BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

BACKGROUND:Studies have shown that platelet-derived growth factor BB can stimulate the proliferation and osteogenic differentiation of mesenchymal stem cells and accelerate the calcification process of osteoblast-like cells.However,its clinical application has problems such as short half-life and easy decomposition.Loading the growth factor onto a suitable biomaterial scaffold can enable its slow and continuous release and maintain an effective concentration,which has become a hot topic in current research.OBJECTIVE:To observe the effect of chitosan/reduced graphene oxide scaffolds loaded with platelet-derived growth factor BB on the repair of alveolar bone defect in rats.METHODS:(1)Chitosan/reduced graphene oxide scaffolds(referred to as CS/rGO scaffolds)and chitosan/reduced graphene oxide scaffolds loaded with different mass concentrations(5,10,15,and 20 mg/L)of platelet-derived growth factor BB(referred to as CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds)were prepared respectively.The five groups of scaffolds were co-cultured with rat periodontal ligament stem cells.The cell proliferation and migration were detected by CCK-8 assay and Transwell chamber assay,respectively,to screen the appropriate growth factor loading mass concentration for subsequent experiments.CS/rGO scaffolds(or extracts)and CS/rGO/PDGF-BB-15 scaffolds(or extracts)were co-cultured with rat periodontal ligament stem cells,and the osteogenic differentiation and angiogenic ability of the cells were detected.(2)The alveolar bone defect model was prepared in front of the bilateral maxillary first molars of 16 SD rats,and the rats were randomly divided into 4 intervention groups:the blank control group did not receive any intervention,the simple scaffold group was implanted with CS/rGO/PDGF-BB-15 scaffold,the control group was implanted with CS/rGO scaffold and rat periodontal ligament stem cell complex,and the experimental group was implanted with CS/rGO/PDGF-BB-15 scaffold and rat periodontal ligament stem cell complex,with 4 rats in each group.Twelve weeks after surgery,the bone repair of the alveolar bone defect was observed by Micro CT scanning and hematoxylin-eosin staining.RESULTS AND CONCLUSION:(1)CS/rGO/PDGF-BB-5,CS/rGO/PDGF-BB-10,CS/rGO/PDGF-BB-15,and CS/rGO/PDGF-BB-20 scaffolds could promote the proliferation and migration of rat periodontal ligament stem cells.Among them,the CS/rGO/PDGF-BB-15 scaffold had the most significant effect on promoting cell proliferation and migration,and this scaffold was used for subsequent experiments.Compared with the CS/rGO scaffold,the CS/rGO/PDGF-BB-15 scaffold could promote the osteogenic and angiogenic differentiation of rat periodontal ligament stem cells.(2)Micro CT scanning and hematoxylin-eosin staining results showed that the experimental group had the best alveolar bone defect repair effect,and a large amount of new bone tissue and blood vessel formation could be seen.(3)The chitosan/reduced graphene oxide scaffold loaded with platelet-derived growth factor BB can effectively promote the repair of rat alveolar bone defects by promoting the proliferation,migration,angiogenic and osteogenic differentiation of rat periodontal ligament stem cells.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective To explore the efficacy of total laparoscopic subtotal colectomy with transrectal specimen retrieval for the treatment of slow transit constipation(STC).Methods A total of 18 patients with STC underwent laparoscopic subtotal colectomy with transrectal specimen retrieval from June 2022 to December 2024.A portion of the ileocecal region was reserved.The colon specimen was removed from the rectum and anus,and ileocecal rectal anastomosis was performed.The efficacy of treatment was evaluated by using the Wexner constipation score and Gastrointestinal Quality of life index(GIQLI).Results All the operations in the 18 patients were completed smoothly.There was no conversion to laparotomy or addition of abdominal wall incision for specimen retrieval.The operation time was240-480 min(median,360 min),the intraoperative blood loss was 20-100(median,60 ml),and the length of the resected intestinal tube was 70-110 cm(median,95 cm).The gastrointestinal function recovery time of the patients after surgery was 1-3 d(median,2 d),and the hospital stay was 8-13 d(median,10 d).All the patients recovered smoothly after surgery,without serious complications such as anastomotic leakage and abdominal infection.The Wexner constipation score at 6 months after surgery was(5.7±2.8)points,which was significantly lower than the preoperative score[(16.2±2.1)points,t=21.401,P=0.000].The GIQLI score at6 months after surgery was(114.9±9.1)points,which was significantly higher than the preoperative score[(85.2±7.2)points,t=-28.865,P=0.000].Conclusions Total laparoscopic subtotal colectomy with transrectal specimen retrieval is effective for STC.The patients'defecation status and quality of life are improved after surgery,which has certain clinical promotion value.

