Early secreted antigenic target of 6 kDa protein (ESAT-6) is the major virulence factor of Mycobacterium tuberculosis (MTB), which can resist the clearance of MTB in bodies by inhibiting macrophage phagocytosis and autophagy reaction, thus impeding the immune defense function of the body against MTB infection. In addition, ESAT-6-induced apoptosis of macrophage and massive necrosis of innate immune cells can foster MTB proliferation and colonization, leading to systemic MTB infection. Moreover, ESAT-6 hampers the protective immune response of Th1 cells, reducing the secretion of pro-inflammatory cytokines and contributing to immune dysfunction, thus accelerating the course of MTB infection. During the process, the high immunogenicity of ESAT-6 can be leveraged as a dominant antigen in the development of new TB vaccines, making it a promising candidate with broad prospects for further development.
Humans ; Mycobacterium tuberculosis ; Vaccines ; Cytokines ; Apoptosis ; Autophagy ; Sepsis

Objective To investigate the level of coagulation factor Ⅺ(FⅪ)in patients with venous thrombosis of lower limbs and its correlation with recurrence risk.Methods A total of 220 pa-tients with deep vein thrombosis(DVT)admitted in our hospital from February 2018 to February 2019 were enrolled as the study group,and another 50 healthy individuals taking physical exami-nation during same period served as the control group.After a 3 years followed,the study group ultimately included 197 cases,according to the results of restricted cubic spline(RCS),the study group was divided into low(FⅪ＜10.3 U/L,94 cases),medium-(10.3-12.1 U/L,52 cases)and high-level groups(＞12.1 U/L,51 cases).The plasma level of FⅪ was detected in the study group 1 month after the end of anticoagulant therapy,and the results were compared with those of the control group during physical examination.Cox model was used to analyze the influence of FⅪ on the recurrence of DVT,and RCS was employed to analyze the relationship between DVT recur-rence and FⅪ level.Kaplan-Meier curve was plotted to analyze the recurrence risk of DVT with different FⅪ levels.The patients from the study group were followed up for 3 years.Results The FⅪ level was significantly higher in the study group than the control group(P＜0.05).During fol-low-up period,33 patients(16.75％)had DVT recurrence.The Cox model analysis after adjust-ment of sex and age showed that FⅪ level was a risk factor for DVT recurrence(P＜0.05).When the FⅪ level was set into tertile and the risk ratio was calculated after adjustment,FⅪ＜10.3 U/L,and the average FⅪ level at this stage was 9.2 U/L,the risk ratio was 0.82(95％CI:0.673-0.984);Patients with FⅪ between 10.3 and 12.1 U/L,and the average FⅪ at this stage was 11.4 U/L,the risk ratio of 1.04(95％CI:0.813-1.432).The those with FⅪ＞12.1 U/L,and the average FⅪ at this stage was 13.8 U/L,hazard ratio of 1.38(95％CI:0.921-1.563).Kaplan-Meier curve analysis showed that the recurrence risk was 28.62％(95％CI:25.633-31.609),30.10％(95％CI:27.594-32.606)and 38.06％(95％CI:34.306-41.371),respectively for the low-,medium-,and high-level groups,with significant correlation among the three groups(x2=6.631,P=0.036).Conclusion Compared with healthy individuals,plasma FⅪ level is at a high level in the DVT patients.With the increment of FⅪ level,the risk of DVT recurrence increases.Two FⅪ levels,10.3 U/L and 12.1 U/L,can be used as reference points for the obvious increase of DVT recur-rence rate.

