Development and validation of a nomogram for prediction of recovery from moderate-severe xerostomia post-radiotherapy in nasopharyngeal carcinoma patients.

PURPOSE: Aim to create and validate a comprehensive nomogram capable of accurately predicting the transition from moderate-severe to normal-mild xerostomia post-radiotherapy (postRT) in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We constructed and internally verified a prediction model using a primary cohort comprising 223 patients who were pathologically diagnosed with NPC from February 2016 to December 2019. LASSO regression model was used to identify the clinical factors and relevant variables (the pre-radiotherapy (XQ-preRT) and immediate post-radiotherapy (XQ-postRT) xerostomia questionnaire scores, as well as the mean dose (Dmean) delivered to the parotid gland (PG), submandibular gland (SMG), sublingual gland (SLG), tubarial gland (TG), and oral cavity). Cox proportional hazards regression analysis was performed to develop the prediction model, which was presented as a nomogram. The models' performance with regard to calibration, discrimination, and clinical usefulness was evaluated. The external validation cohort comprised 78 patients. RESULTS: Due to better discrimination and calibration in the training cohort, age, gender, XQ-postRT, and Dmean of PG, SMG, and TG were included in the individualized prediction model (C-index of 0.741 (95% CI:0.717 to 0.765). Verification of the nomogram's performance in internal and external validation cohorts revealed good discrimination (C-index of 0.729 (0.692 to 0.766) and 0.736 (0.702 to 0.770), respectively) and calibration. Decision curve analysis revealed that the nomogram was clinically useful. The 12-month and 24-month moderate-severe xerostomia rate was statistically lower in the SMG-spared arm (28.4% (0.230 to 35.2) and 5.2% (0.029 to 0.093), respectively) than that in SMG-unspared arm (56.8% (0.474 to 0.672) and 12.5% (0.070 to 0.223), respectively), with an HR of 1.84 (95%CI: 1.412 to 2.397, p = 0.000). The difference in restricted mean survival time for remaining moderate-severe xerostomia between the two arms at 24 months was 5.757 months (95% CI, 3.863 to 7.651; p = 0.000). CONCLUSION: The developed nomogram, incorporating age, gender, XQ-postRT, and Dmean to PG, SMG, and TG, can be used for predicting recovery from moderate-severe xerostomia post-radiotherapy in NPC patients. Sparing SMG is highly important for the patient's recovery.

Electro-acupuncture treatment ameliorates intestinal inflammatory injury in cerebral ischemia-reperfusion rats via regulating the balance of Treg / γδ T cells.

Electro-acupuncture (EA) has an anti-inflammatory role in ischemic stroke, but whether the protective effect of EA involves the regulation of the intestine barrier and Treg/ γδ T cells is unclear. Cerebral ischemia-reperfusion (I/R) injury was induced by middle cerebral artery occlusion(MCAO) for 2 h followed by reperfusion for 24 h. The rats have treated with EA at the "Baihui" acupoint(GV20). Triphenyl tetrazolium chloride (TTC) staining and Longa neurologic score were performed to evaluate the outcomes after ischemic stroke. Inflammatory factor expression levels in the serum, ischemic hemisphere brain, and small intestine were detected by ELISA or RT-qPCR. Additionally, the morphology change of the small intestine was evaluated by analyzing villus height and smooth muscle thickness. Meanwhile, the expression of tight-junction proteins, including Zonula Occludens-1 (ZO-1), Occludin, and Claudin-1, were detected to evaluate the impact of EA on mucosal permeability in the small intestine. The percentages of regulatory T cells (Tregs) (CD45+CD4+Foxp3+) and γδ T cells (CD45+CD4-γδ T+) were measured to assess the effect of EA on intestinal T cells. EA decreased the brain infarction volume and intestine barrier injury in ischemic stroke rats. At the same time, it effectively suppressed the post-stroke inflammation in the brain and small intestine. More importantly, EA treatment increased the percentage of Tregs in the small intestine while reducing the rate of γδ T cells, and ultimately increased the ratio of Treg/ γδ T cells. These results demonstrated that EA ameliorated intestinal inflammation damage by regulating the Treg/ γδ T cell polarity shift and improving the intestine barrier integrity in rats with I/R injury. This may be one of the mechanisms underlying the anti-ischemic injury effects of acupuncture on stroke.

