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 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 explore the effectiveness and safety of different salvage therapies for local recurrence of tumor following primary prostate cryoablation so as to provide the reference for the treatment of prostate similar cases. 【Methods】 The clinical data of patients with prostate cancer (cT1c-4N0M0) who received salvage therapy for local recurrence of tumor following primary prostate cryoablation in the Sun Yat-Sen University Cancer Center during June 2014 and Dec. 2020 were retrospectively analyzed. Salvage therapies included local therapy (salvage radiotherapy, salvage cryoablation or salvage radical prostatectomy) and androgen deprivation therapy (ADT). 【Results】 Altogether 8 patients were involved. The median age was 71(63-76) years, the median prostate specific antigen (PSA) at the first diagnosis was 17.650(10.380-325.100) ng/mL, the median nadir post-cryoablation PSA was 0.041(0.003-0.541) ng/mL, and the median PSA at local recurrence was 3.030(2.090-19.180) ng/mL. Abnormal digital rectal examination was found in 3 cases, and radiographic evidence of local recurrence was found in 7 cases. Prostate biopsy was performed in 4 cases, 2 of which had positive results. The median follow-up after salvage therapy lasted for 54 (9-75) months. Four cases received salvage radiotherapy, 2 of which developed bloody stool, hematuresis and urinary tract infection, and recovered after conservative treatment; 1 case received salvage cryoablation without side effects; 1 case underwent radical prostatectomy and radiotherapy, developed lymphorrhagia and recovered after conservative treatment; 2 cases received ADT alone, one experienced hot flashes and recovered after conservative treatment, and the other progressed into castration-resistant prostate cancer after 63 months. No other progression or death occurred at the termination of follow-up. 【Conclusion】 Salvase therapy (salvage radiotherapy, salvage cryoablation, salvage radical prostatectomy) and ADT can be used for local recurrence of tumor following primary prostate cryoablation. However, large-scale prospective research is needed to confirm the effectiveness and safety of different therapies.

Objective:To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Methods:This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO 2), peak metabolic equivalents (peak MET), and other indicators. Weber′s classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients′ psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results:A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO 2 (15.04±3.93) ml·min -1·kg -1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min -1·kg -1, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes ( P<0.05). Conclusion:The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients′ cardiopulmonary function.

Objective:To analyze the influencing factors of achieving textbook outcome (TO) after pancreaticoduodenectomy (PD) in patients with pancreatic ductal adenocarcinoma, and to construct a nomograph model to explore its predictive value in TO.Methods:The clinical data of 205 patients with pancreatic ductal adenocarcinoma treated by PD in Henan University People's Hospital from January 2019 to December 2022 were analyzed retrospectively, including 88 males and 117 females with the age of (61.3±9.8) years old. Patients were divided into two groups based on whether they achieved TO after surgery: TO group ( n=113) and non-TO group ( n=92). Clinical data such as age, gender, intraoperative blood loss, operation time, blood transfusion volume, pancreatic CT value, and tumor differentiation degree were collected. Logistic regression analysis screened the influencing factors of PD postoperative TO and built a nomogram model. The performance of the nomogram model was evaluated using receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis. Results:Multivariate logistic regression analysis showed that the higher the degree of tumor differentiation was in patients with pancreatic ductal adenocarcinoma (high differentiation to medium differentiation: OR=7.20, 95% CI: 1.20-43.28; high differentiation to low differentiation: OR=16.55, 95% CI: 2.01-136.11), CT value>38.45 Hu ( OR=0.29, 95% CI: 0.13-0.65), blood transfusion volume ≤350 ml ( OR=8.05, 95% CI: 2.94-22.01) and operative time ≤407.5 min ( OR=10.88, 95% CI: 3.90-30.41), the easier it was to achieve TO after PD (all P<0.05). Based on the above influencing factors, a nomogram model of the postoperative effect of PD on TO was established, and the consistency index of this column graph model was 0.863 (95% CI: 0.816-0.911). The sensitivity and specificity of ROC curve were 0.804 and 0.752, respectively. The calibration diagram showed that the calibration curve fits well with the ideal curve, and the decision curve showed that the model had obvious positive net benefit. Conclusion:The degree of tumor differentiation, CT value, blood transfusion volume, and operation time are independent influencing factors for the achievement of TO after PD in patients with pancreatic ductal adenocarcinoma, and the nomogram model constructed based on which has good predictive performance for TO.

