OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

Objective To analyze the distribution and drug resistance patterns of carbapenem-resistant Acinetobacter baumannii(CRAB),and evaluate the antimicrobial effects in vitro of colistin(COL)combined with cefoperazone/sulbactam(SCF),tigecycline(TGC),imipenem(IPM),meropenem(MEM),amikacin(AK),and levofloxacin(LEV)against CRAB to provide guidance for anti-infective therapy.Methods A total of 75 non-duplicate CRAB strains isolated from clinical specimens in 2022 were collected.WHONET 5.6 software was used for retrospective analysis of their clinical distribution and resistance profiles.Among them,25 strains were selected for combined antimicrobial susceptibility tests using broth microdilution to determine minimum inhibitory concentrations(MICs).The fractional inhibitory concentration(FIC)index was calculated based on checkerboard method to assess the combined effects.Results In 2022,a total of 145 Acinetobacter baumannii strains were isolated,including 75 CRAB(detection rate of 51.7％).CRAB was most prevalent in the patients over 70 years old(40.0％),mainly from blood(41.3％)and sputum(37.3％)specimens,and the intensive care unit was the top isolating department.All the 75 CRAB strains were resistant to piperacillin,piperacillin/tazobactam,ceftriaxone,1PM and MEM with resistance rates of 100％.The resistance rates for ampicillin/sulbactam,cefepime and tri-methoprim/sulfamethoxazole were all exceeded 95％.The resistance rates were 86.7％for LEV,82.7％for SCF,77.4％for AK,2.4％for TGC,and 0.0％for COL.The results of combined tests of 25 strains revealed the synergy rates of 92％and 80％for COL+SCF and COL+TGC respectively with sums of both synergy and additive rates of 100％.Synergy rates for COL combined with IPM,MEM,AK and LEV were 64％,72％,56％and 48％respectively.No antagonism was observed in any combination.Conclusion The drug resist-ance of CRAB exhibited high levels at our hospital,and the elderly and ICU patients were the major susceptible populations.Among all the combinations tests,COL+SCF showed optimal synergy while COL+LEV only had the lowest combined effect with the findings that warrants clinical consideration.

Objective:To investigate the predictive value of inflammatory and nutritional indices for postoperative survival of elderly patients with esophageal squamous carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 130 elderly patients with esophageal squamous carcinoma who were admitted to Sichuan Cancer Hospital from January 2019 to April 2020 were collected. There were 102 males and 28 females, aged (70±4)years. Mea-surement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test. Receiver opera-ting characteristic (ROC) curves were plotted. The area under the curve (AUC) and optimal cut-off values were calculated. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for survival analysis. The COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Postoperative survival of elderly patients with esophageal squamous carcinoma predicted by inflammatory and multitional indices. Results of ROC curves analysis showed that the best cut-off values of preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI) for predicting postoperative survival of elderly patients with esophageal squamous carcinoma were 470.71×10 9/L, 1.11, 2.07, 136.24, and 46.28, respectively. (2) Risk factors analysis of postoperative survival of elderly patients with esophageal squamous carcinoma. Results of multivariate analysis showed that preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI<46.28, score of preoperative patient-generated subjective global assessment (PG-SGA) ≥4, postoperative pathological stage Ⅳ and post-operative complications were independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma ( hazard ratio=3.30, 2.50, 0.36, 4.86, 1.57, 1.97, 95% confidence interval as 1.10?9.88, 1.07?5.88, 0.16?0.81, 1.13?20.87, 1.20?2.06, 1.02?3.82, P<0.05). (3) Follow-up. All the 130 patients were followed up for 39(range, 1?60)months. Of the 130 patients, 81 cases survived, 49 cases died, and the median overall survival time was not reached. The 1- and 3-year survival rates of the 130 patients were 83.85% and 54.62%, respectively. ① The median overall survival time was 25(0,43)months for patients with SII ≥470.71×10 9/L, and unreached for patients with SII <470.71×10 9/L, showing a significant difference between them ( χ2=60.59, P<0.05). ② The median overall survival time was 26(0,44)months for patients with SIRI ≥1.11, and unreached for patients with SIRI <1.11, showing a significant difference between them ( χ2=45.57, P<0.05). ③ The median overall survival time was unreached for patients with PNI ≥46.28, and 38(0,47)months for patients with PNI <46.28, showing a significant difference between them ( χ2=12.53, P<0.05). ④ The median overall survival time was unreached for patients with PG-SGA <4 and ≥4, showing a signifi-cant difference between them ( χ2=14.41, P<0.05). ⑤ The median overall survival time was 25(1,47)months for patients in pathological stage Ⅲ, 12(1,32)months for patients in stage Ⅳ, and unreached for patients in stage 0, Ⅰ, Ⅱ, respectively, showing a significant difference among them ( χ2=58.75, P<0.05). ⑥ The median overall survival time was 33(1,47)months for patients with postoperative complication, and unreached for patients without postoperative complication, showing a significant difference between them ( χ2=14.27, P<0.05). Conclusions:Preoperative SII, SIRI and PNI have good predictive value for postoperative survival in elderly patients with esophageal squamous carcinoma. Preoperative SII ≥470.71×10 9/L, preoperative SIRI ≥1.11, preoperative PNI <46.28, score of preoperative PG-SGA ≥4, postoperative pathological stage Ⅳ, and postoperative complications are independent risk factors for the overall survival time of elderly patients with esophageal squamous carcinoma. Patients with preoperative SII <470.71×10 9/L, preoperative SIRI <1.11, preoperative PNI >46.28, score of preoperative PG-SGA <4, postoperative pathological stage 0, Ⅰ, Ⅱ, and non post-operative complications have better survival.

