ObjectiveTo investigate the mechanism of Huangqin Tang （HQT） in regulating metabolic reprogramming during the inflammation-cancer transformation in colitis-associated colorectal cancer （CAC）. MethodsCAC mouse model was established using the carcinogen azoxymethane （AOM） combined with the inflammatory agent dextran sulfate sodium （DSS）. HQT treatment was adopted. Serum metabolomics analysis was performed at three stages （inflammation， proliferation， and tumor formation） using liquid chromatography-tandem mass spectrometry （LC-MS/MS） untargeted metabolomics coupled with multivariate statistical analysis to explore the mechanism of HQT intervention in metabolism in CAC. ResultsThe results revealed that HQT significantly reversed the disturbance of key metabolites in CAC mice. A total of 52， 67， and 45 differential metabolites were identified in the model group， compared to the normal group， during inflammation， proliferation， and tumor stages， respectively. Lactate， linoleic acid， oleic acid， elaidic acid， and betaine were characteristic metabolites persistently enriched throughout colitis-cancer transformation. Pathway enrichment analysis of differential metabolites showed that linoleic acid metabolism and arachidonic acid metabolism were the most significantly disturbed in CAC pathogenesis. The proliferation stage featured expanded amino acid metabolic networks， while the tumor stage uniquely exhibited two new pathways of nicotinate and nicotinamide metabolism and phosphoinositide metabolism. HQT exerted stage-specific regulatory effects： targeting arachidonic acid metabolism in the inflammation stage， correcting the dysregulation of choline-carnitine metabolism in the proliferation stage， and rescuing nicotinamide and tryptophan metabolic collapse in the tumor stage. ConclusionHQT exerts regulatory effects on metabolic disorders at various stages of the colitis-cancer transformation process， thereby effectively slowing the progression from colitis to cancer. The study also reveals the dynamic metabolic characteristics of colorectal "inflammation-cancer transformation，"providing new insights for research on the targeted mechanisms of traditional Chinese medicine in anti-tumor therapy based on metabolic reprogramming.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

Background::Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).Methods::Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.Results::A total of 355 RNAm-SNPs related to m 6A, m 1A, m 5C, m 7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m 6A-SNPs, highlighting the potential functional relevance of m 6A in physiological processes influencing BP. Notably, m 6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion::The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

Background::Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).Methods::Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.Results::A total of 355 RNAm-SNPs related to m 6A, m 1A, m 5C, m 7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m 6A-SNPs, highlighting the potential functional relevance of m 6A in physiological processes influencing BP. Notably, m 6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion::The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

BACKGROUND: Bone defect difficult to manage clinically and it is a big challenge to repair it. Secondary metabolites source from herb has shown potential for the treatment of bone defect. METHODS: Mesenchymal stem cells (MSCs) were isolated from mice and incubated with urolithin A (UA) (10, 25, and 50 lg/mL). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to estimate apoptosis and mineralisation was evaluated by alkaline phosphatase assay and alizarin red S staining. A middle femoral defect was induced in mice and bone tissue was prepared for endochondral ossification by treating with UA. The effect of UA was estimated by determining markers of osteoblast proliferation in serum and micro-computed tomography to analyse bone defects. RESULTS: UA enhanced mineralisation of MSCs and osteogenic gene markers in MSCs in vitro. Also, the bone defect score and bone mineral density were improved by UA. Moreover, UA ameliorated the altered Wnt3a protein and histopathological changes in bone defect mice. CONCLUSION Presented report conclude that UA enhances osteoblast proliferation in bone-defect mice by activating the Wnt pathway.

