Objective To explore the non-invasive diagnostic criteria of magnetocardiography (MCG) for coronary microvascular dysfunction (CMVD), and its value in dynamically assessing drug treatment for CMVD. Methods Patients who presented with chest tightness or chest pain at Zhongshan Hospital, Fudan University from September 2024 to March 2025 were consecutively enrolled, and all of whom had non-obstructive coronary arteries on angiography. Using the coronary angiography-derived index of microcirculatory resistance (caIMR) as the gold standard, patients were divided into a normal microcirculation group (caIMR≤40 U) and a CMVD group (caIMR＞40 U). MCG testing was performed using a domestic device (MD-U041001, Mind Medical). Patients in the CMVD group received adenosine treatment and underwent repeat MCG after medication. Differences in MCG parameters between the two groups were analyzed, and a diagnostic model was established. The value of the diagnostic model was analyzed using receiver operating characteristic (ROC) curves. Results A total of 311 patients were included, with 135 in the normal microcirculation group and 176 in the CMVD group. The CMVD group had a significantly higher proportion of males (61.9% vs 47.4%, P＝0.012), and lower high-density lipoprotein cholesterol (HDL-C) levels ([1.16±0.31] mmol/L vs [1.24±0.29] mmol/L, P＝0.029) than the normal group. Eleven MCG parameters showed significant differences between the two groups (P＜0.05), among which increased values of mfm_QR_epav, mfm_RS_epmse, space_zeroRTrot, as well as decreased value of mfm_QR_v1 were independent predictors of CMVD. The diagnostic model based on these 11 MCG parameters yielded an area under the curve (AUC) of 0.688 (95%CI 0.629-0.747). The integrated diagnostic model combining clinical risk factors (male, smoking history, HDL-C) with MCG parameters had an AUC of 0.701 (95%CI 0.643-0.759). After adenosine treatment, patients in the CMVD group showed significant decreases in mfm_QR_epav (P＝0.010), mfm_RS_sad (P＝0.013), and mfm_RS_epmse (P＝0.046). Conclusions The model based on MCG parameters demonstrates good diagnostic ability for CMVD; dynamic changes in MCG parameters following adenosine intervention may serve as potential objective indicators for evaluating microcirculatory treatment efficacy.

Xi Jinping Thought on Culture is an important guideline for cultural construction in the new era,providing a new theoretical vision and action guide for the cultural construction of public hospitals.Since the Party's 18th National Congress,a series of reform practices in public hospitals have laid a solid foundation for cultural con-struction and shaped the eight elements of cultural construction in public hospitals.A public cancer specialized hospi-tal in Beijing closely focuses on the spiritual essence of Xi Jinping Thought on Culture,actively explores and practic-es,and builds an all-round hospital culture construction system and action path in the new era.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective:To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation.Methods:A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlations were analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children′s Medical Center (Ethics No.: 2022-406B00).Results:The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c. 2668C>T; p. Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case reports has associated it with this phenotypic spectrum. It was not observed in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. Conclusion:This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c. 2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies in prenatal diagnostics. Above findings have advanced our understanding of pleiotropic effects in type Ⅱ collagen disorders and lay the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities in high-risk families.