Objective:To compare the clinical efficacy of navigation system and orthopedic robot-assisted nail placement in the treatment of lower cervical fracture and dislocation.Methods:A retrospective cohort study was conducted to analyze the clinical data of 49 patients with fracture and dislocation of the lower cervical spine who were admitted to Honghui Hospital, Xi′an Jiaotong University School of Medicine from May 2021 to October 2022, including 38 males and 11 females, aged 29-61 years [(39.3±7.3)years]. Injury segments involved C 3 in 12 patients, C 4 in 11, C 5 in 8, C 6 in 9 and C 7 in 9. Twenty-one patients were treated with S8 navigation system (navigation group, 84 screws), and 28 with TINAVI orthopedic robot (robot group, 112 screws). The two groups were compared in terms of the total surgical duration, single screw placement time, total screw placement time, distance between the screw and the anterior cortex, incision length, intraoperative radiation dose, intraoperative blood loss and length of hospital stay. The height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and American Spinal Injury Association (ASIA) grade were assessed before surgery and at 3 days after surgery. Visual analogue scale (VAS), Japanese Orthopedic Association (JOA) score and neck dysfunction index (NDI) before surgery, at 3 days, 3 months after surgery and at the last follow-up were compared. The accuracy of screw placement, intraoperative invasion rate of adjacent facet joints and rate of postoperative complications (infection, screw loosening, etc.) were evaluated. Results:All the patients were followed up for 12-16 months [(13.6±1.9)months]. In the navigation group, the total surgical duration, distance from the screw to the anterior cortex and the intraoperative radiation dose were (236.2±30.6)minutes, (2.0±0.2)mm and (374.3±90.3)mGy respectively, which were significantly shorter or less than those in the robot group [(278.4±20.7)minutes, (10.6±2.9)mm and (448.4±77.9)mGy] ( P<0.01). The single screw placement time, total screw placement time, incision length and intraoperative blood loss were (3.5±0.4)minutes, (23.9±0.5)minutes, (9.1±2.4)cm and (422.2±30.4)ml respectively, which were significantly longer or more than those in the robot group [(2.6±0.2)minutes, (17.9±0.7)minutes, (6.6±2.6)cm and (360.3±56.3)ml] ( P<0.01). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). No significant differences were observed in the height of the intervertebral space, Cobb angle, sliding distance between the vertebral bodies and ASIA grade between the two groups ( P>0.05). At 3 days after surgery, the height of intervertebral space, Cobb angle, sliding distance between vertebral bodies and ASIA grade in both groups were significantly improved when compared with those before surgery ( P<0.05 or 0.01). There were no significant differences in VAS, JOA scores or NDI between the two groups before surgery, at 3 days, 3 months after surgery and at the last follow-up ( P>0.05). The VAS, JOA scores and NDI in both groups were gradually improved at 3 days, 3 months and at the last follow-up after surgery when compared with those before surgery ( P<0.05). There was no significant difference in the accuracy of screw placement of levels 0 and 0+1 between the two groups ( P>0.05). No significant difference in the intraoperative invasion rate of adjacent facet joints between the two groups was found ( P>0.05). There were no serious complications such as infection or screw loosening after surgery in both groups. Conclusions:For lower cervical fracture and dislocation, although there are more advantages in total surgical duration, screw holding force and radiation control regarding the navigation system, and more outstanding performance in screw placement efficiency, incision length and intraoperative blood loss regarding the orthopedic robot, both of them can effectively rebuild the cervical structure, improve neurological function, relieve postoperative pain, improve screw placement accuracy and reduce facet joint injury and serious complications. Selection of the best auxiliary screw placement system should comprehensively consider patients′ conditions and the experience of the surgical team.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective To investigate the relationship between daily intake of monounsaturated fatty acids(MUFAs)and polyunsaturated fatty acids(PUFAs)and non-alcoholic fatty liver disease(NAFLD),and to determine the threshold values of daily MUFAs and PUFAs intake for NAFLD risk.Methods Date were collected from the Dryad database.We enrolled a total of 1 068 healthy subjects aged 18 years and older(534 in the control group and 534 with NAFLD group)who had physical check-up in the Affiliated Nanping First Hospital of Fujian Medical University from April 2015 to August 2017.Comprehensive medical histories were obtained through questionnaires;information on dietary intake was collected using a semi-quantitative food frequency questionnaire and daily MUFAs and PUFAs intake were calculated.Baseline characteristics were compared between the two groups,and Logistic regression and restricted cubic spline(RCS)analyses were used to explore the relationship between daily MUFAs or PUFAs intake and NAFLD.Results Compared with the control group,the prevalence of hypertension,tea drinking,body mass index(BMI),daily energy intake,and daily MUFAs and PUFAs intakes were significant higher in patients with NAFLD(all P＜0.05),but the proportion of physical activities was significantly lower(P＜0.05).Logistic regression analysis revealed that after adjusting other confounding factors such as age,gender and BMI,for every 10 g increase in daily MUFAs or PUFAs intake,the risk of NAFLD increased by 53％(95％ CI:1.25-1.87,P＜0.001)and 3.30 times(95％ CI:2.98-6.20,P＜0.001),respectively.RCS indicated an approximately linear relationship between daily MUFAs intake and NAFLD(P for nonlinearity=0.064)and a nonlinear relationship between daily PUFAs intake and NAFLD(P for nonlinearity＜0.05).Subgroup analysis results were generally consistent,and there was statistical evidence of interactions between MUFAs and factors such as gender,hypertension and education level,with interaction between PUFAs and BMI observed(P＜0.05).Conclusion Increased daily intake of MUFAs or PUFAs is significantly associated with an increased risk of NAFLD,and further research is needed to clarify their specific roles in hepatic lipid accumulation.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets