The functional modulation of deep brain structures plays a crucial role in the treatment of psychiatric disorders; however, current approaches primarily rely on invasive techniques such as deep brain stimulation. Temporal Interference (TI) transcranial electrical stimulation is an emerging non-invasive neuromodulation technique capable of precisely regulating the activity of deep brain nuclei, offering an innovative and promising approach for psychiatric disorder treatment. In recent years, studies conducted on healthy individuals and patients with neurological disorders (e.g., Parkinson's disease) have provided preliminary evidence supporting the deep brain modulation capabilities of TI. Meanwhile, multiple registered clinical studies are actively investigating its potential applications in psychiatric treatment. This review systematically summarizes the fundamental principles, neuromodulatory mechanisms, and recent research advances of TI in psychiatric disorders. Additionally, it highlights key scientific issues that need to be addressed to facilitate further basic research and clinical translation in this field.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

Objective To explore the application value of dynamic airway computed tomography(DACT)based on retrospective ECG-gating technology in the diagnosis of cardiovascular-related airway stenosis.Methods A retrospective analysis was performed on the bronchoscopy and DACT data of 48 children clinically suspected of having congenital heart disease(CHD)or cardiovascular-related airway stenosis.The image quality of DACT was assessed,and the accuracy differences in diagnosing airway abnormalities between bronchoscopy and DACT were compared.The correlation between DACT and bronchoscopy in diagnosing the degree of airway steno-sis was also evaluated.Results The DACT image quality met diagnostic requirements for all children.There was no significant statistical difference in the diagnosis of airway abnormalities between DACT based on retrospective ECG-gating technology and bronchoscopy.A good correlation was observed between DACT and bronchoscopy in the grading of tracheal stenosis.Conclusion DACT based on retrospective ECG-gating technology can effectively address the issue of motion artifacts in CT scans among infants and young children.It has certain value in clarifying the diagnosis of cardiovascular-related airway stenosis,guiding treatment,and assessing prognosis.

BACKGROUND:Epidemiologic investigations and some experiments have shown that there is a close relationship between peripheral blood cells and osteoporosis,but the causal relationship between the two at the genetic level is still unclear. OBJECTIVE:To explore the causal relationship between peripheral blood cells and osteoporosis using Mendelian randomization methods. METHODS:Genome-wide association study data sets on peripheral blood cells,overall bone density at different ages,and calcaneal bone density were obtained from databases such as Blood Cell Consortium and MRC Integrative Epidemiology Unit. Blood cells were used as exposure data,with bone density at different ages and calcaneal bone density serving as outcome data. Mendelian randomization analyses were performed using methods such as inverse variance weighting,MR-Egger,weighted median method,and simple median. The results were assessed for heterogeneity,pleiotropy,and sensitivity using Cochran's Q,MR-Egger regression,and Leave-one-out method. The causal relationship between exposure and outcomes was evaluated using β values. RESULTS AND CONCLUSION:Due to the heterogeneity revealed by Cochran's Q test in the Mendelian randomization results,the results of the study were based on the inverse variance weighting method. The inverse variance weighting results showed that when age-specific bone density was used as an outcome,there was a negative causal relationship between white blood cell count and whole-body bone mineral density at the age of 45-60 years[β=-0.07,95％ confidence interval (CI):-0.13,-0.01,P=0.02],a positive causal relationship between monocyte count and whole-body bone mineral density at the age of 45-60 years (β=0.05,95％ CI:0.00,0.10,P=0.037),a negative causal relationship between white blood cell and basophil counts and whole-body bone mineral density over 60 years old (β=-0.04,95％ CI:-0.07,-0.01,P=0.005;β=-0.04,95％ CI:-0.07,-0.00,P=0.038),a positive causal relationship between hemoglobin concentration and hematocrit and whole-body bone mineral density over 60 years old (β=0.04,95％ CI:0.01,0.08,P=0.012;β=0.04,95％ CI:0.00,0.07,P=0.039),and a negative causal relationship between white cell count and whole-body bone mineral density at an undistinguished age (β=-0.10,95％ CI:-0.16,-0.03,P=0.002). When heel bone mineral density was used as an outcome,there was a negative causal relationship between white cell count and heel bone mineral density (β=-0.04,95％ CI:-0.07,-0.01,P=0.016),and a positive causal relationship between hemoglobin concentration and hematocrit and heel bone mineral density (β=0.05,95％ CI:0.01,0.08,P=0.007;β=0.05,95％ CI:0.01,0.08,P=0.004). To ensure the robustness of the results,meta-analyses of Mendelian randomization results of peripheral blood cells and whole-body bone mineral density as well as heel bone mineral density in different age groups were conducted. The results suggested that for every standard deviation decrease in log-transformed white blood cell count,there was a 5％ reduction in the risk of decreased bone mineral density (OR=0.95,95％ CI:0.94,0.97,P<0.001);whereas for every standard deviation increase in hemoglobin concentration and hematocrit,there was a 4％ reduction in the risk of decreased bone density (OR=1.04,95％ CI:1.03,1.06,P<0.001). In conclusion,increased white blood cell count in peripheral blood is a risk factor for bone mineral density;whereas increased hematocrit and hemoglobin concentration are protective factors for bone mineral density.

