Objective To report the diagnosis, treatment, and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent, and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders. Methods A 14-year-old patient presented with primary amenorrhea on April 3, 2020, at the First Affiliated Hospital of Hebei North University, exhibiting female sexual characteristics. The patient underwent ultrasonic/magnetic resonance imaging of gonads, assessment of gonadal axis function, chromosomal karyotype, and molecular genetic testing, as well as pelvic exploration, malignant gonads resection, and hormone replacement therapy, resulting in drug-induced menstruation. During the diagnosis and treatment, it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results. Subsequently, samples from the three germ layer cells were taken, and fluorescence in situ hybridization (FISH) was used to detect the sex chromosomes in each germ layer cell. XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads, and changes in anti-Müllerian hormone (AMH) levels before and after surgery were compared. Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease. Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues. The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30% (6/20), in peripheral blood lymphocytes derived from the mesoderm was 9.7% (11/114), and in bladder shed cells derived from endoderm was 20.4% (22/108). The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome; where the epididymal structure area had a 45,X cell line mosaic of 50.0%, and the malignant area had a normal "Y" content. After gonadal resection, AMH levels significantly dropped from 7.28 pmol/L to <0.07 pmol/L. Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum, most with features of Turner syndrome, and female phenotypes are at risk of gonadal tumors. Conclusions In the diagnosis of difficult cases of sex development disorders, when performing peripheral blood karyotype testing, the number of counted cells and analyzed cells should be increased as much as possible, and multi-germ layer cell sampling should be performed. Gonads with a high "Y" mosaic rate are more prone to malignancy in the abdominal cavity. Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

Objective To investigate the expression of the histone deacetylase SIRT7 in glioma cells and its impact on epithelial-mesenchymal transformation (EMT), as well as its effects on proliferative, migratory and invasive capabilities of glioma cells. Methods Bioinformatics analysis was conducted on data from glioma patients in the Cancer Genome Atlas (TCGA) and the Chinese glioma Genome Atlas (CGGA) databases to explore the expression of SIRT7 gene in gliomas and its correlation with tumor grading, molecular characteristics and patient clinical prognosis. Glioma cells were randomly divided into control, SIRT7 knockdown, SIRT7 overexpression, drug treatment (10 μmol/L hydrochlorothiazide) and drug (10 μmol/L hydrochlorothiazide)+SIRT7 overexpression groups. The CCK-8 assay, cell scratch assay and Transwell assay were used to observe the effects of upregulating and downregulating SIRT7 expression on glioma cell proliferation, migration and invasion. RT-qPCR and Western blotting were employed to detect the effects of SIRT7 on the expression of neural cadherin (N-cadherin), Vimentin, E-cadherin, transforming growth factor-β (TGF-β), Ki-67, and Smad3 protein in glioma cells. Nude mouse tumor-bearing experiments were conducted to observe the effect of SIRT7 knockdown on glioma growth. Results Higher expression levels of SIRT7 gene were associated with poorer clinical prognosis (P<0.0001). SIRT7 expression levels were significantly correlated with tumor grading and 1p19q coding status (P<0.01). Compared with normal HA cells, glioma cells showed significantly increased SIRT7 expression levels (P<0.01). CCK-8 assay results indicated that, compared with control group, the proliferation activity of glioma cells in SIRT7 knockout group was significantly decreased (P<0.01), while SIRT7 overexpression group showed significantly increased proliferation activity (P<0.01). EdU assay results showed that, compared with control group, the proportion of glioma cells in the proliferative stage was significantly decreased in SIRT7 knockdown group (P<0.01), and significantly increased in SIRT7 overexpression group (P<0.01). Western blotting results revealed that, compared with control group, the protein expression levels of TGF-β, Smad3, N-cadherin and Vimentin were significantly decreased in SIRT7 knockdown group (P<0.01), while the expression level of E-cadherin protein was significantly increased (P<0.05). SIRT7 overexpression group showed significantly increased protein expression levels of TGF‑β, Smad3, N-cadherin and Vimentin (P<0.05), and a significantly decrease in E-cadherin protein expression level (P<0.05). Scratch assay results indicated that, compared with control group, the migration ability of cells in SIRT7 knockdown group and drug group was significantly decreased (P<0.01), and SIRT7 overexpression group showed significantly increased cell migration ability (P<0.05). Compared with drug group, drug+SIRT7 overexpression group exhibited significantly increased cell migration ability (P<0.01). Transwell assay results showed that, compared with control group, the migration and invasion abilities of cells in SIRT7 knockdown group and drug group were significantly decreased (P<0.01), and SIRT7 overexpression group exhibited significantly increased migration and invasion abilities (P<0.01). Compared with drug group, drug+SIRT7 overexpression group showed significantly increased migration and invasion abilities (P<0.01). Nude mouse tumor-bearing assay results indicated that the volume and weight of glioma in SIRT7 knockdown group were significantly reduced compared with control group (P<0.01). Conclusions Glioma patients with high SIRT7 expression have poorer clinical prognosis. SIRT7 can regulate the TGF-β/Smad3 pathway to mediate EMT, promoting the proliferation and migration of glioma cells. SIRT7 knockdown can inhibit the growth of transplanted gliomas in nude mice.