OBJECTIVE: To carry out genetic testing and clinical phenotypic characterization on a four-generation Chinese pedigree affected with Stickler syndrome type I and explore its genotype-phenotype correlation. METHODS: A child presented at the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine in February 2023 for micrognathia, glossoptosis and cleft palate and his family members were selected as the study subjects. Clinical data were collected from the affected members, and peripheral blood samples were obtained from 17 participants (including 4 patients and 13 asymptomatic individuals). Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genotype-phenotype correlation was analyzed by integrating the sequencing data with evidence from existing literature. This study has bee granted by the Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine and Guangzhou Women and Children's Medical Center (Ethics No.: 2022-406B00). RESULTS: The four-generation pedigree has comprised 19 members. In addition to the proband, 5 affected individuals had manifested with high myopia, congenital cataracts, and progressive vision loss. Two deceased members reportedly exhibited similar ocular manifestations. Among the four living patients, two had developed retinal detachment, while two others presented with chronic joint pain onset between 35 ~ 40 years of age. One patient required hip replacement surgery at age 42 secondary to femoral head necrosis. The proband, the youngest affected member, exhibited characteristic phenotypes including congenital micrognathia and cleft palate, consistent with Pierre-Robin syndrome. Genetic analysis revealed a heterozygous nonsense mutation in COL2A1 (NM_001844.5: c.2668C>T; p.Gln890Ter) segregating with the disease in all four symptomatic patients. This variant was absent in asymptomatic family members and unaffected controls. While the mutation is listed in ClinVar, no clinical case report has associated it with this phenotypic spectrum. It was not recorded in population databases (gnomAD v4.1.0, 1000 Genomes Project, or ExAC), supporting its potential pathogenicity. CONCLUSION This study has diagnosed a four-generation Chinese pedigree with Stickler syndrome type I attributed to the pathogenic COL2A1 variant c.2668C>T (p.Gln890Ter), which is a rare nonsense mutation associated with ocular predominance and variable skeletal involvement. Notably, this family exhibited marked clinical heterogeneity despite sharing the identical genotype, which highlighted the challenges in phenotype-genotype correlation. The autosomal dominant transmission pattern observed in this pedigree has provided critical insights into COL2A1-related collagenopathies and underscored the necessity of ultrasonographic monitoring for ocular anomalies during prenatal diagnosis. Above findings have advanced our understanding of the pleiotropic effects in type Ⅱ collagen disorders and laid the foundation for precision-based genetic counseling, enabling targeted cascade screening and implementation of tertiary prevention strategies against congenital disabilities for high-risk families.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Arthritis/genetics* ; Collagen Type II/genetics* ; Connective Tissue Diseases/genetics* ; Exome Sequencing ; Genetic Association Studies ; Genotype ; Hearing Loss, Sensorineural/genetics* ; Mutation ; Pedigree ; Phenotype ; Retinal Detachment/genetics* ; East Asian People/genetics*

Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Da Qinjiaotang is the 54^th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas （the first batch） ，and it originated from the Collection of Writings on the Mechanism of Disease， Suitability of Qi， and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla， Glycyrrhizae Radix et Rhizoma， Ligusticum chuanxiong， Angelica sinensis， Paeonia lactiflora， Asari Radix et Rhizoma， Notopterygium incisum， Saposhnikoviae Radix， Scutellariae Radix， Gypsum， Angelica dahurica， Atractylodis Macrocephalae Rhizoma， Rehmanniae Radix， Rehmanniae Radix Praeparata， Poria， and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke， peripheral facial paralysis， cervical spondylosis， rheumatic arthritis， neurodermatitis， and other multisystem diseases. Therefore， following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas， the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data， involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution， composition， dosage， method of preparation， and preparation of the original medicinal materials of Da Qinjiaotang， a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes， stroke （144） was the most， accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon"， featuring "hands and feet cannot move， stiff tongue hinders speaking"， as well as other symptoms， such as slant of the mouth， hemiplegia， numbness of the limbs， paroxysmal pain， and acerbic syncope. The treatment scope was expanded， covering tendon dryness， clonic convulsion， spasm syndrome， and arthralgia syndrome. At the same time， it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors， created the theory of "hot stroke"， and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs， 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula， with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL， decocted once， and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang， the paper clarified its historical evolution and confirmed its key information， so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.

