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.

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 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.

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．

The triple energizer is the pathway for the transportation and metabolism of qi,blood and body fluid in the body,and the xuanfu(sweat pores)is the way for the ascending,descending,exiting,and entering of qi movement in the muscular striae and the exterior.Professor Li Huilin believes that the pathogenesis of acne is usually due to the dysfunction of triple energizer and the stagnation of depressed yang-heat,which result into the abnormal opening and closing of the xuanfu and the accumulation of heat-toxin in the muscular striae.For the treatment of acne with traditional Chinese medicine,it is necessary to pay attention to the regulation of triple energizer-xuanfu.The treatment should be based on unblocking therapy,and the therapeutic principle of unblocking triple energizer and opening xuanfu should be taken into account.In clinical practice,it is necessary to identify the syndromes of upper energizer,middle energizer and lower energizer.The syndrome of the upper energizer is often due to fire-heat,which results from the wind-heat in lung meridian or the exuberance of heart fire.The upper-energizer syndrome can be treated by the therapy of relieving and clearing the pathogens with light and mild drugs,expelling fire-heat to open sweat pores,and through the modified use of Mahuang Lianqiao Chixiaodou Decoction,Ma Xing Shi Gan Decoction,or Puji Xiaodu Decoction.The syndrome of the middle energizer is usually due to the qi stagnation,which results from intense stomach-heat,damp-heat in the spleen and stomach,liver depression and qi stagnation,or spleen deficiency with dampness accumulation.The middle-energizer syndrome can be treated by the therapy of regulating qi movement to relieve stagnation and open sweat pores,and through the modified use of Qingwei san,Sanren Decoction,Huanglian Wendan Decoction,Chaihu Shugan Powder,or Heqi Powder.The syndrome of the lower energizer is often due to healthy-qi deficiency,which results from yin deficiency of liver and kidney,or deficiency-cold in lower energizer.The lower-energizer syndrome can be treated by the therapy of cultivating the vital essence and consolidating vital base,supplementing deficiency to open sweat pores,and through the modified use of Liuwei Dihuang Pills or Yanghe Decoction.

Objective To investigate the acupoint selection patterns for treating diabetic cardiac autonomic neuropathy(DCAN)using data mining techniques,providing evidence for clinical practice.Methods Literature on acupuncture treatment for DCAN was retrieved from CNKI,Wanfang,VIP,and PubMed.The publication dates of the included literature ranged from the inception of each database to April 2024.Descriptive analysis,association rule analysis,and cluster analysis were performed on acupoint prescriptions,with the selection patterns of meridians and acupoints were summarized.Results A total of 27 articles were included,involving 18 acupoints.The top 10 high-frequency acupoints were Neiguan(PC6),Xinshu(BL15),Pishu(BL20),Zusanli(ST36),Sanyinjiao(SP6),Shenmen(HT7),Taixi(KI3),Lingtai(GV10),Shendao(GV11),and Shenshu(BL23).The primary meridians selected were the bladder meridian of foot-taiyang and the pericardium meridian of hand-jueyin.Specific acupoint categories predominantly included back-shu points and five transport points.Association rule and cluster analyses identified core acupoint combinations centered on Xinshu,Neiguan,Pishu,and Zusanli.Conclusion The core acupoint combination for treating DCAN with acupuncture comprises Xinshu,Neiguan,Pishu,and Zusanli.

Objective To explore the medication rules of Professor Li Huilin in treating Hashimoto's thyroiditis(HT)complicated with hypothyroidism using data mining techniques based on the R language.Methods Prescription data of the patients with HT complicated with hypothyroidism treated by Professor Li Huilin in outpatient clinics from March 2023 to March 2024 were collected.A database was established using Microsoft Excel 2021,and R language was employed to analyze the frequency,efficacy,properties and flavors,and meridian tropism of the medicinals from Chinese herbal prescriptions.Additionally,correlation analysis,association rule analysis,and cluster analysis were performed on the medicines from Chinese herbal prescriptions.Results A total of 57 Chinese herbal prescriptions involving 125 medicinals with 782 medication frequencies were included.The top 10 frequently-used medicinals were Glycyrrhizae Radix et Rhizoma Praeparata cum Melle(Zhigancao),Angelicae Sinensis Radix(Danggui),Atractylodis Macrocephalae Rhizoma(Baizhu),Astragali Radix(Huangqi),Bupleuri Radix(Chaihu),Cinnamomi Ramulus(Guizhi),Leonuri Herba(Yimucao),Paeoniae Radix Alba(Baishao),Poria(Fuling),and Fici Simplicissimae Radix(Wuzhimaotao).Most of the medicinals had therapeutic action of tonifying deficiency.The analysis of properties and flavors showed that the majority of medicinals were mild or warm in nature,and sweet in flavor.The top three meridians having the tropism of medicinals were the liver,lung,and spleen meridians.Correlation analysis identified five strongly-correlated herbal combinations.Association rule mining revealed a core herbal combination consisting of seven medicinals of Zhigancao,Huangqi,Danggui,Chaihu,Codonopsis Radix(Dangshen),Baizhu,and Cyperi Rhizoma(Xiangfu).Cluster analysis of medicinals with a frequency of≥5 yielded five groups of herbal combination.Conclusion For the treatment of HT complicated with hypothyroidism,Professor Li Huilin follows the principle of addressing the root cause of the disease,and focuses on strengthening the spleen and replenishing qi.Moreover,attention is given to soothing the liver and regulating qi,harmonizing qi and blood simultaneously,and treating symptoms and root cause simultaneously.

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.

Marine work environment is associated with unique risk factors,such as high salinity,high humidity,noise and vibration,and chemical pollution.Males make up the majority of marine workers.Prolonged exposure to these environmental factors may have adverse effects on male fertility,resulting in sperm quality reduction,endocrine disorder,and reproductive organ damage.Therefore,the potential harm of marine work environment to male reproductive health deserves attention.This review focused on the key exposure factors in marine work environment,and systematically explored the factors affecting male fertility,mechanisms,and physiological pathways.The aim is to provide scientific evidences to improve marine work environment,develop protective measures,and safeguard the reproductive health of workers,while also offering guidance for future research in this field.