Sodium content targets for pre-packaged foods, China: a quantitative study and proposal.

Objective: To determine the contribution of pre-packaged foods to population sodium intake in China, and to propose sodium content targets for food subcategories used for the World Health Organization's (WHO's) global sodium benchmarks. Methods: The impact of four different approaches to reducing the sodium content of pre-packaged foods on population sodium intake was estimated using data from national databases covering the nutrient content and ingredients of 51 803 food products and food consumption by 15 670 Chinese adults. We recategorized food products using a food categorization framework developed for WHO's global sodium benchmarks and adapted for China-specific foods. Findings: Pre-packaged foods, including condiments, contributed 1302.5 mg/day of sodium intake per adult in 2021, accounting for 30.1% of population sodium intake in China. Setting maximum sodium content levels using a 90th-percentile target would reduce sodium intake from pre-packaged foods by 96.2 mg/day, corresponding to a 1.9% reduction in population intake. Using the 75th-percentile, a fixed 20% reduction and WHO benchmark targets would further reduce intake by 262.0 mg/day (5.2% population intake), 302.8 mg/day (6.0% population intake) and 701.2 mg/day per person (13.9% population intake), respectively. Maximum sodium content levels based on revised 20% reduction targets were proposed because they should result in substantial and acceptable reductions in sodium content for most food subcategories: overall sodium intake would decline by 305.0 mg/day per person, and population intake by 6.1%. Conclusion: This study provides the scientific rationale for government policy on setting targets for food sodium content in China. Simultaneous action on discretionary salt use should also be taken.

Effectiveness and safety of basal insulin therapy in type 2 diabetes mellitus patients with or without metformin observed in a national cohort in China.

BACKGROUND: Though many randomized control trials had examined the effectiveness and safety of taking insulin therapy with or without metformin, there are limited real-world data, especially among Chinese type 2 diabetes patients initiating basal insulin (BI) with uncontrolled hyperglycemia by oral agents. This study was designed to assess the effectiveness and safety of BI therapy combined with or without metformin in a real-world national cohort study. METHODS: Patients with type 2 diabetes mellitus who initiated BI treatment due to uncontrolled hyperglycemia (HbA1c≥7 %) by oral antidiabetic drugs (OADs) were recruited in Chinese real-world settings between 2011 and 2013. A total of 12,358 patients initiated BI without bolus insulin and completed a 6-month follow-up were selected as the study population and divided into BI with metformin or BI without metformin group based on whether metformin was simultaneously prescribed or not at baseline. Propensity score adjustment was used to balance baseline covariates between two groups. A sub-analysis was also conducted among 8,086 patients who kept baseline treatment regimen during the follow-up. Outcomes were HbA1c, hypoglycemia, weight gain and insulin dose in two groups. RESULTS: 53.6 % (6,621 out of 12,358) patients initiated BI therapy concomitant with metformin. After propensity score adjustment, multivariate regression analysis controlled with number of OADs, total insulin dose, physical activity and diet consumption showed that BI with metformin group had a slightly higher control rate of HbA1c <7.0 % (39.9 % vs. 36.4 %, P = 0.0011) at 6-month follow-up, and lower dose increment from baseline to 6-month (0.0064 vs. 0.0068 U/day/kg, P = 0.0035). The sub-analysis with patients remained at same BI therapy further showed that BI with metformin group had higher HbA1c control rate (47.9 % vs. 41.9 %, P = 0.0001), less weight gain (-0.12 vs. 0.15 kg P = 0.0013), and lower dose increment during 6-month follow-up (0.0033 vs. 0.0037 U/day/kg, P = 0.0073) when compared with BI without metformin group. CONCLUSIONS: In alliance with current guidelines, the real-world findings also support the insulin initiation together with metformin. Continuous patients' education and clinicians training are needed to improve the use of metformin when initiating BI treatment.

Sodium content of restaurant dishes in China: a cross-sectional survey.