Objective To explore the role of serum leucine-rich-alpha-2-glycoprotein1(LRG1),neopterin(NPT)and virus antibodies during the progression of viral meningitis(VM)and their value in evaluating the condition and predicting the prognosis of VM in children.Methods A total of 130 pediatric patients with VM admitted to Kaifeng Children's Hospital from August 2020 to February 2023 were selected as the observation group,and at the same time,another 130 pediatric patients with VM symptoms who were diagnosed as non central nervous system infectious diseases by lumbar puncture cerebrospinal fluid examination were selected as the control group.After admission,2 mL peripheral venous blood of children in the two groups was collected,and the levels of serum LRG1 and NPT were assessed by enzyme-linked immunosorbent assay.Before treatment,1 mL cerebrospinal fluid sample of children in the two groups was collected by lumbar puncture,and the host specific immuno-globulin G(IgG)against herpes simplex virus-I(HSV-I),cytomegalovirus(CMV),Epstein-Barr virus(EBV),and parain-fluenza virus(PIV)in cerebrospinal fluid was detected by enzyme-linked immunosorbent assay.The levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG were compared between the two groups.The VM children were then divided into the severe group(n=54)and mild group(n=76)according to the disease severity,and they were divided into the good prognosis group(n=37)and poor prognosis group(n=93)based on the prognosis.The levels of serum IRG1 and NPT and the positive rate of virus antibody IgG were compared in children with different disease severity and prognosis.The correlation of serum LRG1,NPT and virus antibody with the disease severity or disease progression for pediatric VM was analyzed,and their interactive effects on the disease progression of children with VM were analyzed.The predictive value of serum LRG1,NPT and virus antibody for pediatric VM outcome was analyzed by the receiver operating characteristic(ROC)curve.Results The levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the obser-vation group were significantly higher than those in the control group(P＜0.05);the levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the severe group were significantly higher than those in the mild group(P＜0.05);the levels of serum LRG1 and NPT,as well as the positive rate of virus antibody IgG of children in the poor prognosis group were significantly higher than those in the good prognosis group(P＜0.05).High level of serum LRG1 with high positive rate of virus antibody IgG and high level of serum NPT with high positive rate of virus antibody IgG showed positive interactions in leading to poor prognosis in children with VM odds ratio(OR)=15.238,9.684).The submultiplicative models were applied for the high levels of serum LRG1 with high positive rate of virus antibody IgG(OR=15.238)and high levels of serum NPT with high positive rate of virus antibody IgG(OR=9.684).The area under the curve(AUC)for predicting poor prognosis in children with VM after 2 weeks of treatment by serum LRG1,NPT and virus antibody IgG were 0.786,0.794 and 0.919,respectively,and the AUC for the combined prediction of the three was 0.933;the AUC of LRG1,NPT and positive rate of virus antibody IgG for predicting poor prognosis in children with VM after 2 weeks of treatment was greater than that of the three alone(P＜0.05).Conclusion NPT and LRG1 may be involved in the development of VM.The levels of serum LRG1 and NPT are positively correlated with the severity and progression of VM.The levels of serum NPT and LRG1 and the positive rate of virus antibody IgG have certain value in the disease evaluation and prognosis prediction of VM,and the combination of the three has a higher predictive value for the prognosis of VM.There is a positive interaction between high LRG1 with high positive rate of virus antibody IgG,and high NPT with high positive rate of virus antibody IgG in children with VM.

Background Currently,the diagnosis of depressive disorder relies on symptomatology,which is greatly influenced by subjective factors such as clinicians' experience.Finding more accurate and reliable quantitative diagnostic methods is currently an urgent problem.Objective To explore the value of Fisher discriminant function based on inflammatory cytokines in the diagnosis of depressive disorder,so as to provide references for clinical diagnosis.Methods A total of 136 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria,who underwent inpatient treatment at Hebei Mental Health Center from April 2020 to November 2020,were enrolled as study group.67 healthy participants matched for age and gender,was recruited during the same period.Serum levels of inflammatory cytokine were measured using enzyme-linked immunosorbent assay(ELISA).Fisher discriminant model was employed to establish a discriminant function for inflammatory cytokines exhibiting significant statistical differences between study group and control group,which was then validated.Results The levels of pro-inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),interferon-γ(INF-γ)and tumor necrosis factor-α(TNF-α)were higher in the study group compared with control group,with statistically significant differences(U=9.115,5.239,4.431,5.428,P<0.01).Conversely,the levels of anti-inflammatory cytokines interleukin-4(IL-4),interleukin-10(IL-10)and interleukin-13(IL-13)were lower in the study group compared with control group,with statistically significant differences(U=7.398,7.331,7.614,P<0.01).The retrospective test in Fisher discriminant function achieved a correct discrimination rate of 89.66%,and the cross validation achieved a correct discrimination rate of 88.67%.Conclusion The Fisher discriminant function developed in this study may serve as a valuable auxiliary method in the diagnosis of depressive disorder.

