This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

Compared with total knee arthroplasty, unicondylar knee replacement has the advantage of preserving the knee tissue structure and motor function to the greatest extent. Pre-clinical in-vitro test is an important tool to evaluate the safety and effectiveness of unicondylar knee prostheses, and it is also a key focus of the product registration process. Through collection, comparison, and analysis of current regulations, technical standards, guidelines, and related research literature, this paper expounds on the relevant research methods for the pre-clinical in-vitrotesting of unicondylar knee prostheses. At the same time, in conjunction with current evaluation requirements and experience, the study discusses the focus of pre-clinical performance research for unicondylar knee prostheses during the registration process to clarify the performance evaluation requirements of this product category. This aims to provide a reference for the pre-clinical performance research of unicondylar knee prostheses and to standardize industry testing standards.
Knee Prosthesis ; Arthroplasty, Replacement, Knee ; Humans ; Prosthesis Design ; Materials Testing

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

ObjectiveTo investigate the quality markers of Xiaoqinglong granules（XQLG） for treating bronchial asthma using the analytic hierarchy process（AHP）-entropy weight method（EWM）， network pharmacology and high performance liquid chromatography（HPLC） content determination. MethodsEffectiveness， testability and peculiarity component data of XQLG in treating bronchial asthma were constructed through database retrieval， literature review， and network pharmacology. Subsequently， AHP-EWM was used to quantitatively identify and weight the control layer and element layer， the relevant compounds were selected as candidate quality markers based on comprehensive scores. Further comparison of reference substances and establishment of HPLC content determination method were used to determine the potential quality markers of XQLG， which were verified by molecular docking with disease targets. ResultsA total of 13 components， including glycyrrhizic acid， paeoniflorin， schisandrol A， isoliquiritigenin， 6-gingerol， ephedrine， liquiritin， albiflorin， liquiritigenin， 6-shogaol， pseudoephedrine， cinnamic acid and cinnamaldehyde， were identified as potential quality markers of XQLG by AHP-EWM. Quantitative analysis indicated that all aforementioned quality markers could be detected in 13 batches of XQLG， indicating that it had stable testability as a quality marker. Among these 13 batches of samples， ephedrine and paeoniflorin exhibited good consistency in content， while pseudoephedrine and cinnamaldehyde showed poor consistency. Molecular docking analysis revealed that the 13 compounds exhibited binding energies with the core targets -2.11 kcal·mol^-1， indicating that the 13 compounds could spontaneously bind to the disease targets， which may be the material basis for the treatment of bronchial asthma with XQLG. ConclusionIn this study， 13 compounds were screened by AHP-EWM combined with network pharmacology and HPLC as quality markers for the treatment of bronchial asthma by XQLG， laying the foundation for enhancing the quality standards of this preparation.

