Patient 1, a 3-year-6-month-old male, presented with feeding difficulties and delayed motor development. He exhibited poor responsiveness at birth, weak crying, intellectual and motor delays, low immunity, recurrent respiratory infections, hypotonia of the limbs, and distinctive facial features (low-set ears, double chin, and high arched palate), as well as a single transverse palmar crease on the right hand. Genetic testing revealed a c.1096C>T heterozygous variant in the SMARCB1 gene. Patient 2, a 3-year-old male, presented with developmental delay and distinctive facial features. Genetic testing identified the same pathogenic mutation as in Patient 1. The two patients are unrelated, and clinical phenotyping and genetic testing confirmed both cases as Coffin-Siris syndrome type 3. Coffin-Siris syndrome is a rare genetic disorder, and early genetic testing can aid in diagnosis.
Child, Preschool ; Humans ; Male ; Abnormalities, Multiple/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Ear/abnormalities* ; Face/abnormalities* ; Hand Deformities, Congenital/genetics* ; Intellectual Disability/genetics* ; Micrognathism/genetics* ; Mutation ; Neck/abnormalities*

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

Objective:To analyze the human immunodeficiency virus (HIV) screening status and the resulting residual risk (RR) among blood donors across 17 provincial blood centers in China.Methods:This study used a cross-sectional study. Data on HIV infection markers per 100 000 first-time donors (FD) and repeat donors (RD) from January 2015 to December 2024 were extracted from the National Blood Establishment Performance Comparison Information Management System. Questionnaires were used to collect each center′s HIV screening strategy, algorithm, serological test (ST) kit manufacturers, gray-zone setting for ST, and nucleic acid test (NAT) modality, method, and platform. The incidence-window-period model was used to calculate the residual risk for first-time donors (RR FD), repeat donors (RR RD), and total donors (RR TD) at each center. Horizontal and vertical analysis of RR FD, RR RD, and RR TD across centers and years were performed. Results:All 17 centers applied the same HIV screening strategy which was two rounds of ST followed by one round of NAT. Eight of them operated a single screening algorithm, six employed two algorithms and three used three. Eleven centers used both imported and domestic ST kits, five relied on domestic ST kits only, and one used imported ST kits only, while four centers never set a grey zone for ST throughout the decade. For NAT modalities, eight centers adopted both individual nucleic acid test (ID-NAT) and minipool nucleic acid test (MP-NAT), eight used MP-NAT only and one used ID-NAT only. Seven centers combined transcription mediated amplification (TMA) and polymerase chain reaction (PCR), nine used PCR only and one used TMA only, and fourteen centers ran both imported and domestic NAT systems, two used imported systems only and one used a domestic system only. Over the ten-year period, the mean RR FD across the centers ranged from 2.22 to 12.33 per 10 6 person-years, RR RD from 0.83 to 3.29 per 10 6 person-years and RR TD from 1.59 to 9.29 per 10 6 person-years, with center Z4 consistently showing the lowest values for all three metrics and center U4 recording the highest RR FD and RR TD, while center D2 had the highest RR RD. In 2024 compared with 2015, eleven centers achieved a lower RR FD and ten centers achieved lower RR RD and RR TD. The RR FD and RR TD of centers W2 and U4 displayed pronounced fluctuations and an upward trend in recent years. Conclusions:The 17 provincial blood centers maintain consistent HIV screening strategies, while demonstrating variations in screening algorithm, ST kit manufacturers, NAT modalities, methods, and platform. And the RR FD, RR RD, and RR TD differ across centers. Although most centers show declining trend in RR over the ten-year period, some centers exhibite data fluctuations with a rising trend, suggesting potential for further optimization of HIV screening protocols.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.