Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

Objective:To explore the correlation between the clinical manifestations and genetic variations in six Chinese Stargardt disease pedigrees.Methods:Six Stargardt disease pedigrees due to ABCA4 gene variants that visited Shanxi Eye Hospital from June 2021 June 2023 were selected as the study subjects. A retrospective study method was used to collect the clinical and family history data of all members of these pedigrees. Peripheral venous blood samples of the examinees were collected, and genomic DNA was extracted for trio-WES. Candidate variants the ABCA4 gene were verified by Sanger sequencing. According to the " Standards and Guidelines for the Classification of Sequence Variants" (hereinafter referred to as the " ACMG Guidelines" ) formulated by American College of Medical Genetics and Genomics (ACMG), the variant sites of the ABCA4 gene were classified for pathogenicity. This study has been approved by the Medical Ethics Committee of Shanxi Eye Hospital (Ethics No. SXYYLL-20200620). Results:From June 2021 to June 2023, 7 patients from families with Stargardt disease with ABCA4 variants were selected as the study subjects. The age of the patients was between 7 to 53 years old, and the age of onset was between 6 to 15 years old. All patients exhibited moderate-to-severe visual impairment with macular atrophy, and yellow white spots were seen in all patients except patient Ⅱ 2 in family 5. Optical coherence tomography (OCT) results showed that the in all patients the macular fovea was significantly thinner, and IS/OS or ellipsoid zone had disappeared. Autofluorescence showed low autofluorescence in the macula, with abnormal dot autofluorescence in the paramacular and periphery retina. ERG grouping classified three pedigrees as Group 3, two as Group 1, and one as Group 2. Pedigree analysis showed that all six pedigrees had autosomal recessive inheritance, family 1, 2, 3, 4, 6 had compound heterozygous variants of the ABCA4, and family 5 had homozygous variants. A total of 11 pathogenic mutations were detected in the ABCA4 gene, of which 3 were found for the first time, including p. Glu1704Gly, p. Gly1965Glu and p. Ser1531Phe. Those carrying nonsense or frameshift mutations include patient 1 (family 1, Ⅱ 1), patient 2 (family 1, Ⅱ 2), patient 4 (family 3, Ⅱ 1), patient 6 (family 5, Ⅱ 2), and patient 7 (family 6, Ⅱ 1), whose clinical manifestations were more severe than those of patient 3 (family 2, Ⅱ 2) and patient 5 (family 4, Ⅱ 1) carrying missense mutations in terms of best corrected visual acuity(BCVA) damage. Conclusion:The ABCA4 gene variation may be the genetic cause of the Stargardt disease in this study, and the discovery of the ABCA4 gene disease variants p. Glu1704Gly, p. Gly1965Glu, p. Ser1531Phe has enriched the mutational spectrum of of Stargardt disease.

BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective To investigate the correlations of CALLY index in early pregnancy with the onset and severity of preeclampsia.Methods A total of 987 pregnant women were prospectively en-rolled as study subjects,with 42 lost during follow-up,resulting in a final inclusion of 945 subjects.Based on the occurrence and severity of preeclampsia during follow-up,the pregnant women were di-vided into preeclampsia group(n=47),severe preeclampsia group(n=49),and normal group(n=849).General information and laboratory test results were collected from all pregnant women,and the CALLY index was calculated.The Pearson correlation analysis was used to explore the correlation be-tween CALLY index and severity of preeclampsia(mean arterial pressure);the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficacy of each indicator for pre-eclampsia;Cox regression analysis was used to explore the influencing factors for the onset of preeclamp-sia.Results The mean arterial pressure and 24-hour urine protein levels were higher in the severe pre-eclampsia group than those in the preeclampsia group and normal group,and higher in the preeclampsia group than those in the normal group(P＜0.05).The CALLY index was lower in the severe preeclamp-sia group than in the preeclampsia group and normal group,and lower in the preeclampsia group than in the normal group(P＜0.05).Pearson correlation analysis showed a negative correlation between CALLY index and mean arterial pressure(r=-0.571,P＜0.001).The ROC curve showed that the area under the curve(AUC)of CALLY index for predicting preeclampsia was 0.941(95％CI,0.900 to 0.981).Multivariate Cox regression analysis showed that an increased CALLY index was an independent protective factor for the onset of preeclampsia(HR=0.185,95％CI,0.092 to 0.374,P＜0.001).Conclusion The CALLY index is negatively correlated with the severity of preeclampsia and is an independent influencing factor for the onset of preeclampsia,which can be used as an auxiliary indicator to assess the onset and severity of preeclampsia in pregnant women.

