OBJECTIVE: To evaluate the effectiveness of the innervated medial plantar flap for reconstructing soft tissue defects, particularly in the weight-bearing zone, after resection of foot tumors. METHODS: A retrospective analysis was conducted on 12 patients with malignant skin and soft tissue tumors of the foot treated between October 2023 and December 2024. The cohort included 8 males and 4 females, aged 42-67 years (mean, 57.5 years). Tumor types comprised malignant melanoma (5 cases), squamous cell carcinoma (4 cases), arsenical keratosis (2 cases), and tumor-induced osteomalacia (1 case). Soft tissue defects located in the heel weight-bearing region in 10 cases and non-weight-bearing ankle region in 2 cases, with defect sizes ranging from 4.0 cm×3.0 cm to 6.0 cm×4.0 cm. Preoperative photon-counting CT angiography (PC-CTA) was performed to assess the medial plantar artery and its perforators. All patients underwent radical tumor resection with confirmed negative margins. The resulting defects were reconstructed using a innervated medial plantar flap incorporating sensory branches of the medial plantar nerve. The flap donor site was covered with a split-thickness skin graft harvested from the ipsilateral inguinal region. RESULTS: The operation was successfully completed in all 12 patients. All flaps survived completely without vascular compromise, partial necrosis, or total loss. Incisions healed primarily without dehiscence or infection. Minor skin graft necrosis occurred at the donor site in 3 patients, which healed within 2-3 weeks with routine dressing changes. No donor site complication (e.g., tendon or nerve injury) occurred. Patients were followed up 2-16 months (mean, 10.3 months). At last follow-up, there was no tumor recurrence. Flaps exhibited good color and texture match with surrounding tissue, restored sensation, and all feet achieved normal weight-bearing activity. CONCLUSION The innervated medial plantar flap, precisely designed based on PC-CTA localization, provides reliable blood supply and effective sensory restoration. It is an ideal method for reconstructing soft tissue defects after foot tumor resection, especially in the heel weight-bearing region.
Humans ; Male ; Middle Aged ; Female ; Plastic Surgery Procedures/methods* ; Adult ; Aged ; Retrospective Studies ; Soft Tissue Neoplasms/surgery* ; Surgical Flaps/blood supply* ; Foot/surgery* ; Skin Neoplasms/surgery* ; Soft Tissue Injuries/surgery* ; Carcinoma, Squamous Cell/surgery* ; Treatment Outcome ; Skin Transplantation/methods* ; Melanoma/surgery*

OBJECTIVE: To explore the application value and clinical effect of 3D printing combined with customized bone plate in the treatment of acetabular fracture. METHODS: From June 2020 to June 2022, 11 patients with acetabular fractures underwent preoperative planning using 3D printing technology and were treated with customized bone plates including 8 males and 3 females, aged 25 to 66 years old. The fractures were classified according to Letournel-Judet:4 posterior wall fractures, 2 T-type fractures, 2 transverse posterior wall fractures, 2 double column fractures, and 1 anterior column with posterior semi-transverse fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, postoperative drainage volume, postoperative fracture healing time, and hip function score were recorded and analyzed. RESULTS: The operation time of 11 patients was 80 to 150 min, intraoperative blood volume was 150 to 700 ml, fluoroscopy frequency was 2 to 6, postoperative drainage flow was 60 to 195 ml, and the fracture healing time was 2.5 to 6.0 months. Fracture reduction was evaluated according to Matta score:anatomical reduction in 3 cases and satisfactory reduction in 8 cases. Eleven patients were followed up for 7 to 18 months. The hip Merle d'Aubigne function scores were excellent in 6 cases, good in 3 cases, fair in 1 case and poor in 1 case. Incision fat liquefaction occurred in 1 case and obturator nerve traction in 1 case. CONCLUSION The application of 3D printing technology combined with customized bone plates in the treatment of acetabular fracture is effective. In addition, the printed model can provide the operator with the results of the three-dimensional shape of the fracture, which is convenient for surgical reduction and effectively improves the efficiency of surgery.
