Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Primary pulmonary nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare and highly aggressive thoracic malignancy that poses significant diagnostic and therapeutic challenges in clinical practice. This tumor is characterized by its heterogeneous clinical presentations and poor prognosis, often evading accurate initial diagnosis. In this study, we present two cases of primary pulmonary NMC treated with an integrated therapeutic approach combining anti-angiogenic agents, platinum-based chemotherapy, and radiotherapy. This multimodal strategy achieved survival durations of 32 and 13 months, respectively, surpassing the currently reported median survival of advanced NMC. Through a systematic literature review of reported cases, we have summarized the currently used diagnostic methods and treatment modalities for NMC. Our findings suggest that multimodal therapy incorporating anti-angiogenic treatment may offer superior clinical outcomes compared to conventional monotherapy regimens, particularly for patients who are not eligible for surgery. This comprehensive investigation enhances our understanding of NMC management by elucidating diagnostic pitfalls through histopathological correlation and proposing an effective therapeutic combination that demonstrates improved survival outcomes. By providing valuable insights into the diagnosis and treatment of primary pulmonary NMC, we hope to contribute to the development of more effective strategies for managing this rare and aggressive malignancy.
Humans ; Angiogenesis Inhibitors/therapeutic use* ; Carcinoma/therapy* ; Combined Modality Therapy ; Lung Neoplasms/diagnosis* ; Nuclear Proteins ; Oncogene Proteins ; Neoplasm Proteins

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.

[Objective]To explore the warming and nourishing thought and diagnostic and therapeutic characteristics of FENG Zhaozhang,a doctor of the Zhejiang faction of traditional Chinese medicine.[Methods]Using the method of literature research,this study sorted out the relevant discussions on the warming and nourishing thought in the Fengshi Jinnang Milu,combined with FENG Zhaozhang's own medical cases and relevant theoretical knowledge of the warming and nourishing school,and summarized FENG Zhaozhang's warming and nourishing thought and diagnostic and therapeutic characteristics.[Results]FENG Zhaozhang's warming and nourishing thought embodies the concept of"taking Kan and filling Li".It takes true Yin and Yang as the innate and postnatal basis,and clarifies that the essence of internal injury and fever is caused by fire emptiness.By distinguishing the pulses of the congenital and central viscera,the pathogenesis is identified,and a treatment method of"regulating,calming,following and soothing"is proposed;FENG's theory emphasizes regulating and nourishing true Yin and Yang,making good use of medicinal herbs to restrain fire and bringing it back to its original state.He paid attention to the way and dosage form of medication to exert its efficacy,proposed the principle of"supplementing and proceeding",and attached importance to nourishment in the later stage of the disease.His self-created formula Quanzhen Yiqi Decoction,is a representative formula that embodies the idea of"taking Kan and filling Li"for warming and nourishing.[Conclusion]FENG Zhaozhang's diagnosis and treatment of diseases is based on the principle of prioritizing Yin and Yang,with a fundamental approach,strict principles and precise medication.This provides an effective diagnostic and treatment approach for treating severe and stubborn diseases,as well as difficult and miscellaneous diseases,which is worth promoting and learning from.

Covalently closed circular DNA(cccDNA)in hepatocytes is the replication intermediate of hepa-titis B virus(HBV),which is closely related to HBV replication.Meanwhile,it is the transcriptional template of pregenomic RNA(pgRNA),and most of the HBV RNA in serum is derived from unreversed transcribed pgRNA.In recent years,many studies have demonstrated that HBV RNA has an important role in monitoring disease progression and predicting the prognosis of chronic HBV-infected patients,and is a potential biomarker of chronic viral hepatitis B.This article provides an overview of the molecular characterisation of HBV RNA,detection methods and research progress in clinical applications.

Aim To investigate the levels of a disintegrin and metalloprotease 10(ADAM-10)and soluble uro-kinase plasminogen activator receptor(suPAR)in the serum of hypertension patients with atherosclerosis and their relation-ship with the severity of disease.Methods From February 2021 to February 2023,125 hypertension patients with atherosclerosis who visited our hospital were collected as the study group,and 76 healthy people were collected as control group.The patients in the study group were grouped into mild group(n=40),moderate group(n=42)and severe group(n=43)according to the degree of atherosclerosis,after 60 days of treatment,the patients were grouped into a good prog-nosis group(n=74)and a poor prognosis group(n=51)based on their prognosis.Enzyme linked immunosorbent assay(ELISA)was applied to measure serum ADAM-10 and suPAR levels;Clinical data of patients with different prognosis were compared;Pearson method was applied to analyze the relationship between serum ADAM-10,suPAR levels and carotid in-tima-media thickness(IMT)in patients with hypertension and atherosclerosis;Multivariate Logistic regression was applied to analyze the influencing factors of poor prognosis in patients with hypertension and atherosclerosis;Receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of ADAM-10 and suPAR alone and jointly for poor prognosis of hypertension with atherosclerosis.Results The levels of serum ADAM-10 and suPAR were significantly higher in the study group than those in control group(P＜0.05);The serum ADAM-10 and suPAR levels in moderate group and severe group were obviously higher than those in mild group(P＜0.05),while the serum ADAM-10 and suPAR levels were obviously higher in severe group than those in moderate group(P＜0.05);The serum ADAM-10 and suPAR levels,left and right IMT,systolic blood pressure,and diastolic blood pressure of patients with poor prognosis were signifi-cantly higher than those of patients with good prognosis(P＜0.05);Pearson correlation analysis showed that serum ADAM-10 and suPAR levels in patients with hypertension and atherosclerosis were positively correlated with systolic blood pres-sure,diastolic blood pressure and IMT(P＜0.001);Logistic regression analysis showed that the increased levels of systolic blood pressure,diastolic blood pressure,ADAM-10,suPAR and IMT were risk factors for poor prognosis of hypertension patients with atherosclerosis(P＜0.05);ROC curve analysis showed that the area under the curve(AUC)of serum AD-AM-10 and suPAR levels alone and jointly predicting poor prognosis of hypertension with atherosclerosis was 0.819,0.830 and 0.900,respectively,the combination of the two was superior to their individual predictions(Zcombination-AD AM-10=2.766,P=0.006;Zcombination-suPAR=2.602,P=0.009).Conclusion The levels of serum ADAM-10 and suPAR in patients with hypertension and atherosclerosis are significantly increased,and are positively correlated with the severity of atherosclero-sis.Both of them have a high predictive value for evaluating the prognosis of patients with hypertension and atherosclerosis.

