BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Gastrointestinal (GI) cancers are a leading cause of cancer morbidity and mortality worldwide. Despite advances in treatment, cancer relapse remains a significant challenge, necessitating novel therapeutic strategies. In this study, we engineered nanobody-based chimeric antigen receptor (CAR) natural killer (NK) cells targeting cadherin 17 (CDH17) for the treatment of GI tumors. In addition, to enhance the efficacy of CAR-NK cells, we also incorporated CV1, a CD47-SIRPα axis inhibitor, to evaluate the anti-tumor effect of this combination. We found that CDH17-CAR-NK cells effectively eliminated GI cancers cells in a CDH17-dependent manner. CDH17-CAR-NK cells also exhibit potent in vivo anti-tumor effects in cancer cell-derived xenograft and patient-derived xenograft mouse models. Additionally, the anti-tumor activity of CDH17-CAR-NK cells is synergistically enhanced by CD47-signal regulatory protein α (SIRPα) axis inhibitor CV1, likely through augmented macrophages activation and an increase in M1-phenotype macrophages in the tumor microenvironment. Collectively, our findings suggest that CDH17-targeting CAR-NK cells are a promising strategy for GI cancers. The combination of CDH17-CAR-NK cells with CV1 emerges as a potential combinatorial approach to overcome the limitations of CAR-NK therapy. Further investigations are warranted to speed up the clinical translation of these findings.

Background and purpose:The standard therapy for locally advanced rectal cancer(LARC)is neoadjuvant chemoradiotherapy(nCRT)followed by surgery.NCRT can make the tumor regress and downstage,and increase the R0 resection rate.However,individual differences in rectal cancer are large,and some patients respond poorly to nCRT and cannot benefit from nCRT.Therefore,it is necessary to establish effective screening measures to identify patients with poor response to nCRT.This study aimed to analyze the influencing factors of nCRT for LARC and construct the tumor regression prediction model.Methods:Data of 158 LARC patients who underwent total mesenteric resection after receiving nCRT at the First Hospital Affiliated to Air Force Medical University from January 2016 to December 2020 were collected.Baseline clinical indicators before nCRT were collected,including laboratory examination,tumor markers and magnetic resonance imaging(MRI).According to the tumor size reported by MRI before and after nCRT,Response Evaluation Criteria in Solid Tumors(RECIST)was used to evaluate the extent of tumor regression after nCRT.After receiver operating characteristic(ROC)curve was used to standardize the clinical baseline indicators,logistic regression analysis was carried out to screen the factors affecting the tumor regression.The tumor regression prediction model was constructed by logistic regression,and the performance of the model was evaluated based on decision curve analysis(DCA)and the calibration curve.The accuracy of the model was tested by 10-fold cross-validation.Results:This retrospective cohort study enrolled 158 patients,in which,98 patients achieved complete response(CR)or partial response(PR).The objective response rate was 62%.Sixty patients had poor response to nCRT,either stable disease(SD)or progressive disease(PD).Multivariate logistic regression analysis showed that tumor diameter before treatment(P＜0.001),time to surgery after nCRT(P = 0.006),D-dimer(P = 0.010),prognostic nutrition index(PNI)(P = 0.035),carcinoembryonic antigen(CEA)(P = 0.004)and extramural vascular invasion(EMVI)(P = 0.026)were significantly related to tumor regression after nCRT.The area under ROC curve(AUC)of tumor regression after nCRT prediction model for LARC was 0.84(95%CI:0.780-0.899),sensitivity was 85.0%,and specificity was 72.4%.In the calibration curve,the predicted results were in good agreement with the actual results,and the prediction accuracy was good.The DCA showed that the tumor regression prediction model could bring clinical net benefit to diagnosis.Conclusion:Tumor diameter before treatment,time to surgery after nCRT,D-dimer,PNI,CEA and EMVI are independent risk factors for the tumor regression after nCRT in LARC patients.The tumor regression prediction model based on the above factors has good predictive efficacy for the tumor regression after nCRT in LARC patients.