Objective To explore the relationship between serum Visfatin,pentraxin 3(PTX3),and carbo-hydrate antigen 19-9(CA19-9)levels and prognosis in patients with acute cholecystitis.Methods A total of 228 patients with acute cholecystitis admitted to a hospital from September 2020 to September 2023 were se-lected as the study objects.According to the severity of the patients,228 patients were divided into mild group(n=81),moderate group(n=102)and severe group(n=45).The patients were divided into good prognosis group(n=186)and bad prognosis group(n=42).General data of patients were collected,serum Visfatin and PTX3 levels were detected by enzyme linked immunosorbent assay,and serum CA19-9 levels were determined by chemiluminescence immunoassay.Univariate and multivariate analysis of prognostic factors in patients with acute cholecystitis was performed,and the diagnostic value of serum Visfatin,PTX3 and CA19-9 levels in patients with acute cholecystitis was analyzed by drawing receiver operating characteristic curve.Results Ser-um Visfatin,PTX3 and CA19-9 in moderate and severe groups were significantly different from those in mild group(P＜0.05).There were significant differences in serum Visfatin,PTX3 and CA19-9 between severe group and moderate group(P＜0.05).Gallbladder thickness,long diameter and short diameter of gallbladder,serum Visfatin,PTX3 and CA19-9 levels in the poor prognosis group were significantly different from those in the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that serum Visfatin,PTX3 and CA19-9 levels were the influential factors for poor prognosis of patients(P＜0.05).The area under the curve of serum Visfatin,PTX3 and CA19-9 combined diagnosis was significantly larger than that of Visfa-tin alone diagnosis(Z=4.577,P＜0.001)and PTX3 alone diagnosis(Z=3.132,P=0.002)and the area un-der the curve of CA19-9 diagnosis alone(Z=2.766,P=0.006).Conclusion Serum Visfatin,PTX3 and CA19-9 are elevated in patients with acute cholecystitis,which is related to the patient's condition.The combi-nation of the three is of better value in the diagnosis of poor prognosis.

Anterior cervical discectomy and fusion is one of the classic procedures for the treatment of cervical spondylosis, and dysphagia is a common perioperative complication of this procedure, which affects patients′ recovery to different degrees. This paper summarizes and analyzes the perioperative assessment and interventions in the care of patients with dysphagia after anterior cervical discectomy and fusion, aiming to improve clinical nursing staff′s attention to dysphagia in patients after anterior cervical discectomy and fusion, and provide scientific basis for the prevention and treatment of high-risk groups.

Objective: To study the buccolingual inclination of posterior premolars and molars and the curve of Wilson in patients with different sagittal skeletal patterns, to explore the compensation mechanism of horizontal inclination of posterior teeth in patients with different sagittal skeletal patterns and to provide a reference for the control of posterior tooth inclination in the treatment of bone malocclusion. Methods: This study was reviewed and approved by the Ethics Committee, and informed consent was obtained from the patients. Ninety CBCT scans of adults and ninety scans of adolescents before orthodontic treatment were evaluated in this cross-sectional study. There were 30 skeletal Class I, Class Ⅱ, and Class Ⅲ patients in the adult group and adolescent group. The inclination angles of posterior teeth and the curve of Wilson of first and second molars were measured, and data were analyzed between adolescents and adults with different sagittal skeletal patterns. Results : Compared with skeletal Class Ⅰ adult patients, the upper posterior molar inclination of skeletal Class Ⅱ patients was significantly lower, and the lower posterior molar inclination was significantly higher. Compared with skeletal ClassⅠ adult patients, the upper posterior molar inclination of skeletal Class Ⅲ adult patients was higher, and the lower posterior molar inclination was significantly lower. The Wilson curve of the second molar in skeletal Class Ⅱ adult patients was significantly higher than that in the other groups. Compared with skeletal ClassⅠ adolescent patients, skeletal Class Ⅲ adolescent patients had a significantly higher upper posterior molar inclination; however, no difference was found between the inclination of the posterior teeth between skeletal Class Ⅰ, Class Ⅱ and Class Ⅲ adolescent patients. Comparing adolescent and adult samples, in skeletal Class Ⅱ patients, adults showed more lingual inclination than adolescents in the upper posterior teeth and less lingual inclination in the lower posterior teeth except for the mandibular first molar. Comparing adolescent and adult samples, in skeletal Class Ⅲ patients, adults showed more lingual inclination than adolescents in the lower posterior teeth except for the mandibular second molars and showed no difference in the upper posterior teeth. Conclusions The inclination of the posterior teeth and the curve of Wilson show significant differences between the three sagittal skeletal patterns. Compared with those of skeletal Class Ⅰ patients, the posterior teeth of skeletal Class Ⅱ patients show more lingual inclination in the upper arch and less lingual inclination in the lower arch. Meanwhile, posterior teeth of skeletal Class Ⅲ patients show more lingual inclination in the lower arch and maintain the inclination in the upper arch.

