BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

BACKGROUND:Macrophage polarization plays a key role in chronic inflammatory joint diseases such as rheumatoid arthritis.Cerium dioxide(CeO2)nanoparticles have a wide range of biomedical applications such as modulating the local inflammatory microenvironment of tissues.OBJECTIVE:To investigate the role of CeO2 nanoparticles on macrophage polarization and inflammatory factor expression,as well as inflammatory modulation in a co-culture system of macrophages and fibroblasts.METHODS:(1)CeO2 nanoparticles were dispersed and observed morphologically by transmission electron microscopy.(2)Human leukemia monocytes(THP-1)were induced to differentiate and establish the M1 macrophage pro-inflammatory cell model of rheumatoid arthritis.The cells were divided into M0 group(undifferentiated macrophages),M1 group(successful macrophage modeling),CeO2 nanoparticle treatment group(M1 group with CeO2 nanoparticle treatment),and dexamethasone control group(M1 group with dexamethasone treatment)and incubated for 48 hours.The effects of CeO2 nanoparticles on the expression of inflammatory factors(endogenous nitric oxide synthase,CD86,CD80)in M1 macrophages and M1 macrophage phenotype(CD80,CD206)were detected by RT-qPCR,western blot assay,and flow cytometry.(3)A co-culture system of macrophages and fibroblasts was established,and CeO2 nanoparticles acted on the upper macrophages.The regulation of CeO2 nanoparticles on the expression of inflammatory factors(interleukin-6,tumor necrosis factor-α,cyclooxygenase-2,and endogenous nitric oxide synthase)of fibroblasts in the co-culture system was observed at the mRNA and protein levels.RESULTS AND CONCLUSION:(1)Transmission electron microscopy showed that the diameter of CeO2 nanoparticles was(19.5±2.0)nm.(2)Compared with the M0 group,the mRNA of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the M1 group were upregulated.Compared with the M1 group,the mRNA expression of endogenous nitric oxide synthase and CD86,and the protein expression of endogenous nitric oxide synthase and CD80 in the CeO2 nanoparticle treatment group were downregulated.Flow cytometry showed that 20 nm CeO2 nanoparticles downregulated the number of M1 macrophages.(3)Compared with the M1 group,20 nm CeO2 nanoparticles downregulated the mRNA and protein expression of inflammatory factors(tumor necrosis factor α,interleukin 6,cyclooxygenase 2,and endogenous nitric oxide synthase)in the co-culture system HFL1 cells.(4)The results showed that 20 nm CeO2 nanoparticles can alleviate inflammation in the co-culture system by inhibiting the expression of pro-inflammatory factors in M1 macrophages,providing a new idea for the treatment of inflammatory diseases such as rheumatoid arthritis.

BACKGROUND: The role of inflammation in the development of gestational diabetes mellitus (GDM) has recently become a focus of research. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), novel indices, reflect the body's chronic immune-inflammatory state. This study aimed to investigate the associations between the SII or SIRI and GDM. METHODS: A prospective birth cohort study was conducted at Beijing Obstetrics and Gynecology Hospital from February 2018 to December 2020, recruiting participants in their first trimester of pregnancy. Baseline SII and SIRI values were derived from routine clinical blood results, calculated as follows: SII = neutrophil (Neut) count × platelet (PLT) count/lymphocyte (Lymph) count, SIRI = Neut count × monocyte (Mono) count/Lymph count, with participants being grouped by quartiles of their SII or SIRI values. Participants were followed up for GDM with a 75-g, 2-h oral glucose tolerance test (OGTT) at 24-28 weeks of gestation using the glucose thresholds of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Logistic regression was used to analyze the odds ratios (ORs) (95% confidence intervals [CIs]) for the the associations between SII, SIRI, and the risk of GDM. RESULTS: Among the 28,124 women included in the study, the average age was 31.8 ± 3.8 years, and 15.76% (4432/28,124) developed GDM. Higher SII and SIRI quartiles were correlated with increased GDM rates, with rates ranging from 12.26% (862/7031) in the lowest quartile to 20.10% (1413/7031) in the highest quartile for the SII ( Ptrend <0.001) and 11.92-19.31% for the SIRI ( Ptrend <0.001). The ORs (95% CIs) of the second, third, and fourth SII quartiles were 1.09 (0.98-1.21), 1.21 (1.09-1.34), and 1.39 (1.26-1.54), respectively. The SIRI findings paralleled the SII outcomes. For the second through fourth quartiles, the ORs (95% CIs) were 1.24 (1.12-1.38), 1.41 (1.27-1.57), and 1.64 (1.48-1.82), respectively. These associations were maintained in subgroup and sensitivity analyses. CONCLUSION The SII and SIRI are potential independent risk factors contributing to the onset of GDM.
Humans ; Female ; Pregnancy ; Diabetes, Gestational/immunology* ; Prospective Studies ; Adult ; Inflammation/immunology* ; Glucose Tolerance Test ; Birth Cohort

