OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

Objective To analyze survival outcomes and influencing factors among patients with colorectal cancer in Yunnan Province. Methods Clinical data were retrospectively collected from 4 892 patients with colorectal cancer. Survival data were obtained through follow-up. Overall survival (OS) was calculated by using the Kaplan-Meier method. Univariate analysis was performed by applying the log-rank test. Meanwhile, multivariate analysis employed the Cox proportional hazards regression model. Results The 1-, 3-, 5-, and 10-year OS rates for the entire cohort were 91.90%, 74.40%, 64.40%, and 28.70%, respectively. Univariate analysis revealed that age, ethnicity, region, differentiation grade, TNM stage, clinical stage, metastatic status, histological type, and treatment modality (chemotherapy, radiotherapy, and surgery) were associated with patient prognosis (all P<0.05). Multivariate analysis identified age (HR=1.250), region (HR=1.262), differentiation grade (HR=0.761), clinical stage (HR=3.128), and treatment modality (chemotherapy, HR=0.644; radiotherapy, HR=1.605; surgery, HR=0.384) as independent factors affecting survival prognosis in patients with colorectal cancer (all P<0.001). Conclusion Age, region, clinical stage, and treatment modality are independent factors influencing survival among patients with colorectal cancer in Yunnan Province. In clinical practice, these factors should be integrated to develop individualized prevention and treatment strategies, thereby improving patient outcomes.

In the context of the modernization of traditional Chinese medicine （TCM）， the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system， such as the homogenization of talent cultivation models， lack of standardized mentoring practices， and monotonous evaluation method， which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence （AI）-assisted inheritance of famous doctors' experiences， this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions， including data authenticity assurance， interdisciplinary collaboration mechanisms， and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era， aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation"， providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.

ObjectiveTo investigate the characteristics of gray matter structure and clinical symptoms in patients with Alzheimer's disease （AD） comorbid with apathy （AD-A）. MethodsThe study included 30 patients with AD-A， 30 AD disease patients without apathy （AD without apathy， AD-NA）， and 30 healthy controls （HCs） matched in gender， age， and years of education. All participants underwent a comprehensive neuropsychological assessment and magnetic resonance imaging （MRI） scans. Voxel-based morphometry （VBM） was used to analyze changes in gray matter volume among the three groups. Additionally， the correlation between the identified abnormal brain regions and apathy scale scores was analyzed. ResultsThere were no statistically significant differences among the three groups in terms of age， gender， years of education， or total intracranial volume. Compared with the HCs group， both the AD-A and AD-NA groups showed significantly lower scores in cognitive function （P<0.001）. The AD-A group exhibited significantly higher apathy scale scores compared with the AD-NA group （P<0.001）. Compared with the AD-NA group， the AD-A group showed reduced gray matter volume in the bilateral caudate nucleus， left orbitofrontal cortex， lingual gyrus， inferior frontal gyrus， superior frontal gyrus， entorhinal cortex， right middle frontal gyrus and posterior cingulate cortex （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-A group exhibited reduced gray matter volume in the bilateral middle temporal gyrus， left fusiform gyrus， calcarine sulcus， postcentral gyrus， right inferior frontal gyrus and supramarginal gyrus （FWE-corrected， P<0.05 for all）. Compared with the HCs group， the AD-NA group showed reduced gray matter volume in the left precuneus， inferior temporal gyrus， and right inferior temporal gyrus （FWE-corrected， P<0.05 for all）. In the AD-A group， changes in the gray matter volume of the left caudate nucleus （r= -0.557， P=0.002） and right middle frontal gyrus （r=-0.620， P=0.001） were negatively correlated with the apathy evaluation scale （AES） scores. ConclusionPatients in the AD-A group exhibited significant atrophy in the frontal-temporal-basal ganglia circuit， and the degree of gray matter atrophy was correlated with the severity of apathy.

Objective To analyze the epidemiologic burden of colorectal cancer in Xishan District, Kunming City, Yunnan Province from 2018 to 2020. Methods Indicators of epidemiologic burden were calculated, including incidence rate, mortality rate, age-specific incidence/mortality rates, potential years of life lost (PYLL), and disability-adjusted life years (DALY) based on the National Disease Control and Prevention Center’s "Cancer Information Registration and Reporting System" and "Cause of Death Registration System". Results From 2018 to 2020, the ASR (China) for the incidence of colorectal cancer in Xishan District, Kunming City increased from 25.27/10⁵ to 26.29/10⁵, while the ASR (China) for mortality decreased from 17.11/10⁵ to 16.03/10⁵. The PYLL in 2018–2020 were 1399.63, 1376.78, and 1571.56 person-years, respectively, whereas the DALY in 2018–2020 were 1927.74, 1875.05, and 1945.17 person-years, respectively. The morbidity, mortality, PYLL, and DALY were generally higher in males than in females over 45 years of age. Conclusion Given the parallel trends of persistent incidence risk and steadily declining mortality for colorectal cancer in Xishan District, Kunming City, a three-tier prevention and control system centered on "lifestyle intervention–regular screening–positive case tracking" should be established, with a focus on covering high-risk populations, particularly males over 45 years of age.

