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Objectives: Our study analyzed the performance of Xpert MTB/RIF Ultra (Ultra) on stool and gastric aspirate (GA) samples for the diagnosis of pediatric pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis in a high-burden area of China. Methods: Children with presumptive TB were enrolled in two hospitals in Sichuan Province (July 2019–Oct 2020). Because of the unavailability of sputum for etiological testing, gastric samples were aspirated and tested by bacterial culture, acid-fast bacillus microscopy, and Ultra. Stool samples were tested simultaneously using Ultra and Xpert. Results: In total, 141 children with active TB and 34 with non-TB respiratory tract infections were enrolled. Ultra-stool (60.3%, 85/141) and Ultra-GA (52.5%, 74/141) tests were similarly sensitive (p = 0.187). Among the subset of 48 children with confirmed TB, Ultra testing was equally sensitive on stool and GA samples (85.4%, 41/48). The agreement between Ultra-stool and Ultra-GA was moderate in children with active TB (kappa value = 0.527). After integrating Ultra-GA and Ultra-stool outcomes, 70.9% (100/141) of the children were considered to have confirmed TB. The specificities of Ultra-stool and Ultra-GA were 97.1% (33/34) and 100% (34/34), respectively (p = 0.314). Conclusions: In children, stools can be used as alternative samples to GAs for Ultra tests. Stool- and GA-based Ultra tests are appropriate for bacteriological TB confirmation.

Background and Aims The role of serum uric acid (SUA) in stroke remains controversial and analyses of changes in SUA and stroke are limited. The objective of the study was to investigate the associations of changes in SUA with stroke and its subtypes (ischemic and hemorrhagic stroke). Methods and Results A total of 51 441 participants (mean age 52.69±11.71 years) without history of myocardial infarction or stroke were enrolled. Participants were divided into four groups based on SUA level changes during 2006 and 2010: stable low, increasing, decreasing, and stable high. SUA score was quantified on a 3-point scale with 1 point awarded for hyperuricemia at either year 2006, 2008 or 2010. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs). During 7.03-year follow up, 1611 stroke (1410 ischemic stroke, 199 hemorrhagic stroke, and 47 subarachnoid hemorrhage) were identified. Participants with stable high SUA had higher risk of hemorrhagic stroke, the HR was 1.93 (95% CI: 1.06-3.51), compared to those with stable low SUA. Furthermore, cumulative high SUA exposure also increased the risk of hemorrhagic stroke, the HR (95%CI) was 2.99 (1.55-5.74), compared with cumulative low SUA exposure. However, no significant evidence indicated changes in SUA was associated with the risk of total and ischemic stroke, the HRs (95% CIs) were 0.98 (0.74-1.29) and 0.88 (0.65-1.19), respectively. Conclusions Stable high SUA was positively associated with the risk of hemorrhagic stroke, but not with total and ischemic stroke risk.

Introduction: Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA. Methods: We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68–4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04–1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04–1.37). Similar trends were found in ischemic stroke and combined vascular events. Conclusions: Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management.

Study design Retrospective case series. Objectives This study aimed to determine the prevalence and risk factors for orthostatic hypotension (OH) in adolescents undergoing posterior spinal fusion for spinal deformity correction. Methods The data of 282 consecutive adolescents who underwent posterior spinal fusion for spinal deformity correction in our center over 12 months were retrieved. Patient characteristics, including whether laminectomy or osteotomy was performed during the surgery, the occurrence of postoperative nausea and vomiting (PONV), perioperative hemoglobin albumin changes, perioperative blood transfusion, length of bed rest, willingness to ambulate, length of postoperative exercises of the lower limbs, and length of hospital stay, were collected and compared statistically between patients who did and did not develop postoperative OH. Results Of 282 patients, 197 (69.86%) developed OH postoperatively, and all cases completely resolved 5 days after the first out-of-bed exercises. Significant differences in the incidence of PONV, the willingness to ambulate and the length of postoperative exercises of the lower limbs were observed. The mean length of hospital stay of the patients with OH was longer than that of the patients without OH. Conclusion Our study suggests that temporary OH is a common manifestation following posterior spinal fusion for spinal deformity correction in adolescents. Postoperative OH may increase the length of hospital stay in these patients. Patients with PONV, who are not willing to ambulate and who perform postoperative lower limb exercises for a shorter time are more likely to have OH.

Medical treatment and endovascular therapy are widely used for intracranial atherosclerotic stenosis, but the best treatment strategy remains uncertain. The goal of this study was to compare the safety and effectiveness of medical treatment, stenting, and primary balloon angioplasty (PBA). We searched PubMed, MEDLINE, and EMBASE for trials comparing these three treatments for intracranial stenosis up to December 24, 2020. We performed a network meta-analysis with random-effects models. The primary outcome was any stroke or death during a long-term follow-up. Secondary outcomes included ischemic stroke, intracranial hemorrhage, and death. This network meta-analysis included 14 trials with 1520 participants. No significant difference was found between the three groups in the primary outcome, while PBA was probably the best treatment according to the ranking plot. Medical treatment had significantly lower rate of any stroke or death (odds ratio (OR), 0.31; 95% CI, 0.17-0.56), ischemic stroke (OR, 0.43; 95% CI, 0.23-0.81), and intracranial hemorrhage (OR, 0.12; 95% CI, 0.02-0.71) within 30 days than stenting but did not differ from PBA. The ranking plot demonstrated that PBA was also most likely to rank the highest for ischemic stroke during the long-term follow-up and beyond 30 days, although no significant difference was identified. Medical treatment had lower risk of any stroke or death within 30 days than stenting but did not differ from PBA. All the treatments had similar effects on the prevention of long-term stroke, while PBA had the highest probability of being the most effective.