Objective To investigate the protective effects of paeonol (PAE) on autophagy in human neuroblastoma cells (SH-SY5Y) induced by overexpression of α-synuclein (α-Syn), and to explore its related mechanism. Methods SH-SY5Y cells served as control group, while those induced with A53T-α-Syn mutation were used as model group. Additional groups included PAE (150 μg/ml) group, 3-MA (1 mmol/L) group, and PAE(150 μg/ml)+3-MA (1 mmol/L) group. Cell viability was assessed using CCK-8 method, cell morphology was observed under an optical microscope, and protein expressions of α-Syn, LC3-Ⅱ, p62, Beclin-1, phosphorylated c-Jun N-terminal kinase (p-JNK), and p-Bcl-2 were determined by Western blotting. Results Compared with control group, model control exhibited decreased cell survival (P<0.01), increased α-Syn expression (P<0.001), reduced expression of autophagy-related proteins LC3-Ⅱ and Beclin-1 (P<0.01, P<0.05), elevated autophagy substrate protein p62 (P<0.05), and decreased expression of autophagy pathway-related proteins p-JNK and Bcl-2 (P<0.05, P<0.01). Compared with model group, PAE group showed increased cell survival (P<0.01), decreased α‑Syn and p62 protein expression (P<0.01, P<0.05), and increased expression of LC3-Ⅱ, Beclin-1, p-JNK and Bcl-2 (P<0.05). Compared with PAE group, 3-MA+PAE group demonstrated increased α-Syn expression (P<0.05). Conclusions PAE could attenuate the injury of SH-SY5Y cells induced by A53T-α-Syn and eliminate over-expressed α‑Syn by activating autophagy pathway, which may be associated with the upregulation of JNK/Bcl-2 mediated autophagy pathway.

Objective To investigate the effect of miR-373-3p in diabetic retinopathy (DR), as well as the underlying mechanisms. Methods Serum samples from 35 DR patients and 35 non-DR patients visiting Tianjin Fifth Central Hospital from February 2021 to February 2022 were collected, and expression levels of miR-373-3p and vascular endothelial growth factor A (VEGFA) mRNA were detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). An in vitro DR model was constructed using high glucose (HG)-treated human retinal microvascular endothelial cells (HRMEC). HRMECs were divided into control group (5 mmol/L glucose and 25 mmol/L mannitol treatment), HG group (30 mmol/L glucose treatment), HG+miR-373-3p mimic-negative control (miR-con) group (30 mmol/L glucose treatment after transfection with miR-con), HG+miR-373-3p mimic group (30 mmol/L glucose treatment after transfection with miR-373-3p), HG+miR-373-3p+vector group (30 mmol/L glucose treatment after co-transfection with miR-373-3p and vector), and HG+miR-373-3p+vascular endothelial growth factor A (VEGFA) group (30 mmol/L glucose treatment after co-transfection with miR-373-3p and VEGFA). The expression levels of miR-373-3p, VEGFA mRNA and protein were analyzed by qRT-PCR and Western blotting. CCK-8, immunofluorescence, Transwell assay, angiogenesis assay, and Western blotting were used to evaluate HRMEC proliferation, migration and angiogenesis abilities. The relationship between miR-373-3p and VEGFA was determined by dual luciferase reporter assay. Results Compared with non-DR patients, DR patients exhibited significantly lower expression levels of miR-373-3p (P<0.05) and higher expression levels of VEGFA mRNA (P<0.05) in serum. Compared with control group, HG group showed decreased expression of miR-373-3p (P<0.05), increased expressions of the mRNA and protein of VEGFA (P<0.05), higher cell viability, proliferation rate, proliferating cell nuclear antigen (PCNA) and Cylin D1 protein, and numbers of migrating cells and angiogenesis ability (P<0.05) in HRMECs. Compared with HG+miR-con group, HG+miR-373-3p group showed increased expression of miR-373-3p (P<0.05), decreased expressions of VEGFA (P<0.05), lower cell viability, proliferation rate, PCNA and Cylin D1 protein (P<0.05), and lower numbers of migrating cells and angiogenesis ability (P<0.05) in HRMECs. Compared with HG+miR-373-3p+vector group, HG+miR-373-3p+VEGFA group showed increased expression of VEGFA (P<0.05), higher cell viability, proliferation rate, PCNA and Cylin D1 protein, and numbers of migrating cells and angiogenesis ability (P<0.05) in HRMECs. The results of dual luciferase reporter assay showed decreased enzymatic activity of luciferase after cotransfection of miR-373-3p and VEGFA sequence (P<0.05). Conclusion MiR-373-3p is lowly expressed in the serum of DR patients, and its potential mechanism may involve targeting VEGFA to inhibit HG-induced HRMEC dysfunction.

The Golgi apparatus (GA), an essential membrane organelle in eukaryotes positioned between the endoplasmic reticulum and the plasma membrane, is responsible for transporting and modifying proteins and lipids generated by the endoplasmic reticulum. The homeostasis of the endoplasmic reticulum and GA plays a crucial role in regulating cellular life. When GA is unable to bear the load of protein or lipid processing and transportation, it enters a state of stress. Cells sense this and activate Golgi-related quality control mechanisms. By regulating the structure and function of GA, it provides important protection for the cell or induces programmed cell death, known as the GA stress response. Understanding the mechanisms and outcomes of cellular GA stress is of great significance for exploring Golgi dynamics and its impact on human diseases. This review summarizes the structure and function of GA under physiological conditions, the phenomenon of GA stress under pathological conditions, and the role of GA in infectious diseases, aiming to provide a basis for the clinical study of new strategies for the prevention and treatment of infectious diseases.

Cardiogenic shock (CS) is a disease characterized by reduced cardiac output leading to inadequate end-organ perfusion and remains a significant issue in cardiovascular medicine. Despite significant therapeutic advancements in recent years, the mortality rate associated with CS remains high. Mechanical circulatory support (MCS) has emerged as an innovative therapeutic strategy, capable of maintaining hemodynamic stability and ensuring systemic perfusion of vital organs, thereby effectively improving patient prognosis and lowering mortality rates. This review summarizes the latest research progress on commonly used MCS devices, both domestically and internationally, covering aspects of CS overview, left and right heart assist, bicardial and total heart assist, as well as the selection and limitations of MCS devices. We provide an overview of the types of MCS devices currently available and their indications for use, aiming to offer better clinical guidance to physicians and enhance the treatment level of CS.