Objective:To analyze the influencing factors of not achieving textbook outcome (TO) after laparoscopic radical surgery in patients with malignant pancreatic body and tail tumor, and to establish and evaluate a nomogram for predicting the failure to achieve TO.Methods:The clinical data of 111 patients with malignant pancreatic body and tail tumors undergoing laparoscopic radical surgery in the Department of Hepatobiliary and Pancreatic Surgery in Henan Provincial People's Hospital from January 2020 to December 2022 were retrospectively analyzed, including 44 males and 67 females, aged (53.8±14.7) years. All patients were staged TNM I to II, including pancreatic ductal adenocarcinoma ( n=102, 91.9%), pancreatic neuroendocrine tumor ( n=5, 4.5%), and pancreatic intraductal papillary mucinous tumors ( n=4, 3.6%). The patients were randomly divided into a training set ( n=78) and a test set ( n=33) at a ratio of 7∶3. The 78 patients in the training set were further divided into TO group ( n=28) and control group ( n=50, not achieving TO). Based on the univariate and multivariate logistic regression analysis of training set, the influencing factors of failure to achieve TO after laparoscopic radical surgery in patients with pancreatic body and tail tumor were analyzed. A nomogram based on the multi-factors were established to predict the failure to achieve TO. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) were utilized to evaluate the nomogram. Results:There were significant differences in tumor diameter, positive lymph nodes, operation time and CT value of pancreas between the TO and control groups (all P<0.05). Multivariate logistic regression analysis showed that tumor diameter >4 cm ( OR=9.673, 95% CI: 2.198-42.579), positive lymph node ( OR=5.385, 95% CI: 1.514-19.154), pancreatic CT value ( OR=0.594, 95% CI: 0.392-0.902) were the influencing factors for patients who did not achieve TO (all P<0.05). Based on the results of multiple factors, a nomogram was established to predict the failure to achieve TO after laparoscopic radical surgery. The area under the ROC curve of the nomogram was 0.849 (95% CI: 0.757-0.940) and 0.873 (95% CI: 0.730-1.000) in the training and test sets, respectively. The calibration curve was close to the ideal curve and the predicted results of the nomogram matched well with the actual results. The DCA showed that the nomogram has obvious positive net benefit. Conclusion:The nomogram constructed with tumor diameter > 4 cm, positive lymph nodes and CT value of pancreas for prediction of the patients with pancreatic body and tail malignant tumor after laparoscopic radical surgery did not achieve TO has good performance.

OBJECTIVE: N6-methyladenosine (m ⁶A) is a common epigenetic modification in eukaryotes. In this study, we explore the potential impact of m ⁶A-associated single nucleotide polymorphisms (m ⁶A-SNPs) on heart failure (HF). METHODS: Data from genome-wide association studies (GWAS) investigating HF in humans and from m ⁶A-SNPs datasets were used to identify HF-associated m ⁶A-SNPs. Their functions were explored using expression quantitative trait locus (eQTL), gene expression, and gene enrichment analyses. Mediation protein quantitative trait locus (pQTL)-Mendelian randomization (MR) was used to investigate the potential mechanism between critical protein levels and risk factors for HF. RESULTS: We screened 44 HF-associated m ⁶A-SNPs, including 10 m ⁶A-SNPs that showed eQTL signals and differential expressions in HF. The SNP rs1801270 in CDKN1A showed the strongest association with HF ( P = 7.75 × 10 ^-6). Additionally, MR verified the genetic association between the CDKN1A protein and HF, as well as the mediating effect of blood pressure (BP) in this pathway. Higher circulating level of CDKN1A was associated with a lower risk of HF (odds ratio [ OR] = 0.82, 95% confidence interval [ CI]: 0.69 to 0.99). The proportions of hypertension, systolic BP, and diastolic BP were 48.10%, 28.94%, and 18.02%, respectively. Associations of PDIA6 ( P = 1.30 × 10 ^-2) and SMAD3 ( P = 4.80 × 10 ^-2) with HF were also detected. CONCLUSION Multiple HF-related m ⁶A-SNPs were identified in this study. Genetic associations of CDKN1A and other proteins with HF and its risk factors were demonstrated, providing new ideas for further exploration of the molecular mechanisms of HF.
Humans ; Polymorphism, Single Nucleotide ; Heart Failure/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Cyclin-Dependent Kinase Inhibitor p21/metabolism* ; Quantitative Trait Loci ; Adenosine/metabolism* ; Male ; Female ; Genetic Predisposition to Disease