A Randomized Study on the Effect of Metformin Combined with Intensive-Exercise Diet Therapy on Glucose and Lipid Metabolism and Islet Function in Patients with Renal Cell Carcinoma and Diabetes.

Objective: To evaluate the effect of metformin combined with intensive-exercise diet therapy on glucose and lipid metabolism and islet function in diabetes patients with localized renal cell carcinoma after laparoscopic resection. Methods: A total of 120 renal cancer patients with diabetes mellitus treated in the oncology department of our hospital from January 2018 to December 2020 were recruited and assigned via random number table method at a ratio of 1 : 1 to receive either metformin (control group) or metformin plus intensive exercise diet therapy (study group) after laparoscopic nephrectomy. Outcome measures included glucose and lipid metabolism, pancreatic islet function, lifestyle, clinical efficacy, and adverse reactions. Results: After the intervention, the fasting blood glucose (FBG), 2 h postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of the two groups of patients decreased significantly, and the study group had significantly lower results. After treatment, the two groups had elevated levels of high-density lipoprotein cholesterol (HDL-C), fasting serum insulin (FINS), and homeostasis model assessment of ß-cell function (HOMA-ß), and higher results were obtained in the study group (P < 0.05). After the intervention, the study group showed higher results of health promoting lifestyle profile-II (HPLP-II) and a 12-month progression-free survival rate than the control group. There were no significant differences in the incidence of adverse reactions between the two groups. Conclusion: Metformin combined with intensive-exercise diet therapy significantly improves the glucose and lipid metabolism and islet function of renal cancer patients with diabetes and effectively enhances the 12-month progression-free survival. Further trials are, however, required prior to clinical application.

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded. Results: At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433). Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

Comparison of the pre-treatment functional MRI metrics' efficacy in predicting Locoregionally advanced nasopharyngeal carcinoma response to induction chemotherapy.

BACKGROUND: Functional MRI (fMRI) parameters analysis has been proven to be a promising tool of predicting therapeutic response to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC). The study was designed to identify and compare the value of fMRI parameters in predicting early response to IC in patients with NPC. METHODS: This prospective study enrolled fifty-six consecutively NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion weighted imaging (DWI), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocols were performed before and after IC. Parameters maps (ADC, MD, MK, Dslow, Dfast, PF, Ktrans, Ve and Kep) of the primary tumor were calculated by the Functool post-processing software. The participants were classified as responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between RG with NRG. Logistic regression analysis and ROC were performed to further identify and compare the efficacy of the parameters. RESULTS: After IC, the mean values of ADC(p < 0.001), MD(p < 0.001), Dslow(p = 0.001), PF(p = 0.030) and Ve(p = 0.003) significantly increased, while MK(p < 0.001), Dfast(p = 0.009) and Kep(p = 0.003) values decreased dramatically, while no significant difference was detected in Ktrans(p = 0.130). Compared with NRG, ADC-pre(p < 0.001), MD-pre(p < 0.001) and Dslow-pre(p = 0.002) values in RG were lower, while MK-pre(p = 0.017) values were higher. The areas under the ROC curves for the ADC-pre, MD-pre, MK-pre, Dslow-pre and PRE were 0.885, 0.855, 0.809, 0.742 and 0.912, with the optimal cutoff value of 1210 × 10- 6 mm2/s, 1010 × 10- 6 mm2/s, 832 × 10- 6, 835 × 10- 6 mm2/s and 0.799 respectively. CONCLUSIONS: The pretreatment conventional DWI (ADC), DKI (MD and MK), and IVIM (Dslow) values derived from fMRI showed a promising potential in predicting the response of the primary tumor to IC in NPC patients. TRIAL REGISTRATION: This study was approved by ethics board of the Chinese PLA General Hospital, and registered on January 30, 2021, in Chinese Clinical Trial Registry ( ChiCTR2100042863 ).

