OBJECTIVE: To investigate the genetic etiology of a fetus diagnosed with Mandibulofacial dysostosis with microcephaly (MFDM). METHODS: A fetus that underwent prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, on May 19, 2025 was selected for analysis. Results of fetal ultrasound findings, chromosomal karyotyping, copy number variation sequencing (CNV-seq), and whole-exome sequencing (WES) were collected. Sanger sequencing was performed for familial validation of the pathogenic variant. The Human Protein Atlas (HPA), STRING, and Simple ClinVar databases were queried to characterize the biological features of the candidate gene. Three-dimensional structures of the wild-type and variant proteins were modeled and analyzed, and the evolutionary conservation of the affected amino acid was assessed using UGENE. Prenatal phenotypes associated with EFTUD2 variants were summarized through a review of the literature. This study was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Ethics No.: 2025-KY-029-01). RESULTS: At 23⁺² weeks of gestation, ultrasound examination revealed bilateral microtia with low-set ears, mild micrognathia with a reduced mandibular-facial angle, a single umbilical artery, a slightly narrow aortic diameter, and trivial mitral regurgitation. Amniotic fluid karyotyping and CNV-seq showed no abnormalities. WES identified a de novo, previously unreported EFTUD2 variant, c.698dupA (p.V235Gfs*27), in the fetus. This frameshift variant is predicted to alter the structural integrity of the EFTUD2 protein. Literature review indicated that micrognathia and microtia or low-set ears are the most common sonographic features in fetuses with EFTUD2 variants, while secondary findings may include abnormal stomach bubble, cleft palate, single umbilical artery, gastrointestinal atresia, polyhydramnios, and reduced aortic diameter. CONCLUSION The EFTUD2: c.698dupA (p.V235Gfs*27) variant is likely the genetic cause underlying MFDM in this fetus.
Humans ; Mandibulofacial Dysostosis/diagnostic imaging* ; Microcephaly/diagnostic imaging* ; Female ; Pregnancy ; Ribonucleoprotein, U5 Small Nuclear/chemistry* ; Peptide Elongation Factors/chemistry* ; Fetus ; DNA Copy Number Variations/genetics* ; Adult ; Ultrasonography, Prenatal

OBJECTIVE To investigate the requirements for infusion sets specified in the package inserts of monoclonal antibody drugs commonly used for intravenous infusion in China， and to provide a reference for the rational selection of infusion sets for this class of drugs in clinical practice. METHODS The “Drug Query” section of the official website of the National Medical Products Administration， including the “Domestically Manufactured Drugs” and “Overseas Manufactured Drugs” databases， as well as the DXY “Yongyao Zhushou” database， were searched to collect the package inserts of monoclonal antibody drugs available on the domestic market as of November 2025 that had requirements for intravenous infusion sets. Relevant requirements for infusion set materials， filter pore size， and filter materials were extracted， classified， and analyzed. RESULTS A total of 55 monoclonal antibody drugs for intravenous infusion were included， comprising 45 anticancer drugs （81.82%）， 5 immunomodulatory drugs （9.09%）， and 5 drugs for other diseases （9.09%）. The package inserts of 44 drugs （80.00%） had clear requirements for the filter pore size of infusion sets， of which 36 drugs （65.45%） required a pore size of 0.2 μm or 0.22 μm. The package inserts of 16 drugs （29.09%） specified the filter material， all of which recommended polyethersulfone. The package inserts of 25 drugs （45.45%） specified the infusion set material， primarily polyvinyl chloride， polyethylene， or polypropylene. CONCLUSIONS The requirements for infusion sets vary among different monoclonal antibody drugs， with differences mainly concentrated in two aspects： material compatibility and filter pore size. In clinical practice， the selection should be based on the drug package inserts， following the principles of “compatibility first， appropriate filtration， and system integration”， and standardized management should be achieved through the development of quick-reference manuals specifically addressing the requirements for infusion sets and the integration of relevant requirements into the prescription review and dispensing systems.

As one of the common systemic vasculitides in children， IgA vasculitis is closely associated with the interaction of "Wind pathogen" and "turbid stasis" in its pathogenesis. Based on the blood turbidity theory， this paper proposes "wind agitating blood turbidity and collateral damage" as the core pathogenesis. Regarding treatment， the sequential therapeutic principle of "stanch bleeding， activating blood circulation， and nourishing blood" is adopted， and combined with the dynamic application of wind-dispelling medicinals to "expel， search， and guard against wind"， turbidity-removing method is applied throughout all stages. In the acute stage，it is recommended to clear heat and purify turbidity， stanch bleeding and secure the collaterals. In the prolonged stage， the method of dissipating stasis and clearing up turbidity should be used， as well as activating blood circulation and unblocking the collaterals. In the recovery stage， it is advised to nourish blood to flourish the collaterals， reinforce healthy qi and resolve turbidity. This therapeutic system integrates the elimination of pathogens and the reinforcement of healthy qi to clear and resolve blood turbidity， ultimately achieving holistic collateral repair through securing， unblocking， and nourishing the collaterals， which provides new insights into the treatment of this disease in traditional Chinese medicine.

