An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective:To analyze the positioning error of vacuum pad and breast bracket in base note radiotherapy for breast cancer with breast conserving surgery based on cone beam CT (CBCT).Methods:A total of 120 patients who received IMRT after breast conserving surgery for breast cancer in the radiotherapy department of Nantong Cancer Hospital from April 2020 to April 2022 were retrospectively selected. According to the fixation method, the patients were divided into two groups: group A ( n=60) was fixed with a vacuum pad, and group B ( n=60) was fixed with a breast bracket. CBCT was used to evaluate the placement, and the placement errors and the occurrence of radiation dermatitis in each group were analyzed. Results:The translation errors of group A and group B in the left and right directions were (0.33±0.12)cm and (0.34±0.15)cm, respectively, and there was no statistically significant difference between the groups ( P>0.05). The errors in the direction of the abdomen and back were 0.32(0.11, 0.42)cm and 0.15(0.09, 0.21)cm, respectively, while the errors in the direction of the head and foot were 0.34(0.16, 0.34) cm and 0.23(0.15, 0.37)cm, respectively. The translation errors of the head, foot, and abdomen and back in group B were smaller than those in group A (all P<0.05). Patients in group B had significantly smaller translation errors in the left and right directions [group A: (0.31±0.13)cm, group B: (0.18±0.05)cm, P<0.05], and after rotation in the ventral and dorsal directions [group A: (0.31±0.11)cm, group B: (0.23±0.08)cm, P<0.05]. There was no statistically significant difference in translation errors after rotation in the head and foot directions ( P>0.05). The rotation error in the left and right directions of group B was smaller than that of group A [A: (0.98 0.12)°, group B: (0.67±0.31)°, P<0.05]. There was no statistically significant difference in the comparison of head foot and abdominal back rotation errors (all P>0.05). The planned center point (MIDM) of group B patients was located 10 cm to the left and right horizontally (MIDL, MIDR), with MIDM moving 8 cm to the head side (SM), MIDL moving 8 cm to the head side (SL), MIDR moving 8 cm to the head side (SR), MIDM moving 8 cm to the foot side (IM), MIDL moving 8 cm to the foot side (IL), and MIDR moving 8 cm to the foot side (IR). The thickness of the phantom was lower than that of group A (all P<0.05). At the completion of treatment, the total incidence of high-grade radiation dermatitis in group A was 61.67%(37/60), while the total incidence of high-grade radiation dermatitis in group B was 41.67%(25/60). The incidence of high-grade radiation dermatitis in group B was lower than that in group A ( P<0.05). Conclusions:Using breast bracket for breast fixation after breast conserving surgery for breast cancer can reduce the positioning error, the phantom thickness and the incidence of high-grade radiation dermatitis during intensity modulated radiotherapy, which is of high clinical value.

Objective This study aims to investigate the therapeutic effect and mechanism of Naoxinqing on non-alcohol fatty liver disease (NAFLD) induced by a high-fat diet through network pharmacology,molecular docking and in vitro and in vivo experiments. Methods ApoE-/-mice were given a high-fat diet for 12 weeks to establish the NAFLD model,followed by a 12-week Naoxinqing administration. To evaluate the therapeutic effect of Naoxinqing on NAFLD induced by a high-fat diet,biochemical and histopathological experiments were performed,including assessment of blood lipids,liver function,serum inflammatory factors,as well as Hematoxylin and eosin (HE),Oil red O,and Sirius red staining of liver. Subsequently,network pharmacology and molecular docking techniques were employed to predict the key targets of Naoxinqing. Finally,the mechanism of Naoxinqing was validated by Western Blot in HepG2 cells and liver tissue. Results The results of serum biochemistry and liver