Despite the success of immune checkpoint blockade against melanoma, many "cold" tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical prostate cancer and resisted T cell infiltration even in the context of CTLA-4 and PD-1 blockade. We demonstrated that the hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia in these tumors. Combination therapy with this hypoxia-prodrug and checkpoint blockade cooperated to cure more than 80% of tumors in the transgenic adenocarcinoma of the mouse prostate-derived (TRAMP-derived) TRAMP-C2 model. Immunofluorescence imaging showed that TH-302 drives an influx of T cells into hypoxic zones, which were expanded by checkpoint blockade. Further, combination therapy reduced myeloid-derived suppressor cell density by more than 50%, and durably reduced the capacity of the tumor to replenish the granulocytic subset. Spontaneous prostate tumors in TRAMP transgenic mice, which completely resist checkpoint blockade, showed minimal adenocarcinoma tumor burden at 36 weeks of age and no evidence of neuroendocrine tumors with combination therapy. Survival of Pb-Cre4, Ptenpc-/-Smad4pc-/- mice with aggressive prostate adenocarcinoma was also significantly extended by this combination of hypoxia-prodrug and checkpoint blockade. Hypoxia disruption and T cell checkpoint blockade may sensitize some of the most therapeutically resistant cancers to immunotherapy.

Hypertension is becoming an important health problem in many countries. The 'small baby syndrome hypothesis' suggests that an inverse linear relationship exists between birth weight and later risk of hypertension; however, this relationship is under debate. We conducted a meta-analysis to examine the association between birth weight and subsequent blood pressure. Among 78 studies reporting on the association between birth weight and subsequent blood pressure, 20 articles (reporting 27 original studies) were eligible for inclusion. Low birth weight (< 2500 g) compared with birth weight greater than 2500 g was associated with an increased risk of hypertension (odds ratio [OR] 1.21; 95% confidence interval [CI] 1.13, 1.30); high birth weight (> 4000 g) compared with birth weight less than 4000 g was associated with a decreased risk of hypertension (OR 0.78; 95% CI 0.71, 0.86). When low birth weight (< 2500 g) was compared with birth weight greater than 2500 g, mean systolic blood pressure (SBP) increased by 2.28 mmHg (95% CI 1.24, 3.33); when high birth weight (> 4000 g) was compared with birth weight less than 4000 g, mean SBP decreased by 2.08 mmHg (95% CI -2.98, -1.17). These findings indicate that there is an inverse linear association between birth weight and later risk of hypertension, and that this association primarily exists between birth weight and SBP.

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Neither positively linear nor J- or U-shaped relations exist between birth weight and overweight/obesity in adults. It is high birth weight, not low birth weight, that is associated with increased risk of overweight/obesity in adults.

Some studies have found a significant relationship between birth weight (BW) and the risk of coronary heart disease (CHD) in adulthood, but results were inconsistent. The purpose of this study was to characterize the association between BW and the risk of CHD in adults. Among 144 papers detected by our search, 27 papers provided data on the relationship between BW and CHD, of which 23 papers considered BW as a continuous variable, and 14 articles considered BW as a categorical variable for this meta-analysis. Based on 23 papers, the mean weighted estimate for the association between BW and the combined outcome of non-fatal and fatal CHD was 0.83 [95% confidence interval (CI), 0.80-0.86] per kilogram of BW (P<0.0001). Low birth weight (LBW<2500 g) was associated with increased risk of CHD [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.11-1.27] compared with subjects with BW⩾2500 g. LBW, as compared with normal BW (2500-4000 g), was associated with increased risk of CHD (OR, 1.16; 95% CI, 1.08-1.25). High birth weight (HBW⩾4000 g) was associated with decreased risk of CHD (OR, 0.89; 95% CI, 0.81-0.98) compared with subjects with BW<4000 g. In addition, there was an indication (not quite significant) that HBW was associated with a lower risk of CHD (OR, 0.89; 95% CI, 0.79-1.01), as compared with normal BW. No significant evidence of publication bias was present. These results suggest that LBW is significantly associated with increased risk of CHD and a 1 kg higher BW is associated with a 10-20% lower risk of CHD.

Our study proves the necessity of colonoscopy when incidental FDG uptake is found on PET/CT imaging. The false-positive FDG uptake is more commonly observed in the right colon. Although the SUVmax value is higher in cancer patients, a high SUVmax value does not necessarily result in malignancies.

These findings suggested that there was a positive correlation between Chinese traditional dietary pattern and healthy BMI and BMD and that this same association existed between calcium food pattern and BMD in Chinese freshmen. In contrast, the Western-style diet was negatively correlated with healthy BMI in Chinese freshmen.