Changes in the nutritional status of nine vitamins in patients with esophageal cancer during chemotherapy.

BACKGROUND: Many studies have investigated the relationships between vitamins and esophageal cancer (EC). Most of these studies focused on the roles of vitamins in the prevention and treatment of EC, and few studies have examined the changes in vitamin nutritional status and their influencing factors before and after chemotherapy for EC. Chemotherapy may have a considerable effect on EC patients' vitamin levels and hematological indicators. AIM: To research the nutritional status of multiple vitamins in EC patients during chemotherapy and to assess its clinical significance. METHODS: EC patients admitted to our center from July 2017 to September 2020 were enrolled in this study. Serum concentrations of nine vitamins (A, D, E, B9, B12, B1, C, B2 and B6), hemoglobin, total protein, albumin, blood calcium, blood phosphorus concentrations and body mass index (BMI) were measured in all EC patients. The changes in nine vitamins, hematological indicators and BMI were compared before and after two cycles of chemotherapy. The possible influential factors were analyzed. RESULTS: In total, 203 EC patients receiving chemotherapy were enrolled in this study. Varying degrees of vitamin A, D, C and B2 deficiency and weight loss were found in these patients, and the proportions of vitamin B2 and vitamin C deficiencies increased significantly after chemotherapy (both P < 0.05). Serum concentrations of vitamins A, C, B2 and B6 and BMI before and after chemotherapy were statistically significant (all P < 0.05). Multivariate analysis showed that vitamin A levels significantly differed between male and female EC patients, whereas vitamin D concentration significantly differed in EC patients in different stages (all P < 0.05). Correlations were observed between the changes in serum concentrations of vitamin A and C before and after two cycles chemotherapy and the change in BMI (P < 0.05). Hemoglobin, total protein, serum albumin and blood calcium concentrations significantly decreased in EC patients after chemotherapy (all P < 0.05), while the blood phosphorus level significantly increased after chemotherapy (P < 0.05). Using the difference in vitamin concentrations as the independent variables and the difference in BMI as the dependent variable, logistic regression analysis revealed statistically significant differences for vitamin A, vitamin D and vitamin C (F = 5.082, P = 0.002). CONCLUSION: Vitamin A, D, C and B2 were mainly deficient in patients with EC during chemotherapy. Multivitamin supplementation may help to improve the nutritional status, chemotherapy tolerance and efficacy.

[Influencing Factors and Prevation of Infection in Leukemia Patients after Allogeneic Peripheral Blood Stem Cell Transplantation].

OBJECTIVE: To explore the influencing factors and countermeasures of infection in leukemia patients after allogeneic peripheral blood hematopoietic stem cell transplantation. METHODS: A total of 126 patients with leukemia admitted in our hospital from August 2016 to March 2018 were selected. The number of infected patients after transplantation was recorded, and the causes of infection were analyzed. RESULTS: Among the 126 patients, 43 were positive for infection, and the infection rate was 34.13%. A total of 89 pathogens were detected, of which bacteria accounted for 64.05%; virus accounted for 22.47%, and fungi accounted for 13.48%. The patient's age, donor type, pre-transplant infection, prophylactic use of antibiotics and aGVHD all were factors influencing the patient's infection (P＜0.05). The follow-up results showed that the incidence of infection in the intervention group significantly decreased after intervention with prevention program (P＜0.05). After reasonable nursing intervention, the incidence of infection in the intervention group after follow-up for 12 months was lower than that in the control group (P＜0.05). CONCLUSION: Pre-transplant infection and prophylactic use of antibiotics are factors influencing the infection after allogeneic hematopoietic stem cell transplantation. The incidence of infection can be reduced by reasonable infection prevention.

Association of diabetic vascular complications with poor sleep complaints.