[Objective] To investigate the protective effect of Salvia miltiorrhiza injection (SMI) on the kidneys of HBOC-CHP01 resuscitated haemorrhagic shock rats. [Methods] A 50% haemorrhagic shock rat model was established, with 12 rats divided into two groups: SMI + HBOC-CHP01 group and HBOC-CHP01 group, with 6 rats in each group. The rats in the SMI+ HBOC-CHP01 group were given an equal volume of HBOC-CHP01 for resuscitation after haemorrhagic shock, and an 8 mL/kg dose of SMI. Rats in the HBOC-CHP01 group were resuscitated by administering an equilibrium blood loss volume of HBOC-CHP01 and given an 8 mL/kg dose of 0.9% NaCl solution. Blood was taken from rats at five points: before bloodletting (baseline), during haemorrhagic shock (HS), immediately after resuscitation (RS0h), 1 h after resuscitation (RS1h), and 24 h after resuscitation (RS24h). A blood gas analyser was used to detect the lactate level (Lac), glucose content (Glu), residual base (BEecf), pH, bicarbonate (HCO3-), high iron haemoglobin (MetHb). White blood cells (WBC), platelets (PLT), haemoglobin content (Hb), carboxyhaemoglobin (COHb) were detected using a quintuple classification. Blood creatinine (SCr), uric acid (UA), kidney-related indexes were detected using biochemistry instrument. Kidney tissues of the rats were taken after 24 h of resuscitation and after execution, and the inflammation of kidneys of the rats of the two groups was analyzed using HE staining. Fluorescence staining was used to detect the level of ROS in the kidneys of rats in both groups. [Results] At RS 0h, the Beecf, Glu and Lac levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group, and the pH level of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group, and the Glu levels of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group at RS 1h. At RS 0h, the WBC, PLT and COHb contents of rats in the SMI+HBOC-CHP01 group were all significantly higher than those of rats in the HBOC-CHP01 group, and at RS 1h, the WBC content of rats in the SMI+HBOC-CHP01 group was significantly higher than that of rats in the HBOC-CHP01 group; at RS 1h, the UA content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the SCr content of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC-CHP01 group; at RS 24h, the inflammation level of kidney tissues of rats in the SMI+HBOC-CHP01 group was significantly lower than that of rats in the HBOC -CHP01 group rats, and the ROS and MPO levels in the kidney tissues of rats in the SMI+HBOC-CHP01 group were significantly lower than those of rats in the HBOC-CHP01 group. [Conclusion] The combination of Salvia miltiorrhiza injection during the resuscitation of rats with severe haemorrhagic shock by HBOC-CHP01 can alleviate renal injury by reducing inflammatory response and oxidative stress.