Intervertebral disc degeneration (IDD) is a prevalent clinical degenerative disease that currently can only be treated through conservative and surgical treatments, which only alleviate symptoms and are not significantly effective. In recent years, nanoparticles have been widely studied in the biomedical field due to their biodegradability, biocompatibility, extended body circulation, sustained and controlled release, and precise drug targeting. Nanoparticle drug delivery systems have the potential to deliver a range of therapeutic agents including proteins, drugs, genes, and cells, thereby promoting tissue and cell repair and regeneration, which offers hope for IDD treatment. However, there are still challenges in translating experimental data into practical therapies applicable to humans. This review summarizes recent research progress on drug delivery systems for IDD treatment based on nanoparticles and provides insights and prospects for the challenges faced by nanoparticles, aiming to provide a reference for the clinical translation of nanoparticle-based treatment for IDD.

Sebaceous glands are vital appendages of the skin, primarily functioning in the secretion of a variety of lipid substances. These lipid substances play crucial physiological roles in the body, such as participating in body temperature regulation, maintaining skin homeostasis, and modulating the immune system. Abnormalities in the function of sebaceous glands can lead to a range of skin disorders, with acne being the most common one. Acne arises from the overproduction of sebum by sebaceous gland, leading to hair follicle blockage, bacterial infection, and inflammation response. Additionally, sebaceous gland carcinoma is a rare but severe malignant tumor of the skin, and its exact mechanisms are not fully understood. Organoids are closely resemble in vivo counterparts in terms of cell types, spatial structure, and function. Sebaceous gland organoids serve as an ideal platform for studying sebaceous glands and their associated diseases. This review summarizes the structure, function, homeostasis of sebaceous glands, as well as the construction and applications of sebaceous gland organoids, aiming to provide reference for research on the pathogenesis and treatment of sebaceous gland related diseases.

Objective To explore the changing patterns of electrocardiogram (ECG) and echocardiography in healthy young people during their descent from high altitude to the plain. Methods A prospective cohort study was carried out. Fifty-five healthy young volunteers who had migrated to an altitude of 4800-5500 m on the Qinghai-Tibet Plateau within one year were recruited as the plateau-migration group. ECG examinations were performed at an altitude of 3700 m (first time), on the 5th day after returning to 1300 m (second time), and on the 15th day after returning to 1300 m (third time). Echocardiography was conducted at 3700 m and on the 5th day after returning to 1300 m. A plain control group of 55 healthy youngsters from the plains (1300 m) was matched. The results of ECG and echocardiography between the two groups were compared. Results Intragroup analysis of the plateau-migration group revealed that compared with the first ECG results, the number of normal ECGs decreased in the second and third ECG results (P<0.05), and the proportions of sinus rhythm irregularity, sinus bradycardia, and U-wave appearance increased (P<0.05). There was no statistically significant difference in abnormal ECG results between the second and third ECGs (P>0.05). Compared with plain control group, there was no significant difference in the abnormal results of the first ECG of plateau-migration group (P>0.05). In the second and third ECG results, the number of normal ECGs was significantly reduced, and the proportions of sinus bradycardia, sinus rhythm irregularity, and U-wave appearance were significantly increased compared with plain control group (P<0.001). Intragroup analysis of plateau-migration group revealed that compared with the first ECG, the heart rate decreased in the second and third ECGs (P<0.05 or <0.001). Compared with plain control group, in the first ECG of plateau-migration group, the PR interval was significantly prolonged, the QTc interval was shortened, and the QRS axis degree was increased (P<0.05). In the second ECG, the heart rate significantly decreased, the PR interval was prolonged, and the QTc interval was shortened (P<0.05). In the third ECG, the heart rate decreased, the PR interval was prolonged, the QTc interval was shortened, and the QRS axis degrees was increased (P<0.05). The QRS axis of the first, second, and third ECGs of plateau-migration group was statistically significantly different from that of plain control group (P<0.001). Intragroup analysis of plateau-migration group showed that compared with the first echocardiogram, the left ventricular end-systole diameter, left ventricular end-diastolic diameter, and left atrial anteroposterior diameter all significantly increased in the second echocardiogram (P<0.001). Compared with plain control group, in the first echocardiogram of plateau-migration group, the left ventricular end-systole diameter and right atrial transection diameter significantly decreased, the right ventricular transection diameter significantly increased, and the left ventricular fractional shortening rate (FS) significantly decreased (P<0.05); In the second echocardiogram, the left atrial anteroposterior diameter, right atrial transverse diameter, and right ventricular transverse diameter all significantly increased, and FS increased (P<0.05). Conclusions In healthy young people returning from high altitude to the plain, as the altitude decreased, the heart rate significantly drops. The number of people with frontal QRS axis right deviation significantly reduces. The number of normal ECGs significantly decreases, while the numbers of people with sinus bradycardia, sinus arrhythmias, and U-wave appearance significantly increase. During high-altitude stay, the left ventricular systolic and diastolic function is affected to some extent.