Background and aims: High remnant cholesterol is associated with cardiovascular disease (CVD), but whether CVD risk attributable to remnant cholesterol vary between young and later adults remains unknown. The study aimed to assess age differences in the association between remnant cholesterol and CVD. Methods: This prospective study included 95 663 participants without CVD and lipid-lowering treatment at baseline, including 16 254 young adults (age 18–39 years) and 79 409 later adults (age ≥40 years). Individuals were grouped by clinically meaningful remnant cholesterol concentrations of

Background Previous studies found that lactate dehydrogenase (LDH) levels predicted poor outcomes in hemorrhagic stroke, but the prognostic role of LDH in ischemic stroke (IS) remains unclear. The aim of this study is to investigate the association between LDH and adverse clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods All patients were enrolled from the Third China National Stroke Registry (CNSR-III). Adverse outcomes included all-cause death and poor functional outcomes [defined as modified Rankin Scale (mRS) score 3-6 and 2-6] at 3 months and 1 year. Multivariable Cox proportional hazards models and logistic regressions were used to evaluate the association of LDH with risk of all-cause death and poor functional outcomes, respectively. Results Among 9,796 included patients, the median [interquartile range (IQR)] of LDH was 175.00 (151.00-205.40) U/L. After adjustment for confounding factors, patients in the highest LDH quartile had a higher risk of all-cause death [hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.27-3.90], and a higher proportion of mRS score 3-6 [odds ratio (OR), 1.54; 95% CI, 1.26-1.90] and mRS score 2-6 (OR, 1.56; 95% CI, 1.32-1.84) at 3 months. We also observed a J-shaped association between LDH and risk of each outcome. Consistent results were found at 1 year. Conclusions Higher LDH levels are independently associated with adverse outcomes in patients with AIS or TIA.

The rupture of an unstable atherosclerotic plaque is one of the major causes of thrombosis. However, there was limited evidence on the relationship of triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, with the carotid plaque stability. This study aimed to investigate the association between the TyG index and carotid plaque stability in nondiabetic adults.The study included 4748 nondiabetic participants from the Asymptomatic Polyvascular Abnormalities Community study. Carotid plaque stability was assessed using ultrasonography. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Logistic regression was used to evaluate the association of the TyG index with carotid plaque stability by calculating odds ratio (OR) and 95% confidence interval (CI). Of the 4748 participants, 1192 (25.11%) participants had stable carotid plaque, and 1247 (26.26%) had unstable carotid plaque. The prevalence of unstable carotid plaque substantially increased with increasing TyG index tertile (P for trend0.0001). In the fully adjusted model, the OR comparing participants in the highest versus the lowest tertile of the TyG index was 1.31 (95% CI, 1.09-1.57). The optimal cutoff point for the TyG index in case of unstable carotid plaque was 8.56. However, we did not observe a statistically significant association between the TyG index and stable carotid plaque.Elevated the TyG index was significantly associated with the prevalence of unstable carotid plaque in nondiabetic adults.

We aimed to identify the joint associations of modifiable lifestyle and metabolic factors with the incidences of cardiovascular disease and all-cause mortality. We recruited 94,831 participants (men, 79.76%; median age, 51.60 [43.47–58.87]) without a history of cardiovascular disease from the Kailuan study during 2006 and 2007 and followed them until a cardiovascular disease event, or death occurred, or until December 31, 2017. Baseline metabolic health status was assessed using Adult Treatment Panel III criteria, and details of the lifestyles of the participants were recorded using a self-reported questionnaire. We used Cox proportional hazards models to evaluate the joint associations. During a median follow-up of 11.03 years, we recorded 6590 cardiovascular disease events and 9218 all-cause mortality. Participants with the most metabolic risk components and the least healthy lifestyle had higher risk of cardiovascular disease (hazard ratio 2.06 [95% confidence interval (CI) 1.77–2.39]) and mortality (HR 1.53 [95% CI 1.31–1.78]), than participants with fewer metabolic risk components and the healthiest lifestyle. Compared with those in participants with the healthiest lifestyle, the HRs for cardiovascular disease in participants with the least healthy lifestyle were 1.26 (95% CI 1.17–1.37), 1.16 (95% CI 1.03–1.31), and 1.07 (95% CI 0.90–1.27) for those with low, medium, and high metabolic risk, respectively. Healthy lifestyle is associated with a lower risk of cardiovascular disease and there is no significant interaction between metabolic risk and a healthy lifestyle. Therefore, a healthy lifestyle should be promoted, even for people with high metabolic risk.