Objective:This study aims to construct an evaluation index system suitable for the core competency of Clinical Research Coordinators (CRCs) in Investigator-Initiated Trials (IITs) in China.Methods:This study developed a system framework through the Onion Model, literature research, and expert interviews, utilized the Delphi method to build the index system. and analyzed the weight of each indicator through the Analytic Hierarchy Process (AHP).Results:Four first-level indicators were basic knowledge (0.143), job skills (0.300 8), professional quality (0.483 9), and personality traits (0.072 3). Besides, 18 second-level indicators and 49 third-level indicators were developed through the Delphi method. According to the third round expert′s consultation, the average scores of all indexes were >3.50, the authoritative coefficient was 0.86, the coefficient of variation of each index was <0.30, and Kendall coefficients of concordance were 0.183~0.366 ( P<0.001). The consistency ratios of single-sort were<0.1, and the overall sort of all indexes was 0.043 7, which showed good logical reliability. Conclusions:This evaluation index system for Clinical Research Coordinators is of great scientific sense. It provides IIT-conducting investigators in institutions with a proficient assessment tool to help them find qualified and reliable CRCs.

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

Objective:To investigate the impact of body composition and inflammatory nutritional indicators on postoperative complications in patients with obstructive colorectal cancer,and to develop and validate a nomogram model.Methods:This is a retrospective case series study. The clinical data of 293 patients with obstructive colorectal cancer who were treated at the Department of Gastrointestinal Surgery,the Affiliated Hospital of Qingdao University,between January 2016 and January 2024,were retrospectively collected. The cohort included 182 males and 111 females,aged (65.0±12.1) years (range: 18 to 80 years). The dataset was randomly divided into a training group ( n=196) and a validation group ( n=97) with a 7∶3 ratio. Independent sample t test and multivariate logistic regression analysis were employed to identify independent risk factors associated with postoperative complications in patients with obstructive colorectal cancer. A preoperative nomogram model was subsequently developed for predicting postoperative complications,which was further validated using a validation cohort. Results:The training group comprised 119 males and 77 females,with 68 cases experiencing postoperative complications and 128 cases without complications. The validation group included 63 males and 34 females,with 30 cases experiencing postoperative complications and 67 cases without complications.Univariate analysis and multivariate analysis revealed that low skeletal muscle index ( OR=0.867,95% CI: 0.795 to 0.947),high visceral fat index ( OR=1.058,95% CI: 1.028 to 1.089),high systemic immune inflammation index ( OR=1.002, 95% CI: 1.000 to 1.003), low prognostic nutritional index ( OR=0.847,95% CI: 0.782 to 0.917),and preoperative anemia ( OR=2.714,95% CI: 1.161 to 6.344) were independent risk factors for postoperative complications (all P<0.05). A nomogram prediction model based on these five indicators was established. The area under the receiver operating characteristic (ROC) curve for the prediction model was 0.878 (95% CI: 0.829 to 0.928) in the training group and 0.849 (95% CI:0.767 to 0.930) in the validation group. Conclusions:The preoperative nomogram model,which incorporates inflammatory and nutritional indicators,demonstrates a good accuracy in predicting postoperative complications for patients with obstructive colorectal cancer. This model can effectively assist in guiding treatment decisions.

Osteosarcoma(OS)is a common primary malignant bone tumor with high mortality,disability,metastasis,and recurrence rates and a complex pathogenesis,Resulting in serious effects on patient quality of life and huge economic burdens on families and society.Traditional Chinese medicine(TCM)has"multi-target,multi-component and multi-pathway"characteristics.Recent studies using animal and cell models demonstrated that the mechanism of OS progression was related to Notch,mitogen-activated protein kinase,Wnt/β-catenin,phosphatidylinositol 3-kinase/AKT,Hedgehog and nuclear factor-κB,transforming growth factor-β/Smad and signal transducer and activator of transcription pathways.TCM can exert anti-tumor effects by influencing biological processes such as cell proliferation,migration,invasion,apoptosis,and autophagy via interfering with the above signaling pathways.This review considers the roles of these signaling pathways in OS and summarizes the current research status of TCM interventions in the prevention and treatment of OS,with the aim of providing a reference for future studies of TCM treatments of OS and to provide new ideas for its clinical treatment.

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.