Objective:To analyze the clinical presentations and diagnostic and treatment process of one patient with autoimmune encephalitis(AE)with double positive anti-N-methyl-D-aspartate receptor(NMDAR)and anti-γ-aminobutyric acid B receptor(GABABR)secondary to herpes simplex virus encephalitis(HSVE),and to improve the clinicians'awareness of this disease.Methods:The clinical data of one AE patient with double positive anti-NMDAR and anti-GABABR secondary to HSVE were collected,the diagnostic and therapeutic processes were summarized,and the relevant literatures were reviewed.Results:The patient,a 36-year-old male,developed a headache followed by limb convulsions,and progressed to disturbed consciousness.After admission,the routine biochemistry of the cerebrospinal fluid(CSF)was abnormal,and the herpes simplex virus-1(HSV-1)IgG antibody showed positive in the CSF;both CSF and serum tests for NMDAR antibodies were positive;the head magnetic resonance imaging(MRI)results showed abnormal signals in the right occipital white matter,leading to the diagnosis of HSVE secondary to anti-NMDAR encephalitis.Several months later,the patient experienced psychiatric behavior abnormalities,cognitive dysfunction,and sleep disorders,and both the serum NMDAR and GABABR antibodies showed positive results,prompting the diagnosis of HSVE secondary anti-NMDAR encephalitis and anti-GABABR encephalitis.After treatment with steroid pulse therapy and intravenous immunoglobulin(IVIG),the patient's condition was improved and the patient was discharged.At one-year follow-up,the patient's psychiatric symptoms had completely resolved,leaving mild cognitive impairment.Conclusion:If the clinical symptoms of the patients recovering from antiviral treatment for HSVE is worsened,secondary AE should be highly suspected;it is important to complete autoimmunity antibody testing as soon as possible for the early diagnosis and treatment to improve the prognosis of the patient.

Purpose To investigate the effect and molecu-lar mechanism underlying SOX9 during esophageal squamous cell carcinoma(ESCC)cells.Methods Immunohistochemistry(IHC)was used to detect the expression of SOX9 in ESCC tis-sues and adjacent normal tissues.The correlation of SOX9 ex-pression with clinicopathological features and prognosis of ESCC was analyzed.The differentially expressed genes in Eca109-Vec-tor and Eca109-SOX9 cells were detected by Affymetrix miRNA array.qRT-PCR was used to determine the differential gene in TE-1 and TE-1-siSOX9 cells.The relationship between SOX9 and active/unphosphorylated β-catenin levels was detected by Western blot.The effects of Wnt inhibitor LGK974 on the prolif-eration of ESCC cells were detected by CCK-8.Results SOX9 was highly expressed in ESCC(4.58±3.04)as compared with that in adjacent normal tissues(1.56±2.08,P＜0.001).SOX9 was related to histopathological grade and invasion depth(P＜0.05).Kaplan-Meier analysis indicated high SOX9 expres-sion in ESCC was significantly correlated with shorter overall sur-vival(P＜0.05).Transcriptome profiling and qRT-PCR analysis suggested that SOX9 contributed to the regulation of AXIN2,FZD7 and WNT5A.Overexpression of SOX9 in Eca109 cells in-creased active/unphosphorylated β-catenin levels,whereas silen-cing SOX9 caused a decrease.Significant attenuation of cell pro-liferation was observed at various concentrations of LGK974 with-out affecting SOX9 expression on SOX9-expressing cell lines.As expected,this inhibitory effect was not obvious in Eca109-Vector cells when compared with Eca109-SOX9 cells treated with the same concentration of LGK974.Conclusion SOX9 is highly ex-pressed in ESCC and SOX9-mediated Wnt/β-catenin signal path-way activation at least partially contributes to the SOX9-induced ESCC growth.These findings suggest that SOX9 is a promising prognostic marker and therapeutic target for ESCC.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

Objective This study aimed to investigate the physical activity status of liver transplant patients,explore the relevant influencing factors,and provide a basis for developing a physical activity management program for this population.Methods A convenience sampling method was used from January to May 2023 to investigate 250 liver transplant patients in a tertiary hospital in Guangzhou,using a general situation questionnaire,international physical activity questionnaire,exercise fear scale,and organ transplant patient symptom and happiness scale.Ordinal logistic regression analysis was used to analyze the relevant influencing factors of physical activity in liver transplant patients.Results 240 valid questionnaires were collected,and the median total metabolic equivalent of physical activity in liver transplant patients was 2 433(506,30263)MET-min/week patients.Ordinal logistic regression analysis revealed that body mass index(BMI),time to transplantation,postoperative follow-up,fear of exercise,and quality of life were significant factors influencing physical activity in liver transplant patients(P＜0.05).Conclusion Liver transplant patients have lower levels of physical activity,mainly with light activity intensity such as walking.Medical staff need to pay attention to the management of physical activity in liver transplant patients,especially for obese and low-quality of life patients.Postoperative follow-up should be strengthened to improve their fear of exercise and promote early and regular exercise.

