Abstract: To study the protective effect of asiaticoside(AS) on Isoproterenol Hydrochloride(ISO)-induced myocardial injury in mice. Methods: Sixty male C57BL/6 mice were randomly divided into blank control(CON) group, model group [ISO,ISO 10/(kg·d)], Low dose group [ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)], Medium dose group [ISO+AS-M, ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)], High dose group [ISO+AS-H, ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)]. Heart mass ratio was counted; changes were observed in electrocardiogram; Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-1β and cardiac troponin T(cTn-T) in serum; Masson staining was used to observe the fibrosis of mouse myocardial tissue; Western blot was used to detect the ratio of Bax and Bcl-2 protein expression levels(Bax/Bcl-2) and the expression levels of Caspase-3 and NLRP3 proteins in myocardial tissue; real-time quantitative polymerase chain reaction(qPCR) was used to detect the mRNA expression levels ofANP,BNP,β-MHC,TNF-α, IL-6, Type Ⅰ collagen(COLⅠ), and Type Ⅲ collagen(COLⅢ). Results: Compared with the CON group, the ISO group had an elevated heart-to-mass ratio(P<0.01), a lower heart rate(P<0.05), a prolonged QT interval(P<0.05), elevated expression of myocardial injury markers cTn-T,ANP,BNP, andβ-MHC(P<0.01); increased expression of IL-1β in the serum(P<0.01), increased expression ofTNF-αin the cardiac tissue and increasedIL-6expression(P<0.001), and NLRP3 protein expression was elevated(P<0.05); myocardium showed a large number of collagen fibers bluish staining(P<0.001),COLⅠ,COLⅢmRNA expression levels increased(P<0.001), and Bax/Bcl-2 ratio(P<0.001) and Caspase-3 expression were significantly elevated(P<0.05). Compared with ISO group, heart-to-mass ratio of mice in ISO+AS-L and ISO+AS-M groups decreased(P<0.05), heart rate increased, QT interval was shortened, cTn-T, ANP, BNP and β-MHC decreased(P<0.001), myocardial collagen fiber blue-staining decreased(P<0.01). The mRNA expression levels ofCOLⅠandCOLⅢdecreased(P<0.05). The expression levels of IL-1β and TNF-α decreased(P<0.01). NLRP3, Caspase-3 protein expression and Bax/Bcl-2 ratio decreased(P<0.05). The expression level ofIL-6in ISO+AS-M group decreased(P<0.01). The expression levels ofANP,BNP, andTNF-αmRNA expression were reduced in the ISO+AS-H group(P<0.001); the degree of myocardial fibrosis was improved(P<0.05), and the expression levels ofCOLⅠandCOLⅢmRNA were reduced(P<0.05). Conclusion AS has a protective effect against ISO-induced myocardial injury in mice by ameliorating cardiac fibrosis, inhibiting cardiomyocyte apoptosis and attenuating myocardial tissue inflammatory response.

BACKGROUND:Apoptosis plays an important role in secondary brain injury.Therefore,to explore the pathophysiological mechanism of promoting nerve cell survival after traumatic brain injury provides a new direction and theoretical basis for the prevention and treatment of traumatic brain injury. OBJECTIVE:To explore the expression changes of Lnx1 molecule in mammalian cortical neurons after brain injury and the possible mechanism involved in secondary brain injury. METHODS:Eighty adult SD rats were divided into 20 male and 20 female mice in sham operation group and 20 male and 20 female mice in traumatic brain injury group.The traumatic brain injury rat model was established by heavy falling method.At 6,12,24,48,and 72 hours after brain injury,the expression of related molecules in damaged cortical neurons was analyzed by RT-qPCR,western blot assay,and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The brain tissue of traumatic brain injury group was bleeding and obvious tissue injury could be observed.Water content of brain tissue increased after traumatic brain injury.(2)Compared with the sham operation group,the expression of Lnx1 in cortical neurons after traumatic brain injury increased significantly at 24 hours after injury.(3)After traumatic brain injury,the expression of PBK and BCR protein decreased,and the pro-survival factor ctgf increased.(4)These findings suggest that after traumatic brain injury,the expression of Lnx1 is up-regulated in neurons,which may be due to the decrease of the expression of its target molecules PBK and BCR,and further promote the expression of living factor ctgf,which has a protective effect on the damaged neurons.

