Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To investigate the regulatory effects of transcutaneous auricular vagus nerve stimulation (taVNS) on functional connectivity (FC) of thalamic subregions in patients with premenstrual syndrome (PMS).Methods:This study was a cross-sectional investigation. Clinical, laboratory, and imaging data were retrospectively collected from 56 PMS patients (PMS group) and 66 healthy controls (control group) recruited from various universities and hospitals in Nanning between November 2021 and June 2024. Resting-state functional MRI (fMRI) data and fMRI data during taVNS immediate stimulation (2 Hz, 25 Hz) were acquired from subjects during their late luteal phase. Using thalamic subregions (anterior thalamic nucleus, lateral nucleus, ventral nucleus, medial nucleus, central nucleus, posterior nucleus) as seeds, two-sample t-tests or paired t-tests were employed to analyze alterations in thalamic subregion FC in PMS patients and the regulatory effects of taVNS on these changes. Independent samples t-test were used to compare the differences in clinical and laboratory indicators between the PMS group and the control group. The relationship between taVNS regulation of thalamic subregion FC in PMS patients and thalamic internal functional connectivity were analyzed using mediation effect analysis. Results:Compared to the control group, patients in the PMS group showed increased scores on the Daily Record of Severity of Problems, Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Hamilton Anxiety Rating Scale 17, and Hamilton Depression Rating Scale 14 during the late luteal phase ( P<0.05). At baseline, PMS patients exhibited higher FC between the left thalamic lateral nucleus and the left insula, and lower FC between the left medial nucleus, posterior nucleus, and ventral nucleus of the thalamus and the right middle frontal gyrus (MFG) compared to the control group (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 2 Hz taVNS immediate stimulation in PMS group, FC between the left thalamic medial nucleus, posterior nucleus, ventral nucleus and the right MFG, as well as the FC between the left thalamic ventral nucleu and the left MFG increased compared to baseline levels; meanwhile, FC between the left thalamic posterior nucleus, ventral nucleus and the left insula decreased compared to baseline levels (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). During 25 Hz taVNS immediate stimulation, the FC between the left thalamic ventral nucleus and the right MFG decreased compared to the baseline level (GRF corrected, voxel-level P<0.001, cluster-level P<0.05). Mediation effect analysis showed that the FC between the left thalamic posterior nucleus and the left lateral nucleus mediated part of the association between the FC of the left lateral thalamic nucleus-left insula and the FC of the left ventral thalamic nucleus-left putamen/insula; there were significant direct effects between the FC of the left lateral thalamic nucleus-the left posterior nucleus and FC of the left lateral thalamic nucleus-the left insula, as well as between the FC of the left ventral thalamic nucleus-the left MFG and FC of the left ventral thalamic nucleus-the right MFG. Conclusions:taVNS can modulate abnormal FC of the left thalamic subregions in PMS patients, restoring it toward normalization. The regulatory effects of 2 Hz stimulation are more pronounced than those of 25 Hz stimulation. This modulation primarily operates through two pathways: the left thalamic lateral nucleus-left insula-left thalamic ventral nucleus pathway and the left MFG-left thalamic ventral nucleus-right MFG.

Objective:To describe functional disability rate of anxiety disorders in Chinese community adults and explore related risk factors of functional disability.Methods:To conduct in-depth data analysis on China Mental Health Survey(CMHS).The diagnostic tool for anxiety disorders was the Composite International Diagnostic Inter-view-3.0,according to the Diagnostic and Statistical Manual for Mental Disorders,Fourth Edition(DSM-Ⅳ).The World Health Organization Disability Assessment Schedule,2nd edition,was the functional disability assessment standard for anxiety disorders.Weighted 12-month functional disability rate of DSM-Ⅳ anxiety disorder with co-morbidities and only anxiety disorder in population and those in patients,as well as days of partial disability were calculated.The effects of anxiety disorders comorbid other mental disorders and physical diseases and demographic factors on the severity and occurrence of functional disability were analyzed by multiple linear regression and logis-tic regression.Results:The functional disability rate of anxiety disorder with comorbidities in population was 1.7％,and 42.2％in patients,in which constituent rate of grade-four disability was the highest as 84.1％.The functional disability rate of only anxiety disorder in population was 0.3％,and 17.8％in patients.The medians of days of partial disability days in the past 30 days were from 0 to 14.42.Multiple linear regression showed a positive association between comorbid anxiety disorder with other mental disorders and physical diseases(β=0.24),comor-bid other mental disorders and physical diseases(β=0.21),physical diseases(β=0.18),comorbid anxiety disor-der and physical diseases(β=0.15),comorbid anxiety disorder with other mental disorders(β=0.08),other men-tal disorders(β=0.07),only anxiety disorder(β=0.06),lower education level(β=0.12),lower economic status(β=0.08),older age(β=0.06),non-marital status(β=0.06),male(β=0.02)and the severity of functional dis-ability.Logistic regression showed that comorbid anxiety with other mental disorders and physical diseases(OR=64.07),comorbid anxiety disorders with other mental disorders(OR=36.75),comorbid other mental disorders with physical diseases(OR=20.60),comorbid anxiety with physical diseases(OR=18.88),anxiety disorder(OR=9.20),other mental disorders(OR=6.65),physical diseases(OR=4.00),65 years old and over(OR=4.40),50 to 64 years old(OR=2.33),low economic status(OR=2.10),illiterate and below primary school educational level(OR=1.89),middle economic status(OR=1.70),elementary school educational level(OR=1.59),non-marital status(OR=1.47),male(OR=1.16)were the risk factors of the occurrence of functional disability.Conclusion:Comorbidity of anxiety disorders and other mental disorders,and physical diseases increases severity and occurrence of functional disability.Comorbidity,male,gender,older age,lower economic and educa-tional level and non-marital are risk factors of anxiety disorder functional disability.