OBJECTIVE: To design customized titanium alloy lunate prosthesis, construct three-dimensional finite element model of wrist joint before and after replacement by finite element analysis, and observe the biomechanical changes of wrist joint after replacement, providing biomechanical basis for clinical application of prosthesis. METHODS: One fresh frozen human forearm was collected, and the maximum range of motions in flexion, extension, ulnar deviation, and radialis deviation tested by cortex motion capture system were 48.42°, 38.04°, 35.68°, and 26.41°, respectively. The wrist joint data was obtained by CT scan and imported into Mimics21.0 software and Magics21.0 software to construct a wrist joint three-dimensional model and design customized titanium alloy lunate prosthesis. Then Geomagic Studio 2017 software and Solidworks 2017 software were used to construct the three-dimensional finite element models of a normal wrist joint (normal model) and a wrist joint with lunate prosthesis after replacement (replacement model). The stress distribution and deformation of the wrist joint before and after replacement were analyzed for flexion at and 15°, 30°, 48.42°, extension at 15°, 30°, and 38.04°, ulnar deviation at 10°, 20°, and 35.68°, and radial deviation at 5°, 15°, and 26.41° by the ANSYS 17.0 finite element analysis software. And the stress distribution of lunate bone and lunate prosthesis were also observed. RESULTS: The three-dimensional finite element models of wrist joint before and after replacement were successfully constructed. At different range of motion of flexion, extension, ulnar deviation, and radial deviation, there were some differences in the number of nodes and units in the grid models. In the four directions of flexion, extension, ulnar deviation, and radial deviation, the maximum deformation of wrist joint in normal model and replacement model occurred in the radial side, and the values increased gradually with the increase of the range of motion. The maximum stress of the wrist joint increased gradually with the increase of the range of motion, and at maximum range of motion, the stress was concentrated on the proximal radius, showing an overall trend of moving from the radial wrist to the proximal radius. The maximum stress of normal lunate bone increased gradually with the increase of range of motion in different directions, and the stress position also changed. The maximum stress of lunate prosthesis was concentrated on the ulnar side of the prosthesis, which increased gradually with the increase of the range of motion in flexion, and decreased gradually with the increase of the range of motion in extension, ulnar deviation, and radialis deviation. The stress on prosthesis increased significantly when compared with that on normal lunate bone. CONCLUSION The customized titanium alloy lunate prosthesis does not change the wrist joint load transfer mode, which provided data support for the clinical application of the prosthesis.
Humans ; Lunate Bone/surgery* ; Finite Element Analysis ; Titanium ; Wrist Joint/surgery* ; Artificial Limbs ; Range of Motion, Articular ; Biomechanical Phenomena

A patient suffered a sustained soft tissue necrosis and infection at the radial interphalangeal joint of left thumb after laser nevus removal. He was treated in the Department of Orthopaedics, No. 920 Hospital of Joint Logistic Support Force of Chinese People's Liberation Army in February 2020. CTA combined with digital technology of Mimics software was used to accurately locate the perforator of posterior tibial artery septal perforator flap at the appropriate part of the calf and the super flap (1.20 cm×0.80 cm×0.46 cm) for the repair was designed. After 1 year of follow-up, the left thumb flap had no swelling with a satisfactory texture and appearance. The sensory recovered to S 3, and the left thumb movement was completely normal. Only a linear scar remained at the donor site of the calf.

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.