tissue pathology showed that Naoxinqing can significantly improve high-fat diet-induced hepatic lipid accumulation,hepatocellular injury,and inflammation. Network pharmacology and molecular docking analysis results suggested that Naoxinqing may affect lipid metabolism through the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway. Finally,in vitro cell experiment confirmed that the main mechanism of Naoxinqing is to activative the AMPK/SIRT1 pathway,upregulate the expression of downstream carnitine palmitoyltransferase 1 (CPT1A),promote fatty acid oxidation,and ultimately improve NAFLD. Conclusion This study demonstrated that Naoxinqing improved NAFLD by promoting fatty acid oxidation through the activation of the AMPK/SIRT1 pathway.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Objective To investigate the influencing factors for low-level viremia (LLV) in patients with chronic hepatitis B (CHB) or hepatitis B liver cirrhosis (LC) receiving antiviral therapy and the association of LLV with the progression of liver inflammation and liver fibrosis. Methods A total of 417 patients with CHB or LC who attended the outpatient service of liver diseases in The Affiliated Hospital of Qingdao University from July 1, 2020 to November 30, 2021 were enrolled, and all patients received oral administration of nucleos(t)ide analogues as antiviral therapy for ≥1 year and had an HBV DNA level of < 2000 IU/mL. According to the HBV DNA level, the patients were divided into LLV group (10 IU/mL ≤HBV DNA < 2000 IU/mL) and complete virologic response (CVR) group (HBV DNA < 10 IU/mL). The two groups were compared in terms of general data, virology, biochemistry, and liver fibrosis markers before and after antiviral therapy to investigate the influencing factors for LLV. Meanwhile, the degree of changes in liver inflammation and liver fibrosis markers after antiviral therapy was compared between the two groups to analyze the association of LLV with the progression of liver inflammation and liver fibrosis. The independent samples t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kendall's tau- b method was used for correlation analysis, and a multivariate logistic regression analysis was used to investigate the influencing factors for LLV. Results Among the 417 patients with CHB or LC, 173 developed LLV, and the constituent ratio of LLV was 41.5%; the patients with 10 IU/mL≤HBV DNA < 1000 IU/mL accounted for 94.8%. The logistic regression analysis showed that positive HBeAg (odds ratio [ OR ]=3.009, 95% CI : 1.346-6.729, P =0.007), a family history of LC or HCC ( OR =2.929, 95% CI : 1.344-6.383, P =0.007), and HBV DNA > 1.0×10 8 IU/mL ( OR =10.790, 95% CI : 1.265-92.007, P =0.030) before antiviral therapy were risk factors for the development of LLV, while aspartate aminotransferase (AST) > 40 U/L ( OR =0.355, 95% CI : 0.171-0.737, P =0.005) was a protective factor against LLV; positive HBeAg after antiviral therapy ( OR =4.394, 95% CI : 1.962-9.841, P < 0.001) was still a risk factor for LLV, and course of antiviral therapy ≥2 years and < 3 years ( OR =0.175, 95% CI : 0.046-0.674, P =0.010) and course of antiviral therapy ≥3 years ( OR =0.170, 95% CI : 0.048-0.600, P =0.006) were protective factors against LLV. Compared with the LLV group, the CVR group had significantly greater changes in AST, alpha-fetoprotein (AFP), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) (ΔAST, ΔAFP, ΔAPRI, and ΔFIB-4, respectively) (all P < 0.05). Correlation analysis showed that ΔAST ( τ =-0.192, P = < 0.001), ΔAFP ( τ =-0.192, P < 0.001), ΔAPRI ( τ =-0.210, P =0.002), and ΔFIB-4 ( τ =-0.202, P =0.003) were all negatively correlated with LLV. Conclusion A highly sensitive HBV DNA detection method helps with the early diagnosis of LLV. Strong antiviral therapy should be given to patients with a family history of LC or HCC, a high HBV DNA level, positive HBeAg, or a low AST level, and HBV DNA, AST, and HBeAg should be closely monitored to identify LLV as early as possible.

