Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo explore the value of a multimodal MRI-based radiomics nomogram for differentiating human epidermal growth factor receptor-2 （HER-2） negative breast cancer molecular subtypes.MethodsA retrospective analysis was conducted on 190 patients with HER-2 negative breast cancer who underwent multimodal MRI examination， and the patients were divided into two molecular subtype groups： a HER-2 low expression group （n=108） and a HER-2 zero expression group （n=82）. The cases were randomly stratified and sampled at a ratio of 7∶3 and divided into a training set of 133 cases and a testing set of 57 cases. The clinical and radiological features of the patients were collected， the radiomics features based on T2-weighted imaging （T2WI）， diffusion-weighted imaging （DWI）， and dynamic contrast-enhanced （DCE）-MRI were extracted， and the clinical-radiological model， unimodal radiomics model， multimodal radiomics model， and combined model were constructed respectively. Then the nomogram combined multimodal radiomics signature （radsocre） with clinical-radiological features was used to construct a visualized predictive model， and the area under the curve （AUC） was used to compare the effectiveness of different models in distinguishing HER-2 low expression and zero expression subtypes.ResultsA significant difference in radscore was demonstrated between the HER-2 low and HER-2 zero expression groups in both the training （P<0.000 1） and testing sets （P<0.01）. The AUC of the multimodal radiomics model in the training set and the testing set were 0.914 and 0.836， respectively， which was superior to any unimodal radiomics model. The nomogram demonstrated great diagnostic efficacy （AUC=0.930 in training set； AUC=0.865 in testing set）.ConclusionA multimodal MRI-based nomogram incorporating radsocre and clinical-radiological features can accurately distinguish the subtypes of HER-2 negative breast cancer.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Regaining offspring is the most common medical demand for families who lost their only-child in China. However, couples who lost their only-child are often unable to have children naturally due to their old age. With the maturity of assisted reproductive technology (ART), embryo donation is a potentially effective method to help families regain their offspring. However, there is still lack of corresponding laws and operating standards in our country. This article reviews the research progress of embryo donation at home and abroad, and the experience of ART in our hospital, and discusses the feasibility of using ART to regain offspring of families who lost their only child, as well as the medical and ethical issues that need to be considered in practical operation, so as to provide reference for relevant departments.

Objective To introduce the formulation and effect evaluation of performance appraisal scheme for pharmacists in comprehensive pharmacy.Methods A comprehensive evaluation method formulated by critical event method and grade scoring method was adopted to evaluate the workload,work ability,learning ability,and work discipline.Results From September 2022 to August 2023,the average score of monthly pharmacist assessment increased from 73.9 to 87.9,the satisfaction rate increased from(7.5±1.52)to(11.5±2.66)(P＜0.05),and the number of patients with drug consultation increased from 5 cases to 61 cases.Conclusion The performance appraisal scheme can significantly improve the work ability and enthusiasm of pharmacists.

Objective To investigate the expression of circular RNA ubiquitin-associated protein 2(circ-UBAP2)and RAS-related C3 botulinum toxin substrate 1(Rac1)in cervical cancer tissues and their relation-ship with radiotherapy efficacy and prognosis.Methods A total of 96 patients with cervical cancer admitted to the hospital from January 2019 to May 2021 were selected as the research subjects.Detect the expression of circ-UBAP2 and Rac1 in the cancer tissues and adjacent tissues of the patients.The clinical data of the patients were recorded.According to the radiotherapy efficacy,they were divided into patients with effective radiother-apy(n=62)and patients with ineffective radiotherapy(n=34),and the relationship between the expressions of circ-UBAP2 and Rac1 and the radiotherapy efficacy was analyzed.The survival conditions of the patients were followed up for 3 years and they were divided into the survival group(n=81)and the death group(n=15),and the clinical data of the two groups were compared.The relationship between the expressions of circ-UBAP2 and Rac1 and the survival prognosis of patients was analyzed by Kaplan-Meier.The risk factors influ-encing the prognosis of patients were analyzed by Cox regression.Results The circ-UBAP2 expression and the positive rates of Rac1 expression in cancer tissues were both higher than those in adjacent tissues,and the difference was statistically significant(P＜0.05).The effective rate of radiotherapy in patients with high ex-pression of circ-UBAP2 and Rac1 in cancer tissues was lower than that in patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).The 3-year overall survival rate and average survival duration of patients with high expression of circ-UBAP2 and Rac1 in cancer tissues were lower than those of patients with low expression of circ-UBAP2 and Rac1,and the difference was statistically significant(P＜0.05).There were statistically significant differences in clinical stage,tumor differentiation degree,expressions of circ-UBAP2 and Rac1,and the proportion of lymph node metastasis between the two groups(P＜0.05).The results of Cox regression analysis showed that clinical stage Ⅱ B-Ⅲ,poorly differen-tiated tumor degree,high expression of circ-UBAP2 and Rac1,and lymph node metastasis were risk factors af-fecting the prognosis of patients(P＜0.05).Conclusion circ-UBAP2 and Rac1 are abnormally highly ex-pressed in cervical cancer tissues and are related to the radiotherapy efficacy and prognosis.