OBJECTIVE: To explore the correlation between clinical manifestations and genetic variations in six Chinese Stargardt disease pedigrees. METHODS: Six Stargardt disease pedigrees due to ABCA4 gene variants that visited Shanxi Eye Hospital from June 2021 June 2023 were selected as the study subjects. A retrospective study method was used to collect the clinical and family history data of all members of these pedigrees. Peripheral venous blood samples of the examinees were collected, and genomic DNA was extracted for trio-WES. Candidate variants of the ABCA4 gene were verified by family Sanger sequencing. According to the "Standards and Guidelines for the Classification of Sequence Variants" (hereinafter referred to as the "ACMG Guidelines") formulated by American College of Medical Genetics and Genomics (ACMG), the variant sites of the ABCA4 gene were classified for pathogenicity. This study has been approved by the Medical Ethics Committee of Shanxi Eye Hospital (Ethics No. SXYYLL-20200620). RESULTS: From June 2021 to June 2023, 7 patients (patient 1 to 7) from families with Stargardt disease with ABCA4 variants were selected as the study subjects. The age of the patients was between 7 to 53 years old, and the age of onset was between their 6 to 15 years old. All patients had exhibited moderate-to-severe visual impairment with macular atrophy, and yellow white spots were seen in all patients except patient II2 in family 5. Optical coherence tomography (OCT) results showed that all patients' macular fovea was significantly thinner, with IS/OS or ellipsoid zone disappeared. Autofluorescence showed low autofluorescence in the macula, and abnormalities dot autofluorescence in the paramacular and periphery retina. ERG grouping classified three pedigrees as Group 3, two as Group 1, and one as Group 2. Genetic analysis results showed that all pedigrees had autosomal recessive inheritance, five had compound heterozygous variants in the ABCA4, and one had homozygous variants. In total 11 pathogenic mutations were detected in the ABCA4 gene, of which 3 were found for the first time, including p.Glu1704Gly, p.Gly1965Glu and p.Ser1531Phe. Patients carrying nonsense or frameshift mutations include patient 1 (family 1, II1), patient 2 (family 1, II2), patient 4 (family 3, II1), patient 6 (family 5, II2), and patient 7 (family 6, II1), whose clinical manifestations are more severe than those of patient 3 (family 2, II2) and patient 5 (family 4, II1), whom carried missense mutations in terms of best corrected visual acuity (BCVA) damage. CONCLUSION The ABCA4 gene variations may be the genetic cause of the Stargardt disease in this study, and the discovery of the ABCA4 gene p.Glu1704Gly, p.Gly1965Glu, p.Ser1531Phe variants has enriched the mutational spectrum of Stargardt disease.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; ATP-Binding Cassette Transporters/genetics* ; China ; Genetic Variation ; Macular Degeneration/congenital* ; Mutation ; Pedigree ; Retrospective Studies ; Stargardt Disease/genetics* ; East Asian People/genetics*

With the discovery of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the crucial role of the immune microenvironment in tumor therapy has been increasingly recognized. In recent years, as research on the interaction between ionizing radiation and the immune system has deepened, low-dose radiotherapy (LDRT) has emerged, based on the concept that LDRT can alleviate the immunosuppressive state of the tumor microenvironment. High-dose radiotherapy (HDRT), on the other hand, can kill in-situ tumors and thus release more tumor antigens. Therefore, combining HDRT with LDRT and integrating it with immunotherapy-collectively known as the "radiotherapy-induced scopal effect" (RadScopal)-has become a promising new therapeutic approach. This review summarizes the mechanisms and clinical studies of this mixed-dose irradiation strategy, aiming to provide a detailed theoretical basis and reference for the clinical application of RadScopal technology.