OBJECTIVE: To evaluate the therapeutic effect of Yu Melody relaxation training (YMRT) combined with Jianpi Jieyu Decoction (JJD) in treating patients with insomnia disorders (ID). METHODS: In this randomized controlled study, 94 ID patients were included from Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2022 to January 2024. They were randomly assigned to the YMRT group (47 cases, YMRT plus JJD) and the control group (47 cases, oral JJD) using a random number table. Both treatment administrations lasted for 4 weeks, with a 2-week follow-up. The primary outcome was change in Insomnia Severity Index (ISI) scores from baseline to 4 weeks of intervention. Secondary outcomes included ISI response at week 4, as well as ISI, Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder 7-item (GAD-7) scores at baseline and weeks 1, 2, 3, 4, and 6. Additionally, Pittsburgh Sleep Quality Index (PSQI) scores were evaluated at baseline and weeks 4 and 6. Adverse events (AEs) were recorded and compared between groups. RESULTS: Five patients in each group did not complete the protocol requirements. The overall dropout rate was 10.64%. The full analysis set included all 47 cases in each group. The ISI score decreased significantly at week 4 from baseline in the YMRT group compared with the control group, with a between-group difference of -3.2 points [95% confidence interval (CI): -5.08 to -1.34; P<0.05]. The ISI response at week 4 in the YMRT group was significantly higher than that in the control group (85.11% vs. 51.06%), with a between-group difference of 34.05% (95% CI: 13.77% to 50.97%; P<0.05). At week 6, the YMRT group demonstrated greater reductions from baseline than the control group, with between-group differences of -2.1 points (-95% CI: -3.49 to -0.64; P<0.05) for PHQ-9 scores, -3.5 points (95% CI: -5.21 to -1.85; P<0.05) for PSQI scores, and -1.9 points (95% CI: -3.47 to -0.28; P<0.05) for GAD-7 scores. Moreover, at weeks 4 and 6, the ISI and PSQI scores in the YMRT group were significantly lower than those in the control group (P<0.05); and at week 6, the PHQ-9 score in the YMRT group was significantly lower (P<0.05). There was no significant difference in the incidence rates of AEs between the two groups (8.51% vs. 4.26%, P>0.05). CONCLUSIONS YMRT combined with oral JJD could improve sleep quality and alleviate depressive and anxiety symptoms in patients with ID. This combined therapy was effective and safe, and its effect was superior to oral JJD alone. (Registration No. ChiCTR2200063884).
Humans ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Relaxation Therapy/methods* ; Middle Aged ; Adult ; Treatment Outcome ; Combined Modality Therapy

OBJECTIVE: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome. METHODS: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored. RESULTS: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01). CONCLUSIONS EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Humans ; Female ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Electroacupuncture ; Granulosa Cells/metabolism* ; Adult ; Mitochondria/metabolism* ; Pregnancy Outcome ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Infertility, Female/therapy*

Objective:To explore the clinical manifestations of IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland, the diagnostic criteria for IgG4-related diseases and parotid malignant tumors, treatment regimens, and the application of fine-needle aspiration in disease diagnosis, so as to reduce clinical misdiagnosis and missed diagnosis. Methods:A retrospective analysis was conducted on the case data of a patient with IgG4-related diseases（IgG4-RD） complicated with moderately differentiated adenosquamous carcinoma of the parotid gland admitted to our department in March 2024. The clinical characteristics, imaging findings, preoperative puncture results, and postoperative pathological features were analyzed, and relevant literatures on both diseases were reviewed and summarized. Results:The elderly male patient was admitted due to "a mass in the parotid area in front of the right ear for more than 3 months". Through clinical examination, imaging examination, laboratory examination, and preoperative needle biopsy, the diagnosis of "right parotid moderately differentiated adenosquamous carcinoma complicated with IgG4-related disease" was considered. It was also considered that IgG4-related disease did not involve other organs before surgery, so no systemic hormone therapy was given before or after surgery. After surgery combined with postoperative radiotherapy, follow-up showed that neither the parotid tumor nor IgG4-related disease recurred. Conclusion:"IgG4-related disease complicated with moderately differentiated adenosquamous carcinoma"is a rare clinical disease. Both lack typical clinical manifestations and specific imaging features, and the diagnosis is mostly unclear before surgery. Pathological examination is of great significance in the diagnosis of the disease, while fine-needle aspiration has limited value in the diagnosis, which should attract the attention of clinicians. In addition, for patients with both diseases, individualized treatment plans should be formulated.
Humans ; Parotid Neoplasms/pathology* ; Male ; Carcinoma, Adenosquamous/pathology* ; Immunoglobulin G4-Related Disease/complications* ; Parotid Gland/pathology* ; Retrospective Studies ; Aged ; Biopsy, Fine-Needle ; Immunoglobulin G

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.