BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

"Global cancer statistics 2022" based on the latest GLOBCAN data from the International Agency for Research on Cancer (IARC) was recently released, providing a systematic analysis of the incidence and mortality of 36 types of cancer across 185 countries worldwide. The international burden of cancer is expected to continue to increase over the next 30 years, posing a severe public health and social challenge for many countries, including China. This article offers a key point interpretation of the "Global cancer statistics 2022", focusing on the evolution of cancer epidemiology and future development trends. The aim is to broaden the international perspective on cancer prevention and treatment, with the hope of providing reference and guidance for cancer prevention and treatment efforts in our country.

This study aims to investigate the impact of hepatocyte nuclear factor 1β (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR^-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE^-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.
Mice ; Animals ; Polygonatum/metabolism* ; Sumoylation ; Hepatocyte Nuclear Factor 1-beta/metabolism* ; Atherosclerosis/metabolism* ; Flavones ; Lipids

Objective:To establish a mortality risk prediction model of severe bacterial infection in children and compare it with the pediatric early warning score (PEWS), pediatric critical illness score (PCIS) and pediatric risk of mortality score Ⅲ (PRISM Ⅲ).Methods:A total of 178 critically ill children were selected from the PICU of the Children's Hospital of Nanjing Medical University from May 2017 to June 2022. After obtaining the informed consent of the parents/guardians, basic information such as sex, age, height and weight, as well as indicators such as heart rate, systolic blood pressure and respiratory rate were collected from all children. A standard questionnaire was used to score the child 24 h after admission to the PICU. The children were divided into the survival and death groups according to their survival status at 28 d after admission. A mortality risk prediction model was constructed and nomogram was drawn. The value of the mortality risk prediction model, PEWS, PCIS and PRISM in predicting the risk of death was assessed and compared using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC).Results:Among the 178 critically ill children, 11 cases were excluded due to severe data deficiencies and hospitalization not exceeding 24 h. A total of 167 children were included in the analysis, including 134 in the survival group and 33 in the death group. A mortality risk prediction model for children with severe bacterial infection was constructed using pupillary changes, state of consciousness, skin color, mechanical ventilation, total cholesterol and prothrombin time. ROC curve analysis showed that the AUCs of mortality risk prediction model was 0.888 ( P<0.05). The AUCs of PEWS, PCIS and PRISM Ⅲ in predicting death in children with severe bacterial infection were 0.769 ( P< 0.05), 0.575 ( P< 0.05) and 0.759 ( P< 0.05), respectively. Hosmer-Lemeshow goodness-of-fit test showed the best agreement between risk of death and PEWS predicted morbidity and mortality and actual morbidity and mortality (χ 2 = 5.180, P = 0.738; χ 2 = 4.939, P = 0.764), and the PCIS and PRISM Ⅲ predicted mortality rates fitted reasonably well with actual mortality rates (χ 2= 9.110, P= 0333; χ 2 = 8.943, P= 0.347). Conclusions:The mortality risk prediction model for predicting the death risk has better prognostic value than PEWS, PCIS and PRISM Ⅲ for children with severe bacterial infection.

Objective:To explore the value of application and manipulation technique of neuroendoscope in microsurgical clipping of ruptured posterior communicating artery(PCoA)aneurysms via keyhole approaches.Methods:From January 2018 to December 2020, the clinical data of 52 patients who received microsurgical clipping for ruptured via keyhole approach were retrospectively analysed. Forty-one patients had the intraoperative endoscopic monitoring. The supraorbital keyhole approach or pterional keyhole approach was applied based on the characteristics of the aneurysms. According to the in-surgery requirement, a 30° rigid neuroendoscope was used before and/or after clipping. All patients entered postoperative follow-up in outpatient clinic and were evaluated with the modified Rankin Scale(mRS).Results:All 52 patients had 52 ruptured PCoA aneurysms. Eighteen of the patients were treated via supraorbital keyhole approach and 34 via pterion keyhole approach. Pre-and post-clipping endoscopic observation were carried out in 12 cases and 29 only with post-clipping endoscopic observation. Residual aneurysmal neck was detected in 3 patients. Missed clipping of perforators was found in 2 patients and followed by proper adjustment of clips. All patients received follow-up angiographic examinations. Total obliteration of the aneurysm and an intact of internal carotid artery and PCoA were found in 41 patients by the intraoperative endoscopic observation. Two residual aneurysmal neck were detected in 11 patients without intraoperative endoscopic observation. After 11 to 45 months of follow-up, all patients had good recovery(mRS 0-1).Conclusion:It is a safe and effective method with endoscopic observation during microsurgical clipping procedure for ruptured PCoA aneurysms via keyhole approaches. It can effectively make up for the insufficient visual angle of microscope, realise the anatomical relationship between the aneurysm and adjacent structures, and avoid residual aneurysmal neck and an iatrogenic injury to the parent artery and perforators.