Objective To investigate the protective mechanisms of huanglian jiedu decoction(HLJDD)against hypertensive cardiac hypertrophy(HCH)in rats.Methods The HCH model was constructed in SD rats through abdominal aortic constriction(AAC).Rats were randomly divided into the sham operation(Sham)group,model(Mod)group,Mod+HLJDD high,medium and low-dose(Mod+H,Mod+M,Mod+L)groups,and Mod+Captopril(Cap)group using a simple random sampling method.Blood pressure,echocardiography,hematoxylin-eosin staining,and Masson staining were performed to assess the impact of HLJDD on HCH.Based on the results of part one,rats were further randomly divided into Sham group,Mod group,Mod+Notch1 inhibitor(DAPT)group,Mod+Notch1 agonist(Jagged-1)group,Mod+HLJDD high-dose(HLJDD)group,Mod+HLJDD high-dose+Notch1 inhibitor(DAPT+H)group,and Mod+HLJDD high-dose+Notch1 agonist(Jagged-1+H)group using a simple random sampling method.Hematoxylin-eosin staining and Masson staining were observed.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the expression levels of related inflammatory factors,to further explore the mechanisms of HLJDD.Results Compared with the Mod group,rats in the Mod+H group exhibited reduced blood pressure(P＜0.05),improved cardiac func-tion(P＜0.05),relieved myocardial injury and decreased myocardial fibrosis(P＜0.05).Compared with the Mod group,the DAPT group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05),and increased ex-pression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jagged-1 group and HLJDD group showed opposite results.Compared with HLJDD group,the DAPT+H group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05,P＜0.01),and increased expression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jag-ged-1+H group showed opposite results,indicating that HLJDD can partially activate the Notch1signaling pathway while inhibiting the NF-κB signaling pathway and the release of inflammatory factors.Conclusion HLJDD can alleviate AAC-induced HCC in rats,and its mechanism may be achieved through the modulation of the Notch1/NF-κB signaling pathway.Additionally,a certain negative feed-back regulatory relationship exists between the Notch1 signaling pathway and the NF-κB signaling pathway.

Xi Jinping Thought on Culture is an important guideline for cultural construction in the new era,providing a new theoretical vision and action guide for the cultural construction of public hospitals.Since the Party's 18th National Congress,a series of reform practices in public hospitals have laid a solid foundation for cultural con-struction and shaped the eight elements of cultural construction in public hospitals.A public cancer specialized hospi-tal in Beijing closely focuses on the spiritual essence of Xi Jinping Thought on Culture,actively explores and practic-es,and builds an all-round hospital culture construction system and action path in the new era.

Objective To investigate the protective mechanisms of huanglian jiedu decoction(HLJDD)against hypertensive cardiac hypertrophy(HCH)in rats.Methods The HCH model was constructed in SD rats through abdominal aortic constriction(AAC).Rats were randomly divided into the sham operation(Sham)group,model(Mod)group,Mod+HLJDD high,medium and low-dose(Mod+H,Mod+M,Mod+L)groups,and Mod+Captopril(Cap)group using a simple random sampling method.Blood pressure,echocardiography,hematoxylin-eosin staining,and Masson staining were performed to assess the impact of HLJDD on HCH.Based on the results of part one,rats were further randomly divided into Sham group,Mod group,Mod+Notch1 inhibitor(DAPT)group,Mod+Notch1 agonist(Jagged-1)group,Mod+HLJDD high-dose(HLJDD)group,Mod+HLJDD high-dose+Notch1 inhibitor(DAPT+H)group,and Mod+HLJDD high-dose+Notch1 agonist(Jagged-1+H)group using a simple random sampling method.Hematoxylin-eosin staining and Masson staining were observed.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the expression levels of related inflammatory factors,to further explore the mechanisms of HLJDD.Results Compared with the Mod group,rats in the Mod+H group exhibited reduced blood pressure(P＜0.05),improved cardiac func-tion(P＜0.05),relieved myocardial injury and decreased myocardial fibrosis(P＜0.05).Compared with the Mod group,the DAPT group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05),and increased ex-pression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jagged-1 group and HLJDD group showed opposite results.Compared with HLJDD group,the DAPT+H group displayed aggravated myocardial injury and fibrosis,decreased expression levels of Notch1 and Hes1(P＜0.05,P＜0.01),and increased expression levels of inflammatory factors and NF-κB p65(P＜0.05).The Jag-ged-1+H group showed opposite results,indicating that HLJDD can partially activate the Notch1signaling pathway while inhibiting the NF-κB signaling pathway and the release of inflammatory factors.Conclusion HLJDD can alleviate AAC-induced HCC in rats,and its mechanism may be achieved through the modulation of the Notch1/NF-κB signaling pathway.Additionally,a certain negative feed-back regulatory relationship exists between the Notch1 signaling pathway and the NF-κB signaling pathway.