OBJECTIVE: To evaluate the effectiveness of functional perforator flaps utilizing the superficial circumflex iliac artery as a vascular pedicle, as well as chimeric iliac bone flaps, in the reconstruction of composite tissue defects in the hand and foot. METHODS: A retrospective review of the clinical data from 13 patients suffering from severe hand or foot injuries, treated between May 2019 and January 2025, was conducted. The cohort comprised 8 males and 5 females, with ages ranging from 31 to 67 years (mean, 48.5 years). The injuries caused by mechanical crush incidents (n=9) and traffic accidents (n=4). The distribution of injury sites included 8 cases involving the hand and 5 cases involving the foot. Preoperatively, all patients exhibited bone defects ranging from 2.0 to 6.5 cm and soft tissue defects ranging from 10 to 210 cm². Reconstruction was performed using functional perforator flaps based on the superficial circumflex iliac artery and chimeric iliac bone flaps. The size of iliac bone flaps ranged from 2.5 cm×1.0 cm×1.0 cm to 7.0 cm×2.0 cm×1.5 cm, while the size of the soft tissue flaps ranged from 4 cm×3 cm to 15 cm×8 cm. In 1 case with a significant hand defect, a posterior interosseous artery perforator flap measuring 10.0 cm×4.5 cm was utilized as an adjunct. Likewise, an anterolateral thigh perforator flap measuring 25 cm×7 cm was combined in 1 case involving a foot defect. All donor sites were primarily closed. Postoperative flap survival was monitored, and bone healing was evaluated through imaging examination. Functional outcomes were assessed based on the location of the defects: for hand injuries, grip strength, pinch strength, and flap two-point discrimination were measured; for foot injuries, the American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analogue scale (VAS) score, Maryland Foot Score, plantar pressure distribution and gait symmetry index (GSI) were evaluated. RESULTS: All flaps survived completely, with primary healing observed at both donor and recipient sites. All patients were followed up 6-18 months (mean, 12.2 months). No significant flap swelling or deformity was observed. Imaging examination showed a bone callus crossing rate of 92.3% (12/13) at 3 months after operation, and bone density recovered to more than 80% of the healthy side at 6 months. The time required for bone flap integration ranged from 2 to 6 months (mean, 3.2 months). One patient with a foot injury exhibited hypertrophic scarring at the donor site; however, no major complication, such as infection or bone nonunion, was noted. At 6 months after operation, grip strength in 8 patients involving the hand recovered to 75%-90% of the healthy side (mean, 83.2%), while pinch strength recovered to 70%-85% (mean, 80%). Flap two-point discrimination ranged from 8 to 12 mm, approaching the sensory capacity of the healthy side (5-8 mm). Among the 5 patients involving the foot, the AOFAS score at 8 months was 80.5±7.3, VAS score was 5.2±1.6. According to the Maryland Foot Score, 2 cases were rated as excellent and 3 as good. Gait analysis at 6 months after operation showed GSI above 90%, with plantar pressure distribution closely resembling that of the contralateral foot. CONCLUSION The use of functional perforator flaps based on the superficial circumflex iliac artery, combined with chimeric iliac bone flaps, provides a reliable vascular supply and effective functional restoration for the simultaneous repair of composite bone and soft tissue defects in the hand or foot. This technique represents a viable and effective reconstructive option for composite tissue defects in these anatomical regions.