Objective To explore the application value of dynamic airway computed tomography(DACT)based on retrospective ECG-gating technology in the diagnosis of cardiovascular-related airway stenosis.Methods A retrospective analysis was performed on the bronchoscopy and DACT data of 48 children clinically suspected of having congenital heart disease(CHD)or cardiovascular-related airway stenosis.The image quality of DACT was assessed,and the accuracy differences in diagnosing airway abnormalities between bronchoscopy and DACT were compared.The correlation between DACT and bronchoscopy in diagnosing the degree of airway steno-sis was also evaluated.Results The DACT image quality met diagnostic requirements for all children.There was no significant statistical difference in the diagnosis of airway abnormalities between DACT based on retrospective ECG-gating technology and bronchoscopy.A good correlation was observed between DACT and bronchoscopy in the grading of tracheal stenosis.Conclusion DACT based on retrospective ECG-gating technology can effectively address the issue of motion artifacts in CT scans among infants and young children.It has certain value in clarifying the diagnosis of cardiovascular-related airway stenosis,guiding treatment,and assessing prognosis.

The functional modulation of deep brain structures plays a crucial role in the treatment of psychiatric disorders; however, current approaches primarily rely on invasive techniques such as deep brain stimulation. Temporal Interference (TI) transcranial electrical stimulation is an emerging non-invasive neuromodulation technique capable of precisely regulating the activity of deep brain nuclei, offering an innovative and promising approach for psychiatric disorder treatment. In recent years, studies conducted on healthy individuals and patients with neurological disorders (e.g., Parkinson's disease) have provided preliminary evidence supporting the deep brain modulation capabilities of TI. Meanwhile, multiple registered clinical studies are actively investigating its potential applications in psychiatric treatment. This review systematically summarizes the fundamental principles, neuromodulatory mechanisms, and recent research advances of TI in psychiatric disorders. Additionally, it highlights key scientific issues that need to be addressed to facilitate further basic research and clinical translation in this field.

【Objective】 To explore the efficacy of flexible ureteroscopic lithotripsy (FURL) under local anesthesia (LA) in the treatment of upper urinary tract calculi, and to analyze the risk factors of pain. 【Methods】 Clinical data of 255 patients treated during Apr.2022 and Sep.2022 were reviewed, including visual analogue score (VAS) of pain during ureteroscopy, sheath placement, holmium laser lithotripsy, 1 hour and 8 hours after operation. VAS ≥5 was defined as significant pain. Clinical and follow-up data of the significant pain group and non-significant pain group were analyzed with logistic regression to analyze the risk factors of pain in FURL under LA. 【Results】 Altogether 198 patients (77.6%) successfully completed the operation, and the stone-free rate (SFR) was 89.9% (178/198). The VAS of ureteroscopy was the highest (4.49±1.08), and 73 patients (28.6%) experienced significant pain. Univariate analysis showed that significant pain was associated with gender, previous surgical history, age, body mass index (BMI), education level, and ASA classification (P<0.05). Multivariate analysis showed that male (OR=2.896, 95%CI:1.413-5.933, P=0.040) and BMI≥28 (OR=7.776, 95%CI:2.268-26.657, P=0.001) were independent risk factors of significant pain, while age ≥65 years (OR=0.237, 95%CI:0.083-0.672, P=0.007) and previous surgical history (OR=0.156, 95%CI:0.032-0.754, P=0.021) were the protective factors. 【Conclusion】 It is feasible and effective to treat upper urinary tract calculi with FURL under LA. The presence of significant pain is associated with factors such as gender, age, BMI and previous surgical history.

Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Objective:To investigate the prevalence of liver fibrosis in patients with HBV infection detected by ultrasound transient elastography.Methods:A total of 2 689 patients with HBV infection who received liver transient elastography examination at the Department of Hepatology, Zhongnan Hospital of Wuhan University from November 2021 to April 2022 were enrolled in the study. The severity of liver fibrosis was graded according to the liver stiffness value. The association of liver fibrosis detection rate with gender, age and physiological stages of patients was analyzed, and the correlation between liver stiffness value and HBV DNA, HBsAg, HBeAg level, alanine aminotransferase (AST), aspartate aminotransferase (ALT) and serum albumin levels was further analyzed.Results:Among 2 689 patients with chronic HBV infection, there were 1 417 males aged 46 (34, 57) years and 1 272 females aged 45 (33, 55) years. A total of 1 382 patients (51.03%) showed varying degrees of liver fibrosis, including 381 cases (14.20%) of significant liver fibrosis and 259 (9.60%) cases of progressive fibrosis. Male patients had a significantly higher prevalence of liver fibrosis than that of female patients [60.78%(840/1 382) vs. 39.22%(542/1 382), χ2=74.566, P<0.001]. There were significant differences in liver stiffness values and liver fibrosis detection rates ( F=46.516, 199.079, P<0.001) among patients of different age groups. The liver stiffness index (9.41±4.49 vs. 8.10±3.89, t=9.011, P<0.001) and the prevalence of liver fibrosis in males was higher than those in females in age groups younger than 60 years [61.59%(643/1 044) vs. 38.41%(401/1 044), χ2=78.418, P<0.001]; However, there was no significant gender difference in people over 60 years of age [73.80%(200/271) vs. 71.71%(142/198), χ2=0.252, P>0.05; 20.30%(55/271) vs. 21.21%(42/198), χ2=0.059, P>0.05]. The prevalence of liver fibrosis was significantly lower in premenopausal and perimenopausal females than that in males of the same age groups [29.70%(188/633)and 52.20%(154/295) vs. 64.50%(202/313), χ 2=56.683, P<0.001; χ 2=9.519, P=0.029], whereas there was no significant difference between postmenopausal females and males in the same age group [65.40%(220/336) vs. 72.20%(319/441), χ 2=5.822, P=0.061]. The prevalence of liver fibrosis increased significantly in postmenopausal females as compared to premenopausal females[38.40%(497/1 294) vs. 67.50%(532/787), χ 2=56.683, P=0.002]. The value of liver stiffness in patients with chronic HBV infection was positively correlated with total bilirubin, AST and ALT levels( r=0.208, 0.227, 0.218, P<0.05). Conclusions:The prevalence of liver fibrosis detected by ultrasound transient elastography in chronic HBV-infected patients is substantial, the liver stiffness value and detection rate are higher in males than those in females, however, the prevalence is increased in postmenopausal females. The liver stifness value is related to some biochemical indicators of the liver.

Objective:To investigate the serum levels, diagnosis and prognosis value of endothelin-1(ET-1) in children suffering from lung metastasis of osteosarcoma.Methods:A total of 84 children with osteosarcoma, 67 children with lung metastasis of osteosarcoma and 35 healthy people from January 1, 2013 to January 1, 2018 in Second People′s Hospital of Nanyang were retrospectively included.The serum level of ET-1 was measured by performing enzyme linked immunosorbent assay(ELISA) methods and the influencing factors of serum ET-1 levels in children with lung metastasis of osteosarcoma were conducted by Logistic regression analysis.The clinical value of ET-1 in the prediction of the incidence of lung metastasis in children with osteosarcoma was analyzed by receiver operating characteristic (ROC) curve.Forty-five children with lung metastasis of osteosarcoma were followed up for 18 months and the prognosis value of serum ET-1 levels in children with lung metastasis of osteosarcoma was evaluated by Kaplan-Meier survival analysis. Results:The serum ET-1 level in children with lung metastasis of osteosarcoma was 97.23 (65.13, 134.98) ng/L and significantly higher than osteosarcoma group 60.21 (43.12, 74.63) ng/L and healthy control group 34.45 (12.01, 63.03) ng/L, respectively ( Z=-5.671, -4.92, all P<0.05), with significant differences. Logistic regression analysis proved that lung bilateral involvement ( OR=3.449), numbers of lung metastases (more than 3)( OR=3.449), average diameter of lung metastases (more than 5 cm) ( OR=6.501) and extrapulmonary metastasis ( OR=4.369) were independent risk factors for elevated serum ET-1 levels in children developing lung metastasis of osteosarcoma.The predictive value of ET-1 in the incidence of lung metastasis in children with osteosarcoma was significant (area under ROC curve: 0.841). When the cut-off value was 94.27 ng/L, the sensitivity and specificity were 88.5% and 92.6%, respectively.Survival analysis revealed that higher levels of ET-1 was correlated with poor prognosis ( OR=3.287, 95% CI: 1.119-9.547). Conclusions:The serum levels of ET-1 in children with lung metastasis of osteosarcoma are significantly elevated.ET-1 is a serological marker for the differential diagnosis of lung metastasis of osteosarcoma.Moreover, the higher levels of ET-1 are correlated with poor prognosis in children with lung metastasis of osteosarcoma.