Objective To investigate the impact and related mechanisms of L-carnitine on lipid metabolism,microinflammation,and oxidative stress status in hemodialysis patients with chronic kidney disease,and explore the potential mechanisms.Methods The data of patients with chronic kidney disease receiving dialysis admitted to Xingtai People's Hospital from January 2022 to January 2023 were collected,and they were divided into levocanidin group(levocanidin+conventional treatment)and conventional treatment group.The two groups were compared in terms of treatment safety and renal function indexes[blood creatinine(Scr)and urea nitrogen(BUN)],lipid metabolism status[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),apolipoprotein A1(ApoA1),apolipoprotein B(ApoB),and serum free carnitine(FC)],microinflammatory markers[interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor alpha(TNF-α),and C-reactive protein(CRP)]and oxidative stress markers[malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)].Results A total of 120 patients were included in the study,with 60 in each group.After 6 months of treatment,there was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05),but the Scr and BUN of the patients in the levocanidin group were lower than those in the conventional treatment group(P＜0.05),and the therapeutic efficacy rate was higher than that in the conventional treatment group(P＜0.05).Regarding lipid metabolic status,serum TC,TG,LDL-C and ApoB levels of patients in the levocanitine group decreased compared with those before treatment(P＜0.05),while serum ApoA1 and FC were elevated(P＜0.05);and serum ApoB levels of patients in the conventional treatment group decreased compared with those before treatment(P＜0.05).The levels of TC,TG,LDL-C and ApoB were significantly lower and the levels of ApoA1 and FC were significantly higher in the leucovorin group than in the conventional treatment group(P＜0.05),whereas there was no significant difference in the levels of serum HDL-C(P＞0.05).In terms of microinflammatory status,IL-6,IL-8,TNF-α,and CRP levels decreased in both groups compared with those before treatment(P＜0.05),but IL-6,IL-8,TNF-α,and CRP levels of patients in the leucovorin group were significantly lower than those in the conventional treatment group(P＜0.05).As for the oxidative stress indexes,the SOD and MDA levels of patients in both groups decreased(P＜0.05),while the GSH-Px levels increased(P＜0.05)compared with the pretreatment;and compared with the conventional treatment group,patients in the levocanitine group had higher levels of GSH-Px,and lower levels of SOD and MDA(P＜0.05).Conclusion The use of L-carnitine may further ameliorate microinflammation and oxidative stress by improving lipid metabolism in dialysis patients with chronic kidney disease.

Objective:To explore the mediating effect of self-regulation fatigue between acceptance of hearing impairment and work withdrawal behavior in young and middle-aged patients with sudden deafness, so as to provide reference for the formulation of intervention measures for job withdrawal behavior.Methods:A cross-sectional survey was conducted to facilitate the selection of 326 young and middle-aged patients with sudden deafness who were treated in the Department of Otolaryngology, Head and Neck Surgery in the First Affiliated Hospital and the Second Affiliated Hospital of Air Force Military Medical University of the Chinese PLA from February 2021 to January 2022. The survey was carried out by general information questionnaire, the Revised Acceptance Disability Scale, the Self-Regulatory Fatigue Scale, and the Work Withdrawal Behavior Scale. Structural equation model method was used to analyze the mediating effect.Results:The acceptance of hearing impairment score in young and middle-aged patients with sudden deafness was (59.82 ± 10.99) points, the self-regulation fatigue score was (60.38 ± 8.84) points, and the work withdrawal behavior score was (39.06 ± 6.51) points. Self-regulation fatigue was negatively correlated with acceptance of hearing impairment ( r=-0.541, P<0.01). Work withdrawal behavior was negatively correlated with acceptance of hearing impairment ( r=-0.488, P<0.01), and was positively correlated with self-regulation fatigue ( r=0.587, P<0.01). Self-regulation fatigue played a partial mediating effect between the acceptance of hearing impairment and work withdrawal in young and middle-aged patients with sudden deafness, and the mediating effect ratio was 56.30%. Conclusions:The acceptance of hearing impairment can not only directly affect the work withdrawal behavior of young and middle-aged patients with sudden deafness, but also indirectly affect their work withdrawal behavior through self-regulation fatigue. Medical staff should pay attention to the internal relationship between the acceptance of hearing impairment, self-regulation fatigue and work withdrawal behaviors, so as to improve the acceptance of hearing impairment of patients, relieve their self-regulation fatigue, and avoid the occurrence of work withdrawal behaviors.

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.