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 causes and management strategies for lower limb ischemic necrosis following xenogeneic heterotopic heart transplantation from a multigene-edited pig to a rhesus monkey. Methods A xenogeneic heterotopic heart transplantation was performed on December 16, 2023, at the Institute of Experimental Animals of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, using a quintuple-gene-edited pig as the donor and a rhesus monkey as the recipient. On postoperative day (POD) 9, the recipient monkey underwent left lower limb amputation due to ischemic necrosis. Blood samples were collected at various time points after transplantation for analysis of hematologic parameters, liver and renal function, myocardial enzymes, and coagulation profiles. Ultrasound and computed tomography (CT) were used to evaluate anastomotic patency and cardiac structure. Immunological assays, including complement-dependent cytotoxicity (CDC) and IgG/IgM antibody detection, combined with clinical observations, were employed to assess rejection type and therapeutic response. Results The recipient monkey survived for 46 days after transplantation. Echocardiography demonstrated preserved biventricular systolic function in the recipient’s native heart, with left ventricular ejection fraction (LVEF) consistently exceeding 50%. In the donor pig heart, left ventricular endocardial thickening was noted on POD 9, followed by right ventricular endocardial thickening on POD 24, while LVEF remained around 35%. No hyperacute or acute rejection was detected immunologically. CDC positivity ranged between 3.4% and 5.1%, with IgG/IgM antibody binding trends consistent with CDC results. Following amputation, the recipient exhibited elevated inflammatory markers, coagulopathy, and reactive thrombocytosis, which later normalized. Immunohistochemical staining of the necrotic limb revealed arterial and venous thrombosis; however, no T-cell or B-cell infiltration was observed in vascular structures, thrombi, nerves, muscles, fascia, or skin tissues, with CD3 and CD20 staining both negative. Conclusion Limb ischemia after xenogeneic heart transplantation may be associated with lower extremity vascular thrombosis triggered by local trauma in the context of transplantation-induced inflammatory activation and coagulation dysfunction. While no clear lymphocyte-mediated rejection was observed, further studies are needed to explore the potential role of non-lymphocyte-mediated immune mechanisms.

Objective:To investigate the possible mechanism of Zaogong Erteng decoction (ZGETD) in the treatment of endometritis.Methods:Femal mice were injected 2.5 mg/mL lipopolysaccharide into uterine horn to induce endometritis model. After modelling, low-dose ZGETD, high-dose ZGETD or amoxicillin was given once a day for 7 d. The appearance of the uterus and pathological changes of uterine tissue were observed 7 d later, and the uterine index was calculated. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in mouse uterine tissue was detected by enzyme-linked immunosorbent assay. The activity of myeloperoxidase (MPO) in mouse uterine tissue was measured by redox reaction. The active ingredients of ZGETD and the target and signal pathway of treatment of endometritis were analyzed by network pharmacology. Western blotting and qRT-PCR were used to detect the expressions of Toll-like receptor 4 (TLR4), P65, p-P65, interferon regulatory factor 3 (IRF3) and p-IRF3 proteins and chemokines CXCL5 and CXCL8 in the mouse uterus, respectively. Terminal dUTP nick end labeling detected endometrial cell apoptosis and endometrial thickness was measured. After treatment, the female rats were mated with the male rats, and the mating rate, the pregnancy rate and the number of implantation sits in the injected uterine horn on day 8 of gestation were counted. Results:Both ZGETD and amoxicillin have atherapeutic effect on endometritis, but compared with low-dose ZGETD and amoxicillin, high-dose ZGETD can significantly alleviate the edema and congestion of uterine tissue and reduce the uterine index (all P=0.001). After treatment, the uterine cavity epithelium of mice was smooth and complete, the uterine gland structure was normal, and no bleeding area and inflammatory cell aggregation were observed. Compared with amoxicillin, high-dose ZGETD significantly decreased the expression of inflammatory factors (TNF-α, IL-1β and IL-6) and MPO activity (all P<0.001). The expression of chemokines ( CXCL5 and CXCL8) was significantly reduced (all P<0.05). The signaling pathways TLR4, nuclear factor kappa-B (NF-κB) and TNF related to the treatment of endometritis by ZGETD were screened by network pharmacology, and their action targets (TLR4, NF-κB and IRF3) were verified. Quercetin, fisetin and luteolin were found to be the most active ingredients acting on these targets. High-dose ZGETD significantly inhibited the activation of TLR4/NF-κB and TLR4/IRF3 pathways ( P<0.05), decreased endometrial cell apoptosis ( P<0.05), and increased endometrial thickness ( P<0.001), mating rate ( P<0.001), pregnancy rate ( P<0.001) and implantation site number of uterine horn on the injection side of LPS after treatment ( P=0.001). Conclusion:High-dose ZGETD has a significant therapeutic effect on endometritis, which may be closely related to the down-regulation of TLR4 signaling pathway.

