ObjectiveTo employ Helicobacter hepaticus (H.hepaticus, H.h) to induce intestinal fibrosis in vitamin D receptor deletion (VDR^-/-) mice, thereby establishing a model of inflammatory bowel disease to investigate its pathological characteristics and underlying mechanisms. MethodsFive male WT and five male VDR^-/- mice were orally administered a suspension containing 2×10⁸ CFU of H.hepaticus (referred to as the WT+H.h group and the VDR^-/-+H.h group, respectively), with treatments occurring every other day for three administrations. Concurrently, two uninfected control groups were established, consisting of five WT and five VDR^-/- mice, which were administered an equivalent volume of PBS. Seven days after the final administration, the infection status of the mice was assessed, and their body weight was recorded weekly. At the 16^th week post-infection, the mice were dissected, and the length of the colon tissue was measured, with fecal moisture content analyzed. The colon tissue was partitioned into four parts: one for paraffin embedding for HE, alcian blue-periodic acid Schiff (AB-PAS), Masson's trichrome staining, and immunohistochemical analysis; one for DNA extraction to evaluate the colonization levels of H.hepaticus through real-time fluorescent quantitative polymerase chain reaction (RFQ-PCR), thereby assessing the impact of the infection; one for RNA extraction to analyze cytokine expression via reverse transcription-PCR (RT-PCR); and one for protein extraction to measure the expression levels of alpha smooth muscle actin (α-SMA) and interleukin (IL)-33 using Western blotting. Results All mice in the infected groups successfully were infected with H. hepaticus after three oral gavages. Compared to VDR^-/- control group, VDR^-/- mice exhibited significant weight loss (P<0.05), intestinal hemorrhage, and higher fecal water content after 16 weeks of H. hepaticus infection than the uninfected control group and the WT+H.h group (P<0.05). Compared to the WT+H.h group, HE staining of the VDR^-/-+H.h group showed inflammatory cell infiltration, AB-PAS staining revealed irregular atrophy of intestinal glands and reduced acini, and Masson staining showed increased collagen area. RT-PCR demonstrated that the transcription levels of inflammation and fibrosis-related genes, including IL-6, IL-33, tumor necrosis factor-α (TNF-α), and α-SMA (P < 0.000 1), were significantly upregulated in the colon tissues of VDR^-/-+H.h group. Additionally, immunohistochemical analysis and Western blotting showed that the protein expression levels of IL-33 and α-SMA were markedly increased (P<0.001) in the VDR^-/-+H.h group. ConclusionVDR^-/- mice infected with H.hepaticus exhibit more severe inflammatory responses, including mucosal inflammatory infiltration, impaired mucosal tissue function, and collagen deposition, indicating successful construction of the inflammatory bowel disease model. Further research suggests that VDR deficiency may exacerbate the intestinal fibrosis process associated with inflammatory bowel disease by affecting IL-33 expression.

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Soil cadmium pollution can adversely affect the cultivation of the ornamental plant, Coleus scutellarioides. Upon cadmium contamination of the soil, the growth of C. scutellarioides is impeded, and it may even succumb to the toxic accumulation of cadmium. In this study, we investigated the effects of arbuscular mycorrhizal fungi (AMF) on the adaptation of C. scutellarioides to cadmium stress, by measuring the physiological metabolism and the degree of root damage of C. scutellarioides, with Aspergillus oryzae as the test fungi. The results indicated that cadmium stress increased the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the content of malondialdehyde (MDA) and proline (Pro) within the cells of C. scutellarioides, but inhibited mycorrhizal infestation rate, root vigour and growth rate to a great degree. With the same cadmium concentration, the inoculation of AMF significantly improved the physiological indexes of C. scutellarioides. The maximum decrease of MDA content was 42.16%, and the content of secondary metabolites rosemarinic acid and anthocyanosides could be increased by up to 27.43% and 25.72%, respectively. Meanwhile, the increase of root vigour was as high as 35.35%, and the DNA damage of the root system was obviously repaired. In conclusion, the inoculation of AMF can promote the accumulation of secondary metabolites, alleviate root damage, and enhance the tolerance to cadmium stress in C. scutellarioides.