Polyetheretherketone (PEEK) as a new type of thermoplastic engineering plastic, has good biological activity, elastic modulus close to human cortical bone and radiation permeability, and has been widely used in medical field. This study aims to explore the safety and clinical efficacy of using 3D printing personalized PEEK materials to repaire scapular bone defects after bone tumor resection. A total of 6 patients who underwent the implantation of 3D printed PEEK scapular prosthesis from January 2020 to December 2021 in Yunnan Cancer Hospital were retrospectively analyzed. There were 3 males and 3 females, with age ranged from 14 to 52 years. There were 1 case of synovial sarcoma, 1 of Ewing's sarcoma, and 4 of chondrosarcoma. PEEK prosthesis was designed and fabricated based on CT data before surgery. Tumor resection and prosthesis replacement were performed under the premise of ensuring safe surgical boundaries, including 2 cases of total scapular prosthesis replacement and 4 cases of partial scapular prosthesis replacement. The operation time was 90-170 min, and the intraoperative blood loss was 100-400 ml. All 6 patients received satisfactory follow-up, with a tumor progression free survival time of 16-28 months. No tumor recurrence or metastasis was observed, and all patients survived tumor free. At last follow-up, the Constant-Murley shoulder joint score was a minimum of 62 points and a maximum of 68 points. The Japanese Orthopaedic Association's shoulder joint score was 63 points minimum and 78 points maximum. Computer-aided design 3D printing PEEK material prosthesis has certain advantages in the treatment of scapular tumor limb salvage. It has light weight, well adapted, relatively simple installation, good histocompatibility, and can obtain a better appearance and function of the shoulder joint after operation. It can become one of the options for limb salvage treatment of scapular tumor.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. METHODS: Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. RESULTS: A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. CONCLUSIONS This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; Adenocarcinoma ; Cancer-Associated Fibroblasts ; Prognosis ; Tumor Microenvironment ; Sulfotransferases

Objective:To evaluate the role of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in intestinal ischemia-reperfusion (I/R) injury in mice and the relationship with ferroptosis.Methods:Thirty SPF-grade healthy male C57BL/6 mice, aged 8-10 weeks, weighing 21-25 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), intestinal I/R + NCOA4 silencing group (I/R+ NCOA4 shRNA group), intestinal I/R + autophagy inhibitor 3-methyladenine (3-MA) group (I/R+ 3-MA group), and intestinal I/R + NCOA4 silencing + autophagy activator rapamycin (RAPA) group (I/R+ NCOA4 shRNA + RAPA group). The intestinal I/R injury model was developed by clamping the superior mesenteric artery for 45 min followed by reperfusion in anesthetized animals.At 2 weeks before developing the model, AAV-NCOA4-shRNA 1×10 11 vp was injected via the tail vein in group I/R+ NCOA4 shRNA and group I/R+ NCOA4 shRNA+ RAPA, and AAV shCtrl (adenovirus control) 1 x10 11 vp was injected in Sham, I/R and I/R+ 3-MA groups.Rapamycin 4 mg/kg was intraperitoneally injected once a day starting from 7 days before developing the model in group I/R+ NCOA4 shRNA+ RAPA.In group I/R+ 3-MA, 3-MA 10 mg/kg was intraperitoneally injected at 1 h before developing the model.The animals were sacrificed at 2 h of reperfusion, and intestinal tissues were obtained for determination of contents of malondialdehyde (MDA), glutathione (GSH) and Fe 2+ (by colorimetry), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) (by enzyme-linked immunosorbent assay), and expression of NCOA4, microtubule-associated protein 1 light chain 3 (LC3), long-chain fatty acyl-CoA synthase 4 (ACSL4), ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) (by Western blot). The LC3Ⅱ/LC3Ⅰ ratio was calculated.Intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score and contents of MDA, Fe 2+ , TNF-α and IL-1β were significantly increased, GSH content was decreased, the expression of NCOA4 and ACSL4 was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased, and the expression of GPX4 and FTH1 was down-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score and contents of MDA, Fe 2+ , TNF-α and IL-1β were significantly decreased, and GSH content was increased in I/R+ NCOA4 shRNA and I/R+ 3-MA groups, the expression of NCOA4 and ACSL4 was significantly down-regulated, and the expression of GPX4 and FTH1 was up-regulated in group I/R+ NCOA4 shRNA ( P<0.05), and ACSL4 expression was significantly down-regulated, LC3Ⅱ/LC3Ⅰ ratio was decreased, and the expression of GPX4 and FTH1 was up-regulated in group I/R+ 3-MA ( P<0.05). Conclusions:NCOA4-mediated ferritinophagy can promote ferroptosis, which is involved in the pathophysiological mechanism of intestinal I/R injury in mice.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) at Neiguan on dexmedetomidine-induced bradycardia in patients.Methods:Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 20-50 yr, weighing 48-60 kg, scheduled for elective gynecological surgery under general anesthesia, were divided into 2 groups ( n=30 each) using a random number table method: control group (group C) and TEAS group (group T). Dexmedetomidine 1 μg/kg was infused intravenously over 10 min followed by intravenous infusion 0.5 μg·kg -1·min -1 in two groups, and the patients in group T simultaneously received TEAS (frequency 2/100 Hz, disperse-dense wave, intensity 5-10 mA according to the current that could be tolerated) at bilateral Neiguan acupoints.The stimulator was only connected, and no current was given in group C. Before the infusion of dexmedetomidine (T 0) and at 10 min of dexmedetomidine infusion (T 1), mean arterial pressure (MAP) and heart rate (HR) was recorded, and electrocardiogram (ECG) was collected to calculate the PR interval, QT interval, QT interval, Tp-e interval and index of cardiac electrophysiological balance (iCEB). The development of arrhythmia was recorded. Results:Compared with the baseline value at T 0, HR was significantly decreased, and QT interval and PR interval were prolonged at T 1 in two groups, and iCEB was increased, and Tp-e interval was prolonged at T 1 in group C ( P<0.05). Compared with group C, HR was significantly increased, PR interval and Tp-e interval were shortened at T 1, and the incidence of bradycardia and atrioventricular block was increased in group T ( P<0.05). Conclusion:TEAS at Neiguan can decrease the risk of bradycardia induced by dexmedetomidine, and the mechanism may be related to shortening atrioventricular conduction time and reducing heterogeneity of ventricular repolarization in patients.