Objective:To describe disability rates of dementia in community residents aged 65 years and over in China,and explore related risk factors of disability.Methods:This study conducted an in-depth data analysis of the China Mental Health Survey.World Health Organization Disability Assessment Schedule 2.0(WHODAS 2.0)was used to assess dementia disability,Community Screening Interview for Dementia(CSID)and Geriatric Mental Status Examination(GMS)were used for dementia screening and diagnosing.Univariate analysis was used to calcu-late the weighted disability rates of dementia in population and in patients,and their population distribution.Multiple linear regression and logistic regression were used to analyze the risk factors of the occurrence of dementia disability and its severity.Results:The weighted disability rate of dementia was 2.1％in population,and 38.6％in pa-tients.The disability rates of comorbid dementia in population and in patients were higher than those of patients with only dementia.Female,older age,lower education level,lower economic status,and lower cognitive test scores in CSID had higher disability rates of dementia in population.Female and urban resident had higher disability rates of dementia in patients.Multiple linear regression showed economic status(β=0.11),gender(β=0.11),age(β=0.10),and treatment in the last 12 months(β=-0.20)were statistically associated with WHODAS 2.0 scores.Multiple logistic regression showed female(OR=2.81)and treatment in the last 12 months(OR=2.38)were statistically associated with disability.Conclusions:Persons with low economic status,female and elderly peo-ple are the high-risk groups for dementia disability.It should be paid attention to prevent dementia and its conse-quential disabilities.

Objective:To examine the effect of anemia on the prognosis of elderly patients with acute coronary syndrome.Methods:We searched PubMed, Scopus, OVID, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, China Biology Medicine Disc, the WanFang and Weipu databases for studies on the association between anemia and the prognosis of acute coronary syndrome in elderly patients.The date range included the period from the establishment of the database to December 10, 2022.Two reviewers independently completed the literature screening and data extraction according to the inclusion and exclusion criteria for the literature.Stata 16.0 software was used to analyze the data.Results:Of 1 399 references retrieved from the initial search, 13 met the inclusion criteria, including a total of 9540 patients with a mean age of 70.3 years.2872 of these patients had concurrent anemia and 6 668 patients had no anemia.In elderly patients with acute coronary syndrome, those with anemia showed significantly increased risk of death, compared with those with no anemia( RR=2.28, 95% CI: 1.74-3.00). Anemia also increased the incidence of ischemia( RR=1.36, 95% CI: 1.13-1.64)and bleeding events( RR=2.18, 95% CI: 1.59-3.01)( P<0.05 for all). Conclusions:Anemia significantly increases the risk of death and is associated with poor prognosis in elderly patients with acute coronary syndrome.

BACKGROUND: Corneal disease is second only to cataract considered as the leading cause of blindness in the world, with high morbidity. Construction of corneal substitutes In Vitro by tissue engineering technology to achieve corneal regeneration has become a research hotspot in recent years. We conducted in-depth research on the biocompatibility, physicochemical and mechanical properties of rat bone marrow mesenchymal stem cells (rBM-MSCs)-seeded gelatin methacrylate (GelMA) as a bioengineered cornea. METHODS: Four kinds of GelMA with different concentrations (7, 10, 15 and 30%) were prepared, and their physicchemical, optical properties, and biocompatibility with rBM-MSCs were characterized. MTT, live/dead staining, cell morphology, immunofluorescence staining and gene expression of keratocyte markers were performed. RESULTS: 7%GelMA hydrogel had higher equilibrium water content and porosity, better optical properties and hydrophilicity. In addition, it is more beneficial to the growth and proliferation of rBM-MSCs. However, the 30%GelMA hydrogel had the best mechanical properties, and could be more conducive to promote the differentiation of rBM-MSCs into keratocyte-like cells. CONCLUSION As a natural biological scaffold, GelMA hydrogel has good biocompatibility. And it has the ability to promote the differentiation of rBM-MSCs into keratocyte-like cells, which laid a theoretical and experimental foundation for further tissue-engineered corneal stromal transplantation, and provided a new idea for the source of seeded cells in corneal tissue engineering.