BACKGROUND: Sodium intake in China is extremely high and eating in restaurants is increasingly popular. Little research has explored the sodium level of restaurant dishes. The present study aims to assess the content and sources of sodium in Chinese restaurants. METHODS: Cross-sectional data were obtained from the baseline survey of the Restaurant-based Intervention Study (RIS) in 2019. A total of 8131 best-selling restaurant dishes with detailed recipes from 192 restaurants in China were included. Sodium content per 100 g and per serving were calculated according to the Chinese Food Composition Table. The proportion of restaurant dishes exceeding the daily sodium reference intake level in a single serving and the major sources of sodium were determined. RESULTS: Median sodium content in restaurant dishes were 487.3 mg per 100 g, 3.4 mg per kcal, and 2543.7 mg per serving. For a single serving, 74.9% of the dishes exceeded the Chinese adults' daily adequate intake for sodium (AI, 1500 mg per day), and 62.6% of dishes exceeded the proposed intake for preventing non-communicable chronic diseases (PI, 2000 mg per day). Cooking salt was the leading source of sodium in Chinese restaurant dishes (45.8%), followed by monosodium glutamate (17.5%), food ingredients (17.1%), soy sauce (9.4%), and other condiments/seasonings (10.2%). More types of salted condiments/seasonings use were related to higher sodium level. CONCLUSIONS: The sodium levels in Chinese restaurant dishes are extremely high and variable. In addition to cooking salt, other salted condiments/seasonings also contribute a large proportion of sodium. Coordinated sodium reduction initiatives targeting the main sources of sodium in restaurant dishes are urgently needed.

The effectiveness of postpartum interventions aimed at improving women's mental health after medical complications of pregnancy: a systematic review and meta-analysis.

BACKGROUND: Postpartum mental disorders including depression and anxiety are common. Medical complications of pregnancy, such as preeclampsia and gestational diabetes, are thought to increase the risk of mental disorders postpartum. However, it is unclear which interventions may be effective for preventing and/or treating postpartum mental disorders following a medically complicated pregnancy. We aimed to systematically review published literature on the effectiveness of postpartum interventions to improve women's mental health after medical complications of pregnancy. METHODS: Systematic review (PROSPERO: CRD42021220030) was performed. ELIGIBILITY CRITERIA: (1) randomized controlled trials (RCTs), published 1st Jan 2001-12th August 2021 (2) outcome measures reported on postpartum mental disorders (3) participants had ≥ 1 medical complication during pregnancy (4) intervention entirely postpartum or contained a postpartum component (5) full-text available in English or Chinese. Risk of bias was assessed using the Revised Cochrane Criteria Risk of Bias. Random effects inverse-variance weighted meta-analysis was used to pool the individual standardized mean differences (SMD) in depression or anxiety scores between intervention and control groups. RESULTS: Of 5928 studies screened, 9 met inclusion criteria, and were based on non-pharmaceutical, combined lifestyle interventions that began shortly after childbirth, or as part of extended care packages beginning during pregnancy. Of these, 2 were rated as low risk of bias, 1 with some concerns, and 6 were at high risk. Meta-analysis was performed for 8 studies using standardized measures of depression and 7 for anxiety. There were statistically significant reductions in depression (SMD - 1.48; 95%CI: -2.41 to -0.55), and anxiety scores (SMD - 1.98; 95%CI: -3.03 to -0.94) in intervention versus control groups. Considerable heterogeneity was noted for pooled depression (I2 = 97.9%, p < 0.05), and anxiety (I2 = 96.8%, p < 0.05) results. CONCLUSION: Limited intervention studies aimed at improving postpartum mental disorders after medically complicated pregnancy were found, most with a high risk of bias. There was some evidence to suggest that postpartum depression and anxiety scores improved after early intervention. However, in general the current quality of evidence is low. Further, high-quality, interventional research is required in this understudied field.

The value of process evaluation for public health interventions: field-case studies for non-communicable disease prevention and management in five countries.

Complex interventions are needed to effectively tackle non-communicable diseases. However, complex interventions can contain a mix of effective and ineffective actions. Process evaluation (PE) in public health research is of great value as it could clarify the mechanisms and contextual factors associ-ated with variation in the outcomes, better identify effective components, and inform adaptation of the intervention. The aim of this paper is to demonstrate the value of PE through five case studies that span the research cycle. The interven-tions include using digital health, salt reduction strategies, use of fixed dose combinations, and task shifting. Insights of the methods used, and the implications of the PE findings to the project, were discussed. PE of complex interventions can refute or confirm the hypothesized mechanisms of action, thereby enabling intervention refinement, and identifying implementation strategies that can address local contextual needs, so as to improve service delivery and public health outcomes.