Humans ; Male ; Middle Aged ; Female ; Perforator Flap/transplantation* ; Adult ; Plastic Surgery Procedures/methods* ; Hand Injuries/surgery* ; Aged ; Retrospective Studies ; Foot Injuries/surgery* ; Ilium/transplantation* ; Iliac Artery/surgery* ; Soft Tissue Injuries/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

OBJECTIVE: To investigate the effectivess of arthroscopic Wafer surgery combined with triangular fibrocartilage complex (TFCC) insertion point reconstruction in the treatment of Palmer type ⅡC combined with typeⅠB ulnar impingement syndrome. METHODS: The clinical data of 14 patients with Parlmer type ⅡC combined with type ⅠB ulnar impingement syndrome who met the selection criteria between July 2021 and April 2024 were retrospectively analyzed. There were 7 males and 7 females with an average age of 43 years ranging from 16 to 59 years. The causes of injury were fall in 8 cases and sprain in 6 cases. The time from injury to operation ranged from 1 to 6 months, with an average of 2.3 months. Distal radioulnar joint instability was found in all cases. Arthroscopic Wafer surgery combined with TFCC insertion point reconstruction was used. The effectiveness was evaluated by comparing the wrist flexion-dorsiflexion range of motion, wrist ulnar deviation-radial deflection range of motion, forearm pronation-supination range of motion, visual analogue scale (VAS) score, and modified Mayo wrist score before and after operation. RESULTS: All patients were followed up 6-12 months, with an average of 9.1 months. The positive variation of ulna was (3.2±0.7) mm before operation, and the negative variation of ulna was (2.2±0.6) mm after operation. There was a significant difference in ulna variation between pre- and post-operation ( t=23.851, P<0.001). The pain symptoms and forearm rotation function of the patients after operation significantly improved. At last follow-up, the wrist flexion-dorsiflexion range of motion, wrist ulnar deviation-radial deflection range of motion, forearm pronation-supination range of motion, VAS score, and modified Mayo wrist score significantly improved when compared with those before operation ( P<0.05). CONCLUSION Arthroscopic Wafer surgery combined with TFCC insertion point reconstruction can effectively relieve wrist pain, enhance the stability of the distal radioulnar joint, and restore the function of the wrist in patients with Palmer type ⅡC combined with type ⅠB ulnar impingement syndrome.
Humans ; Male ; Adult ; Arthroscopy/methods* ; Female ; Triangular Fibrocartilage/surgery* ; Middle Aged ; Range of Motion, Articular ; Retrospective Studies ; Wrist Joint/physiopathology* ; Adolescent ; Young Adult ; Ulna/surgery* ; Treatment Outcome ; Wrist Injuries/surgery* ; Plastic Surgery Procedures/methods* ; Joint Instability/surgery*

OBJECTIVE: To investigate the effectiveness of posterior lateral perforator flap in lower limb combined with free fibula for maxillary tissue defect repair. METHODS: Between December 2018 and December 2023, 16 patients with the maxillary malignant tumors were admitted. There were 10 males and 6 females, with an average age of 64.3 years (range, 54-75 years). There were 7 cases of maxillary gingival cancer, 5 cases of hard palate cancer, and 4 cases of maxillary sinus cancer. According to the 2017 American Joint Committee on Cancer (AJCC) TNM stage, there were 8 cases of stage Ⅲ, 6 cases of stage Ⅳa, and 2 cases of stage Ⅳb. After resection of the lesion, the remaining maxillary defects were classified into class Ⅱa in 3 cases, class Ⅱb in 5 cases, and class Ⅲb in 8 cases according to Brown's classification. The size of soft tissue defects ranged from 4 cm×3 cm to 8 cm×6 cm. The posterior lateral perforator flap in lower limb in size of 5 cm×4 cm-9 cm×7 cm were harvested to repair soft tissue defects, and free fibula in length of 6-11 cm were used to repair bone defects. The donor sites of the lower limb were sutured directly (6 cases) or repaired with free skin grafting (10 cases). Six patients with positive lymph node pathology were treated with radiotherapy after operation. At 6 and 12 months after operation, the self-assessment was performed by the University of Washington Quality of Survival Questionnaire Form (QUW-4) in five dimensions (facial appearance, swallowing function, chewing function, speech function, and mouth opening), and swallowing function was evaluated by using the Kubota water swallowing test. RESULTS: Postoperative pathological