Background and purpose:Salivary duct carcinoma(SDC)is a group of rare and highly heterogeneous diseases.It predominantly arises in the parotid glands of middle-aged and elderly males,with high rates of recurrence and metastasis,as well as a poor prognosis.Currently,there is a lack of clinical data on SDC.This study aimed to evaluate the clinical characteristics of SDC patients and explore high-risk factors affecting prognosis,so as to provide clinical references for physicians.Methods:Clinical data of patients with primary SDC who were admitted to Tianjin Medical University Cancer Institute and Hospital and Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine from 2012 to 2024,were collected retrospectively.Inclusion criteria:① patients diagnosed with primary SDC;② availability of American Joint Committee on Cancer(AJCC)staging data.Exclusion criteria:① concurrent other malignant tumors;② incomplete or missing medical records;③ death due to non-SDC causes;④ duplicate cases from the two participating hospitals.Data retrieved encompassed epidemiological information(gender,age)and clinical details(time of diagnosis,tumor characteristics,treatment regimen,recurrence and metastasis status,and pathological data).Survival analysis was performed using the Kaplan-Meier method,and factors related to prognosis were explored through univariate COX proportional hazards regression model analysis.This study was approved by the Ethics Committee of Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine(ethics number:PH2023-B-016),and patient informed consent was waived.Results:A total of 87 patients with primary SDC were included in this study,among whom 77%were male,69%had primary lesions in the parotid gland,29.9%in the submandibular gland,and one patient had a primary lesion in the minor salivary gland of the nasal cavity.49.3%of the patients had concurrent cervical lymph node metastasis.The median overall survival(OS)of the entire group was 31.2 months,the median progression-free survival(PFS)was 20.3 months,and the 5-year OS rate was 52.6%.The 5-year OS rate for tumors originating from the parotid gland was 60%,which was better than the 32.9%for those originating from the submandibular gland.Among the 85 patients who received surgical treatment,65.9%underwent both resection of the primary tumor and neck dissection.Postoperative radiotherapy was administered to 49 patients.During the follow-up period,46%of the patients developed recurrence or metastasis,with lung and bone metastases being the most common.The median OS and local progression-free time in the postoperative radiotherapy group were significantly longer compared with those in the group without radiotherapy,however,the difference was not statistically significant.Conclusion:SDC is a malignant and aggressive disease that predominantly occurs in the parotid glands of middle-aged and elderly males,with a high rate of lymph node metastasis and poor prognosis.Clinically,it is recommended that patients with SDC undergo radical resection of the primary lesion and cervical lymph node dissection,combined with postoperative adjuvant radiotherapy.Targeted therapy and immunotherapy are worthy of further exploration.

Background and purpose:Salivary duct carcinoma(SDC)is a group of rare and highly heterogeneous diseases.It predominantly arises in the parotid glands of middle-aged and elderly males,with high rates of recurrence and metastasis,as well as a poor prognosis.Currently,there is a lack of clinical data on SDC.This study aimed to evaluate the clinical characteristics of SDC patients and explore high-risk factors affecting prognosis,so as to provide clinical references for physicians.Methods:Clinical data of patients with primary SDC who were admitted to Tianjin Medical University Cancer Institute and Hospital and Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine from 2012 to 2024,were collected retrospectively.Inclusion criteria:① patients diagnosed with primary SDC;② availability of American Joint Committee on Cancer(AJCC)staging data.Exclusion criteria:① concurrent other malignant tumors;② incomplete or missing medical records;③ death due to non-SDC causes;④ duplicate cases from the two participating hospitals.Data retrieved encompassed epidemiological information(gender,age)and clinical details(time of diagnosis,tumor characteristics,treatment regimen,recurrence and metastasis status,and pathological data).Survival analysis was performed using the Kaplan-Meier method,and factors related to prognosis were explored through univariate COX proportional hazards regression model analysis.This study was approved by the Ethics Committee of Tianjin Stomatological Hospital Affiliated to Nankai University School of Medicine(ethics number:PH2023-B-016),and patient informed consent was waived.Results:A total of 87 patients with primary SDC were included in this study,among whom 77%were male,69%had primary lesions in the parotid gland,29.9%in the submandibular gland,and one patient had a primary lesion in the minor salivary gland of the nasal cavity.49.3%of the patients had concurrent cervical lymph node metastasis.The median overall survival(OS)of the entire group was 31.2 months,the median progression-free survival(PFS)was 20.3 months,and the 5-year OS rate was 52.6%.The 5-year OS rate for tumors originating from the parotid gland was 60%,which was better than the 32.9%for those originating from the submandibular gland.Among the 85 patients who received surgical treatment,65.9%underwent both resection of the primary tumor and neck dissection.Postoperative radiotherapy was administered to 49 patients.During the follow-up period,46%of the patients developed recurrence or metastasis,with lung and bone metastases being the most common.The median OS and local progression-free time in the postoperative radiotherapy group were significantly longer compared with those in the group without radiotherapy,however,the difference was not statistically significant.Conclusion:SDC is a malignant and aggressive disease that predominantly occurs in the parotid glands of middle-aged and elderly males,with a high rate of lymph node metastasis and poor prognosis.Clinically,it is recommended that patients with SDC undergo radical resection of the primary lesion and cervical lymph node dissection,combined with postoperative adjuvant radiotherapy.Targeted therapy and immunotherapy are worthy of further exploration.

