Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective To explore the expression level of visceral adipose tissue-derived serine protease inhibitor(Vaspin)and secreted frizzled-related protein5(SFRP5)in the serum of children with idiopathic short stature(ISS)and its diagnostic value.Methods 70 children with ISS diagnosed in the First Hospital of Zhangjiakou from December 2021 to February 2023 were selected as the disease group,while 72 healthy volunteer children who underwent physical examination were collected as the control group.Immunoluminescence was applied to detect the expression level of VASPIN,Enzyme-linked immunosorbent assay(ELISA)was applied to detect the expression level of SFRP5 the clinical data of children in two groups were analyzed.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of serum Vaspin and SFRP5 for ISS,multivariate Logistic regression was used to analyze the influencing factors of ISS.Results Compared with the control group,the serum Vaspin level in the disease group was obviously increased(2.89±0.92 ng/ml vs 1.81±0.42 ng/ml),while the SFRP5 level was obviously reduced(10.22±2.84 pg/ml vs 13.21±3.53 pg/ml),the differences were statistically significant(t=9.040,5.552,all P＜0.05).The weight,height,body mass index(BMI)and proportion of sexual development stage II～V of children in the disease group were obviously lower than those in the control group,and the differences were statistically significant(t=7.687,6.330,5.559,7.024,all P＜0.05).The area under ROC curve showed that the AUC of Vaspin and SFRP5 and their combined detection in the diagnosis of ISS were 0.768,0.849 and 0.925,respectively,the combined diagnosis efficacy of Vaspin and SFRP5 was better than that of serum Vaspin and SFRP5 alone(Z =3.829,P＜0.001;Z =2.141,P=0.032).Multivariate Logistic regression analysis showed that BMI(OR=0.508,95%CI:0.260～0.991),Vaspin(OR=3.458,95%CI:1.125～10.631)and SFRP5(OR=0.378,95%CI:0.153～0.935)were the influencing factors for ISS(all P＜0.05).Conclusion The expression level of Vaspin in the serum of children with ISS is obviously increased,while the expression level of SFRP5 is obviously reduced.The two are influencing factors of ISS,and the combined detection of their expression levels has certain value in the diagnosis of ISS.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

The family readiness for discharge of premature infants in the Neonatal Intensive Care Unit (NICU) is an important index to evaluate the safe discharge of premature infants, and a good family discharge readiness is the basic guarantee for the smooth recovery and healthy growth of premature infants. This article summarizes the concept, influencing factors, and intervention strategies of family discharge readiness for premature infants in NICU, in order to provide reference for the formulation and improvement of discharge readiness measures for premature infants in NICU.

Objective:To evaluate the effect of intermittent fasting on postoperative cognitive function in aged rats and the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in it.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), postoperative cognitive dysfuction (POCD) group (group P), intermittent fasting + POCD group (group IF+ P), and intermittent fasting+ JAK2/STAT3 signaling pathway agonist C-A1+ POCD group (group IF+ A+ P). IF+ P group and IF+ A+ P group underwent a 4-week intermittent fasting procedure: fasting for 24 h followed by free eating for 24 h, without limiting water intake throughout the entire process, in addition C-A1 100 μg/kg was intraperitoneally injected daily during intermittent fasting in IF+ A+ P group. Rats underwent exploratory laparotomy under sevoflurane anesthesia to prepare POCD models in P group, IF+ P group and IF+ A+ P group. Three days after surgery, open field tests were conducted to evaluate the autonomous motor function of rats, and Morris water maze tests were conducted to evaluate the cognitive function of rats on 3-7 days after surgery. After the Morris water maze tests, the rats were sacrificed and the hippocampal CA1 area was removed for determination of the expression of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3) (by Western blot) and contents of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for microscopic examination of pathological changes of hippocampal CA1 region (using HE staining). Results:There was no statistically significant difference in the speed, distance and duration of stay at the center of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage occurred in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were decreased ( P<0.05), and the pathological damage in the hippocampal CA1 area was significantly alleviated in IF+ P group. Compared with IF+ P group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage in the hippocampal CA1 area was aggravated in group IF+ A+ P. Conclusions:Intermittent fasting can improve postoperative cognitive function in aged rats, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway and reducing the neuroinflammatory responses in the hippocampal CA1 region.

