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: 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

Neural crest-derived mesenchymal stem cells (MSCs) are known to play an essential function during tooth and skeletal development. PRX1⁺ cells constitute an important MSC subtype that is implicated in osteogenesis. However, their potential function in tooth development and regeneration remains elusive. In the present study, we first assessed the cell fate of PRX1⁺ cells during molar development and periodontal ligament (PDL) formation in mice. Furthermore, single-cell RNA sequencing analysis was performed to study the distribution of PRX1⁺ cells in PDL cells. The behavior of PRX1⁺ cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model. Although PRX1⁺ cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars, their distribution in third molars is highly limited. The PDL formation is associated with a high number of PRX1⁺ cells; during transplanted teeth PDL reconstruction, PRX1⁺ cells from the recipient alveolar bone participate in angiogenesis as pericytes. Overall, PRX1⁺ cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.
Animals ; Cell Differentiation ; Mesenchymal Stem Cells ; Mice ; Molar ; Osteogenesis/physiology* ; Periodontal Ligament

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.

As China has not yet established a sound regional trauma treatment system and standardized trauma centers at all levels, the trauma treatment capability in China is poorer than that in the developed countries. At present, Shaanxi Province has not established a regional trauma treatment system and standardized trauma centers at all levels. Based on the analysis of the characteristics of geography, population and social environment in Shaanxi Province, the authors explore the concept of the trauma treatment system and the construction of trauma centers at all levels in Shaanxi Province on the platform of the trauma center of Shaanxi People's Hospital ( Grade I trauma center) . The authors clarify the respective hardware facilities, team structure, treatment process and quality control goals, training and management system of professional trauma teams in trauma centers at all levels, so as to provide reference for improving the overall level of trauma treatment in Shaanxi Province.

Objective To investigate the management of Graves' disease in Jiangsu province. Methods According to the 2011 management of GD survey from American Thyroid Association and the 2013 survey from European Thyroid Association, a questionnaire was designed for this survey to acquire the diagnosis, treatment, and follow-up of Graves' disease among endocrinologists from 35 tertiary hospitals in Jiangsu province. Results A total of 476 valid questionnaires were collected. For patients with symptoms of hyperthyroidism, a large majority of respondents monitored serum FT3 , FT4 , TSH, thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody, and finding of thyroid ultrasound, accounted for 95. 6％, 95. 0％, 95. 4％, 95. 8％, 90. 3％, 90. 5％, and 93. 9％physicians, respectively. 91.2％ of physicians preferred anti-thyroid drugs as the first-line treatment, and 92. 6％ of them gave priority to the use of methimazole. For the duration of anti-thyroid drugs therapy, 41.2％of endocrinologists chose 24 months, while 20％ chose 18 months. When patients have moderate and active ophthalmopathy, most respondents with medium or senior professional titles preferred anti-thyroid drugs, while most resident physicians chose radioactive iodine plus corticosteroids. When pregnancy was confirmed in the patients of Graves' disease, 88％ of respondents preferred propylthiouracil during the first trimester of pregnancy, and 58. 4％ of them would continue propylthiouracil into the second trimester. Conclusions The mastering of basic perception of Graves' disease knowledge is satisfactory among the endocrinologists. But by comparing to the American and European survey results and related guidelines, there are still some differences in diagnosis and treatment. Therefore, physicians should notice those differences and make improvement on standardized treatment for patients to raise the response ratio while reducing the recurrent events.

Objective To evaluate the efficacy and safety of epalrestat, an aldose reductase inhibitor, and epalrestat plus methylcobalamine on diabetic peripheral neuropathy, as compared with methylcobalamine. Methods A total of 444 subjects with diabetic neuropathy were enrolled in the study, and divided into methylcobalamine group ( n= 145 ) , epalrestat group ( n = 143 ) , and methylcobalamine combined with epalrestat group ( n = 156 ) . Therapeutic efficacay was assessed in terms of clinical symptoms and physical examinations by using Michigan Neuropathy Screening Instrument ( MNSI ) , and electrophysiological assessments. Results After 4 to 12-weeks′treatment, symptoms and signs of neuropathy ( using MNSI ) are significantly improved in the three groups ( P<0. 01). The mean changes of MNSI ( questionnaire) score from baseline were higher in epalrestat group and methylcobalamine combined with epalrestat group as compared with that of methylcobalamine group(P<0. 05), but no difference was detected in the change of MNSI ( physical examination ) score from baseline among three groups. After treatment for 12 weeks, motor nerve conduction velocity ( MNCV ) was significantly improved in epalrestat group and methylcobalamine combined with epalrestat group(P<0. 05), but no difference was detected in MNCV at 12 week among three groups(P>0. 05). Conclusion Epalrestat is effective and safe in the treatment of diabetic neuropathy. Furthermore, epalrestat is more efficacious in ameliorating symptoms and MNCV of neuropathy than methylcobalamine. However, while no improved efficacy is shown with the combined treatment.

Objective To analyze the efficacy and safety of glimepiride treatment as initial monotherapy in newly diagnosed patients with type 2 diabetes mellitus (T2DM).Methods This was a subgroup analysis of the GREAT study,which investigated the efficacy and safety of glimepiride as initial monotherapy in Chinese patients with T2DM.This analysis was performed in 209 patients with disease duration less than 6 months and never received any anti-diabetic drugs.The change of HbA1C,fasting plasm glucose (FPG),2 h postprandial blood glucose (2hPPG),homeostasis model assessment for β-cell function index (HOMA-β),homeostasis model assessment for insulin-resistance index(HOMA-IR),the percentage of patients with HbA1C ＜ 7.0％ at endpoint and the incidence of hypoglycemia were evaluated after 16-weeks treatment.Results After 16-weeks glimepiride treatment,HbA1C value reduced significantly from baseline to endpoint,the reduction was statistically significant (9.21％ ± 1.65％ to 6.69％±0.83％,P＜0.001),69.7％ of the patients achieved HbA1C ＜7.0％ at study endpoint.Glimepiride-treated patients also achieved a significant improvement in FPG [from (10.15 ± 2.13) mmol/L to (7.23 ± 1.50) mmol/L,P＜0.001] and 2hPPG [from (17.21 ±4.14) mmol/L to (11.62 ± 3.34) mmol/L].HOMA-β was improved from 17.21± 15.19 [11.62 (2.90,115.8)] to 41.13 ± 44.12 [28.00 (5.1,360.00)],and HOMA-IR was reduced from 2.32± 1.90 [1.76 (0.60,12.80)] to 2.07 ± 1.74 [1.63 (0.4,12.3)].The incidence of all reported symptomatic hypoglycemia was 18.2％,and the incidence of confirmed hypoglycemia was 3.8％.Conclusion This analysis showed that glimepiride treatment as an initial mono-therapy could effectively improve blood glucose control in newly diagnosed patients with T2DM,and the treatment may improve islet β cell function,and the safety profile is reasonably good.