Evaluation of an mHealth-enabled hierarchical diabetes management intervention in primary care in China (ROADMAP): A cluster randomized trial.

BACKGROUND: Glycemic control remains suboptimal in developing countries due to critical system deficiencies. An innovative mobile health (mHealth)-enabled hierarchical diabetes management intervention was introduced and evaluated in China with the purpose of achieving better control of type 2 diabetes in primary care. METHODS AND FINDINGS: A community-based cluster randomized controlled trial was conducted among registered patients with type 2 diabetes in primary care from June 2017 to July 2019. A total of 19,601 participants were recruited from 864 communities (clusters) across 25 provinces in China, and 19,546 completed baseline assessment. Moreover, 576 communities (13,037 participants) were centrally randomized to the intervention and 288 communities (6,509 participants) to usual care. The intervention was centered on a tiered care team-delivered mHealth-mediated service package, initiated by monthly blood glucose monitoring at each structured clinic visit. Capacity building and quarterly performance review strategies upheld the quality of delivered primary care. The primary outcome was control of glycated hemoglobin (HbA1c; <7.0%), assessed at baseline and 12 months. The secondary outcomes include the individual/combined control rates of blood glucose, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C); changes in levels of HbA1c, BP, LDL-C, fasting blood glucose (FBG), and body weight; and episodes of hypoglycemia. Data were analyzed using intention-to-treat (ITT) generalized estimating equation (GEE) models, accounting for clustering and baseline values of the analyzed outcomes. After 1-year follow-up, 17,554 participants (89.8%) completed the end-of-study (EOS) assessment, with 45.1% of them from economically developed areas, 49.9% from urban areas, 60.5 (standard deviation [SD] 8.4) years of age, 41.2% male, 6.0 years of median diabetes duration, HbA1c level of 7.87% (SD 1.92%), and 37.3% with HbA1c <7.0% at baseline. Compared with usual care, the intervention led to an absolute improvement in the HbA1c control rate of 7.0% (95% confidence interval [CI] 4.0% to 10.0%) and a relative improvement of 18.6% (relative risk [RR] 1.186, 95% CI 1.105 to 1.267) and an absolute improvement in the composite ABC control (HbA1c <7.0%, BP <140/80 mm Hg, and LDL-C <2.6 mmol/L) rate of 1.9% (95% CI 0.5 to 3.5) and a relative improvement of 21.8% (RR 1.218, 95% CI 1.062 to 1.395). No difference was found on hypoglycemia episode and weight gain between groups. Study limitations include noncentralized laboratory tests except for HbA1c, and caution should be exercised when extrapolating the findings to patients not registered in primary care system. CONCLUSIONS: The mHealth-enabled hierarchical diabetes management intervention effectively improved diabetes control in primary care and has the potential to be transferred to other chronic conditions management in similar contexts. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) IOC-17011325.

Resolvin Conjugates in Tissue Regeneration 1 Promote Alveolar Fluid Clearance by Activating Alveolar Epithelial Sodium Channels and Na, K-ATPase in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS), a common and fatal clinical condition, is characterized by the destruction of epithelium and augmented permeability of the alveolar-capillary barrier. Resolvin conjugates in tissue regeneration 1 (RCTR1) is an endogenous lipid mediator derived from docosahexaenoic acid , exerting proresolution effects in the process of inflammation. In our research, we evaluated the role of RCTR1 in alveolar fluid clearance (AFC) in lipopolysaccharide-induced ARDS/acute lung injury (ALI) rat model. Rats were injected with RCTR1 (5 µg/kg) via caudal veins 8 hours after lipopolysaccharide (LPS) (14 mg/kg) treatment, and then AFC was estimated after 1 hour of ventilation. Primary type II alveolar epithelial cells were incubated with LPS (1 ug/ml) with or without RCTR1 (10 nM) for 8 hours. Our results showed that RCTR1 significantly enhanced the survival rate, promoted the AFC, and alleviated LPS-induced ARDS/ALI in vivo. Furthermore, RCTR1 remarkably elevated the protein expression of sodium channels and Na, K-ATPase and the activity of Na, K-ATPase in vivo and in vitro. Additionally, RCTR1 also decreased neural precursor cell expressed developmentally downregulated 4-2 (Nedd4-2) level via upregulating Ser473-phosphorylated-Akt expression. Besides this, inhibitors of receptor for lipoxin A4 (ALX), cAMP, and phosphatidylinositol 3-kinase (PI3K) (BOC-2, KH-7, and LY294002) notably inhibited the effects of RCTR1 on AFC. In summary, RCTR1 enhances the protein levels of sodium channels and Na, K-ATPase and the Na, K-ATPase activity to improve AFC in ALI through ALX/cAMP/PI3K/Nedd4-2 pathway, suggesting that RCTR1 may become a therapeutic drug for ARDS/ALI. SIGNIFICANCE STATEMENT: RCTR1, an endogenous lipid mediator, enhanced the rate of AFC to accelerate the resolution of inflammation in the LPS-induced murine lung injury model. RCTR1 upregulates the expression of epithelial sodium channels (ENaCs) and Na, K-ATPase in vivo and in vitro to accelerate the AFC. The efficacy of RCTR1 on the ENaC and Na, K-ATPase level was in an ALX/cAMP/PI3K/Nedd4-2-dependent manner.