Humans ; Female ; Male ; Middle Aged ; Acetabulum/surgery* ; Printing, Three-Dimensional ; Adult ; Aged ; Bone Plates ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods*

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3⁺ (FOXP3⁺) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics Bacteroides fragilis, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal B. fragilis was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3⁺ Tregs and curbs pro-inflammatory pathways.

Objective To investigate the therapeutic effect and mechanism of Chaihu Guizhi Ganjiang Decoction on non-alcoholic fatty liver disease(NAFLD)rats.Methods The experiment was conducted in five groups:normal group,model group,low-and high-dose groups of Chinese medicine(Chaihu Guizhi Ganjiang Decoction)and GSK872[receptor interacting protein kinase(RIP)3 inhibitor]group.Except for the normal group,the NAFLD rat model was constructed using high-fat chow feeding method in the remaining groups,respectively.At the end of treatment,hepatocyte apoptosis was observed by terminal transferase uridyl nick end labeling(TUNEL)method,and serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lipids[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and the levels of inflammatory factors tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)in liver tissues were measured by enzyme-linked immunosorbent assay(ELISA);and the levels of phosphorylation of RIP1,RIP3,and mixed lineage kinase structural domain-like protein(MLKL)were detected in liver tissues by Western Blot.Results Compared with the normal group,the apoptotic index of rat hepatocytes in the model group was elevated,ALT and AST in serum were significantly elevated,TC,TG and LDL-C levels were significantly elevated,and HDL-C level was significantly reduced,and the contents of TNF-α and IL-1β as well as the phosphorylated expression levels of RIP1,RIP3 and MLKL were significantly elevated in the liver tissues(P＜0.05);compared with the model group,the apoptotic index of hepatocytes in rats in the low-and high-dose groups of Chinese medicine and GSK872 group was reduced,the serum levels of ALT and AST were significantly reduced,the levels of TC,TG and LDL-C were significantly reduced,the level of HDL-C was significantly increased,and the contents of TNF-α and IL-1β and the phosphorylated expressions of RIP1,RIP3 and MLKL in the liver tissues were significantly reduced(P＜0.05);there was no significant difference in the above-mentioned indexes between the low-dose and high-dose groups of Chinese medicine and the GSK872 group(P＞0.05).Conclusion Chaihu Guizhi Ganjiang Decoction can effectively improve NAFLD in rats,and its mechanism may be related to the inhibition of RIP1/RIP3/MLKL signaling pathway activation,which in turn inhibits necrotic apoptosis.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Objective:To investigate the spectrum and antimicrobial resistance of major pathogens causing nosocomial infections in China during 2020-2021.Methods:A total of 1 311 non-duplicated nosocomial pathogens causing bloodstream infections (BSI, n=670), hospital-acquired pneumonia (HAP, n=394) and intra-abdominal infections (IAI, n=297) were collected from 10 teaching hospitals across China. The minimum inhibitory concentrations (MICs) of clinical common strains were determined using agar dilution or broth microdilution method. Interpretation of reults followed the CLSI M100-Ed33 criteria, with data analysis conducted using WHONET-5.6 software. The Chi-square test was used to compare rates. Results:The most prevalent pathogens causing BSI were Escherichia coli (21.2%, 142/670), Klebsiella pneumoniae (14.9%, 100/670) and Staphylococcus aureus (11.5%, 77/670); the most prevalent pathogens causing HAP were K. pneumoniae (27.7%, 109/394), Acinetobacter baumanii (22.1%, 87/394) and Pseudomonas aeruginosa (18.3%, 72/394). IN IAI, E. coli (24.3%, 60/247), Enterococcus faecium and K. pneumoniae (both 14.6%, 36/247) were dominated. All S. aureus strains were susceptible to tigecycline, linezolid, daptomycin and glycopeptides. Rates of methicillin-resistant S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) were 36.5% (42/115) and 74.5% (38/51), respectively. The rate of