examination showed that all patients were squamous cell carcinoma. One patient who was treated with radiotherapy developed osteomyelitis and 1 patient developed venous crisis of skin flap. The rest of the flaps and all skin grafts survived, and the wounds healed by first intention. All patients were followed up 1-5 years (mean, 2.8 years). Two patients died of local recurrence of the tumor at the 4th and 5th years after operation, respectively. Except for the chewing function score and total score at 6 months after operation, which showed significant differences compared to preoperative scores ( P<0.05), there was no significant difference in other QUW-4 scale scores between different time points ( P>0.05). The patients' swallowing function evaluated by Kubota water swallowing test reached normal in 4 cases, suspicious in 9 cases, and abnormal in 3 cases at 6 months after operation, and 10, 6, and 0 cases at 12 months after operation, respectively. The swallowing function at 12 months was significantly better than that at 6 months ( Z=-2.382, P=0.017). CONCLUSION The posterior lateral perforator flap in the lower limb combined with free fibula to repair maxillary tissue defects can repair soft and hard tissue defects at the same time, so that the patient's facial appearance, swallowing function, chewing function, speech function, and mouth opening are satisfactorily restored and the mid-term effectiveness is good.
Humans ; Middle Aged ; Male ; Female ; Fibula/surgery* ; Aged ; Perforator Flap ; Plastic Surgery Procedures/methods* ; Maxilla/surgery* ; Maxillary Neoplasms/surgery* ; Free Tissue Flaps/transplantation* ; Lower Extremity/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

Knee osteoarthritis is a common joint disease within osteoarthritis,characterized by pain,swelling,and limited functionality as the main clinical manifestations.In severe cases,it affects daily life and falls under the category of"impediment syndrome"or"bone impediment"in TCM.The author believes that the theory of"bones,tendons,and muscles"is closely related to this disease.Treatment should focus on simultaneously nourishing the liver,spleen and kidneys,considering tendons,bones and muscles,while also dispelling wind,cold and dampness.The clinical application of Sanbi Decoction has shown good efficacy,and this discussion aimed to provide ideas for the diagnosis and treatment of knee osteoarthritis.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aims to provide theoretical support for the formulation of thyroid nodule prevention and treatment strategies in Northwest China and to investigate the characteristics of thyroid nodules and their association with metabolic indicators in this population.Methods A cross-sectional survey was conducted by retrospectively enrolling healthy individuals who underwent routine health examinations at our hospital between January 1 and December 31,2023.A total of 38 919 participants were included.The detection rate of thyroid nodules was stratified by age and sex.Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for thyroid nodules.Results Among the 38 919 participants,20 395 were men(52.4%)and 18 524 were women(47.6%).The overall detection rate of thyroid nodules was 47.1%(18 317/38 919),including 40.1%(8 187/20 395)in men and 54.7%(10 130/18 524)in women.Across all age groups,women had a significantly higher detection rate than men(P<0.001).The detection rate increased with age in both sexes(χ2trend=1392.867,P<0.001 in men;χ2trend=1521.215,P<0.001 in women).Significant differences were observed between participants with and without thyroid nodules in age,body mass index(BMI),fasting blood glucose(FBG),glycated hemoglobin(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triiodothyronine(T3),thyroid-stimulating hormone(TSH),and anti-thyroglobulin antibodies(TGAB),anti-thyroid microsomal antibodies,the proportion of hypertension and central obesity(all P<0.05).Multivariate binary logistic regression analysis identified female sex(OR=2.158),older age(OR=1.040),central obesity(OR=1.144),elevated FBG(OR=1.039),hypertension(OR=1.095),elevated TGAB(OR=1.008),and elevated T3(OR=1.154)as independent risk factors for thyroid nodules(all P<0.05).Conclusion Women in Northwest China are at higher risk of developing thyroid nodules.Screening and health management should be prioritized for older individuals,those with central obesity,elevated FBG,hypertension,elevated TGAB,and elevated T3 levels.