Quality of stroke guidelines in low- and middle-income countries: a systematic review.

OBJECTIVE: To identify gaps in national stroke guidelines that could be bridged to enhance the quality of stroke care services in low- and middle-income countries. METHODS: We systematically searched medical databases and websites of medical societies and contacted international organizations. Country-specific guidelines on care and control of stroke in any language published from 2010 to 2020 were eligible for inclusion. We reviewed each included guideline for coverage of four key components of stroke services (surveillance, prevention, acute care and rehabilitation). We also assessed compliance with the eight Institute of Medicine standards for clinical practice guidelines, the ease of implementation of guidelines and plans for dissemination to target audiences. FINDINGS: We reviewed 108 eligible guidelines from 47 countries, including four low-income, 24 middle-income and 19 high-income countries. Globally, fewer of the guidelines covered primary stroke prevention compared with other components of care, with none recommending surveillance. Guidelines on stroke in low- and middle-income countries fell short of the required standards for guideline development; breadth of target audience; coverage of the four components of stroke services; and adaptation to socioeconomic context. Fewer low- and middle-income country guidelines demonstrated transparency than those from high-income countries. Less than a quarter of guidelines encompassed detailed implementation plans and socioeconomic considerations. CONCLUSION: Guidelines on stroke in low- and middle-income countries need to be developed in conjunction with a wider category of health-care providers and stakeholders, with a full spectrum of translatable, context-appropriate interventions.

The impact of mental and physical multimorbidity on healthcare utilization and health spending in China: A nationwide longitudinal population-based study.

BACKGROUND: In China, little evidence exists on the effect of mental and physical multimorbidity on individuals and the health system. This study aims to examine the prevalence of mental-physical multimorbidity and its impact on health service utilization and health expenditures. METHODS: We conducted a panel study using two waves of data (in 2011 and 2015) from the China Health and Retirement Longitudinal Study, including 10,181 participants aged 45 years and older. Generalized linear regression models were used to assess the association of multimorbidity with total health expenditure and out-of-pocket expenditure (OOPE) on outpatient and inpatient care. Random-effects logistic regression models were used to examine the impact of multimorbidity on outpatient visits, admission to hospital and incidence of catastrophic health expenditure (CHE). RESULTS: Overall, 3210 participants (31.53% of 10,181) had mental-physical multimorbidity in 2015 in China. Compared to patients with a single physical disease, individuals with physical-mental multimorbidity had over 150% of the increase in the number of outpatient visits and days of hospitalization. The percentage change of OOPE for outpatient and inpatient care was 156.8% and 163.6%, respectively. Mental-physical multimorbidity was associated with an increased likelihood of experiencing CHE (OR = 2.205, 95% CI = 2.048, 2.051). CONCLUSION: Multimorbidity, particularly mental-physical multimorbidity, is associated with higher levels of health service use and a greater financial burden to individuals in China. Healthcare system needs to shift from single-disease models to new financing and service delivery models to more effectively manage mental-physical multimorbidity.

The association between serum alanine aminotransferase and hypertension: A national based cross-sectional analysis among over 21 million Chinese adults.