vancomycin-resistant E. faecium and E. faecalis was 3.3% (3/90) and 1.9% (1/53), respectively. The prevalence of extended-spectrum β-lactamase (ESBL) was 23.7% (58/245) in K. pneumonia and 60.5% (130/215) in E. coli.The rate of carbapenem-resistant K. pneumonia and E. coli was 29.8% (73/245) and 4.2% (9/215), respectively; the percentage of tigecycline-resistant K. pneumonia and E. coli was 1.6% (4/245) and 0, respectively; the rate of colistin-resistant K. pneumonia and E. coli was 1.6% (4/245) and 2.8% (6/215), respectively; the percentage of ceftazidime/avibactam-resistant K. pneumonia and E. coli was 2.0% (5/245) and 2.3% (5/215), respectively. The rate of carbapenem-resistant A. baumanii and P. aeruginosa was 76.7% (125/163) and 28.4% (33/116), respectively. A. baumanii showed low susceptibility to most antimicrobial agents except colistin (98.8%, 161/163) and tigecycline (89.6%, 146/163). Colistin, amikacin and ceftazidime/avibactam demonstrated high antibacterial activity against P. aeruginosa with susceptility rates of 99.1% (115/116), 94.0% (109/116) and 83.6% (97/116), respectively. Conclusions:The major pathogens of nosocomial infections were K. pneumonia, E. coli, A. baumanii, P. aeruginosa and S. aureus. Nosocomial Gram-negative pathogens exhibited high susceptibilities to tigecycline, colistin and ceftazidime/avibactam. Antimicrobial resistance in A. baumannii remains a significant challenge. The increasing prevalence of carbapenem-resistant Enterobacterales underscores the urgency of antibiotics rational applications and hospital infection controls.

Objective To investigate the therapeutic effect of Xuebijing on anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis mice and its effect on the changes of helper T cell 1(Th1)/helper T cell 2(Th2).Methods The experimental groups included control group,model group,low-dose Xuebijing(low-XBJ)group,high-dose Xuebijing(high-XBJ)group,with 10 mice in each group,except the control group,the other 3 groups of mice were treated with antigen injection and immune stimulation to establish anti-NMDAR encephalitis models,the mice in the low-XBJ and high-XBJ groups were intraperitoneally injected with 5 ml/kg and 10 ml/kg of Xuebijing injection,respectively,once every 12 hours for 3 consecutive days;After 2 weeks,HE staining was used to observe the pathological changes of mice brain tissue,Nissl staining was used to observe the morphological changes of mice neurons,TUNEL staining was used to detect the apoptosis of mice neurons,ELISA was used to detect the contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4 and interferon-γ(IFN-γ)in serum and cerebrospinal fluid of mice,immunohistochemical staining and Western blotting were used to detect the expression of IFN-γ and IL-4 in brain tissue,flow cytometry was used to detect the distribution of Th1 and Th2 cells in peripheral blood,and the ratio of Th1/Th2 was calculated.Results Compared with the model group,hippocampal tissue damage was improved in low-XBJ group and high-XBJ group,the morphological changes of neurons were small,the morphology of Nissl bodies was more complete and the number of Nissl bodies was increased,the TUNEL positive rate of neurons decreased,the contents of TNF-α,IL-1β and IFN-γ in serum and cerebrospinal fluid decreased while the content of IL-4 increased,the percentage of IFN-γ positive cells and the relative expression of protein in brain tissue decreased,the percentage of IL-4 positive cells and the relative expression of protein increased,the proportion of cluster of differentiation(CD)4+IFN-γ+labeled Th1 cells and the ratio of Th1/Th2 in peripheral blood decreased,and the proportion of CD4+IL-4+labeled Th2 cells in peripheral blood of mice in high-XBJ group increased,the differences were statistically significant(P＜0.05).In addition,compared with the low-XBJ group,the improvement effect of the above detection indicators in the high-XBJ group was more obvious,and the differences were statistically significant(P＜0.05).Conclusion Xuebijing can improve hippocampal neuronal damage in anti-NMDAR encephalitis mice,which may play a therapeutic role by reducing the expression of IFN-γ,promoting the expression of IL-4 and maintaining the balance of Th1/Th2 cells.