommended after revision） for four articles and C level （not recommended） for five articles. The RIGHT assessment showed high reporting rates for “Basic Information” and “Background”， while other areas needed to be improved. Currently， there was no international standard for the guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and the quality of these guidelines/consensuses needed to be enhanced to ensure comprehensiveness and credibility. ConclusionThere is still potential for improving the quality of guidelines/consensuses on TCM/integrated traditional Chinese and Western medicine diagnosis and treatment of NAFLD， and AGREE Ⅱ and RIGHT checklists should be strictly followed to ensure the fairness， scientific rigor， and transparency of these guidelines/consensuses.

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

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 evaluate the clinical efficacy of Traditional Chinese Medicine （TCM）external treatment methods in alleviating skin pruritus caused by eczema through a Meta-analysis. Methods Randomized clinical trials investigating the use of TCM external treatment methods for skin pruritus caused by eczema were searched in databases including China National Knowledge Infrastructure （CNKI）, VIP, Wanfang, Sinomed, PubMed, Embase, LILACS, and Cochrane, up to December 2024. Two reviewers independently screened and entered the statistical data, conducted bias risk assessment by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0, and performed Meta-analysis using RevMan 5.4.1. Results Ultimately, 14 studies involving 1 788 patients were included. Compared to the control group, TCM external treatment methods （treatment group）showed better improvement in pruritus scores （Z=11.88, P<0.000 01）, better improvement in Eczema Area and Severity Index （EASI） scores （Z=23.15, P<0.000 01）, higher overall clinical efficacy rate （Z=6.21, P<0.000 01）, better improvement in TCM symptoms （Z=5.49, P<0.000 01）, and lower clinical recurrence rate （Z=2.88, P=0.004）. Three of the included studies mentioned adverse reactions, with the treatment group showing lower adverse reactions than the control group. Conclusion The external treatment of TCM was more effective in treating skin pruritus caused by eczema compared to the control group. Given the biases and heterogeneity in the included literature, this conclusion needs to be further substantiated by more large-scale, multi-center, randomized, controlled, and double-blind studies.

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: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:To understand the genomic characteristics and evolutionary trends of three coxsackievirus (CV) subtypes, including CV-A2, CV-A4 and CV-A5, in Suzhou city.Methods:Totally 248 samples were collected during routine monitoring for hand, foot, and mouth disease in Suzhou city from January to June in 2022. The specimens were detected for CV genotypes using Real-time fluorescence-reverse transcription polymerase chain reaction (Real-time RT-PCR). The CV positive samples were sequenced using the Miseq high-throughput sequencing platform. After obtaining the whole genome sequences of CV strains, homology analysis was performed. An evolutionary tree was constructed using molecular evolutionary genetics analysis (MEGA) X. Sequence recombination regions were analyzed using SimPlot and BootScan.Results:During routine monitoring for hand, foot and mouth disease in Suzhou city from January to June in 2022, one strain each of CV-A2, CV-A4, and CV-A5 viruses were identified, and their complete genomes were sequenced. CV-A2 and CV-A4 were clustered with the current prevalent strains in China, and no new amino acid site mutations were found in the whole genome of CV-A2; CV-A4 had several new amino acid site mutations in the non-structural region compared with the prototype strain; CV-A5 belonged to the C1 subgenotype 3 lineage, and the genome of CV-A5 had several new amino acid mutation sites in the non-structural protein region and underwent recombination.Conclusions:The CV-A2 and CV-A4 strains are stable epidemic strains, the CV-A5 strain is recombinant strain in Suzhou city.

Objective:To compare the characteristics of cerebrospinal fluid (CSF) oligoclonal band electrophoresis examination results between patients with multiple sclerosis (MS) and Guillain-Barré syndrome (GBS), and to provide a basis for the differential diagnosis of the two types of neurological demyelinating diseases.Methods:Case analysis.The retrospective study method was used, and the patients who visited Beijing Tiantan Hospital, Capital Medical University from January 2020 to August 2023 were selected as the research subjects, including 70 MS patients[19 males and 51 females, aged 34 (28, 44) years] and 70 GBS patients [44 males and 26 females, aged 50 (36, 61) years]. The oligoclonal band electrophoresis and immunoglobulin G(IgG) index (IgG I) were performed on the clinical specimens from MS and GBS patients, and CSF routine, CSF biochemistry (glucose, chloride, protein), lactate, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), antibodies to herpes simplex virus (HSV), cytomegalovirus (CMV), rubella virus (RV), toxoplasma gondii (TOX), Epstein-Barr virus (EBV), and coxsackievirus were detected simultaneously. The enumeration data were treated with the chi-square test. The measurement data didn′t accord with normal distribution, and were treated with the Mann-Whitney U test. Results:The positive rate of oligoclonal band (OCB) electrophoresis in MS and GBS patients were 80.00% (56/70) and 4.29% (3/70), respectively. The positive rate in MS patients was significantly higher than that in GBS patients (χ 2=82.289, P<0.001). The white blood cells count [5.50 (3.00, 11.00)/μl] and the level of chlorine [127 (125, 128) mmol/L] in CSF of MS patients was higher than that of GBS patients [3.50(2.00, 7.00)/μl, 126(124, 128) mmol/L] ( U=-2.245, P<0.05; U=-2.028, P<0.05), while the levels of CSF protein [33.40(27.61, 39.17)mg/L], glucose [3.59(3.36, 3.88) mmol/L], and lactate [1.55(1.40, 1.73) mmol/L] of MS patients were lower than those of GBS patients [6.71(43.78, 138.30) mg/L, 3.97(3.55, 4.54) mmol/L, 1.80(1.60, 2.00) mmol/L]( U=-6.747, P<0.001; U=-3.651, P<0.001; U=-4.531, P<0.001). The levels of IL-6 [3.36(2.34, 5.02) pg/ml], IL-8 [55.40(46.75, 66.40) pg/ml], and TNF-α [5.63(4.25, 6.63) pg/ml] in CSF of MS patients were lower than those of GBS patients [6.12(3.61, 11.73) pg/ml, 120.00(74.90, 187.80) pg/ml, 6.57(5.25, 8.03) pg/ml]( U=-3.463, P<0.05; U=-5.225, P<0.001; U=-2.785, P<0.05). The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were 36.36% (24/66), 0 and 0, respectively,and the positive rates of those of GBS patients were 85.71% (54/63), 30.16% (19/63), and 19.05% (12/63), respectively. The positive rates of CMV IgG, TOX IgG, and EBVCA IgG in CSF of MS patients were significantly lower than those of GBS patients (χ 2=32.839, P<0.001; χ 2=23.343, P<0.001; χ 2=13.861, P<0.001). Conclusions:The MS patients mainly showed the higher positive rates of OCB. The GBS patients showed elevated CSF protein levels but no significant increase in white blood cell count, namely albuminocytologic dissociation in CSF. Meanwhile, the GBS patients showed elevated levels of intrathecal immunity and inflammation indicators, and a higher positive rate of pathogen antibodies.