Objective To explore the value of constructing a model to predict the number of positive cores in systematic biopsy in prostate cancer (PCa) using a combination of radiomics features based on magnetic resonance imaging and clinical indicators. Methods Retrospectively collected magnetic resonance imaging and clinical data from two medical institutions (Gansu Provincial Hospital from January 2018 to February 2023, Zhangye People's Hospital Affiliated to Hexi College from April 2020 to February 2023). The 155 patients from Gansu Provincial Hospital were randomly divided into a training set (n=109; 80 cases with positive needle count ≥6 and 29 cases with positive needle count <6) and an internal validation set (n=46; 34 cases with positive needle count ≥6 and 12 cases with positive needle count <6) in a 7:3 ratio. The 43 patients from Zhangye People's Hospital Affiliated to Hexi College were used as external validation set. Small field of view high-resolution T₂-weighted imaging (sFOV HR-T₂WI) and contrast-enhanced delayed-phase images were selected to extract radiomic features from the three-dimensional region of interest of the entire prostate, and radiomics model was constructed and Radscores calculated after dimensionality reduction and feature selection. Univariate and multivariate logistic regressions were used to screen for independent risk factors for positive cores in systematic biopsy. Nomogram was constructed using Radscore and clinical independent risk factors to predict the number of positive cores in systematic biopsy in PCa patients, which was then externally validated. Results Age, alkaline phosphatase (ALP), free prostate specific antigen (FPSA), total prostate specific antigen (TPSA), FPSA/TPSA ratio, and prostate specific antigen density (PSAD) were not statistically significantly different between the training, internal validation, and external validation sets (P>0.05). FPSA, TPSA, FPSA/TPSA ratio, and PSAD were significantly different between the positive cores <6 and positive cores ≥6 groups (P<0.001). Univariate logistic regression analysis showed that FPSA (P<0.001), TPSA (P<0.001), FPSA/TPSA ratio (P=0.001), PSAD (P<0.001), and Radscore (P<0.001) were risk factors for positive cores in systematic biopsy in PCa. Multivariate logistic regression analysis showed that PSAD (OR=0.251, 95%CI 0.063-0.996, P=0.049) and Radscore (OR=1.990, 95%CI 1.409-2.812, P<0.001) were independent risk factors for positive cores in systematic biopsy in PCa. The clinical models achieved AUCs of 0.849(95%CI 0.774-0.924), 0.817(95%CI 0.693-0.941), and 0.631(95%CI 0.439-0.822); the 12 features for radiomics models are derived solely from sFOV HR-T₂WI, the radiomics models achieved AUCs of 0.868(95%CI 0.791-0.945), 0.846(95%CI 0.695-0.996), and 0.815(95%CI 0.660-0.970); the nomogram achieved AUCs of 0.921(95%CI 0.869-0.973), 0.868(95%CI 0.743-0.992), and 0.840(95%CI 0.702-0.978) in the training set, internal validation set, and external validation set, respectively. Conclusions The combination of radiomic features extracted from sFOV HR-T₂WI and PSAD can preoperatively be used as a noninvasive manner to predict the number of positive cores of the PCa patients. This approach has a certain value in risk stratification of PCa patients and guiding personalized clinical management.