BACKGROUND: Inconsistent results were found in the association between serum alanine aminotransferase (ALT) and hypertension among population-based studies. This study evaluated the association between ALT and hypertension among Chinese reproductive-age population by utilizing registration data from National Free Pre-pregnancy Checkups Project in 2016-2017. METHODS: The 21,103,790 registered participants were eligible for analysis, including women who were 20-49 years old and men who were 20-59 years old with available data for ALT and blood pressure (BP). Logistic regression was conducted to estimate odds ratio (OR) for the association between ALT and hypertension as a binary outcome. Linear regression was used to examine the association between ALT and BP as a continuous outcome. RESULTS: In total, 4.21% of the participants were hypertensive, and 11.67% had elevated ALT (> 40 U/L). Hypertension prevalence was 3.63% and 8.56% among participants with normal and elevated ALT levels. A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders. The multivariable-adjusted ORs for hypertension were 1, 1.22 (1.21, 1.22), 1.67 (1.65 1.68), 1.78 (1.76, 1.80), and 1.92 (1.90, 1.94) in participants with ALT levels of ≤ 20, 20.01-40, 40.01-60, 60.01-80, and > 80 U/L, respectively. Systolic and diastolic BPs rose by 1.83 and 1.20 mmHg on average, for each 20 U/L increase in ALT (P for trend < 0.001). The association was consistent among subgroups and tended to be stronger among populations who are overweight (body mass index ≥ 24 kg/m2) (χ2 = 52,228, P < 0.001), alcohol drinking (χ2 = 100,730, P < 0.001) and cigarette smoking (χ2 = 105,347, P < 0.001). CONCLUSIONS: Our cross-sectional analysis suggested a linear association between serum ALT and hypertension or BP, which indicated that abnormal liver metabolism marked by elevated serum ALT could play a role in hypertension or elevated BP condition.

Chinese women's attitudes towards postpartum interventions to prevent type 2 diabetes after gestational diabetes: a semi-structured qualitative study.

BACKGROUND: Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women's perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy. METHODS: We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro. RESULTS: Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women's attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate. CONCLUSIONS: Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.

Gestational diabetes mellitus (GDM) is a common pregnancy complication affecting up to 1 in 6 pregnant women worldwide. Whilst the condition usually resolves soon after delivery, women are at high risk of developing type 2 diabetes mellitus (T2DM). In this study, we asked women living in Chengdu, a city in western China, about what they knew about their risk of diabetes and how they felt about participating in interventions after birth to prevent T2DM.After listening to the views of 20 women, we concluded that in this setting most women are happy to attend T2DM screening programs after birth, and would be willing to consider participating in interventions and research after birth to prevent T2DM.The interventions most preferred were those that aimed at lifestyle changes, and many women said would like to receive this information through their smartphone, for example through an app or social media channel. Women were reluctant to take medications to prevent T2DM.The main factors that influenced how women felt towards interventions to prevent T2DM were: (1) their experiences with the health system during pregnancy; (2) whether the home environment was supportive to make changes to diet and lifestyle; (3) any experiences of T2DM in family members; (4) their knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions in the postnatal period, and (7) lifestyle constraints making it difficult to make dietary changes.

Maresin Conjugates in Tissue Regeneration 1 improves alveolar fluid clearance by up-regulating alveolar ENaC, Na, K-ATPase in lipopolysaccharide-induced acute lung injury.

Maresin Conjugates in Tissue Regeneration 1 (MCTR1) is a newly identified macrophage-derived sulfido-conjugated mediator that stimulates the resolution of inflammation. This study assessed the role of MCTR1 in alveolar fluid clearance (AFC) in a rat model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Rats were intravenously injected with MCTR1 at a dose of 200 ng/rat, 8 hours after administration of 14 mg/kg LPS. The level of AFC was then determined in live rats. Primary rat ATII (Alveolar Type II) epithelial cells were also treated with MCTR1 (100 nmol/L) in a culture medium containing LPS for 8 hours. MCTR1 treatment improved AFC (18.85 ± 2.07 vs 10.11 ± 1.08, P < .0001) and ameliorated ALI in rats. MCTR1 also significantly promoted AFC by up-regulating epithelial sodium channel (ENaC) and Na+ -K+ -adenosine triphosphatase (Na, K-ATPase) expressions in vivo. MCTR1 also activated Na, K-ATPase and elevated phosphorylated-Akt (P-Akt) by up-regulating the expression of phosphorylated Nedd4-2 (P-Nedd4-2) in vivo and in vitro. However, BOC-2 (ALX inhibitor), KH7 (cAMP inhibitor) and LY294002 (PI3K inhibitor) abrogated the improved AFC induced by MCTR1. Based on the findings of this study, MCTR1 may be a novel therapeutic approach to improve reabsorption of pulmonary oedema during ALI/acute respiratory distress syndrome (ARDS).