Objective To study the role of partial pressure of oxygen in the treatment of pulmonary hypertension induced by meconium aspiration syndrome. Methods Retrospective analysis was performed on 58 patients with meconium aspirate and pulmonary hypertension from January 1,2007 to December 31,2016, 28 patients in the death group,and 30 patients in the survival group. Blood gas analysis about two groups of children with mechanical ventilation were collected at four different time points:before mechanical ventilation ( 0 h) ,12 hours after mechanical ventilation,24 hours after mechanical ventilation and 72 hours after mechan-ical ventilation. The 80 mmHg(1 mmHg=0. 133 kPa) in blood gas analysis of the partial pressure of oxygen was used as the boundary point to study the effects about different blood oxygen partial pressures on the length of mechanical ventilation time in the survival group. Results Blood gas analysis showed that there were no significant differences in pH,partial pressure of oxygen,HCO3-,and lactic acid before mechanical ventilation in the two groups,but the pH values were significantly higher in the survival group after 12 h, 24 h,and 72 h of mechanical ventilation(t values:-2. 07,-3. 48,-7. 11;P <0. 05). Partial pressure of oxygen were higher in the surviving group at 12 h,24 h,and 72 h than those in the death group(t values-2. 87,-4. 88,-11. 29; P<0. 05). The HCO3-values of the survival group at 12 h,24 h and 72 h were higher than the death group, and the differences were statistically significant ( t values: -3. 90, -5. 60,-5. 76,P<0. 001). The lactic acid of survival group was significantly lower than the death group at 72 h after ventilation (t=5. 12,P<0. 001). Compared with the death group,partial pressure of carbon dioxide in 24 h,72 h decreased significantly in the surviving group(t values:5. 67,7. 60;P<0. 05). In the surviving group,the partial pressure of oxygen was maintained above 80 mmHg in 18 patients and the mechanical venti-lation time was (7. 17 ± 1. 95) d. The partial pressure of oxygen was below 80 mmHg in 12 patients of the surviving group and the mechanical ventilation time was (8. 67 ± 2. 50)d. The difference was statistically sig-nificant(t =12. 02,P <0. 001). Conclusion In the treatment of newborn with pulmonary hypertension caused by meconium aspiration,maintaining a higher pH value and a partial pressure of oxygen higher than 80 mmHg may be beneficial to the recovery of children with pulmonary hypertension.

Objective To investigate the influencing factors for energy balance and the relationship be-tween energy balance and clinical outcome in PICU mechanical ventilation children. Methods Children with mechanical ventilation who were hospitalized in PICU for more than 3 days from June 2015 to May 2016 were collected, resting energy expenditure was measured by resting energy metabolic detector, and the nutrition bal-ance was calculated, the influencing factors on energy balance was analyzed by regression analysis. Results A total of 104 mechanical ventilation children were included with the average energy consumption of ( 265. 4 ± 63. 2) kJ/kg in the first 3 days and the average energy supply of (219. 8±82. 9) kJ/kg, and failed to reach the target value ( P<0. 05) . As the time of hospitalization was prolonged, the supply of energy increased gradu-ally, the SAPS Ⅱ ( r=-0. 609, P=0. 000) , mechanical ventilation time ( r=-0. 456, P=0. 000) , ICU stay time ( r=-0. 646, P=0. 000) , the number of organ failure ( r=-0. 568, P=0. 000) , infection complications ( r=-0. 859, P=0. 000) were negatively correlated to energy supply balance; regression analysis showed that complications of nosocomial infection ( P = 0. 000 ) , number of organ failure ( P = 0. 000 ) , mechanical ventilation time ( P=0. 000) , ICU retention time ( P=0. 001) were predictors of energy supply balance. Con-clusion Insufficient supply of energy for the first three days of mechanical ventilation is high in the critically ill children. Factors affecting energy supply balance include patient's organ failure, infection complications, me-chanical ventilation time, and ICU retention time, which suggest that the strengthening of the nutritional man-agement of the critically ill children with mechanical ventilation will benefit to the clinical outcome.

Objective To retrospectively analyze the different clinical stages of patients with prostate cancer,and to investigate it's correlation with body mass index (BMI).Methods 363 patients with prostate cancer were enrolled from January 2008 to December 2016.There were 141 cases of stage Ⅱ,Ⅲ in 20 cases,202 cases of stage Ⅳ.According to the stratification of BMI (emaciation group,normal group,overweight group,obesity group),clinical data of different groups of prostate cancer patients were compared to analyze there correlation with BMI.Results Patient's age,pre-PSA concentration,Gleason scores and PSA density were significantly correlated with clinical stage (P ＜ 0.05).Prostate volume and weight had no significant correlation with staging.There was a significant correlation between different strata of BMI and clinical stage (P ＜ 0.05).Conclusion The different strata of BMI are closely related to the clinical stage.The higher BMI,the higher risk of the prostate cancer.