Objective:To investigate the clinical features and risk factors of multiple organ dysfunction syndrome (MODS) caused by wasp sting.Methods:A retrospective cohort study was conducted to collect the general data of wasp sting patients who had a clear history of wasp sting disease and clinical manifestations from June 2016 to December 2020 and were first diagnosed as wasp sting in hospital. Patients with hematological diseases, malignant tumors, severe liver and kidney dysfunction, cardiac insufficiency, and patients who had received hormone therapy before admission were excluded. Patients who were unable to obtain effective laboratory results due to hemolysis or other reasons within 48 h of admission were also excluded. The white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), hemoglobin count (HB), myoglobin (Mb/MYO), activated partial thromboplastin time (APTT), albumin (ALB), K, Na, and Cl of the blood samples collected within 48 h after admission were recorded. Patients were divided into the MODS group and non-MODS group according to whether MODS occurred during hospitalization. Uni- and multivariate analysis were used to analyze the factors affecting the occurrence of MODS in wasp sting patients during hospitalization, and the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive effect of myoglobin level on the occurrence of MODS in wasp sting patients during hospitalization.Results:Mb, WBC, NEU, APTT and serum potassium in the MODS group [3890.00 (1416.90-4057.00) ng/mL, (21.99 ± 8.18) × 10 9/L, (19.61 ± 7.33)× 10 9/L, (93.75 ± 45.77) s, and (4.99 ± 0.95) mmol/L] were significantly higher than those in the non-MODS group [73.50 (34.30-264.20) ng/mL, (13.40 ± 4.14)× 10 9/L, (11.18±4.73)× 10 9/L, (37.00 ± 17.16) s, and (4.05 ± 0.56) mmol/L] (all P < 0.05); blood chlorine and ALB [(101.50 (98.25-105.00) mmol/L and (35.36 ± 6.44) g/L)] were significantly lower than those in the non-MODS group [(105.00 (103.00-107.00) mmol/L and (40.71 ± 5.48) g/L)] (all P < 0.05). Multivariate logistic regression analysis showed that NEU ( OR = 0.729, 95% CI: 0.542~0.981), Mb ( OR = 0.999, 95% CI: 0.998~1.000), and APTT ( OR = 0.951, 95% CI: 0.921~0.982) were independent risk factors for MODS in wasp sting patients. ROC curve analysis showed that NEU, Mb and APTT could be used to evaluate the occurrence of MODS in wasp sting patients. Among them, Mb had the highest predictive value (AUC = 0.950, 95 % CI: 0.891~0.982). The optimal cutoff value of Mb for predicting the occurrence of MODS in wasp sting patients was 515.30 ng/mL, and the corresponding sensitivity and specificity were 90.62% and 87.23%, respectively. Conclusion:Mb is an independent risk factor for MODS in wasp sting patients, which can be used as a good predictor of MODS in wasp sting patients.

Objective:To investigate the effect of flap combined with 3D printed microporous titanium(tantalum)prosthesis in the treatment of lower extremity soft tissue defect with large bone defect.Methods:From January 2019 to December 2020, 2 patients with large soft tissue defects on dorsal foot together with large metatarsal bone defect and 4 patients with soft tissue defects of calf with large tibial bone defect were treated. The areas of soft tissue defect were 5.0 cm×8.0 cm-15.0 cm×10.0 cm. The length of the bone defect were 3.8 cm to 7.0 cm, 5.75 cm in average. In the first stage, metatarsal bone defect or tibial bone defect was filled with vancomycin blended bone cement, meanwhile, soft tissue defect was repaired with anterolateral femoral flap(ALTF) with vascular anastomosis in 2 cases of feet, and local fascia flap was trans-positioned in 4 cases of lower extremity defects. The sizes of repairing flap were 6.0 cm×8.5 cm-16.0 cm×11.0 cm. Two to 7 months after the initial surgery, the customer designed microporous titanium prostheses were used(5 cases with microporous titanium and 1 with microporous tantalum) to repair the bone defects. The wound healing, the integration of metatarsal and tibial fractures with 3D printed microporous titanium(tantalum) prostheses, and the walking condition were observed after surgery. The follow-up lasted from 6 to 25 months, with an average of 12.7 months.Results:The wound healing in 5 patients was good. The patients stood on the foot in 2 months after surgery, started to walk with the assistance of crutch in 3 months after surgery, and took walk without assistance in 5-6 months after surgery. Good osseous integration were achieved. One diabetic patient had infection of foot wound 3 months after surgery. After removal of microporous titanium prosthesis and replacement of vancomycin blended interstitial substance of bone cement, the wound healed and the patient resumed walking.Conclusion:It is an effective method to encourage the patients to take early ambulation after the surgery for lower extremity soft tissue defect with large bone defect that was repaired by a flap and 3D printed microporous titanium(tantalum)prosthesis. Further observations are required to investigate the long-term efficacy, and the reduction of prosthesis infection rate requires further exploration.

Traumatic rib fractures are the most common injury in thoracic trauma. Previously，the patients with traumatic rib fractures were mostly treated non-surgically，of which 50%，especially those combined with flail chest presented chronic pain or chest wall deformities and over 30% had long-term disabilities，being unable to retain a full-time job. In the past two decades，thanks to the development of internal fixation material technology，the surgical treatment of rib fractures has achieved good outcomes. However，there are still some problems in clinical treatment，including inconsistency in surgical treatment and quality control in medical services. The current consensuses on the management of regional traumatic rib fractures published at home and abroad mainly focus on the guidance of the overall treatment decisions and plans，and relevant clinical guidelines abroad lacks progress in surgical treatment of rib fractures in recent years. Therefore，the Chinese Society of Traumatology affiliated to Chinese Medical Association and Chinese College of Trauma Surgeons affiliated to Chinese Medical Doctor Association，in conjunction with national multidisciplinary experts，formulate the Chinese Consensus for Surgical Treatment of Traumatic Rib Fractures（2021）following the principle of evidence-based medicine，scientific nature and practicality. This expert consensus puts forward some clear，applicable，and graded recommendations from aspects of preoperative imaging evaluation，surgical indications，timing of surgery，surgical methods，rib fracture sites for surgical fixation，internal fixation methods and material selections，treatment of combined injuries in rib fractures，in order to provide references for surgical treatment of traumatic rib fractures.