Association of attenuated leptin signaling pathways with impaired cardiac function under prolonged high-altitude hypoxia.

Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Hypoxia promotes white adipose tissues browning in rats under simulated environment at altitude of 5000 m.

People living in plains tend to decrease in body weight or body fat percentage after entering the plateau. Previous studies have found that plateau animals can burn fat and release calories through white adipose tissues (WATs) browning. However, these studies have focused on the effect of cold stimulation that induced WATs browning while there's hardly study on the effect of hypoxia. In this study, we investigate that whether and how hypoxia contributes to WATs browning in rats from acute to chronic hypoxia. We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1, 3, 14 and 28 days (Group H) under simulated environment at altitude of 5000 m. We also established normoxic control groups for each time period (Group C), as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate (Group R). We then observed the growth status of rats and recorded dynamic changes in histologic, cellular and molecular levels of perirenal WATs (PWAT), epididymal WATs (EWAT) and subcutaneous WATs (SWAT) in each group. Results showed that (1) Hypoxic rats had lower food intake, significantly lower body weight than control rats, and showed lower WATs index. (2) In group H14, ASC1 mRNA expressions of PWAT and EWAT in rats were lower than that in group C14, and PAT2 mRNA expression of EWAT was higher than that in both group C14 and R14. In group R14, however, ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14, and that of SWAT was also significantly higher than group C14. (3) In group H3, both the mRNA and protein levels of uncoupling protein 1 (UCP1) of PWAT in rats were significantly increased than group C3. And in group H14, those of EWAT in rats were significantly increased than group C14. (4) In plasma of rats, norepinephrine (NE) level was significantly increased in group H3 than group C3, and free fatty acids (FFAs) level was significantly increased in group H14 than both group C14 and R14. In group R1, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated than group C1. In group H3, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated while ATGL mRNA expression of EWAT was up-regulated than group C3. Conversely, in group R14, FASN mRNA expressions of PWAT and EWAT in rats were significantly up-regulated than group C14 and H14. These results suggested that hypoxia promoted different WATs browning in rats under simulated environment at altitude of 5000 m and changed the lipid metabolism in WATs. Furthermore, rats in the chronic hypoxic group showed a completely different lipid metabolism of WATs from that in paired food-restriction group.

Provincial clustering and related factors analysis of clinic antimicrobial resistance in China.

OBJECTIVE: Antimicrobial resistance (AMR) is among the biggest and most pressing risks facing healthcare in China and globally. We aimed to describe the current status regarding the distribution of clinic AMR in China through provincial clustering and analyse the related factors. METHODS: Based on the detection rates of 13 major drug-resistant bacteria in 31 provinces across the country, as reported by the National Bacterial Resistance Surveillance Network in 2019, we carried out a provincial clustering by dividing the conditions of provincial clinical AMR into different groups, and we then examined the potentially related factors, such as the use of antibiotics, economic development status, health service utilization, and health resource allocation. RESULTS: According to the different levels of bacterial resistance, the provinces were clustered into three categories: low, medium, and high detection rates of AMR. The three categories had notable geographic clustering and associations. Economic development status, health service utilization, such as the number of the types of antibacterial drugs (P = 0.025), health resource allocations, such as low licensed pharmacist per 1000 patient visits (P = 0.004) were related to AMR in China. CONCLUSIONS: The levels of AMR in public hospitals within the coastal areas of North China and East China were higher than those in other areas. The regions with higher levels of clinical bacterial resistance also had higher levels of health costs, health services volume and utilization, insufficient health resources per time, and higher probability of overuse of antimicrobials. Targeted measures should be taken in these areas to curb the resistance trends.

Induction chemotherapy followed by intensity-modulated radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma: A retrospective analysis.

OBJECTIVES: The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity-modulated radiotherapy (IC-RT) versus concurrent chemoradiotherapy (CCRT) in NPC. METHODS: Of 448 stage II-IVb NPC patients treated with IC-RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan-Meier curves and log-rank (Mantel-Cox) test. RESULTS: The median follow-up was 66 months (interquartile range, 46-84 months). There was no statistically significant difference in the estimated 5-year overall survival (OS), progression-free survival (PFS), distance metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) between IC-RT group and CCRT group (OS: 89.5% vs 91.7%, P = .568; PFS: 85.2% vs 87.5%, P = .615; DMFS: 90.9% vs 91.7%, P = .847; LRFS: 92.0% vs 96.9%, P = .104). In the multivariate analysis, the treatment group (IC-RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV-DNA level was an independent prognostic factor that was only significantly associated with LRFS. CONCLUSIONS: IC-RT achieves similar survival outcomes and treatment-related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data.

Optimizing number of cycles of induction chemotherapy for patients with nasopharyngeal carcinoma: Retrospective survival analysis.

BACKGROUND: Induction chemotherapy followed by concurrent chemoradiotherapy is one of the standards of care for patients with nasopharyngeal carcinoma, but the optimal number of induction cycles is unclear. Here we compared survival data from patients treated with 2 to 4 cycles. METHODS: Patients with nasopharyngeal carcinoma at West China Hospital of Sichuan University between January 2009 and December 2015 were retrospectively analyzed. RESULTS: Six hundred and seventy three patients met eligibility criteria. After a median follow-up of 53 months (interquartile range, 38-74), there was no difference between 2 and 3 cycles in overall survival (88.14% vs 91.24%). But four cycles were associated with worse overall survival (79.12%) and higher incidence of treatment-related toxicities. Multivariate analysis showed that the number of induction cycles and lymph node classification were prognostic factors. CONCLUSIONS: Two and three cycles of induction chemotherapy are associated with similar survival, while four cycles reduce survival and increase treatment-related toxicity in endemic regions.