Objective:To examine the treatment strategy of congenital tracheal stenosis associated with non-vascular ring cardiac malformations.Methods:This is a retrospective case series study. Clinic data from 24 children with tracheal stenosis who underwent surgical treatment in the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to March 2023 were retrospectively collected. There were 16 males and 8 females, aged ( M(IQR)) 6.5 (19.6) months (range: 2.2 to 66.3 months) and weighted 5.95 (4.76) kg (range: 3.2 to 20.0 kg). All patients had obvious respiratory symptoms. Eighteen patients underwent cardiac malformation correction and tracheoplasty at the same time (simultaneous group). Six patients in the staged operation group were treated with cardiac malformation correction in the first stage operation and tracheoplasty in the second stage operation due to missed diagnosis or delayed diagnosis of tracheal stenosis or no condition for tracheoplasty. Slide tracheoplasty was used to correct tracheal stenosis in both groups. The recovery of the children was followed. Wilcoxon sign rank test was used for comparison between the two groups. Results:There was no death during the perioperative period and hospitalization. In the simultaneous group, 1 case with delayed chest closure underwent bedside chest closure after 52 hours, 2 cases were intubated again after operation, and 1 case was implanted with an endotracheal stent. The duration of mechanical ventilation was 40.5 (39.6) hours (range: 19.0 to 438.8 hours). In the staged group, there was 1 case of re-intubation after operation, combined with left vocal cord paralysis and respiratory multidrug-resistant bacterial infection ( Acinetobacter baumanii). One patient underwent 3 times of bronchoscopic balloon dilatation of the right middle bronchus, and heart rate returned to normal range. The duration of mechanical ventilation was 19.0 (21.4) hours (range: 17.1 to 96.7 hours). During follow-up, a patient in the simultaneous group was prone to respiratory infection and had good exercise tolerance, 1 case in the staged group still had sputum stridor in the throat 3 months after the operation, and symptoms improved significantly 6 months after the operation. The other children didn′t have obvious respiratory symptoms. Conclusions:The diagnosis of tracheal stenosis may be delayed or missed when tracheal stenosis is complicated by non-vascular ring cardiac malformations. One-stage correction of tracheal stenosis and cardiac malformation can achieve a good outcome.