Cadmium/toxicity* ; Mycorrhizae/physiology* ; Plant Roots/drug effects* ; Soil Pollutants/toxicity* ; Stress, Physiological ; Superoxide Dismutase/metabolism*

Objective:To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM).Methods:This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups.Results:The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter ( HR=1.21, 95% CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation ( HR=1.71, 95% CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) ( HR=1.30, 95% CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment ( HR=0.45, 95% CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC ( P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion:An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Objective:To explore the clinical characteristics and prognostic value in hereditary transthyretin amyloidosis cardiomyopathy (hATTR-CM) patients based on cluster analysis, and to explore the risk factors for cardiovascular composite events.Methods:This retrospective cohort study included hATTR-CM patients who were admitted to Peking Union Medical College Hospital from January 2000 to January 2024. These patients were divided into two clusters using cluster analysis, based on genetic information, demographic information and clinical information. During the follow-up period, cardiovascular composite events were defined as all-cause death and hospitalization for heart failure. Both cardiovascular composite events and all-cause death were the endpoints. Kaplan-Meier survival curves and log-rank method were used to compare the prognostic significance of cluster analysis subgroups. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the incidence of cardiovascular composite events.Results:A total of 43 patients were included in this study, 30 were male (69.8%). In cluster 1 ( n=27), whose age of onset was (49.9±13.9) years old, 24(88.9%) of them started with neuropathy or gastrointestinal symptoms, and all clinical phenotypes were mixed type (neurological and cardiac). In cluster 2 ( n=16), whose age of onset was (59.0±10.6) years old, 15(93.8%) of them started with heart failure symptoms, and 13(81.3%) were pure cardiomyopathy. During the median follow-up time of 2.6 years, a total of 16 patients (37.2%) experienced composite cardiovascular events, and a total of 12 patients (27.9%) died. Kaplan-Meier survival curves showed a significantly lower cumulative survival rate for cardiovascular composite endpoint events (log-rank P=0.04) and all-cause death (log-rank P=0.04) in cluster 2 than in cluster 1. Univariate Cox proportional hazard regression model analysis showed that hATTR-CM patients with reduced estimated glomerular filtration rate, left ventricular ejection fraction≤40%, and moderate to severe mitral regurgitation were risk factors for vascular composite events (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that left ventricular ejection fraction≤40% was an independent risk factor ( P<0.01). Conclusions:Cluster analysis is a valuable prediction tool on the prognostic stratification of hATTR-CM. Cluster 2, which is late-onset with onset of heart failure symptoms has a worse prognosis during follow-up period. The occurrence of composite cardiovascular events in hATTR-CM is related to left ventricular ejection fraction≤40%. Cluster analysis is helpful for clinical identification of high-risk groups.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective: To detect the expression of serum exosomal miR⁃30d⁃5p in occupational dermatitis medicamentosa⁃like of trichloroethylene(OMDT) patients and its correlation with liver function , then perform bioinformatics analysis and verify the target gene. Methods : Serum exosomes were extracted from 6 OMDT patients and 6 healthy controls , and miRNA was extracted from exosomes which were identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. The expression of serum exosomal miR⁃30d⁃5p was detected by real⁃time fluorescence quantitative PCR , then the correlation with liver function was analyzed. The target genes of miR⁃30d⁃5p were predicted by the miRWalk and miRBD databases. Gene ontology analysis and KEGG pathways analysis were performed. Finally , RHOB was verified by Dual⁃luciferase reporter assay. Results: The expression of serum exosomal miR⁃30d⁃5p significantly decreased in 6 OMDT patients at the peak of the disease(P < 0. 05) , and it was negatively correlated with the level of AST , ALT and GGT (correlation coefficient : rs = - 0. 943 ,P = 0. 005 ;rs = - 0. 886 , P = 0. 019 ; rs = - 0. 886 , P = 0. 019 ) . Bioinformatics analysis and dual⁃luciferase reporter assay showed that RHOB was the target gene of miR⁃30d⁃5p. Conclusion The expression of serum exosomal miR⁃30d-5p decreases in OMDT patients , which is negatively correlated with the level of liver function , and the target gene RHOB may be involved in the process of liver injury induced by trichloroethylene.

