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The principal treatment strategy in drug-induced autonomic failure is eliminating the offending agent. The quality of evidence is moderate. Longer-term future RCTs are likely to have an important impact on determining the net risk−benefit ratio of the withdrawal of culprit medications.

PCM such as leg crossing and squatting should be encouraged in patients with warning symptoms who are able to perform them. 319

Gravitational venous pooling in older patients can be treated with abdominal binders or compression stockings. 23 , 320 , 321

Sleeping with the head of the bed elevated (>10 degrees) prevents nocturnal polyuria, maintains a more favourable distribution of body fluids, and ameliorates nocturnal hypertension. 104 , 322 , 323

The alpha-agonist midodrine is a useful addition to first-line treatment in patients with chronic autonomic failure. It cannot be regarded as a cure, nor is it helpful in all affected patients, but it is very useful in some. There is no doubt that midodrine increases BP both in the supine and upright posture, and ameliorates the symptoms of OH. Midodrine (2.5–10 mg t.i.d) was shown to be effective in three randomized placebo-controlled trials. 324–326

The desirable effects of midodrine outweigh the undesirable effects. The quality of evidence is moderate and further research is likely to have an important impact on the estimate of benefit.

Fludrocortisone (0.1–0.3 mg once daily) is a mineralocorticoid that stimulates renal sodium retention and expands fluid volume. 327 The evidence in favour of fludrocortisone is from two small observational studies (in combination with head-up sleeping) and one double-blind trial in 60 patients; the observational studies showed haemodynamic benefit and, in the trial, treated patients were less symptomatic with higher BP. 322 , 327 , 328

The desirable effects of fludrocortisone outweigh the undesirable effects. The quality of evidence is moderate and further research is likely to have an important impact on the estimate of benefit.

Additional and less frequently used treatments, alone or in combination, include desmopressin in patients with nocturnal polyuria, octreotide in postprandial hypotension, erythropoietin in anaemia, pyridostigmine, the use of walking sticks, frequent small meals, and the judicious exercise of leg and abdominal muscles, especially swimming. Their efficacy is less established. 104

Droxidopa, a precursor of norepinephrine, is a centrally and peripherally acting alpha/beta-agonist approved by the US Food and Drug Administration for the treatment of symptomatic neurogenic OH. Droxidopa has recently been investigated for the treatment of neurogenic OH in four short-term RCTs 329–332 with a total of 485 patients. They showed a modest increase in standing systolic BP and the symptom benefit of droxidopa over placebo regarding some items of quality of life after 2 weeks of treatment, but its benefit was lost after 8 weeks. 333 Thus, current evidence is insufficient to confirm the efficacy of droxidopa for long-term use.

Regional shifts of planting areas have partly determined the changes of crop compositions and stimulated the growth of maize production. Recent increase of maize production in China, however, greatly exceeds its domestic demand, resulting in huge stockpiles of maize. As a consequence of these changes, China's food production has changed the global trading market. For example, China has changed from a net importer to exporter of maize since 2003. However, in recent years, China is forced to import wheat to meet the shortages in domestic demand (Figure S1 ). The ratio of stock to use for maize in China is the highest among all major maize producing countries in recent years (Figure 6 ). China has 48% of global maize stockpile (Figure 6 ). One analyst estimated that more than 20 million metric tons of China's maize are “so moldy or deteriorated that they are no longer suitable for human consumption or feed use,” which will probably result in losses of more than $10 billion USDA, 2016 ). The government has realized the overproduction of maize and announced to reduce 3.33 million hectares of maize cultivation areas in the Northeast, North, Northwest, and Southwest by 2020 (Ministry of Agriculture of the People's Republic of China, 2015 ).

Figure 6
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The stock to use ratios of maize over the global and the sample countries (solid lines) and the percentages of maize stock in China to the global stock (bars) for 2006–2014.
The stock to use ratios of maize over the global and the sample countries (solid lines) and the percentages of maize stock in China to the global stock (bars) for 2006–2014.

In addition, the increases of planting area in Northeast and Northwest China strongly depend on the expended irrigation conditions because of the low rainfall. It is very important to realize that the expansion of irrigation‐based agriculture has resulted in many negative environmental consequences, such as the depletion of water resources, water pollution, and soil salinization. The increase in cropping areas in these regions has substantially increased the agricultural uses of water and therefore aggravated the shortages of water resources for other uses. Ground water withdrawal for crop production in the North has led to a rapid decline in the water table (−0.8m/year) since the 1970s (Shen et al., 2013 ). Recent study highlighted that groundwater in the North and Northwest has been stressed or overstressed due to the high population and irrigation demand (Richey et al., 2015 ). Moreover, irrigation has led to soil salinization on about 9mha of arable lands in the northern regions, adversely affecting the cropland quality and crop yield (W. P. Chen et al., 2010 ). How long and how extensive this irrigation‐based agriculture can be sustained across various regions in China is a major scientific question that requires immediate attention.

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