PCTR1 improves pulmonary edema fluid clearance through activating the sodium channel and lymphatic drainage in lipopolysaccharide-induced ARDS.

Acute respiratory distress syndrome (ARDS) is a lethal clinical syndrome characterized by damage of the epithelial barriers and accumulation of pulmonary edema fluid. Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenously produced lipid mediator, are believed to exert anti-inflammatory and pro-resolution effects. PCTR1 (1 µg/kg) was injected at 8 hr after lipopolysaccharide (LPS; 14 mg/kg) administration, and the rate of pulmonary fluid clearance was measured in live rats at 1 hr after PCTR1 treatment. The primary type II alveolar epithelial cells were cultured with PCTR1 (10 nmol/ml) and LPS (1 µg/ml) for 8 hr. PCTR1 effectively improved pulmonary fluid clearance and ameliorated morphological damage and reduced inflammation of lung tissue, as well as improved the survival rate in the LPS-induced acute lung injury (ALI) model. Moreover, PCTR1 markedly increased sodium channel expression as well as Na, K-ATPase expression and activity in vivo and in vitro. In addition, PCTR1i also upregulated the expression of LYVE-1 in vivo. Besides that, BOC-2, HK7, and LY294002 blocked the promoted effect of PCTR1 on pulmonary fluid clearance. Taken together, PCTR1 upregulates sodium channels' expression via activating the ALX/cAMP/P-Akt/Nedd4-2 pathway and increases Na, K-ATPase expression and activity to promote alveolar fluid clearance. Moreover, PCTR1 also promotes the expression of LYVE-1 to recover the lymphatic drainage resulting in the increase of lung interstitial fluid clearance. In summary, these results highlight a novel systematic mechanism for PCTR1 in pulmonary edema fluid clearance after ALI/ARDS, suggesting its potential role in a therapeutic approach for ALI/ARDS.

PCTR1 ameliorates lipopolysaccharide-induced acute inflammation and multiple organ damage via regulation of linoleic acid metabolism by promoting FADS1/FASDS2/ELOV2 expression and reducing PLA2 expression.

Gram-negative bacterial infection causes an excessive inflammatory response and acute organ damage or dysfunction due to its outer membrane component, lipopolysaccharide (LPS). Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenous lipid mediator, exerts fundamental anti-inflammation and pro-resolution during infection. In the present study, we examined the properties of PCTR1 on the systemic inflammatory response, organic morphological damage and dysfunction, and serum metabolic biomarkers in an LPS-induced acute inflammatory mouse model. The results show that PCTR1 reduced serum inflammatory factors and ameliorated morphological damage and dysfunction of the lung, liver, kidney, and ultimately improved the survival rate of LPS-induced acute inflammation in mice. In addition, metabolomics analysis and high performance liquid chromatography-mass spectrometry revealed that LPS-stimulated serum linoleic acid (LA), arachidonic acid (AA), and prostaglandin E2 (PGE2) levels were significantly altered by PCTR1. Moreover, PCTR1 upregulated LPS-inhibited fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongase of very long chain fatty acids 2 (ELOVL2) expression, and downregulated LPS-stimulated phospholipase A2 (PLA2) expression to increase the intrahepatic content of AA. However, these effects of PCTR1 were partially abrogated by a lipoxin A4 receptor (ALX) antagonist (BOC-2). In summary, via the activation of ALX, PCTR1 promotes the conversion of LA to AA through upregulation of FADS1, FADS2, and ELOVL2 expression, and inhibits the conversion of bound AA into free AA through downregulation of PLA2 expression to decrease the serum AA and PGE2 levels.

Autophagy dysregulation caused by ApoM deficiency plays an important role in liver lipid metabolic disorder.