Objective To investigate the expression levels of microRNA-152-3p(miR-152-3p)and sex determining region-box transcription factor 5(SOX5)in gastric cancer(GC)tissues and their clinical significance.Methods A total of 120 GC patients were selected as study subjects.Re-al-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-152-3p and SOX5,and their relationships with the clinicopathological characteristics of GC pa-tients were analyzed.The Kaplan-Meier method was applied to draw survival curves,and the Cox re-gression model was used to screen the prognostic influencing factors of GC patients.Results The ex-pression level of miR-152-3p in GC tissues was lower than that in adjacent non-cancerous tissues,while the expression level of SOX5 was higher than that in adjacent non-cancerous tissues(P＜0.05).The expressions of miR-152-3p and SOX5 in GC tissues were all associated with lymph node metastasis,degree of differentiation,and TNM stage(P＜0.05).The expression level of miR-152-3p was negatively correlated with that of SOX5(r=-0.512,P＜0.05),and there were targeted binding sites between miR-152-3p and SOX5.The 5-year specific survival rate of the low miR-152-3p expression group was lower than that of the high miR-152-3p expression group(60.53％versus 84.09％,x2=7.256,P＜0.05).The 5-year specific survival rate of the high SOX5 expression group was 63.10％,which was lower than 83.33％of the low SOX5 expression group,with a statis-tically significant difference(x2=4.840,P＜0.05).Multivariate Cox regression analysis showed that the expression levels of miR-152-3p and SOX5,as well as the TNM stage,were all independent prog-nostic influencing factors for GC patients(P＜0.05).Conclusion Low expressions of miR-152-3p and high expression of SOX5 are observed in GC tissues,and their expression levels are closely re-lated to clinicopathological characteristics such as TNM stage and patients' prognosis.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To analyze the prevalence of chronic diseases, the level of chronic disease prevention and control literacy and its influencing factors among middle-aged and elderly residents in Wenzhou from 2020 to 2023.Methods:Based on a cross-sectional research design, 19 528 usual residents aged 45-69 were retrospectively selected with a multi-stage stratified random sampling method from the health literacy monitoring survey in Wenzhou from 2020 to 2023. The χ2 tests and trend χ2 tests were employed to analyze chronic disease prevalence rates and health literacy possession rates across different population subgroups. Binary logistic regression models were used to identify determinants of chronic disease prevention health literacy among middle-aged and elderly residents in Wenzhou. The results were standardized using data from Wenzhou′s Seventh National Population Census. Results:The numbers of middle-aged and elderly respondents was 5 528, 4 822, 4 575 and 4 603 from 2020 to 2023, respectively, and the prevalence of self-rated chronic diseases was 39.56%, 37.33%, 41.29% and 39.00%, respectively (the standardized rate was 33.49%, 33.58%, 36.43% and 35.34%, respectively) in the each year, and the rates of chronic disease prevention and control literacy was 24.76%, 27.98%, 24.44% and 28.13%, respectively (the standardized rate was 27.95%, 30.11%, 27.57%, 29.78%, respectively). The rates of chronic disease prevention and control literacy was on an upward trend in middle-aged and elderly respondents in Wenzhou from 2020 to 2023 ( χ2trend=5.997, P=0.014). From 2020 to 2023, chronic disease prevention health literacy showed a positive educational gradient, with significantly higher levels observed among more educated populations (both P<0.05). Except for 2020, the residents with household income≥30 000 yuan had a higher chronic disease prevention and control literacy than those with household income less than 30 000 yuan (both P<0.05); in 2021 and 2022, the chronic disease prevention and control literacy in the people of 45-59 years was higher than that in the individuals of 60-69 years (both P<0.05); in 2020 and 2022, the rural residents had a higher chronic disease prevention and control literacy than the urban residents, and the rates of chronic disease prevention and control literacy of employees or retirees in government institutions/doctors/teachers were higher than that in the peasants (both P<0.05); in 2023, the chronic disease prevention and control literacy of the smokers was lower than that in the non-smokers ( P=0.014). Conclusions:The prevalence of chronic diseases among the middle-aged and elderly residents in Wenzhou is relatively low, people with chronic diseases, especially those with multiple chronic diseases, have a low level of chronic disease prevention and control literacy. To prevent and control chronic diseases among them, interventions should be differentiated by the chronic disease status, occupation and household income.

Cerebral small vessel disease （CSVD） is an important etiology of vascular cognitive impairment and stroke， and there are still many challenges in its early diagnosis and pathological mechanisms. As a type of extracellular vesicles that exist stably in body fluids and can cross the blood-brain barrier， exosomes have attracted wide attention in recent years. Studies have shown that various exosomal proteins have a potential value in the diagnosis and treatment of CSVD and related cognitive impairment， providing new research directions for the noninvasive management of these diseases. This article systematically reviews the latest advances in exosomal proteins for the diagnosis and treatment of CSVD and related cognitive impairment， in order to provide new perspectives for the application of exosomal proteins in the precise treatment of CSVD.
Biomarkers

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.