The aim of this trial was to evaluate the feasibility and effect of home-based transcutaneous electrical acupoint stimulation (TEAS) in patients with hypertension. In this randomized pilot trial, patients with hypertension were randomly assigned to the TEAS group or the usual care group. Participants in the usual care group were instructed to continue taking their antihypertensive drugs and received education on lifestyle modifications. In addition, participants in the TEAS group received 4 weekly sessions of noninvasive acupoint stimulation for 12 weeks at home. The primary outcome was the change in office systolic blood pressure at week 12 from baseline. Withdrawal from the study and adverse events associated with TEAS were also recorded. Sixty patients were randomized, with 30 patients in the TEAS group, of whom 1 was lost at week 36, and 30 patients in the usual care group, of whom 3 were lost by week 12. The reduction in systolic blood pressure at week 12 was greater in the TEAS group (−8.53 mm Hg; 95% CI [−13.37, −3.70 mm Hg]) than in the usual care group (−1.70 mm Hg; 95% CI [−4.29, −0.89 mm Hg]), with a between-group difference of −6.83 mm Hg (95% CI, [−12.23, −1.43 mm Hg]; P = 0.014). No TEAS-related adverse events occurred. In conclusion, home-based TEAS added to usual care for patients with hypertension was acceptable and safe and may be a potential treatment option. A larger randomized controlled trial of this intervention is warranted., Home-based transcutaneous electrical acupoint stimulation added to usual care for patients with hypertension was acceptable, safe and may be a potential treatment option. TEAS, transcutaneous electrical acupoint stimulation; SBP, systolic blood pressure.

Aims: Intact intestinal epithelium is essential to maintain normal intestinal physiological function. Irradiation-induced gastrointestinal syndrome or inflammatory bowel disease occurred when epith...

Background Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. Methods In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. Results IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. Conclusions These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.

Background and aim Longitudinal evidence on change in serum (SUA) with risk of cardiovascular disease (CVD) and all-cause mortality is limited, as many prior studies focused on baseline SUA. Further, the optimal threshold range of SUA change is unclear. Methods and results A total of 63,127 participants without history of CVD were enrolled. Change in SUA was determined by the difference of SUA levels between 2006 and 2010, which divided by baseline SUA was percent change in SUA. Multivariable Cox proportional hazards models were used to calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). Our analysis also included restricted cubic spline model and three-piecewise Cox proportion hazards model to address the non-linearity between percent change in SUA and outcomes. During a median follow-up of 7.04 years, 3341 CVD and 3238 deaths occurred. We did not observed a significant association between changes in SUA and CVD. However, changes in SUA at extreme were associated with higher risk of all-cause mortality, the HRs (95% CIs) were 1.15 (1.02–1.29) and 1.20 (1.06–1.35) in the first and fifth quintile group, compared with the third quintile group. We further found a U-shaped association between percent change in SUA and all-cause mortality, and the optimal range was within 20%. Conclusions Changes in SUA at extreme were risk factors for all-cause mortality, but not for CVD in the general population. The findings are relevant for role of SUA in the management of CVD risk and may contribute to improve identification of patients at higher risk.

Prehypertension is a risk factor for cardiovascular disease (CVD) and all‐cause mortality. However, it is unclear whether prehypertension combined with diabetes associate with a higher risk for cardiovascular disease and all‐cause mortality. The purpose of this study was to explore the relationship between prehypertension and the risk of CVD and all‐cause mortality was different among individuals with or without diabetes. In the prospective community‐based Kailuan study, 67 344 participants without hypertension or a history of CVD at baseline (2006) were included. Prehypertension was defined as systolic blood pressure of 120–139 mmHg or diastolic blood pressure of 80–89 mmHg. The outcomes were CVD and all‐cause mortality were followed up through December 31, 2017. We performed Cox proportional hazards models to evaluate the relationships between prehypertension and CVD and all‐cause mortality by diabetes status. During a median follow‐up of 11.03 years, 2981 CVD events and 4655 all‐cause mortality occurred. After adjusting age, sex, and other factors, the associations of prehypertension with risk of CVD and all‐cause mortality were significant in participants without diabetes (hazard ratio and 95% confidence interval: 1.54 [1.38–1.71] and 1.27 [1.17–1.38]), but not in participants with diabetes (1.20 [0.93–1.56] and 0.88 [0.73–1.07]). The interactions between prehypertension and diabetes for the risk of CVD and all‐cause mortality were all significant (all p

OBJECTIVE Among the risk factors of stroke, hypertension was one of the most important and modifiable factors. The current study aimed to assess whether antihypertensive treatment to ideal levels of blood pressure can eliminate stroke risk in a prospective cohort study. METHODS The Kailuan study was a prospective longitudinal cohort study on stroke risk factors and events. We analyzed association of baseline antihypertensive treatment efficacy with the risk of stroke during 11.0-year follow-up, and further evaluated association of newly antihypertensive treatment efficacy at 4-year follow-up with subsequent stroke. Multivariate Cox proportion models were used to calculated hazard ratios and their 95% confidence intervals (CIs) for stroke. RESULTS A total of 97 772 participants (median age: 51.65 years) without previous stroke were included. At baseline, 55 518 participants had normotension, 2339 treated and controlled, 32 331 untreated hypertension and 7584 treated but uncontrolled. Compared with normotension, individuals with treated and controlled, untreated hypertension and treated but uncontrolled, had 83, 97 and 162% higher risk of developing total stroke after adjusting for potential stroke risk factors, respectively (hazard ratio 1.83 [95% CI 1.56-2.15], 1.97 [95% CI 1.85-2.11] and 2.62 [95% CI 2.40-2.86]; all P

Background Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA. Methods A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories. Results Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA. Conclusions Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.