Familial hypercholesterolemia (FH) is a group of autosomal co-dominant genetic diseases mainly characterized by abnormal low-density lipoprotein related metabolism. It is one of the most common inherited diseases in children and one of the most serious lipid metabolism diseases which results in various life-threatening cardiovascular diseases and the complications. In recent years, the treatment protocols for FH have diversified thanks to the deeper understanding of the disease in China and abroad and the development of new lipid-lowering drugs. However, the current awareness and diagnosis rate of FH are very low. The treatment of the disease is much inadequate. This paper summarizes the clinical characteristics, diagnosis, screening strategy, and treatment of FH hoping to enhance the understanding and awareness of the disease in the society.

Objective:To explore the core competency of doctors in tertiary public hospitals in regions of different income levels in China, and provide reference for promoting such competency and related policy formulation.Methods:Using multi-stage stratified cluster sampling method, 195 tertiary public hospitals in 16 provinces of China were selected from November 2021 to March 2022. 200 doctors were sampled from each hospital. A self-designed questionnaire was used to investigate the status of doctors′ core competencies, as well as the status of their postgraduate medical education and continuing medical education. According to the per capita gross regional product of each province in China Statistical Yearbook 2022, each province was divided into high, middle and low income regions, and the questionnaire data were descriptively analyzed, while χ2 test was used to compare the differences between groups. Results:A total of 32 673 valid questionnaires were collected. There were 12 135 doctors (37.14%) in China who had received comprehensive education and training of core competency in all dimensions. Among the dimensions of self-rated core competency of the surveyed doctors, there were 10 019 doctors (30.66%) with insufficient teaching ability and 438 (1.34%) with insufficient professional quality, and there was no significant difference between regions ( P>0.05). There were 2 385 (27.08%), 2 528 (27.55%) and 3 646 (24.82%) doctors in high-, middle- and low-income regions with insufficient lifelong learning ability, respectively. The proportion of doctors in middle- and high-income regions was higher than that in low-income ones ( P<0.05). There were 1 317 (15.57%), 1 290 (14.06%) and 2 719 (18.51%) doctors with insufficient knowledge and skills in high-, middle- and low-income areas, respectively. The proportion of doctors in low-income regions was higher than that in middle- and high-income regions ( P<0.05). The proportion of doctors who did not receive any kind of postgraduate medical education or continuing medical education in low-income regions was 7.33% (1 077 people), higher than that in high-income and middle- income ones ( P<0.05); 50.44% (4 442 people) of surveyed doctors in high-income regions believed that for standardized training of resident physicians (hereinafter referred to as residential training), the clinical teachers were " overworked to take this job", which was higher than that in middle- and low-income regions ( P<0.001); In middle-income regions, 46.16% (4 235 people) and 43.46% (3 987 people) believed that the salary residents and specialized physicians in standardized training (hereinafter referred to as specialized training) was too low, while 42.47% (3 897 people) and 30.44% (2 793 people) believed that the clinical practice opportunities of students were limited, both of which were higher than those in high-income and low-income regions ( P<0.001); 34.91% (5 128 people) of surveyed doctors in low-income regions believed that the investment was insufficient for training bases of residential training, 27.81% (4 085 people) of those held that training bases for specialized training were unevenly distributed, and 33.19% (4 876 people) of those held that continuing medical education was plagued by " insufficient promotion coverage, and insufficient opportunities for primary doctors", all of which being higher than those in high- and middle-income regions ( P<0.001). Conclusions:There is an obvious need to improve the core competence of doctors in the teaching ability dimension of tertiary public hospitals in China, especially in middle- and high-income regions for lifelong learning, and in low-income regions for knowledge and skills; There are differences between postgraduate medical education and continuing medical education systems in regions of different income levels in China. It is necessary to improve the competency oriented postgraduate medical education and continuing medical education systems.