Objective:To assess the core competencies of internal medicine residents undergoing standardized residency training and to explore the effectiveness of core competency evaluation on mobile devices.Methods:The mobile formative evaluation module was developed based on the "Xueyiku" teaching management platform. From January to December 2023, clinical teachers were asked to evaluate 150 internal medicine residents based on the "Resident Core Competency Milestone Evaluation System in China Consortium of Elite Teaching Hospitals", and the results were analyzed using non-parametric tests.Results:Among the six core competencies of internal medicine residents, professionalism received the highest score, whereas teaching skill received a lower score (97.50 vs. 90.00; H=167.31, P<0.001). Second-year residents had significantly higher scores than first-year residents (93.00 vs. 90.00; P<0.001), but similar scores to third-year residents (93.00 vs. 93.00; P>0.05). In addition, there was no significant difference in score among residents with different medical education backgrounds ( P>0.05). Conclusions:More emphasis should be placed on improving the teaching skills of internal medicine residents, along with the implementation of tiered progressive training. The mobile core competency evaluation is an effective means for assessing the comprehensive skills of residents in a timely manner.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective:To explore the value of 18F-FDG PET brain imaging in the auxiliary diagnosis of autoimmune encephalitis (AE) before treatment, and to analyze the regional and course-related characteristics of brain metabolic changes. Methods:The 18F-FDG PET brain imaging data of 49 AE patients (26 males, 23 females, age 48.0(29.0, 61.0) years) who did not receive first-line immunotherapy were retrospectively analyzed. Patients were collected from Renji Hospital, Shanghai Jiao Tong University School of Medicine, between July 2015 and December 2023. Forty-nine age- and gender-matched healthy subjects who underwent routine physical examination at the same time period were selected as the healthy controls (HC). The statistical parametric mapping (SPM) 8 two-sample t test ( P<0.001, k=50) was used to compare the imaging results of AE patients with those of HC. The screening results were adjusted by the cluster-level family-wise error rate (FWER) for P<0.05. Metabolic abnormalities associated with AE were identified, and differences in metabolic patterns at different stages of the disease course (short: ≤1 month; medium: >1 month and ≤3 month; long: >3 month) were compared by subgroup analysis. Mann-Whitney U test was used to analyze the data. Results:In the included AE patients, regions with elevated metabolism were mainly located in the limbic lobe, insula, putamen, and amygdala ( t values: 3.18-5.07, Z values: 3.17-4.76), while local metabolic reduction was observed in the frontal, parietal, and occipital lobes ( t values: 3.18-5.43, Z values: 3.23-5.06), with most of these regions passing FWER correction. In patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis, local metabolism increased in the right superior temporal gyrus ( t values: 3.55-4.79, Z values: 3.67-3.86) and decreased in the left middle temporal gyrus and inferior frontal gyrus ( t values: 3.55-5.43, Z values: 3.45-4.21), but the results did not pass the FWER correction. Subgroup analysis showed that in patients with short disease course ( n=17), regions with locally elevated metabolism included the brainstem, limbic lobe, and cerebellum ( t values: 3.37-5.27, Z values: 3.52-4.44), while regions with reduced metabolism were mainly located in the frontal, parietal, and occipital lobes ( t values: 3.37-6.77, Z values: 3.34-5.30), and these abnormal results all passed FWER correction. In patients with medium ( n=7) to long ( n=25) disease course, the regions with metabolic abnormalities were significantly reduced and did not pass FWER correction. Conclusions:18F-FDG PET can accurately identify brain metabolic abnormalities in AE patients, demonstrating significant regional and course-related characteristics. Metabolic abnormalities are more pronounced in patients with short disease course, while they are relatively less obvious in patients with medium to long disease course.