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 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.

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 compare the effects of 3 rehydration methods before blood donation on the prevention of on-site and delayed blood donation-related vasovagal response (VVR) . 【Methods】 From January to June 2021, 6 250 whole blood donors in 6 fixed blood donation sites signed informed consent and were divided into 198 clusters according to donor sites and dates, then they were randomly assigned to receive either oral rehydration salts (ORS), sugar water, or water group, and each drank 500 mL of ORS, sugar water or water within 20 minutes before blood donation. The researchers recorded the actual intervention accepted on site, and recorded the immediate VVR and related information. At rest after blood donation, donors submitted an electronic questionnaire containing socio-demographic information. At 48 hours after blood donation, the researchers called back every donor to record delayed VVR and related information. Logistic regression based on intention to treat (ITT) was used to analyze the difference of the incidence of VVR among the three groups, and the average treatment effect on treated (ATT) was calculated. PASS 2021was used to estimate the sample size and R (4.2.0) for statistical analysis. 【Results】 The cumulative incidence of blood donation-related VVR was 2.67% (2.29%-3.11%) among street whole blood donors under the 3 rehydration methods, in which, the incidence of immediate and delayed VVR was 1.02% (0.79%-1.31%) and 1.65% (1.36%-2.01%) respectively. ITT analysis found that ORS were more effective than water in reducing the incidence of delayed VVR【OR=0.59,95% CI[0.37,0.94]】.There was no significant difference in the incidence of immediate VVR between any two groups (P > 0.05), and there was no significant difference in the incidence of delayed VVR in the sugar water group compared with the water group (P > 0.05). There was a difference of -0.013 (【95% CI[-0.022, -0.004]】or -0.008【95% CI[-0.017, -0.000]】in the incidence of delayed VVR in the ORS group compared with water group or sugar water group, the difference was significant (P<0.05). The cumulative VVR of the three groups showed similar results to the delayed VVR. 【Conclusion】 Drinking ORS before blood donation is the most effective rehydration method to prevent delayed VVR. The next step is to establish the predictive model of delayed VVR to screen the susceptible population and provide them with ORS before blood donation, while other population can choose any liquid they like, thus achieving personalized blood donation-related VVR prevention and control.

Background::Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD.Methods::Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results::Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions::Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Objective To investigate the determinants of linezolid-associated neurological adverse reactions in patients with multidrug-resistant tuberculosis and develop a risk prediction model for such adverse events.Methods A prospective cohort study design was employed to select 120 patients with drug-resistant pulmonary tuberculosis who received a chemotherapy regimen containing linezolid at Guangzhou Chest Hospital from April 2023 to January 2024 as the study population.Clinical data,adverse reactions,and plasma concentration of linezolid were collected during fasting and at 2 hours post-medication.Univariate analysis and multivariate logistic regression were conducted to identify factors influencing linezolid-related neurological adverse reactions.Furthermore,a prediction model for such adverse reactions was developed,and its predictive efficacy and calibration ability were evaluated using ROC analysis.Results Re-treatment(OR=2.540,P=0.028),coexistence of cavities(OR=4.092,P=0.021),anemia(OR=10.921,P=0.005),and Cmin≥0.7665 mg/L(OR=6.813,P<0.001)are independent risk factors for the occurrence of linezolid-related neurological adverse reactions.The prediction model,based on these four factors,exhibits an AUC of 0.851(95%CI:0.774～0.929),accompanied by a Youden index of 0.590,a sensi-tivity of 66.7%,and a specificity of 92.3%.Moreover,the prediction model demonstrates excellent calibration ability.(Hosmer-lemeshow χ2=8.719,P=0.273).Conclusion In MDR/RR-TB patients,the presence of cavita-tion,retreatment,and anemia may confer a heightened risk of linezolid-related neurological adverse reactions.A risk prediction model incorporating these four indicators demonstrates significant predictive value for the occurrence of such adverse events.