Regaining offspring is the most common medical demand for families who lost their only-child in China. However, couples who lost their only-child are often unable to have children naturally due to their old age. With the maturity of assisted reproductive technology (ART), embryo donation is a potentially effective method to help families regain their offspring. However, there is still lack of corresponding laws and operating standards in our country. This article reviews the research progress of embryo donation at home and abroad, and the experience of ART in our hospital, and discusses the feasibility of using ART to regain offspring of families who lost their only child, as well as the medical and ethical issues that need to be considered in practical operation, so as to provide reference for relevant departments.

Objective To investigate the influence of different embryo development rates on the clinical outcomes of assisted reproductive technology(ART).Methods The clinical data of female patients who underwent in vitro fertilization and intracytoplasmic sperm injection embryo transfer in Reproductive Medicine Center of The First Affiliated Hospital of Naval Medical University from Jan.1,2015 to Dec.31,2023 were retrospectively analyzed.A total of 1 556 cycles were included.Group A was transferred on day 3,and they were assigned to subgroups according to the embryo development rates until day 3:subgroup A1(≤6 cell stages),subgroup A2(7-9 cell cleavage stages),or subgroup A3(≥10 cell cleavage stages).Group B was transferred on day 4,and they were assigned to subgroups according to the embryo development rates until day 4:subgroup B1(cleavage stages),subgroup B2(1st or 2nd period blastocyst or morula stages),or subgroup B3(3rd period blastocyst or higher stages).Group C was transferred on day 5,and they were assigned to subgroups according to the embryo development rates until day 5:subgroup C1(1st or 2nd period blastocyst or morula stages),subgroup C2(4th or 5th period blastocyst stages),or subgroup C3(6th period blastocyst stages).Group D was transferred on day 6,and they were assigned to subgroups according to the embryo development rates until day 6:subgroup D1(morula or 1st or 2nd period blastocyst stages),or subgroup D2(5th or 6th period blastocyst stages).The clinical pregnancy and live birth rates were calculated for each group.Results Pairwise comparisons of the subgroups A1,B1,C1 and D1,all with relatively slow development rates,showed that the clinical pregnancy rates were 23.7%,37.3%,26.9%and 35.9%,respectively(P＜0.05),the live birth rates were 16.4%,28.4%,19.2%and 26.9%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the B1 group.Pairwise comparisons of the subgroups A2,B2,C2 and D2 with normal development rates,the clinical pregnancy rates were 58.0%,59.4%,62.2%and 61.5%,respectively(P＜0.05),the live birth rates were 47.5%,49.4%,53.8%and 52.3%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the subgroup C2.Pairwise comparisons of the subgroups A3,B3 and C3 with relatively fast development rates showed that the clinical pregnancy rates were 62.2%,64.6%and 63.5%,respectively(P＜0.05),the live birth rates were 52.2%,56.9%and 54.1%,respectively(P＜0.05),and the clinical pregnancy rate and live birth rate were both the highest in the subgroup B3.Conclusion The 4th day fast-developing blastocysts have better development potential and clinical outcomes.Embryos with slower development rate should be transferred on the 4th day,and embryos with normal development rate are recommended to be cultured and transferred to the 5th day.