The management of persistent postsurgical pain and neuropathic pain remains a challenge in the clinic. Local anesthetics have been widely used as simple and effective treatment for these two disorders, but the duration of their analgesic effect is short. We here reported a new poly lactic-co-glycolic acid (PLGA)-coated ropivacaine that was continuously released in vitro for at least 6 days. Peri-sciatic nerve injection of the PLGA-coated ropivacaine attenuated paw incision-induced mechanical allodynia and heat hyperalgesia during the incisional pain period, and spared nerve injury-induced mechanical and cold allodynia for at least 7 days post-injection. This effect was dose-dependent. Peri-sciatic nerve injection of the PLGA-coated ropivacaine did not produce detectable inflammation, tissue irritation, or damage in the sciatic nerve and surrounding muscles at the injected site, dorsal root ganglion, spinal cord or brain cortex, although the scores for grasping reflex were mildly and transiently reduced in the higher dosage-treated groups. PERSPECTIVE: Given that PLGA is an FDA-approved medical material, and that ropivacaine is used currently in clinical practice, the injectable PLGA-coated ropivacaine represents a new and highly promising avenue in the management of postsurgical pain and neuropathic pain.

Background and objectives Haemovigilance involves surveillance of the whole chain of blood transfusion with the aim of identifying adverse events and errors and improving outcomes for patients. The Chinese Haemovigilance Network, founded in August 2017, has witnessed a rapid development in the last three years. Materials and methods Based on the 1,022 cases in 2019, we analysed the adverse reactions (ARs) by blood component, clinical outcome severity and demography of recipients in an effort to publish the first annual Chinese haemovigilance report. Results The AR rate associated with blood transfusion in 2019 was 0·2% in China. Allergic reactions and FNHTR were the two most common adverse symptoms, accounting for 97·7% of the reports. Two-thirds of the TAD, AHTR and TACO and all of the HTR and DHTR resulted in hospitalization or prolongation of hospitalization. Plasma and AP were usually associated with allergic reaction (81·1%), whereas red cells more commonly cause FNHTR (68·8%) and all the AHTR, HTR, DSTR and DHTR. 84·1% of patients were aged 16 years or over, and the majority of the TAD, AHTR, TACO and HTR involved patients aged 60 and above. The ratio of serious adverse reactions (SARs) was 8·2%. Allergic reaction and FNHTR were top two (85·7%) SARs. The first case related to anti-D immunoglobulin was detected in a DHTR report. Conclusion This report provides the world's first overview of transfusion-related adverse reactions in China. This report is useful for better understanding transfusion risks in China.

BackgroundThe triglyceride–glucose (TyG) index, which is a simple surrogate marker of insulin resistance, has been suggested as a contributor of cardiovascular disease. However, evidence on the effect of long-term elevation of the TyG index exposure on myocardial infarction (MI) is limited. The current study aimed to evaluate the association of baseline and long-term elevation of the TyG index exposure with the risk of MI.MethodsA total of 98,849 participants without MI at baseline (2006) were enrolled from the Kailuan study. The baseline TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The long-term TyG index was characterized in two ways as follows. The updated mean TyG index was calculated as the mean of TyG index at all previous visits before MI occurred or the end of follow-up; alternatively, the TyG index was calculated as the number of visits with a high TyG index in 2006, 2008, and 2010, ranging from 0 (no exposure) to 3 (had high TyG index at all three study visits). Hazard ratio (HR) and 95% confidence interval (CI) was estimated using multivariable Cox proportion hazard models.ResultsDuring a median follow-up of 11.03 years, 1555 incident MI occurred. In the multivariable-adjusted model, the risk of MI increased with quartiles of the baseline and updated mean TyG index, the HR in quartile 4 versus quartile 1 was 2.08 (95% CI,1.77–2.45) and 1.58 (1.18–2.12), respectively. Individuals with a high TyG index at all three visits had a 2.04-fold higher risk (95% CI, 1.63–2.56) of MI compared with no exposure. Subgroup analyses showed that the associations were more pronounced in women than in men (Pinteraction = 0.0411).ConclusionsElevated levels of the baseline and long-term TyG index are associated with an increased risk of MI. This finding indicates that the TyG index might be useful in identifying people at high risk of developing MI.

Background The role of serum uric acid (SUA) in development of myocardial infarction (MI) is controversial. The current study aimed to investigate the association between both baseline SUA and changes in SUA and the risk of MI. Methods The current study included 71,449 Chinese participants (mean age, 50.9 years) free of MI during the time of follow-up. Participants were divided into 4 categories according to the SUA levels between baseline and the second follow-up: stable low, elevated, reduced and stable high. Multivariate Cox proportion models were used to calculated hazard ratios (HRs) and their 95% confidence intervals (CIs) for MI. Results During a median follow-up of 8.96 years, 837 MI cases were identified. After adjustment for potential confounders, MI risk was only associated with stable high SUA, the HR was 1.42 (95%CI: 1.02–1.92, p = 0.03), compared with those with stable low SUA. However, there was no association between hyperuricemia at baseline and MI, the HR was 1.14 (95%CI: 0.91–1.42, p = 0.19) compared with those with normal SUA. Subgroup analyses stratified by age, sex, hypertension, diabetes and estimated glomerular filtration rate were also confirmed no significant difference (p-interaction >0.05 for all). Furthermore, mediation analyses revealed 14.14% of association was mediated by hypertension. Conclusions Only stable high SUA was associated with increased higher risk of MI. Changes in SUA levels in any other direction or high SUA levels at baseline were not associated with risk of MI.

Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.

BackgroundHypertension is a major pathogenic factor of cardiovascular diseases. Insufficient blood pressure control rate and sub-optimal medication adherence remain challenges for effective management of hypertension. Transcutaneous electrical acupoint stimulation (TEAS) has been used to treat various diseases, including hypertension, but the scientific evidence for its benefit remains insufficient. Therefore, we will perform a randomized, controlled clinical trial in patients with stage 1 hypertension to evaluate the effect of TEAS.Methods/designThe study will be a two-arm parallel, randomized controlled trial. Sixty patients with stage 1 hypertension will be randomly assigned to the TEAS group and the control group in a 1:1 ratio. The participants in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at four acupoints in the upper and lower extremities at home, 4 times weekly for 12 weeks for a total of 48 sessions. Participants in the control group will not receive any form of acupoint stimulation. All participants in both groups will receive lifestyle education on how to control high blood pressure, including diet, weight control, and exercise. The primary outcome measure will be the change of the mean systolic blood pressure from baseline to 12 weeks. Secondary outcomes include the change of mean diastolic blood pressure, quality of life, body mass index, and physical activity level.DiscussionThis pilot, randomized, controlled trial will explore the feasibility of TEAS. It will also provide potential clinical evidence for the efficacy and safety of TEAS in the treatment of patients with stage 1 hypertension. The results of this study will be published in peer-reviewed journals. Furthermore, this pilot trial as the precursor of a large scale randomized controlled trial will inform the sample size of the subsequent trial.Trial registrationChinese clinical trial registry, ChiCTR1900025042, Registered on 8 August 2019 (http://www.chictr.org.cn/showproj.aspx?proj=41496).

This study was a systematic review comparing the clinical outcomes of nonsurgical and surgical management for distal radius fractures. A comprehensive literature search was conducted using multiple databases, including Medline, Embase, and Cochrane. All databases were searched from the earliest records through June 2019 using the following Boolean operators: distal radius fracture, conservative treatment, nonoperative treatment, nonsurgical treatment, surgical treatment, and operative. All prospective and retrospective controlled trials were retrieved that directly compared the functional outcomes between the nonsurgical and surgical groups. Five prospective studies and six retrospective comparative studies were retrieved. A total of 1049 patients were included: 529 in the nonsurgical group and 520 in the surgical group. Both types of treatment led to similar results with respect to DASH and grip strength, as well as and most other functional assessments. However, there was significant difference in radial inclination, radial length, ulnar variance and range of wrist flexion. No significant differences in most functional assessments were found when comparing surgical and nonsurgical management of distal radius fractures. Although there were significant differences in radial inclination, radial deviation, ulnar variance, and wrist flexion, they did not seem to have impacts on the quality of wrist. Nonsurgical treatment for the distal radius fractures should be considered firstly. Indications for operative fixation should be considered carefully in the treatment of DRFs. Therapeutic study (systematic review), Level III.

Background and aims Although serum lipids are widely accepted as independent predictors of myocardial infarction (MI), there is insufficient evidence for associations of changes in lipid levels with MI. The present study aimed at investigating the associations between changes in lipids and incidence of MI in people without lipid-lowering therapy. Methods 64,031 Chinese participants (mean age: 53.42 ± 11.95 years) without previous MI were enrolled in the study. The participants were divided into four categories based on quartiles of lipid changes. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for MI. Results During a median follow-up of 7.03 years, 599 individuals developed MI. After adjustment for covariates, increased total cholesterol (TC), increased low-density lipoprotein cholesterol (LDL-C), increased non-high-density lipoprotein cholesterol (non-HDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) were associated with elevated risk of MI, with HRs (95% CIs) in the highest quartile group compared with the lowest quartile group of 1.56 (1.21–2.01), 1.96 (1.49–2.57), 1.95 (1.52–2.50), and 0.69 (0.53–0.90), respectively. However, changes in triglyceride (TG) were not associated with MI risk (p = 0.8030). Conclusions Changes in levels of TC, LDL-C, non-HDL-C, and HDL-C, but not TG, were associated with risk of MI. Early detection and control of lipid levels may be beneficial and necessary for young people and those with healthy lipid levels at baseline.