Carbon nanotube (CNT) composite materials are very attractive for use in neural tissue engineering and biosensor coatings. CNT scaffolds are excellent mimics of extracellular matrix due to their hydrophilicity, viscosity, and biocompatibility. CNTs can also impart conductivity to other insulating materials, improve mechanical stability, guide neuronal cell behavior, and trigger axon regeneration. The performance of chitosan (CS)/polyethylene glycol (PEG) composite scaffolds could be optimized by introducing multi-walled CNTs (MWCNTs). CS/PEG/CNT composite scaffolds with CNT content of 1%, 3%, and 5% (1%=0.01 g/mL) were prepared by freeze-drying. Their physical and chemical properties and biocompatibility were evaluated. Scanning electron microscopy (SEM) showed that the composite scaffolds had a highly connected porous structure. Transmission electron microscope (TEM) and Raman spectroscopy proved that the CNTs were well dispersed in the CS/PEG matrix and combined with the CS/PEG nanofiber bundles. MWCNTs enhanced the elastic modulus of the scaffold. The porosity of the scaffolds ranged from 83% to 96%. They reached a stable water swelling state within 24 h, and swelling decreased with increasing MWCNT concentration. The electrical conductivity and cell adhesion rate of the scaffolds increased with increasing MWCNT content. Immunofluorescence showed that rat pheochromocytoma (PC12) cells grown in the scaffolds had characteristics similar to nerve cells. We measured changes in the expression of nerve cell markers by quantitative real-time polymerase chain reaction (qRT-PCR), and found that PC12 cells cultured in the scaffolds expressed growth-associated protein 43 (GAP43), nerve growth factor receptor (NGFR), and class III β‍-tubulin (TUBB3) proteins. Preliminary research showed that the prepared CS/PEG/CNT scaffold has good biocompatibility and can be further applied to neural tissue engineering research.
Animals ; Axons ; Biocompatible Materials/chemistry* ; Chitosan/chemistry* ; Nanotubes, Carbon/chemistry* ; Nerve Regeneration ; Polyethylene Glycols ; Porosity ; Rats ; Tissue Engineering/methods* ; Tissue Scaffolds/chemistry*

Organoid models are used to study kidney physiology, such as the assessment of nephrotoxicity and underlying disease processes. Personalized human pluripotent stem cell-derived kidney organoids are ideal models for compound toxicity studies, but there is a need to accelerate basic and translational research in the field. Here, we developed an automated continuous imaging setup with the "read-on-ski" law of control to maximize temporal resolution with minimum culture plate vibration. High-accuracy performance was achieved: organoid screening and imaging were performed at a spatial resolution of 1.1 μm for the entire multi-well plate under 3 min. We used the in-house developed multi-well spinning device and cisplatin-induced nephrotoxicity model to evaluate the toxicity in kidney organoids using this system. The acquired images were processed via machine learning-based classification and segmentation algorithms, and the toxicity in kidney organoids was determined with 95% accuracy. The results obtained by the automated "read-on-ski" imaging device, combined with label-free and non-invasive algorithms for detection, were verified using conventional biological procedures. Taking advantage of the close-to-in vivo-kidney organoid model, this new development opens the door for further application of scaled-up screening using organoids in basic research and drug discovery.
Humans ; Kidney ; Organoids ; Pluripotent Stem Cells