Objective To systematically identify the key genes regulating the exit from na?ve pluripotency in embryonic stem cells(ESCs)in order to provide novel targets and theoretical insights into the mechanisms for pluripotency transition and early cell fate determination.Methods Nanog-green fluorescent protein(Nanog-GFP)reporter-labeled ESCs were infected with a genome-wide Brie knockout library,and further cultured under leukemia inhibitory factor/serum(LIF/S)conditions for 14 d.Flow cytometry was used to sort Nanog-GFP?(na?ve-state)and Nanog-GFP-(primed state)cell populations,followed by genomic DNA extraction and high-throughput sequencing.Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout(MAGeCK)was applied to identify differential genes between GFP?/Input,GFP?/Input,and GFP?/GFP? groups.Metascape and Gene Set Enrichment Analysis(GSEA)were conducted for functional enrichment analysis.Then the obtained candidate genes were employed to construct knockout models,and their roles were assessed through cell morphology observation,Nanog-positive rate detection,colony formation assays,and pluripotency gene expression analysis.Results The GFP?/Input screening revealed 2 921 negatively regulated genes(mainly enriched in basic life processes,such as RNA metabolism and cell cycle)and 1 393 positively regulated genes(enriched in the processes of nervous system development,carbohydrate metabolism,and vascular system development).In the GFP?/Input screening,2 765 negatively regulated genes(enriched in RNA metabolism,cell cycle,and other fundamental processes)and 1 303 positively regulated genes(enriched in neural development,cell survival,and endothelial migration)were identified.The GFP?/GFP? comparison identified 1 001 negatively regulated genes[involved in stress response and inhibition of mitogen-activated protein kinase(MAPK)signaling]and 983 positively regulated genes[related to fibroblast growth factor/extracellular signal-regulated kinase(FGF/ERK)signaling pathway and glucose metabolism).These genes,were not only known pluripotency regulators(e.g.,Nanog,Nr5a2,Klf2,Klf4)and exit-associated genes(e.g.,Gata6,Grb2,Zeb1,Fgfr1),but also some novel candidates(e.g.,Dmrt1,Rxra,Zbtb14 and Tmem41b).Functional validation showed that transient knockout of Dmrt1,Tmem41b,and Hic2 significantly increased the proportion of Nanog? cells(P<0.01),suggesting their role in suppressing ground-state exit.ESCs with stable Dmrt1 knockout exhibited a more na?ve-state phenotype,presenting compact,dome-shaped colonies,with increased ratio of undifferentiated colonies(P<0.01),up-regulation of ground-state markers(Nanog,Nr5a2,Dppa3,P<0.01),and down-regulation of primed-state markers(Fgf5,Lefty1,Dnmt3b,P<0.01).Rescue experiments for Dmrt1 expression reversed these above phenotypes.Conclusion A candidate gene set regulating exit from na?ve pluripotency in ESC is screened out and identified with genome-wide CRISPR.Our findings implicate Dmrt1 plays a critical role in promoting the exit.

Objective: To explore the value of nomogram based on DCE-MRI radiomics combined with clinical-ra- diological features in predicting HR status in breast cancer with Her-2 low expression． Methods: A total of 198 pa- tients of Her-2 low expression breast cancer who underwent standardized breast MRI in our hospital from January 2019 to February 2025 were retrospectively analyzed．Patients were divided into HR ( + ) group ( n = 137) and HR ( －) group ( n = 61) ．The cases were divided into a training set ( 138 cases) and a testing set ( 60 cases) in a 7 ∶ 3 ratio．Clinical-radiological model was based on clinical and traditional radiological features，radiomics model was based on DCE-MRI，and combined model was constructed，respectively．The nomogram was drawn，and re- ceiver operating characteristic curve was used to compare the performance of different models in predicting HR sta- tus． Results: The DCE-MRI radiomics score ( Radscore) between the HR ( + ) group and the HR ( －) group showed statistical differences in both the training and testing sets ( both P＜0. 001) ．The AUC of the clinical-radio- logical model based on lesion mobility，Ki67，TIC type，enhancement pattern and maximum diameter for predicting HR status in the training set and testing set were 0. 643 and 0. 616，respectively．The AUC of the DEC-MRI ra- diomics model in the training set and testing set were 0. 897 and 0. 860，respectively．The nomogram drawn by combining clinical-radiological features and Radscore showed better predictive performance in both the training set ( AUC = 0. 913) and testing set ( AUC = 0. 898) than the clinical-radiological model ( all P＜0. 05) ． Conclusion The nomogram combined by DCE-MRI radiomics and clinical-radiological features can effectively predict HR sta-tus of breast cancer with low Her-2 expression，which is helpful to the building of individualized treatment plan for breast cancer patients．