BACKGROUND: Literatures reported that poor sleep complaints were associated with a great deal of health outcomes. However, there are few studies on the association of poor sleep complaints with diabetic vascular complications. METHODS: Aiming on the association, a cross-sectional survey was conducted among 1220 diabetic patients in this study. Poor sleep complaints were composed of difficulty falling asleep, early final awakening, short sleep and long sleep. The diabetic vascular complications involved in the study were diagnosed according to the Standards of Medical Care in Diabetes (ADA 2016). RESULTS: Our findings indicated that short sleep remained independently associated with diabetic kidney disease (DKD) (OR > 1, P < 0.05) after the adjustments; long sleep independently associated with diabetic retinopathy (DR) (OR > 1, P < 0.05); early final awakening and short sleep independently associated with cardiovascular disease (OR > 1, P < 0.05); short sleep independently associated with peripheral arterial disease (OR > 1, P < 0.05); there was no association between poor sleep complaints and neuropathy (P > 0.05). CONCLUSIONS: The study suggests that the poor sleep complaints were distinguishably associated with diabetic vascular complications. Clinicians should take poor sleep complaints into account in diabetes treatment.

Efficacy and safety of vildagliptin, sitagliptin, and linagliptin as add-on therapy in Chinese patients with T2DM inadequately controlled with dual combination of insulin and traditional oral hypoglycemic agent.

OBJECTIVE: We aimed to evaluate the efficacy and safety of the three dipeptidyl peptidase 4 (DPP-4) inhibitors (vildagliptin, sitagliptin, and linagliptin) as add-on therapy in Chinese patients with type 2 diabetes mellitus (T2DM)inadequately controlled on dual combination of insulin and metformin or acarbose. METHODS: A total of 535 T2DM patients who failed to achieve glycemic control with insulin and a traditional oral hypoglycemic agent were randomized to receive vildagliptin, sitagliptin, or linagliptin. Body mass index, glycosylated hemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG), insulin dose, and adverse events were evaluated during the study. RESULTS: The baseline HbA1c was 9.59 ± 1.84 % (vildagliptin group), 9.22 ± 1.60 % (sitagliptin group), and 9.58 ± 1.80 % (linagliptin group). At week 12 it was 8.16 ± 1.29 % (vildagliptin), 8.56 ± 1.96 % (linagliptin), and 8.26 ± 1.10 % (sitagliptin). The changes in HbA1c from baseline were -1.33 ± 0.11 % (vildagliptin), -0.84 ± 0.08 % (sitagliptin) and -0.81 ± 0.08 % (linagliptin), the vildagliptin group had the greatest reduction in HbA1c (P < 0.05). The proportions of patients that reached target HbA1c were 66.27 % (vildagliptin), 52.73 % (sitagliptin), and 55.49 % (linagliptin), the vildagliptin group had the highest one (P < 0.05). The baseline FPG and PPG values in the three groups were at the same level. At week 12, mean FPG levels in the vildagliptin (7.31 ± 1.50 mmol/L) and linagliptin (6.90 ± 1.55 mmol/L) groups were significantly lower than in the sitagliptin group (8.02 ± 4.48 mmol/L; P < 0.05); the linagliptin group had the lowest mean PPG followed by the vildagliptin group which was also significant lower (P = 0.000) than the sitagliptin group. Additionally, the required insulin dosage in the vildagliptin group was the lowest among the groups at weeks 6 and 12. Only mild AEs were reported during the study. CONCLUSION: The three DPP-4 inhibitors appear to be effective and safe as add-on therapy for T2DM patients on dual combination of insulin and a traditional OHA. Vildagliptin was more effective in decreasing insulin requirement and achieving glycemic control when compared to the other two.

Transmitting information of an object behind the obstacle to infinity.

We propose an illusion device that transforms a metallic cylinder into a Luneburg lens by using transformation optics. Such a transformed focusing lens guides electromagnetic waves to propagate around the central metallic cylinder smoothly and be focused on one spot, and thus the information of an object behind the obstacle can be transmitted to infinity. In order to realize the required-anisotropic parameters with high permittivity and low permeability, we design embedded split-ring resonators (SRRs) to increase the permittivity of the traditional SRR structures. In experiments, we fabricate and measure the transformed lens, and the tested results agree well with the numerical simulations and theoretical predictions. The proposed transformation lens can mimic some properties of Einstein gravitational lens because their wave propagation behaviors are very similar.