Autophagy is thought to be a key mechanism in maintaining the balance of liver lipid metabolism. However, the relationship between apolipoprotein M (ApoM) and autophagy has not been reported, and the role of ApoM in triglyceride metabolism is still unclear. In this study, we investigated the correlation between ApoM and autophagy and liver triglyceride metabolism in ApoM-knockout animal and cellular models. First, we observed that spontaneous hepatic steatosis developed in the liver of adult ApoM-/- mice, which was presented as the accumulation of large quantities of lipid droplets in hepatocytes under electron microscopy; Oil Red O staining showed significant accumulation of triglycerides. At the molecular level, the expression of lipid synthesis-associated proteins (primarily triglyceride synthesis) as well as acetyl-CoA carboxylase alpha (ACACA), fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP1) was upregulated. Moreover, lipid metabolic disorder and accumulation were accompanied by dysfunction in autophagy, which displayed predominantly as inhibition of the degradation pathway; for example, P62 protein accumulated and key proteins involved in the initiation of autophagy including ATG7, ATG5-12, Beclin1 and the LC3BII/LC3BI ratio were upregulated as a feedback response. When the autophagy dysfunction was ameliorated by the activation of autophagy pathways induced by starvation, the lipid metabolic disorder was corrected to a certain extent. This suggests that the autophagy dysfunction caused by the deficiency of ApoM is an important factor in hepatic steatosis (triglyceride accumulation). ApoM plays a key role in normal autophagy activity in the liver and thereby further regulates the metabolism of liver lipids, particularly triglycerides.

Clinical characteristics of type 2 diabetes patients with discordance between HbA1c and fasting plasma glucose in the real world: An analysis of the ORBIT study.

BACKGROUND: We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA1c ) and fasting plasma glucose (FPG) in the real world. METHODS: This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA1c and FPG. RESULTS: Overall, of 6721 patients initiated on basal insulin, 853 achieved HbA1c  < 7% but FPG ≥ 7 mmol/L (group 2), while 997 had FPG < 7 mmol/L but HbA1c  ≥ 7% (group 3) at the end of follow-up. Patients in group 3 had a longer duration of type 2 diabetes compared with those in group 2 (7.22 ± 5.30 vs 6.00 ± 4.80 y, P < .05). Patients on glargine (32.90%) or detemir (36.88%) treatment accounted for a higher proportion of patients with both HbA1c and FPG controlled than those on neutral protamine Hagedorn therapy (23.45%; P < .05). Per the multinomial logistic analysis, higher frequency of self-monitoring of blood glucose (SMBG) and use of glargine or detemir therapy were significantly inversely associated with risk of discordance between HbA1c and FPG, while dose of insulin was a risk factor for discordance at the end of follow-up (all P < .05). CONCLUSIONS: Patients treated with insulin analogues (glargine or detemir), instead of neutral protamine Hagedorn, and with more frequent SMBG are more likely to exhibit concordance between HbA1c and FPG.

Awareness, understanding and use of sodium information labelled on pre-packaged food in Beijing:a cross-sectional study.

BACKGROUND: Nutrition labelling has been mandatory for pre-packaged foods since 2013 in China, and sodium is one of the nutrients required for display on the nutritional information panel (NIP). This study aimed to estimate the awareness, understanding of, and use of sodium labelling information among the population in China. METHODS: A cross-sectional survey was carried out in urban Beijing in 2016 on pre-packaged foods. The researchers randomly selected 380 residents from four convenient but disconnected communities and 370 shoppers from four supermarkets owned by different companies and conducted face-to-face interviews. Questions on nutritional knowledge, health attitude, understanding and use of nutritional labels as well as other related factors were assessed. RESULTS: All of the 380 community residents and 308 of the 370 supermarket shoppers successfully completed the survey. Of those 688 respondents, 91.3% understood that excessive salt intake was harmful, 19.5% were aware that sodium content is listed on the NIP, 5.5% understood the meaning of NRV% (Percentage of Nutrient Reference Values), 47.7% did not know the relationship between sodium and salt, and 12.6% reported they frequently read the label when shopping. Factors for why people were more likely to choose a product because of its low level of salt shown on the label include income level and their level of awareness of the link between salt and diet. CONCLUSIONS: Although the participants had a good understanding of the harmful effects of salt, the awareness, understanding and use of sodium labels was very low in Beijing, and even worse nationwide. Efforts should be taken to educate the public to understand and use the NIP better and design clearer ways of displaying such information, such as front-of pack (FoP) labelling or health-related smartphone applications to improve health and help people make better food choices.