Objective:To investigate the application of patient-based real-time quality control (PBRTQC) using exponentially weighted moving average (EWMA) method in internal quality control (IQC) procedures of thyroid function tests.Methods:The serum thyroid function test results of outpatients and inpatients in the Second Hospital of Shandong University from December 1, 2022 to April 30, 2023 were collected. Based on the PBRTQC professional intelligent software system, normality correction, parameter setting, program preparation and real-time operation of test data were carried out. The results of all patients who underwent thyroid function testing between May 1, 2023 and August 31, 2023 were used as the validation dataset. The estimated EWMA value of thyroid function test results and the cumulative coefficient of variation ( CV) over 4 months were calculated. The cumulative CV was compared with the criteria of precision quality standard (1/3TEa) and the CV of IQC. Westgard 2-2s and 1-3s rules were used for alarm setting. The early warning information of the EWMA quality control program were recorded and the potential causes of performance changes were analyzed. DxLab Mind software was used to conduct normal distribution statistics for all data, and the Kolmogorov-Smirnov test was performed on the test results. Results:The items related to serum thyroid function of the patients were all positively skewed. After data correction by Box-Cox method, the PBRTQC data of free triiodothyronine (FT3) and free thyroxine (FT4) were normally distributed, and their cumulative precisions ( CV) of EWMA within 4 months were 6.26% and 2.86%, respectively, both of which were lower than the precision quality target of 8.33%. However, the data of thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TgAb) were still positive skewed after modification. The EWMA cumulative CV of TSH, TPOAb and TgAb were 13.16%, 15.31% and 16.77%, which were higher than the precision quality targets of 8.33%, 10% and 10%, respectively. The EWMA QC program can detect different out-of-control alarms, including FT4 false alarms due to sample source concentration and TSH result bias caused by changes in reagent performance. In addition, the EWMA QC program can also detect differences in FT3 results between different DXI800 fully automated chemiluminescence instrument instruments. Conclusions:The EWMA program based on PBRTQC professional intelligent software tools can monitor the patient data of the detection system in real time and continuously, dynamically identify and monitor the errors generated during the analysis process and give early warning. It can be used as a useful supplement for the daily IQC of thyroid function items, especially FT3 and FT4, and has good clinical application value.

Objective:Comparison of early cholecystectomy (EC) and delayed cholecystectomy (DC) after percutaneous transhepatic gallbladder drainage (PTGD) for over 80-year-old patients with acute cholecystitis.Methods:Clinical data of 297 over-80-year-old patients of with acute cholecystitis undergoing surgery in Shidong Hospital Affiliated to the University of Shanghai for Science and Technology from January 2016 to January 2023 were retrospectively analyzed, including 123 males and 174 females, aged (86.1±5.2) years. There were 176 cases in EC group and 121 in PTGD-DC group. Demographic data and perioperative outcomes were compared between the groups, including gender, age, ASA score, lab test, grades of acute cholecystitis, symptom, time before EC or PTGD, intraoperative blood loss, conversion, respiratory disfunction, gangrenous cholecystitis, abdominal drainage time, postoperative complication, hospital stay, intensive care time.Results:The baseline characteristics were similar between EC and PTGD-DC groups, including demographics, ASA score, grades of acute cholecystitis, white blood cell counting, platelet counting, level of serum procalcitonin, time before EC or PTGD, and percentage of comorbidity. Compared to PTGD-DC group, Patients in DC group experienced more intraoperative blood loss (118±62 vs 32±31ml], longer operative time (135±43 vs 61±31) min], higher incidence of gangrenouscholecystitis [23.2%(41/176) vs 9.9%(12/121)], more respiratory support [16.5%(29/176) vs 11.6%(14/121)], more conversion to open surgery [22.7%(40/176) vs 9.1%(11/121)], longer postoperative abdominal drainage time (9.1±2.6 vs 3.8±2.3d], longer hospitalization (8.2±3.1 vs 6.1±2.2 d], longer intensive care (9.0±0.3 vs 4.6±0.2 h] (all P<0.05). More complications were observed in EC group, such as bile leakage, postoperative bleeding, unscheduled reoperation, bile duct injury (all P<0.05). Conclusion:PTGD and DC could lower the perioperative risk of elderly patients with acute cholecystitis.

With in-depth research and development of dermoscopy, the dermoscopic features including perifollicular pigments, perilesional pigments, pigment network structure, satellite phenomenon and "tapioca sago" appearance, micro-Koebner phenomenon and comet tail-like phenomenon have provided a basis for the evaluation of vitiligo activity. This review summarizes progress in the evaluation of vitiligo activity with dermoscopy in recent years, aiming to promote the application of dermoscopy in the assessment of vitiligo activity.