Pigs are considered as ideal donors for xenotransplantation because they have many physiological and anatomical characteristics similar to human beings. However, antibody-mediated immunity, which includes both natural and induced antibody responses, is a major challenge for the success of pig-to-primate xenotransplantation. Various genetic modification methods help to tailor pigs to be appropriate donors for xenotransplantation. In this study, we applied transcription activator-like effector nuclease (TALEN) to knock out the porcine α-1, 3-galactosyltransferase gene GGTA1, which encodes Gal epitopes that induce hyperacute immune rejection in pig-to-human xenotransplantation. Meanwhile, human leukocyte antigen-G5 gene HLA-G5, which acts as an immunosuppressive factor, was co-transfected with TALEN into porcine fetal fibroblasts. The cell colonies of GGTA1 biallelic knockout with positive transgene for HLA-G5 were chosen as nuclear donors to generate genetic modified piglets through a single round of somatic cell nuclear transfer. As a result, we successfully obtained 20 modified piglets that were positive for GGTA1 knockout (GTKO) and half of them expressed the HLA-G5 protein. Gal epitopes on the cell membrane of GTKO/HLA-G5 piglets were completely absent. Western blotting and immunofluorescence showed that HLA-G5 was expressed in the modified piglets. Functionally, the fibroblasts from the GTKO/HLA-G5 piglets showed enhanced resistance to complement-mediated lysis ability compared with those from GTKO-only or wild-type pigs. These results indicate that the GTKO/HLA-G5 pigs could be a valuable donor model to facilitate laboratory studies and clinics for xenotransplantation.
Animals ; Animals, Genetically Modified ; Gene Knockout Techniques ; HLA Antigens ; Humans ; Nuclear Transfer Techniques ; Swine ; Transplantation, Heterologous

Brain functional network changes over time along with the process of brain development, disease, and aging. However, most of the available measurements for evaluation of the difference (or similarity) between the individual brain functional networks are for charactering static networks, which do not work with the dynamic characteristics of the brain networks that typically involve a long-span and large-scale evolution over the time. The current study proposes an index for measuring the similarity of dynamic brain networks, named as dynamic network similarity (DNS). It measures the similarity by combining the "evolutional" and "structural" properties of the dynamic network. Four sets of simulated dynamic networks with different evolutional and structural properties (varying amplitude of changes, trend of changes, distribution of connectivity strength, range of connectivity strength) were generated to validate the performance of DNS. In addition, real world imaging datasets, acquired from 13 stroke patients who were treated by transcranial direct current stimulation (tDCS), were used to further validate the proposed method and compared with the traditional similarity measurements that were developed for static network similarity. The results showed that DNS was significantly correlated with the varying amplitude of changes, trend of changes, distribution of connectivity strength and range of connectivity strength of the dynamic networks. DNS was able to appropriately measure the significant similarity of the dynamics of network changes over the time for the patients before and after the tDCS treatments. However, the traditional methods failed, which showed significantly differences between the data before and after the tDCS treatments. The experiment results demonstrate that DNS may robustly measure the similarity of evolutional and structural properties of dynamic networks. The new method appears to be superior to the traditional methods in that the new one is capable of assessing the temporal similarity of dynamic functional imaging data.
Aging/physiology* ; Brain/physiology* ; Brain Mapping ; Humans ; Magnetic Resonance Imaging/methods* ; Nerve Net/physiology* ; Transcranial Direct Current Stimulation/methods*

Objective:The aim of this study was to explore the associations of muscle size and density with handgrip strength(HGS)and the Timed Up and Go(TUG)test.Methods:Totally 301 participants living in the Xinjiekou community near Beijing Jishuitan Hospital were recruited for CT imaging of the hip and a 1-cm slice of the mid-thigh.The cross-sectional area and density of the gluteus maximus and the mid-thigh muscles were estimated by the Osirix viewer based on CT images.HGS and TUG were also performed in these subjects.Logistic regression analysis was used to evaluate the correlations of muscle density and size with TUG and grip strength.Results:In women, after adjustment for age and BMI, the density of the gluteus maximus was negatively correlated with TUG( P trend=0.0366), while the size of the gluteus maximus and the mid-thigh muscles was not correlated with TUG.In men, the density or size of these muscles was not correlated with TUG.After adjustment for age and BMI, the density of the gluteus maximus was positively correlated with grip strength( P trend=0.0334)and the size of the mid-thigh muscles was also positively correlated with grip strength( P trend=0.0155)in men, but they were not correlated with grip strength in women. Conclusions:There were sex differences in the relationship between muscle size or density and grip strength or timed up and go.The density of the gluteus maximus is associated with muscle strength and physical performance while the size of the mid-thigh muscles is correlated with muscle strength.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.