Introduction Lung cancer is the leading cause of cancer-associated mortality worldwide. Recently, long non-coding RNAs (lncRNAs) have been studied as key regulators in some biological processes. Of note, the molecular mechanism and prognostic value of lncRNAs in non-small cell lung cancer (NSCLC) have largely remained unclear. Material and methods In this study, we compared the PTTG3P expression levels between lung cancer and normal lung samples by analyzing 5 public datasets (GSE18842, GSE19804, GSE27262, GSE30219, and GSE19188). Next, pentose phosphate pathway and co-expression networks were constructed to identify key targets of lncRNA PTTG3P. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential roles of lncRNA PTTG3P. Moreover, we constructed PTTG3P-mediated ceRNA networks in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Results In the present study, our analysis showed that PTTG3P expression was higher in high T stage LUAD and LUSC samples, as well as high N stage NSCLC tissues. Of note, we found that higher PTTG3P expression is correlated with shorter survival time in NSCLC patients by analyzing Kaplan-Meier plotter datasets. We found that PTTG3P was significantly associated with NSCLC cell proliferation regulation by affecting a series of cell cycle related biological processes. Conclusions Bioinformatics analysis showed that PTTG3P was associated with NSCLC cell proliferation. These results suggested that PTTG3P could serve as a new therapeutic and prognostic target for NSCLC.

A series of economic, social and political issues have arisen with the aggravation of environmental issues. The public's higher expectations and requirements for environmental quality urge the reform for the most stringent environmental management system, which expedites the environmental tax reform. Pollutant discharge fee (PDF) is the earliest economic means adopted for environmental purpose in China. It has made important contributions to the cause of environmental protection by encouraging businesses to strengthen environmental management and reduce pollutant emissions, and raising environmental protection funds. However, some problems were revealed in the actual implementation process, such as insufficient enforcement rigidity, intervention of local governments and departments, and negotiated payment. On January 1, 2018, China launched the environmental protection tax (EPT) policy, which was China's first green tax aimed at environmental protection, putting an end to PDF that had been in effect for the past 40 years. The policy sets different pollutant equivalent values (PEVs) for pollution factors with different levels of hazard to tax high-hazard pollution factors more heavily. This regulates corporate behavior of pollutant discharge and encourages businesses to reduce pollutant emissions. By mean of rigid taxation, the policy gives full play to its regulatory functions. Overall, the EPT policy has been smoothly implemented for over one year, with some problems encountered in the process. The paper will evaluate the policy impacts in the first year, summarize experiences and identify problems in a timely manner, and propose measures to optimize the policy design and recommendations on tax collection and management, in the hope of facilitating further reform and innovation of China's environmental tax policy.

Xue Tian,1,* Feiyue Yang,2,* Fenghu Li,1 Li Ran,1 Jianying Chang,1 Jiehui Li,1 Wei Hong,3 Lang Shan,1 Yanjun Du,1 Lili Hu,1 Fan Mei,1 Mingyuan He,1 Yongxia Li,1 Heran Wang,1 Kai Zuo,1 Bo Zhou,4 Shuying Chen,1 Wanli Mao1 1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 2Department of Gynecologic Oncology, Guizhou Provincial People’s Hospital, Guiyang, 550004, People’s Republic of China; 3Department of Radiotherapy, The Affiliated Hospital of Guizhou Medical University, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 4Surgical Department of Gynecological Oncology, The Affiliated Hospital of Guizhou Medical University, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fenghu Li; Li Ran Email 769654418@qq.com; ranli171@hotmail.comPurpose: To examine the clinical significance of unoperated cervical cancer patients treated with different neoadjuvant chemotherapy (NACT) schemes followed by concurrent chemotherapy and radiotherapy (CCRT).Methods: This retrospective analysis included women with locally advanced cervical cancer treated with NACT-CCRT between September 2011 and September 2014. Neoadjuvant chemotherapy included paclitaxel plus cisplatin (TP group; 62 patients) or paclitaxel plus loplatin (TL group; 58 patients), which were administered three weekly, and cisplatin or loplatin, which were administered weekly for synchronous chemotherapy. External beam radiation therapy (50.4– 56.35 Gy/28 f, 180– 215 cGy/f, 5 f/w) was followed by intracavitary brachytherapy (5 Gy per fraction, mostly 5 fractions, Ir192 based).Results: One hundred twenty women were included in the analysis. The complete/partial response rate was 99.2% after treatment. The one-year, three-year, and five-year survival rates were 99.2%, 82.5%, and 70.8%, respectively. In the TP and TL groups, the three-year and five-year survival rates were 85.5% vs 77.6% and 75.8% vs 65.5%, respectively, with no significant difference. The 5-year overall survival (OS) rates between patients with stage IIB and stage IIIB disease were not significantly different (69.2% vs 64.7%). In the TP group, grade 3 or 4 digestive reactions were more frequent than those in the TL group. Leukopenia, neutropenia, and thrombocytopenia were more common in the TL group. No significant difference was found in anemia, radiation enteritis, radiation proctitis, or radiation cystitis between the groups.Conclusion: Lobaplatin may be used as an alternative drug for patients with severe digestive system reactions or contraindications to cisplatin, but hematological toxicity must be considered, particularly in dose-intensive schemes. Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy (NACT-CCRT) warrants further prospective study in cervical cancer patients with a wide range of tumor invasion (eg, mass size ≥ 5 cm or stage IIIB).Keywords: cervical cancer, neoadjuvant chemotherapy, survival benefit, side effects