Impact of inflammatory markers on the relationship between sleep quality and incident cardiovascular events in type 2 diabetes.

AIMS: To analyze relevance of sleep quality with CVD in T2D patients and determine whether inflammation prompted by poor sleep has impact on the CVD. METHODS: 332 T2D patients were recruited and their sleep qualities were evaluated by PSQI. The patients with PSQI score >7 were in the poor sleep group, and the others were in the good sleep group. Plasma samples of the patients were obtained to measure inflammatory markers. Correlation analyses and regression analyses were performed to examine the cross-sectional relationships among the poor sleep, inflammatory markers and CVD. RESULTS: The morbidity of CVD was significantly higher in the poor sleep patients compared to the good sleep patients (P=0.000). PSQI score ORs were both >1 for CVD in model 1 and model 2 (P<0.05). PSQI score were positively related to IL-6 and ICAM-1(P<0.05), negatively to FBI (P<0.05), but not related to CRP in linear regression models. Multiple logistic regression analysis showed IL-6 and ICAM-1, but not FBI and CRP, were related to CVD (P<0.05). CONCLUSIONS: Poor sleep is regarded as a plausible risk factor for CVD in T2D patients, and may be mediated by certain inflammatory markers.

Observing abnormally large group velocity at the plasmonic band edge via a universal eigenvalue analysis.

We developed a novel universal eigenvalue analysis for 2D arbitrary nanostructures comprising dispersive and lossy materials. The complex dispersion relation (or complex Bloch band structure) of a metallic grating is rigorously calculated by the proposed algorithm with the finite-difference implementation. The abnormally large group velocity is observed at a plasmonic band edge with a large attenuation constant. Interestingly, we found the abnormal group velocity is caused by the leaky (radiation) loss, not by metallic absorption (ohmic) loss. The periodically modulated surface of the grating significantly modifies the original dispersion relation of the semi-infinite dielectric-metal structure and induces the extraordinarily large group velocity, which is different from the near-zero group velocity at photonic band edge. The work is fundamentally important to the design of plasmonic nanostructures.

Dosimetric comparison between helical tomotherapy and intensity-modulated radiation therapy plans for non-small cell lung cancer.

BACKGROUND: Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT) technique. It is reported that HT plan for non-small-cell lung cancer (NSCLC) can give better dose uniformity, dose gradients, and protection for the lung than IMRT plan. We compared the dosimetric characteristics of HT for NSCLC with those of conventional IMRT to observe the superiority of HT. METHODS: There was a comparative case series comprising 10 patients with NSCLC. Computed tomographic (CT) images of delineated targets were transferred to the PrecisePlan planning system (IMRT) and Tomo planning system (HT). The prescription doses were 70 Gy/33F for the gross tumor volume (GTV) and the visible lymph nodes (GTVnd), and 60 Gy/33F for the clinical target volume (CTV) and the clinical target volume of the visible lymph nodes (CTVnd). The dose restrictions for organs at risk were as follows: the maximum dose to spinal cord ≤ 45 Gy, V20 to the total lungs < 30%, V50 to the heart < 50%, and V55 to the esophagus < 50%. Both plans were evaluated by means of the dose coverage of the targets, dose-volume histograms (DVHs), and other dosimetric indices. RESULTS: The dose coverage, conformity, and homogeneity of the targets' volumes were found to be satisfactory in both plans, but the homogeneity of the HT plan was better than that of IMRT. The high-dose radiation volume (V20-V30) to the lung and the mean lung dose (MLD) decreased (P < 0.05), but the low-dose radiation volume (V5-V10) increased slightly in the HT plan (P > 0.05). The maximum doses to the spinal cord, heart, esophagus and trachea in the HT plan were lower than those in the IMRT plan, but the differences were not statistically significant. CONCLUSIONS: The HT plan provids better dose uniformity, dose gradients, and protection for the organs at risk. It can reduce the high-dose radiation volume for lung and the MLD, but may deliver a larger lung volume of low-dose radiation.