Comparative effectiveness and safety of different basal insulins in a real-world setting.

AIMS: To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study. METHODS: In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months. RESULTS: A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis. CONCLUSION: In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Observational Registry of Basal Insulin Treatment (ORBIT) in patients with type 2 diabetes uncontrolled with oral antihyperglycaemic drugs: Real-life use of basal insulin in China.

AIMS: To examine treatment patterns following basal insulin (BI) introduction in type 2 diabetes mellitus (T2DM) patients under real-world conditions across China. MATERIALS AND METHODS: Overall, 18 995 patients inadequately controlled (HbA1c ≥ 53 mmol/mol [7%]) with oral antihyperglycaemic drugs (OADs) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2) and 6 months (visit 3). Type of BI was initiated at physicians' discretion. RESULTS: Retention with BI therapy at 6 months was 75.6%. Use of long-acting BI predominated, with insulin glargine accounting for 71%, detemir 13% and Neutral Protamine Hagedorn (NPH) insulin 16%. Over 70% of long-acting users maintained the same initial BI at visit 3, while 40% of NPH users switched treatment and 24.4% of participants initiated BI with prandial insulin. The initial mean (± SD) dose of BI and total insulin was 0.18 ± 0.07 and 0.25 ± 0.19 IU/kg, respectively, with a mean increase of daily dose by 0.03 and 0.02 IU/kg after 6 months, respectively. Only 56.6% of insulin users reported dose titration at visit 3. Mean HbA1c was 81 mmol/mol (9.6%) at baseline and 57 mmol/mol (7.4%) at 6 months. The frequency of hypoglycaemia was 1.61 and 2.07 episodes/patient-year at baseline and 6 months, respectively. CONCLUSIONS: In real-world clinical settings, add-on BI therapy in T2DM patients is associated with significant improvement in glycaemic control without overtly compromising safety related to hypoglycaemia and weight gain. Evolution of insulin treatment regimens varied among patients, but dose titration was suboptimal. More active BI dose titration might further improve glycaemic outcome in patients receiving BI therapy. VIDEO ABSTRACT: A free Video Abstract to accompany this article is available at https://vimeo.com/212655959.

Mobile Device-Based Electronic Data Capture System Used in a Clinical Randomized Controlled Trial: Advantages and Challenges.

BACKGROUND: Electronic data capture (EDC) systems have been widely used in clinical research, but mobile device-based electronic data capture (mEDC) system has not been well evaluated. OBJECTIVE: The aim of our study was to evaluate the feasibility, advantages, and challenges of mEDC in data collection, project management, and telemonitoring in a randomized controlled trial (RCT). METHODS: We developed an mEDC to support an RCT called "Telmisartan and Hydrochlorothiazide Antihypertensive Treatment (THAT)" study, which was a multicenter, double-blinded, RCT, with the purpose of comparing the efficacy of telmisartan and hydrochlorothiazide (HCTZ) monotherapy in high-sodium-intake patients with mild to moderate hypertension during a 60 days follow-up. Semistructured interviews were conducted during and after the trial to evaluate the feasibility, advantage, and challenge of mEDC. Nvivo version 9.0 (QSR International) was used to analyze records of interviews, and a thematic framework method was used to obtain outcomes. RESULTS: The mEDC was successfully used to support the data collection and project management in all the 14 study hospitals. A total of 1333 patients were recruited with support of mEDC, of whom 1037 successfully completed all 4 visits. Across all visits, the average time needed for 141 questions per patient was 53 min, which were acceptable to both doctors and patients. All the interviewees, including 24 doctors, 53 patients, 1 clinical research associate (CRA), 1 project manager (PM), and 1 data manager (DM), expressed their satisfaction to nearly all the functions of the innovative mEDC in randomization, data collection, project management, quality control, and remote monitoring in real time. The average satisfaction score was 9.2 (scale, 0-10). The biggest challenge came from the stability of the mobile or Wi-Fi signal although it was not a problem in THAT study. CONCLUSIONS: The innovative mEDC has many merits and is well acceptable in supporting data collection and project management in a timely manner in clinical trial.