CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4+ and CD8+ T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC.

Hyperthyroidism is not a significant risk of benign prostatic hyperplasia: A nationwide population-based study.

Benign prostatic hyperplasia (BPH) is a common disorder in the aging male population. Despite evidence that thyroid status impacts the prostate, the objective of this study was to examine whether patients with hyperthyroidism were at a greater risk for BPH.This study is a retrospective nationwide population-based cohort study of the Chinese population. Data for this study were retrieved from the Taiwan National Health Insurance Research Database (NHIRD). Overall, 1032 male patients aged 40 years or older with hyperthyroidism diagnosed between 2000 and 2006 were included in the hyperthyroidism group, and 4128 matched controls without hyperthyroidism were included in the non-hyperthyroidism group. Both groups were monitored until the end of 2011. A Cox proportional hazards regression model was used to compute and compare the risk of BPH between study participants with and those without hyperthyroidism.Patients with hyperthyroidism exhibited a greater incidence of BPH (18.51% vs 15.53%) than did the controls. Furthermore, the hazard ratio (HR) of the hyperthyroidism group was 1.24 times that of the control group [95% confidence interval (95% CI 1.05-1.46)] signifying that there is a significant 24% increase in the risk of BPH with the presence of hyperthyroidism. This increased risk of BPH with hyperthyroidism, however, failed to remain significant (adjusted HR = 1.11, 95% CI = 0.94-1.3) after adjusting for covariates of age (adjusted HR = 2.72, 95% CI = 2.32-3.2), diabetes (adjusted HR = 1.4, 95% CI = 1.17-1.68), hypertension (adjusted HR = 1.74, 95% CI = 1.49-2.03), hyperlipidemia (adjusted HR = 1.25, 95% CI = 1.03-1.53), neurogenic bladder, cystitis (adjusted HR = 1.23, 95% CI = 0.58-2.59), urethral stricture (adjusted HR = 2.01, 95% CI = 0.28-14.47), urethritis (adjusted HR = 1.52, 95% CI = 0.72-3.21), and urinary tract infection (adjusted HR = 1.77, 95% CI = 1.31-2.39).After adjustment for comorbidities and covariates, hyperthyroidism was not found to be a significant risk factor of BPH in our male study subjects. Further research is warranted to validate our results and elucidate the association of the pathophysiology of these 2 diseases.

Impact of shock wave lithotripsy on heart rate variability in patients with urolithiasis.

The physiological response of the cardiac autonomic nervous system during shock wave lithotripsy (SWL) remains unclear. Heart rate variability (HRV) is an index of cardiac autonomic balance. This study aimed to analyze HRV during SWL in patients with urolithiasis. Electrocardiograms of patients who underwent SWL were obtained. Recordings were obtained before and after SWL. For each time point, the recordings were obtained continuously for 6 min, after which R wave-to-R wave (RR) intervals were extracted. The time digital sequence derived from RR intervals was the HRV signal. Time-domain analysis revealed that the mean of RR intervals (MRR) and standard deviation of normal beat-to-normal beat (NN) intervals (SDNN), but not the square root of the mean squared difference of successive NNs (RMSSD) or triangular interpolation of NN intervals (TINN), significantly increased during SWL. The increase in SDNN persisted after SWL but MRR returned to the initial level. Frequency-domain analysis revealed that very low frequency (VLF), low frequency (LF), and LF/high frequency (HF) ratio significantly increased after SWL, while there was no statistically significant difference in HF. Thus, the patients had significantly high MRR and SDNN during SWL and significantly high SDNN, VLF, LF, and LF/HF ratio after SWL. SWL could alter the functioning of the cardiac autonomic nervous system, resulting in reduction in sympathetic activity and increase in parasympathetic activity. Further studies with larger samples are required to confirm these findings and understand the underlying mechanisms.

Transcutaneous electrical nerve stimulation on ST36 and SP6 acupoints prevents hyperglycaemic response during anaesthesia: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. METHODS: We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. RESULTS: At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. CONCLUSION: We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.