Objective:To explore the correlation between the clinical manifestations and genetic variations in six Chinese Stargardt disease pedigrees.Methods:Six Stargardt disease pedigrees due to ABCA4 gene variants that visited Shanxi Eye Hospital from June 2021 June 2023 were selected as the study subjects. A retrospective study method was used to collect the clinical and family history data of all members of these pedigrees. Peripheral venous blood samples of the examinees were collected, and genomic DNA was extracted for trio-WES. Candidate variants the ABCA4 gene were verified by Sanger sequencing. According to the " Standards and Guidelines for the Classification of Sequence Variants" (hereinafter referred to as the " ACMG Guidelines" ) formulated by American College of Medical Genetics and Genomics (ACMG), the variant sites of the ABCA4 gene were classified for pathogenicity. This study has been approved by the Medical Ethics Committee of Shanxi Eye Hospital (Ethics No. SXYYLL-20200620). Results:From June 2021 to June 2023, 7 patients from families with Stargardt disease with ABCA4 variants were selected as the study subjects. The age of the patients was between 7 to 53 years old, and the age of onset was between 6 to 15 years old. All patients exhibited moderate-to-severe visual impairment with macular atrophy, and yellow white spots were seen in all patients except patient Ⅱ 2 in family 5. Optical coherence tomography (OCT) results showed that the in all patients the macular fovea was significantly thinner, and IS/OS or ellipsoid zone had disappeared. Autofluorescence showed low autofluorescence in the macula, with abnormal dot autofluorescence in the paramacular and periphery retina. ERG grouping classified three pedigrees as Group 3, two as Group 1, and one as Group 2. Pedigree analysis showed that all six pedigrees had autosomal recessive inheritance, family 1, 2, 3, 4, 6 had compound heterozygous variants of the ABCA4, and family 5 had homozygous variants. A total of 11 pathogenic mutations were detected in the ABCA4 gene, of which 3 were found for the first time, including p. Glu1704Gly, p. Gly1965Glu and p. Ser1531Phe. Those carrying nonsense or frameshift mutations include patient 1 (family 1, Ⅱ 1), patient 2 (family 1, Ⅱ 2), patient 4 (family 3, Ⅱ 1), patient 6 (family 5, Ⅱ 2), and patient 7 (family 6, Ⅱ 1), whose clinical manifestations were more severe than those of patient 3 (family 2, Ⅱ 2) and patient 5 (family 4, Ⅱ 1) carrying missense mutations in terms of best corrected visual acuity(BCVA) damage. Conclusion:The ABCA4 gene variation may be the genetic cause of the Stargardt disease in this study, and the discovery of the ABCA4 gene disease variants p. Glu1704Gly, p. Gly1965Glu, p. Ser1531Phe has enriched the mutational spectrum of of Stargardt disease.

With the discovery of programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the crucial role of the immune microenvironment in tumor therapy has been increasingly recognized. In recent years, as research on the interaction between ionizing radiation and the immune system has deepened, low-dose radiotherapy (LDRT) has emerged, based on the concept that LDRT can alleviate the immunosuppressive state of the tumor microenvironment. High-dose radiotherapy (HDRT), on the other hand, can kill in-situ tumors and thus release more tumor antigens. Therefore, combining HDRT with LDRT and integrating it with immunotherapy-collectively known as the "radiotherapy-induced scopal effect" (RadScopal)-has become a promising new therapeutic approach. This review summarizes the mechanisms and clinical studies of this mixed-dose irradiation strategy, aiming to provide a detailed theoretical basis and reference for the clinical application of RadScopal technology.