Based on the theory of "cold qi generates turbidity" described in the Inner Canon of Yellow Emperor （《黄帝内经》）， together with the physiological characteristics of children， who are considered to have an inherent insufficiency of the lung， spleen， and kidney， and the clinical features of recurrent refractory nephrotic syndrome （RNS）， this article proposes that the pathogenesis of RNS in children is characterized by yang deficiency with internal cold， turbidity arising from cold， latent turbidity transforming into toxin， activation by newly contracted pathogens， and turbid toxins damaging the collaterals. The core pathogenesis is identified as yang deficiency， turbidity coagulation， and collateral damage. Accordingly， the general treatment principle is warming yang and eliminating turbidity， with coordination of three methods including warming yang to strengthen the body's foundation， promoting yang to relieve constraint， and raising yang while replenishing qi. Zhenwu Decoction （真武汤） is employed as the basic prescription with modification according to syndrome differentiation， to achieve an effect eliminating turbidity and arresting leakage， restoring kidney function by unblocking the collaterals， and consolidating recovery to prevent relapse.

Background Vascular endothelial damage associated with endothelial progenitor cell dysfunction is considered as an initiating step of hypertension and target organ damage, in which oxidative stress plays a key role. High-intensity intermittent exercise is an effective prevention and treatment method of various chronic diseases; however, little attention has been paid to its effects and mechanisms on endothelial progenitor cells. Objective To observe the effect of high-intensity intermittent exercise on the function of endothelial progenitor cells in patients with hypertension and explore the mechanism of oxidative stress. Methods A total of 60 patients with essential hypertension were randomly divided into a control group and an exercise group. The control group received conventional drug treatment (including diuretics, calcium blockers, and beta-blockers), and the exercise group performed high-intensity intermittent exercise for 8 weeks (3 times·week⁻¹) in addition to the treatment plan of the control group. Before and after intervention, brachial artery flow-mediated vasodilation (FMD) was used to evaluate vascular endothelial function; venous blood was sampled to perfrom circulating endothelial progenitor cell counts; endothelial progenitor cells were cultured in vitro, and the modified Boyden chamber assay and Matrigel lumen formation assay were used to detect their migration and tube formation ability, superoxide fluorescent anion probe method to detect reactive oxygen species levels, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining method to detect cell apoptosis, Western blotting to determine protein expression of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2, NADPH oxidase 4, and superoxide dismutase. Results Four patients (13.3%) in the control group and 2 patients (6.7%) in the exercise group dropped out; the completion rate of the exercise group's training plan was 94.9%. Compared with the before-intervention indicators, blood pressure decreased, brachial artery FMD increased, number of circulating endothelial progenitor cells increased, their migration and tube formation ability were enhanced, reactive oxygen species levels and cell apoptosis rate were reduced, NADPH oxidase 2 and NADPH oxidase 4 protein expressions were down-regulated, and superoxide dismutase protein expression was up-regulated in the after-intervention exercise group, and the differences were all statistically significant (P < 0.05). There was no significant difference in the above indicators in the control group between before and after intervention (P > 0.05). Conclusion High-intensity intermittent exercise regulates oxidative stress mediated by NADPH oxidase, improves endothelial progenitor cell function, and restores vascular endothelial disorders in patients with essential hypertension.

Objective Genetic testing and prenatal diagnosis were conducted in 18 congenital insensitivity to pain with anhidrosis(CIPA)families,laying the foundation for reducing the incidence of CIPA.Methods Genetic testing was performed using whole-genome sequencing and/or PCR-Sanger sequencing to identify candidate patho-genic vari-ants in the probands.For deep intronic variants,the pathogenicity was validated through minigene assays,RT-PCR,Sanger sequencing,and co-segregation analysis.DNA extracted from chorionic villus or amniotic fluid cells was analyzed by PCR and Sanger sequencing to determine the genotype of the fetuses.Maternal DNA contamination was excluded by microsatellite allele genotyping.Additionally,multiplex ligation-dependent probe amplification(MLPA)was employed to detect common chromosomal aneuploidies.Results A total of 21 NTRK1 variants were identified across 18 CIPA pedigrees,including 9 missense variants,2 nonsense variants,5 frameshift variants,and 5 deep intronic variants.Among them,3 were novel pathogenic variants.Prenatal genetic diagnosis was performed in 20 high-risk fetuses,revealing 2 normal fetuses,12 carriers,and 6 affected with CIPA.Microsatellite genotyping confirmed the absence of maternal DNA contamination in fetal samples.Moreover,MLPA analysis excluded common chromosomal aneuploidies associated with syndromic conditions in all tested fetuses.Conclusions This study achieved a 100%molecular diagnosis rate in CIPA families,identified three novel pathogenic variants,and enabled the simultaneous prevention of CIPA and common chromosomal syndromes through integrated prenatal ge-netic testing,thereby providing critical insights for genetic counseling.