OBJECTIVE: To investigate the correlation between postoperative driving pressure (DP) and the prognosis of lung transplantation, and to further evaluate the value of early DP monitoring in lung transplantation. METHODS: A observational study was conducted. The patients after lung transplantation who admitted to the intensive care unit (ICU) of Wuxi People's Hospital from February 1, 2022 to February 1, 2023 were collected. They were divided into low DP group (DP≤15 cmH₂O, 1 cmH₂O ≈ 0.098 kPa) and high DP group (DP > 15 cmH₂O) according to DP within 2 hours after operation. The clinical data including general information, primary disease, chronic diseases, cardiopulmonary function, laboratory indicators, intraoperative condition, postoperative lactic acid (Lac) and ventilator parameters were collected. Primary outcomes included 28-day and 90-day survival, and secondary outcomes included occurrence of primary graft dysfunction (PGD), duration of extracorporeal membrane oxygenation (ECMO), duration of mechanical ventilation, weaning of mechanical ventilation, and length of ICU stay. The general data and observations between the two groups were compared. Kaplan-Meier curve analysis was conducted to analyze the situation of mechanical ventilation and 90-day survival. Receiver operator characteristic curve (ROC curve) was used to evaluate the predictive ability of DP for failed weaning of mechanical ventilation and 90-day death. The dose-response relationship between DP and 90-day death risk was determined by restricted cubic spline model. Univariate analysis was performed using Cox proportional hazards model. RESULTS: A total of 101 patients were enrolled, with 68 patients (67.3%) in the low DP group and 33 patients (32.7%) in the high DP group. No statistically significant difference in general information, chronic diseases, primary diseases, cardiopulmonary function, laboratory indicators, intraoperative conditions, and postoperative Lac between the two groups was found. Compared with the low DP group, the patients in the high DP group had higher inspiratory pressure (Pinsp) and incidence of PGD with grade 3 at 24 hours after operation [Pinsp (cmH₂O): 21.0±0.6 vs. 20.0±0.7, PGD with grade 3 at 24 hours: 60.6% (20/33) vs. 39.7% (27/68), both P < 0.05], longer duration of ECMO, duration of mechanical ventilation, and the length of ICU stay [duration of ECMO (hours): 37 (21, 109) vs. 22 (14, 43), duration of mechanical ventilation (days): 3.1 (1.8, 10.7) vs. 1.9 (1.1, 3.2), length of ICU stay (days): 6 (3, 13) vs. 4 (3, 5), all P < 0.05], and lower successful weaning rate of mechanical ventilation [81.8% (27/33) vs. 95.6% (65/68), P < 0.05). The 28-day and 90-day survival rates in the high DP group were significantly higher than those in the low DP group [28-day: 69.7% (23/33) vs. 86.8% (59/68), 90-day: 63.6% (21/33) vs. 83.8% (57/68), both P < 0.05]. Kaplan-Meier curve showed that the patients in the low DP group were weaned and extubated earlier than high DP group, and the cumulative situation of weaning was better (Log-Rank test: χ ² = 14.054, P < 0.001), and the 90-day cumulative survival rate in the low DP group was significantly higher than that in the high DP group (Log-Rank test: χ ² = 4.791, P = 0.029). ROC curve analysis showed that the area under ROC curve (AUC) of DP for predicting 90-day death was 0.664 [95% confidence internal (95%CI) was 0.540-0.787, P = 0.017], and the AUC for predicting failed weaning of mechanical ventilation was 0.794 (95%CI was 0.667-0.921, P = 0.004). Results of restricted cubic spline model analysis showed that the 90-day death risk continued to increase with the DP < 18 cmH₂O; when DP≥18 cmH₂O, elevated DP did not continue to increase the 90-day death risk, showing a plateau effect. Univariate analysis showed that DP was independent risk factors of 90-day death, and the death risk increased by 9.3% for every 1 cmH₂O increase in DP [hazard ratio (HR) = 1.093, 95%CI was 1.007-1.186, P = 0.033]. CONCLUSIONS DP is an independent risk factor of death after lung transplantation, and early postoperative DP may be used as a predictor of failed weaning of mechanical ventilation and 90-day death after lung transplantation.
Humans ; Lung Transplantation ; Prognosis ; Respiration, Artificial ; Intensive Care Units ; Postoperative Period ; Pressure ; Primary Graft Dysfunction/epidemiology* ; Transplant Recipients ; Female ; Extracorporeal Membrane Oxygenation ; Male ; ROC Curve ; Middle Aged