Exposure to high levels of ozone contributes to insensitivity to glucocorticoids in asthma treatment, but the underlying mechanisms are not known. We built two asthma models: a “T2-high” asthma model was established by ovalbumin (OVA) sensitization/challenge and OVA sensitization/challenge combined with ozone exposure (OVA + ozone) was used to induce airway inflammation with increased numbers of neutrophils to simulate “T2-low” asthma. The expression of T-helper (Th)1/2/17-related cytokines was measured by cytokine antibody arrays. Bronchial provocation tests were carried out to evaluate the lung resistance of mice. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemical (IHC) analyses of alpha-smooth muscle actin were undertaken to observe morphology changes in lungs. The expression of glucocorticoid receptors (GRs) and phosphorylated-GR (p-GR) was measured by western blotting. Nr3c1 mRNA was quantified by RT-qPCR. Protein expression of proinflammatory cytokines, signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling 3 (SOCS3), and CXCL1 was measured through ELISAs, western blotting, or IHC analyses. Resected lung tissue from seven asthma patients and 10 healthy controls undergoing thoracotomy for pulmonary nodules was evaluated by IHC analyses and ELISAs. In both asthma models, mucus hypersecretion, as well as inflammation, hyperresponsiveness, and remodeling of the airways, was present compared with the control group, whereas the OVA + ozone group showed severe neutrophil infiltration. The expression of Th17-related cytokines (interleukin (IL)-6, IL-17A, IL-21), GR protein, and CXCL1 increased in the OVA + ozone group, whereas the expression of p-GR decreased. Dexamethasone (Dex) could not totally reverse the expression of p-GR and histone deacetylase-2 in the OVA + ozone group. STAT3 expression increased in the OVA + ozone group and could not be completely reversed by Dex, and nor could IL-6 expression. A positive correlation between IL-6 or IL-17A and STAT3 and negative correlation between SOCS3 and STAT3 were shown, suggesting that the IL-6/STAT3 pathway may be involved in OVA + ozone–induced corticosteroid-resistant airway inflammation. In clinical samples, IL-17A expression in lung tissue was positively correlated with percent STAT3-positive area and negatively correlated with SOCS3 expression. The IL-6/STAT3 pathway may contribute to corticosteroid insensitivity in OVA + ozone–induced neutrophilic airway inflammation through regulation of Th17 cells and could provide new targets for individual treatment of corticosteroid resistance in asthma.

Background: Both baseline blood pressure (BP) and cumulative BP have been used to estimate cardiovascular event (CVE) risk of higher BP, but which one is more reliable for recommendation to routine clinical practice is unclear.Methods: In this prospective study, conducted in the Kailuan community of Tanshan City, China, a total of 95,702 participants free of CVEs at baseline (2006–2007) were included and followed up until 2017. Time-weighted cumulative BP that expresses the extent of cumulative BP exposure is defined as the sum of the mean of two consecutive systolic or diastolic BP times the interval between the two determinations, then normalized by the total follow-up duration. Incident CVEs during 2006–2017 were confirmed by review of medical records. We performed a competing risk regression analysis to assess CVE risk of the different durations of higher BP exposure. ROC analysis was performed to assess the predictive value of higher BP on CVE occurrence.Results: We found that when the risk of higher BP on CVE occurrence was estimated based on time-weighted cumulative BP, the hazard ratios (HRs) increased with the increase in duration of higher BP exposure in each of the four BP groups: Conclusions: Baseline BP remains a useful indicator for predicting future occurrence of CVEs. Nevertheless, time-weighted cumulative BP could more reliably estimate the CVE risk of higher BP exposure than baseline BP.

Background The association between impaired fasting glucose and cardiovascular disease (CVD) in participants without atherosclerotic CVD (ASCVD) risk factors based on current definitions is unclear. The study aimed to examine the association of fasting glucose levels with CVD and its subtypes in persons without ASCVD risk factors. Methods This study included 38 297 participants [men 62.1%; mean age 47.9 (12.9) years] who were free of a history of CVD and absent of ASCVD risk factors and had a fasting plasma glucose (FPG) level between 70 to 125 mg/dL at baseline from Kailuan Study during 2006 and 2007. Participants were followed until new-onset CVD event, death, or December 31, 2017. Cox proportional hazards models were performed to evaluate the associations. Results During a median follow-up of 11.0 years (interquartile range 10.7-11.2 years), we observed 1217 incident CVD events. Compared with participants with FPG 70 to 99 mg/dL, the multivariable adjusted hazard ratios for CVD among participants with FPG 100 to 109 mg/dL and 110 to 125 mg/dL were 1.18 (95% CI 1.02-1.38) and 1.27 (95% CI 1.03-1.55), respectively. Multivariable-adjusted spline regression model showed a J-shaped association between FPG and the risk of CVD. Conclusions We found that among individuals without diabetes or other traditional ASCVD risk factors, there is an increased risk of incident CVD with increasing abnormal FPG levels. These results highlight the importance of primordial prevention for FPG level increases along with other traditional ASCVD risk factors.

Background The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Methods All patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2–6 and 3–6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes. Results Among 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90–17.70), 3.80 (2.70–5.30), and 9.30 (6.70–12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2–6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19–1.59) and 1 year (OR, 1.31; 95 % CI, 1.13–1.52), and mRS score 3–6 at 3 months (OR, 1.33; 95 % CI, 1.11–1.59) and 1 year (OR, 1.28; 95 % CI, 1.07–1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome. Conclusions Elevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year.