Objective To investigate the influencing factors for early hematoma enlargement(HE)in patients with spontaneous intracerebral hemorrhage(SICH).Methods A total of 311 pa-tients with SICH were selected as research subjects.Based on the occurrence of HE,they were divided into enlargement group and non-enlargement group.Clinical assessment indicators of patients with SICH were collected,and general information between the two groups was compared.The influencing factors for the occurrence of HE in patients with SICH were analyzed.Results Based on the presence of HE at a second CT examination within 6 to 12 hours,311 patients with SICH were divided into en-largement group(n=97)and non-enlargement group(n=214).Univariate analysis revealed signifi-cant differences between the two groups in terms of initial hematoma volume,regularity of hematoma margin,Glasgow Coma Scale(GCS)score,coagulation function,as well as the presence of swirl sign,lobulation sign,black hole sign,blend sign,lymphocyte count and neutrophil count(P＜0.05).Multivariate analysis indicated that GCS score,initial hematoma volume,history of antithrom-botic drug use,abnormal coagulation function and intracranial CT signs were independent influencing factors for HE(P＜0.05).Conclusion The occurrence of HE in patients with SICH is closely re-lated to GCS score,initial hematoma volume,history of antithrombotic drug use,abnormal coagulation function and intracranial CT signs.

ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

Objective To investigate the mechanism of Kuijie Ankang Decoction in regulating immune,autophagy and intestinal flora in the treatment of ulcerative colitis(UC).Methods UC mouse model was established by free drinking with sodium dextran sulfate.The mice were randomly divided into blank control group,model group,Kuijie Ankang Decoction group,salazine sulfopyridine(SASP)group and 3-methyladenine(3-MA)group,with 12 mice in each group.Each drug group was given corresponding drugs for gavage,the blank control group and model group were given the same volume of distilled water for gavage for 7 days.The general condition of mice was observed and the disease activity index(DAI)was scored,the morphology of colon tissue was observed by HE staining,the contents of TNF-α,IL-1β,IL-6,IL-8 and IL-10 in colon tissue were detected by ELISA,the mRNA and protein expressions of LC3,Beclin-1 and p62 in colon tissue were detected by RT-qPCR and Western blot,respectively.16S rDNA sequencing was used to analyze the structure of intestinal flora.Results Compared with the blank control group,the mice in the model group showed a decrease in body mass,an increase in DAI score,a decrease in colon length,serious mucosal injury and inflammatory cell infiltration,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue significantly increased(P<0.05,P<0.01),the content of IL-10 decreased(P<0.01),the mRNA expressions of LC3 and Beclin-1 in colon tissue decreased(P<0.05,P<0.01),the mRNA and protein expression of p62 increased(P<0.01),while the expressions of LC3Ⅱ/LC3Ⅰ and Beclin-1 proteins decreased(P<0.05,P<0.01).Compared with the model group,the body mass of mice in Kuijie Ankang Decoction group and SASP group increased(P<0.05),DAI score decreased(P<0.05),the colon length increased(P<0.05),the pathological damage of colon mucosa was alleviated,the contents of TNF-α,IL-1β,IL-6 and IL-8 in colon tissue decreased(P<0.05,P<0.01),the content of IL-10 increased(P<0.01),the expressions of LC3 and Beclin-1 mRNA in colon tissue increased(P<0.05,P<0.01),the expression of p62 mRNA and protein decreased(P<0.05,P<0.01),the expressions of LC3Ⅱ/LC3Ⅰand Beclin-1 protein increased(P<0.05,P<0.01).16S rDNA sequencing results showed that the diversity and evenness of the intestinal flora in the model group mice decreased,with a decrease in the relative abundance of Firmicutes,Actinobacteria and Patescibacteria(P<0.05),and an increase in the relative abundance of Bacteroidota,Verrucomicrobiota and Proteobacteria(P<0.05);the relative abundance of Bacilli and Coriobacteriia decreased(P<0.05),the relative abundance of Bacteroidia,Clostridia and Verrucomicrobiae increased(P<0.05);the relative abundance of Ligilactobacillus and Dubosiella decreased(P<0.05),the relative abundance of unclassified Muribaculaceae,Lachnospiraceae NK4A136_group,Akkermansia and unclassified Lachnospiraceae increased(P<0.05).Compared with the model group,the diversity and evenness of intestinal flora increased in Kuijie Ankang Decoction group and SASP group,with an increase in the relative abundance of Firmicutes(P<0.05),a decrease in the relative abundance of Bacteroidota and Verrucomicrobiota(P<0.05),the relative abundance of Bacteroidia and Bacilli increased(P<0.05),the relative abundance of Verrucomicrobiae decreased(P<0.05);the relative abundance of unclassified Muribaculaceae and Ligilactobacillus increased(P<0.05),while the relative abundance of Lachnospiraceae NK4A136_group and Akkermansia decreased(P<0.05).Conclusion Kuijie Ankang Decoction can significantly improve the intestinal mucosal injury of UC mice,and the mechanism may be related to the regulation of colon autophagy level and intestinal flora disorder.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.