Background: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. Objectives: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,Ocarboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. Methods: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. Results: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis.In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. Conclusions This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.
Humans ; Rifampin/therapeutic use* ; Isoniazid/therapeutic use* ; Latent Tuberculosis/drug therapy* ; HIV Infections/epidemiology* ; Antitubercular Agents/therapeutic use*

Objective To study the effects of aneurysmal neck angle on stent displacement after endovascular repair of abdominal aortic aneurysm (AAA). Methods The CT images of 28 patients were selected to establish preoperative AAA model, postoperative AAA model and covered stent model respectively, and the models were divided into non-severe angulation group ( n = 14) and severe angulation group ( n = 14) according to the preoperative angle of tumor neck. The geometric shape of each model was measured, and the changes of AAA geometric parameters and postoperative stent displacements before and after surgery were analyzed. The displacement force of the model during the first follow-up was calculated by hemodynamic simulation. Results Significant differences were found in tumor length, maximum diameter, displacement force, tumor neck length and tumor volume between two groups of patients (P<0. 05), while there was no significant difference between COG (the center of gravity) displacement and proximal displacement (P> 0. 05). For the incidence of internal leakage, there were 2 cases in non-severe angulation group and 4 cases in severe angulation group (P>0. 05).Conclusions Severe neck angulation can lead to a significant increase in support displacement force and decrease in proximal anchorage zone, and thus increase the possibility of support displacement. It is suggested that doctors should strengthen postoperative follow-up for patients with severe neck angulation and be vigilant of the occurrence of long-term internal leakage in clinic.

Objective:To investigate the clinical characteristics and gene mutations of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) secondary to familial hemophagocytic syndrome (FHL).Methods:The clinical features, disease evolution, gene mutation and genetic characteristics of 1 SPTCL patient secondary to FHL in Henan Children's Hospital in June 2012 were analyzed retrospectively, and the related literatures were reviewed.Results:The UNC13D of FHL patient was homozygous mutation accompanied by STXBP2 heterozygous mutation, while that of his parents and elder brother was heterozygous mutation. After regular chemotherapy with HLH-2004 regimen, the disease relapsed 4 years later, and secondary SPTCL developed after 1 year of remission with the second chemotherapy. After giving SMILE regimen chemotherapy, allogeneic hematopoietic stem cell transplantation was performed, and now the patient had disease-free survival.Conclusions:The detection of related genes in children with hemophagocytic syndrome should be improved in time to confirm the diagnosis of primary disease. FHL can follow SPTCL, and chemotherapy combined with allogeneic hematopoietic stem cell transplantation can be the only method to cure this disease.

Objective:To evaluate the efficacy of ultrasound combined with a nerve stimulator-guided suprapatellar anterior approach to sciatic nerve block in elderly patients undergoing knee arthroscopic surgery.Methods:Seventy American Society of Anesthesiology physical status Ⅱ or Ⅲ patients, aged>65 yr, scheduled for elective knee arthroscopic surgery, were divided into 2 groups ( n=35 each) using a random number table method: suprapatellar anterior approach group (S group) and traditional anterior approach group (T group). Puncture was performed under the guidance of ultrasound and a nerve stimulator in both groups.When dorsiflexion or plantar flexion was induced by stimulation of 0.3 mA current intensity, 0.25% ropivacaine plus 1% lidocaine (0.4 ml/kg) was injected.The success of puncture and block, depth of puncture, time to complete block, duration of block, insufficient analgesia, responses to tourniquet-induced discomfort, and block-related complications were recorded.The patients were followed up for 48 h after operation for the recovery time of foot dorsiflexion on the affected side. Results:Compared with T group, the success rate of puncture and block were significantly increased, the time to complete nerve block was shortened, the incidence of intraoperative insufficient analgesia was reduced ( P<0.05 or 0.01), and no significant change was found in the depth of puncture, duration of block, and recovery time of foot dorsiflexion on the affected side in S group ( P>0.05). No nerve block-related complications were found in the two groups. Conclusion:Ultrasound combined with a nerve stimulator-guided suprapatellar anterior approach to sciatic nerve block can provide satisfactory analgesia for elderly patients undergoing knee arthroscopic surgery with a higher safety.