Objective:To investigate the application value of dynamic scintigraphy single-photonemission computed tomography (SPECT) 99m-technetium-galactosyl human serum albumin diethy-lenetriamine pentaacetic ( 99Tc m-GSA) scintigraphy in assessing liver function of perihilar cholangio-carcinoma after portal vein embolization (PVE). Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 16 patients with perihilar cholangiocarcinoma who underwent 99Tc m-GSA scintigraphy after PVE in Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from October 2019 to January 2021 were collected. There were 8 males and 8 females, aged from 46 to 78 years, with a median age of 64 years. Observation indicators: (1) liver volume after PVE; (2) liver function after PVE; (3) typical case analysis. Measurement data with normal distribution were represented as Mean± SD. Count data were represented as absolute numbers or percentages. Comparison of data of the same patient was analyzed using the paired t test. Results:(1) Liver volume after PVE:the morphological liver volume and functional liver volume for the 16 patients were (1 420±211)mL and (389±112)mL. The morphological liver volume and functional liver volume were (636±143)mL and (234±106)mL of planning reserved lobe, (784±210)mL and (151±106)mL of planning resection lobe, respectively. The functional liver density (FLD) of planning reserved lobe and planning resection lobe were 0.36±0.12 and 0.19±0.11, showing a significant difference between them ( t=3.794, P<0.05). The planning resection rate of morpholo-gical liver volume and functional liver volume were 37.8%±0.6% and 54.8%±0.2%, showing a significant difference between them ( t=?3.720, P<0.05). (2) Liver function after PVE: 13 of 16 patients completed the indocyanine green (ICG) test, and 3 patients didn't complete the ICG test due to intolerance. For the 13 patients undergoing ICG test, the total ICG-K value was (0.15±0.03)/minutes, and the ICG-K value of planning reserved lobe was (0.07±0.02)/minutes. The total GSA-K value of 16 patients was (0.14±0.10)/minutes, and the GSA-K value of planning reserved lobe was (0.08±0.06)/minutes. (3) Typical case analysis: a 46-year-old male patient with type Bismuth Ⅲa perihilar cholangiocarcinoma was planned to perform perihilar hepatectomy combined with right hepatectomy. The imaging evaluation showed that the volume of reserved liver lobe accounted for 27% of the total liver volume. The serum total bilirubin was 256 μmol/L when admitted and decreased to 118 μmol/L on the day 5 after percutaneous transhepatic biliary drainage. The right anterior and right posterior branches of PVE was performed. SPECT 99Tc m-GSA examination was performed on the day 37 after PVE. The morphological liver volume was 559 mL of planned reserved lobe and 1 461 mL of the whole liver. The planned morphological liver volume resection rate was 61.7%. ICG-K was 0.12/minutes of the whole liver, and 0.04/minutes of planned reserved lobe. The functional liver volume was 134 mL of planned reserved lobe and 309 mL of the whole liver. The planned resection rate of functional liver volume was 56.6%. The GSA-K was 0.20/minutes of the whole liver and 0.09/minutes of planned reserved lobe. R 0 resection was achieved in perihilar hepatectomy combined with right hepatectomy and no liver failure occurred. The survival time of patients was 11 months. Conclusion:Dynamic SPECT 99Tc m-GSA scintigraphy can effectively evaluate the regional function of the reserved liver lobe in patients with perihilar cholangiocarcinoma after PVE.

【Objective】 To explore the protective effects of exogenous hydrogen sulfide （H2S） on oxygen glucose deprivation and re-oxygenation （OGD/R）-induced SH-SY5Y cell injury. 【Methods】 OGD/R model was established in SH-SY5Y cells. Based on interferences， SH-SY5Y cells were divided into control group （no interference）， OGD/R model group， and treatment groups （OGD/R model treated with different concentrations of NaHS （H2S donor）. The cells were cultured in low glucose medium without fetal bovine serum under 37 ℃， 93% N2 and hypoxia （2% O2） for 12 h， then in complete medium under normoxia （5% O2 ） for 24 h. CCK-8 was used to detect cell viability， and flow cytometry was used for assaying the level of cellular apoptosis. Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins including glucose regulatory protein 78 （GRP78）， CCAAT/enhancer-binding homologous protein （CHOP）， NF-κB P65 and COX-2. 【Results】 The cell viability was lower in OGD/R model group than in the control group （P<0.05）. NaHS treatment at a concentration of 0-0.5 mmol/L increased cell viability in OGD/R model group in a dose-dependent manner （P<0.05）. In contrast， NaHS （C>0.5 mmol/L） decreased cell viability of OGD/R （P<0.05）. The apoptosis level of early stage in OGD/R model group was significantly higher than that in control group （P<0.05）. NaHS treatment at concentrations of 0.2 and 0.4 mmol/L lowered the apoptosis level of early stage in OGD/R model group （P<0.05）. Western blot showed that the protein expression levels of GRP78， CHOP， NF-κB p65， and COX-2 were significantly higher in OGD/R model group than those in control group （P<0.05）. When compared with OGD/R model group， the expression levels of GRP78， CHOP， NF-κBp65 and COX-2 were decreased by NaHS at concentrations of 0.2， 0.4 and 4 mmol/L （P<0.05）， but there was no statistically significant difference among the treatment groups （P>0.05）. 【Conclusion】 NaHS can rescue cell viability of OGD/R-induced cell injury. It may be achieved by inhibiting the activation of NF-κBp65 and COX-2 proteins induced by endoplasmic reticulum stress to reduce the level of cell apoptosis.