Objective:To investigate the effect of tidal volume (Vt DI) on pulse pressure variation (ΔPP DI) during deep inspiration maneuvers in spontaneously breathing patients with sepsis and to test if adjusting ΔPP DI by Vt DI can further improve its ability in predicting fluid responsiveness (FR). Methods:Spontaneously breathing, nonintubated sepsis or septic shock patients who were admitted to the Intensive Care Unit of the Characteristic Medical Center of Chinese People's Armed Police Force and Nanjing Gaochun People's Hospital were prospectively enrolled from October 2017 to October 2019. Volume expansion (VE) was performed by infusing 500 mL saline over 20 min. Prior to VE, measurements including pulse pressure variation and tidal volume were obtained during quiet spontaneous breathing (ΔPP TB and Vt TB, respectively) and during the deep inspiration maneuver (ΔPP DI and Vt DI, respectively). Patients were classified as responders if stroke volume (SV) increased ≥ 15% after VE, otherwise non-responders. Multiple linear regression analysis was conducted to investigate the correlation of ΔPP DI with Vt DI and VE-induced percentage changes in SV (ΔSV). Receiver operating characteristic (ROC) curve analysis and the gray zone approach were used to assess the ability of each index to predict FR. Changes in gray zone limits according to the cost ratio (R = cost[false positive (FP)]/cost[false negative (FN)]) were also evaluated. Results:Of the included 31 patients, 17 were responders. There was no significant difference in ΔPP TB between fluid responders and non-responders ( P>0.05), whereas ΔPP DI was significantly higher in responders than in non-responders [(19.1±7.4)% vs (11.2±4.5)%; P=0.001]. The area under the ROC curve (AUC) of ΔPP DI predicted FR was 0.832, sensitivity of 76.47% and specificity of 71.43%, which was significantly higher than ΔPP TB (AUC=0.580, sensitivity of 47.06% and specificity of 71.43%; P<0.05). Multiple linear regression analysis showed that both Vt DI and ΔSV were independently associated with ΔPP DI ( P<0.01), the AUC of ΔPP DI adjusted by Vt DI was signigicantly higher than that of ΔPP DI alone ( P=0.03). Among the ΔPP TB, ΔPP DI and ΔPP DI/Vt DI, ΔPP DI/Vt DI had the narrowest gray zone (12.7-14.5) for the normal fluid policy (R=1), which only included 19% of the patients. When applying "restrictive" fluid management (R=2), the gray zone for ΔPP DI/Vt DI was 12.8-14.5 and included only 2 patients (6.5%). Conclusions:In spontaneously breathing, nonintubated patients with sepsis or septic shock, the ΔPP value obtained during the deep inspiration maneuver predicts FR with moderate accuracy. Given the close correlation between Vt DI and ΔPP DI, ΔPP DI adjusted by Vt DI performs better than ΔPP DI alone in predicting FR.