Objective:To investigate the correlation between triglyceride glucose (TyG) index and severe hypertriglyceridemic pancreatitis (HTGP), and to provide assistance for early evaluation and clinical decision-making of HTGP.Methods:From January 2016 to December 2021, the clinical data of 770 patients diagnosed with HTGP at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were retrospectively collected. According to severity of pancreatitis, the patients were divided into mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) groups, and the differences in TyG index among the 3 groups was compared. According to the quartile range of the TyG index, the patients were divided into TyG Q1, Q2, Q3 and Q4 groups, and the distribution of severity of pancreatitis in each TyG index quartile group was calculated. Kruskal-Wallis H test was used for statistical analysis. Spearman correlation analysis was used to analyze the correlation between TyG index quartile range and the severity of pancreatitis. Linear trend chi-square test was used to analyze the trend of SAP incidence among groups. Binary logistic regression was used to analyze the relationship between TyG index quartile range and the risk of SAP, and the trend test was also conducted. Results:A total of 770 patients with HTGP were included, among them 330 (42.9%), 268 (34.8%) and 172 (22.3%) were MAP, MSAP and SAP, respectively. The TyG indices of MAP, MSAP and SAP group were 11.8(11.3, 12.4), 12.5(11.9, 13.2) and 12.7(12.1, 13.4), respectively, and the differences among the 3 groups were statistically significant ( H=121.77, P<0.001). The TyG index was 12.21 (11.57, 12.94) in the 770 patients. There were 192, 193, 193 and 192 patients enrolled in TyG Q1(TyG index <11.57)、 Q2(TyG index ranged from 11.57 to <12.21)、 Q3(TyG index ranged from 12.21 to <12.94) and Q4(TyG index≥12.94) group, respectively.The correlation test showed that the difference between TyG quartile range and the severity of pancreatitis was statistically significant ( ρ=0.372, P<0.001). The incidence of SAP in TyG Q1, Q2, Q3 and Q4 group was 10.9%(21/192), 14.5%(28/193), 27.5%(53/193) and 36.5%(70/192), respectively. The trend test of SAP incidence among the TyG gruops was statistically significant ( χ2 =44.33, P<0.001). After adjusting for confounding factors, taking the TyG Q1 group as a reference, the OR values of SAP risk (95% confidence interval) of the TyG Q2, Q3 and Q4 groups were 1.250 (0.619 to 2.524), 2.882 (1.506 to 5.514) and 6.660 (3.456 to 12.836), respectively, and the trend test of SAP risk showed a significant difference ( OR=2.508, 95%confidence interval 1.883 to 3.341, P<0.001). Conclusions:There is a correlation between TyG index and severity of pancreatitis in patients with HTGP. As the TyG index increases, the risk of SAP increases in HTGP patients. TyG index may be an early predictor of severe HTGP.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.

Objective:To examine the effect of surgical treatment in children with pulmonary artery sling and the surgical treatment strategy.Methods:Relevant data of 110 children with pulmonary artery sling admitted to the Department of Cardiac Surgery, Children′s Hospital Affiliated to Shandong University from February 2017 to July 2022 were retrospectively analyzed. There were 55 males and 55 females, aging ( M(IQR)) 9.0 (10.6) months (range: 1 to 96 months). The weight was 7.8 (3.5) kg (range: 2.5 to 25.0 kg). Of the 110 patients, 108 had different degrees of tracheal stenosis and 2 had normal trachea. Left pulmonary artery transplantation and tracheoplasty were performed in 78 patients. Left pulmonary artery transplantation was performed in 30 patients (11 in our hospital and 19 in other hospitals) due to the lack of an early tracheoplasty technique, in which 24 patients needed stage Ⅱ tracheoplasty due to obvious respiratory symptoms and limited activity endurance, and 6 cases did not intervene. Two children with normal trachea only underwent left pulmonary artery transplantation. Results:Among the 78 children who underwent surgery in the same period, 70 cases recovered smoothly after surgery, of whom respiratory symptoms were significantly reduced or disappeared during the 1 to 65 months follow-up, with similar activity endurance to normal children of the same age. Eight cases died, including 4 cases of postoperative multi-drug resistant bacteria infection, died from tracheal anastomotic opening or septic shock, 1 cases with severe congenital heart disease died from postoperative low cardiac output syndrome difficult to correct, 1 case died from blood pressure could not be maintained due to the compressed left pulmonary artery after transplantation, 2 cases of postoperative digestive system diseases (adhesive intestinal obstruction, gastrointestinal bleeding, etc.). The 24 patients in the staging group were followed for 1 to 84 months. All patients needed stage Ⅱ tracheoplasty due to respiratory symptoms and decreased endurance to activity. Eight cases of the non-intervention tracheal group were successfully separated from the ventilator, cured and discharged in a short period of time.Conclusions:Most children with pulmonary artery sling have tracheal stenosis. Children with low degree of tracheal stenosis and inconspicuous respiratory symptoms can only undergo left pulmonary artery transplantation by lateral thoracotomy. For patients combined with severe tracheal stenosis or obvious respiratory symptoms, a simultaneous left pulmonary artery transplantat and tracheoplasty is recommended.