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

Background Long-term patterns of serum uric acid (SUA) and their association with the risk of myocardial infarction (MI) and mortality are poorly characterized as prior studies measured SUA at a single time point. This study aimed to identify SUA trajectories and determine their associations with incident MI and all-cause mortality. Methods We included 85,503 participants who were free of MI in or prior 2012 from the Kailuan study. SUA trajectories during 2006–2012 were identified by group-based trajectory modeling. Cox proportional hazard models were used to assess the association of SUA trajectories with MI and all-cause mortality. Results We identified three SUA trajectories during 2006–2012: low-stable (n=44,124, mean SUA: 236–249 μmol/L), moderate-stable (n=34,431, mean SUA: 324–354 μmol/L) and high-stable (n=6,984, mean SUA: 425–463 μmol/L). During a median follow-up of 6.8 years, we documented 817 (0.96%) incident MI and 6498 (7.60%) mortality. Compared with the low-stable group, high-stable group experienced a higher risk of MI (hazard ratio [HR], 1.35; 95% confidence [CI], 1.07–1.71) and all-cause mortality (HR, 1.22; 95% CI, 1.12–1.33). Multiple sensitivity analyses yielded similar results. Additionally, the association of SUA trajectory with MI and all-cause mortality was more pronounced in individuals without a history of hypertension (P-interaction=0.0359) and those aged P-interaction Conclusions Higher SUA trajectories were associated with altered risk of MI and all-cause mortality, suggesting that monitoring SUA trajectory may assist in identifying subpopulations at higher risk of MI and all-cause mortality.

The clinical significance of small airway dysfunction (SAD) determined with spirometry in patients with normal forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) is controversial.To determine whether SAD presents histologic abnormalities in the setting of normal computed tomography (CT) imaging and FEV1 and FEV1/FVC.A cross-sectional study was performed in 64 patients undergoing thoracotomy for pulmonary nodules. Thoracic high-resolution CT (HRCT), bronchodilation test, and fractional exhaled nitric oxide (FENO) and its alveolar component (nitric oxide alveolar concentration [CANO]) were obtained before surgery. Lung pathology and levels of cytokines in lung tissue were measured. The patients were divided into SAD and small airway normal function groups according to forced expiratory flow at 75% and 50% of the FVC (maximal expiratory flow [MEF] 25, MEF50) and maximum midexpiratory flow.The MEF50, MEF25, and maximum midexpiratory flow were strongly negatively correlated with CANO (r, -0.42, -0.42, -0.40, respectively; P ≤ .001 for all). The MEFs were mildly negatively correlated with interleukin (IL)-6 and macrophages in lung tissue (r-0.25, P.001 for all). The CANO (P.001), airspace size (mean linear intercept) (P = .02), macrophages (P = .003), IL-6 (P = .003), and IL-8 (P = .008) in lung tissue were higher in patients with SAD (n = 35) than those with small airway normal function (n = 29). A total of 8 patients (22.86%) with SAD and 2 (6.90%) without SAD had pneumatoceles (P = .10).Patients with pulmonary nodules and SAD were more likely to have abnormal inflammation and emphysematous destruction than patients without SAD. Thus, SAD indicates histologic abnormalities in patients with normal CT imaging and FEV1 and FEV1/FVC.

BACKGROUND: Abnormal electrolytes were closely related to the prognosis of various diseases, the prognostic role of electrolytes in stroke has not been investigated well. We aimed to investigate the association between electrolytes and clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: Data were recruited from the China National Stroke Registry III study. Patients were classified into three groups according to tertiles and the normal range of each electrolyte. Multivariable logistic and Cox proportional hazards regressions were adopted to explore the associations of electrolytes with poor functional outcomes [modified Rankin Scale (mRS) 3–6/2–6] and all-cause death at 3 months and 1 year. RESULTS: A total of 10,299 eligible patients were enrolled. After adjusted for confounding factors, the first tertile electrolytes were associated with increased risk of poor functional outcome (mRS score 3–6) at 1 year, the adjusted odds ratios (95% confidence intervals) were 1.33 (1.14–1.55) for potassium, 1.41 (1.20–1.60) for sodium, 1.27 (1.08–1.48) for chloride, compared with the second tertile. Similar results were found when poor functional outcome was defined as mRS score 2–6 and all-cause death. However, almost no significant association was present of calcium with these outcomes. All results were consistent when each electrolyte was classified into three groups according to the normal range and the outcomes timepoint was set at 3 months. CONCLUSIONS: Lower levels of potassium, sodium, chloride but not calcium were associated with higher risk of poor functional outcomes and death in patients with AIS or TIA.

BackgroundRisk of cardiovascular disease (CVD) is increased in metabolically obese normal weight adults. However, we have limited knowledge of how to prevent CVD in normal-weight people. The triglyceride-glucose index (TyG index) has been considered as a contributor of CVD, while long-term patterns of the triglyceride-glucose index (TyG index) and their effects on CVD among normal-weight adults are poorly characterized. Therefore, this study aimed to identify TyG index trajectories in normal-weight adults and to determine their association with the risk of incident CVD.MethodsThis prospective cohort study included 40,473 normal-weight participants who were free of stroke and myocardial infarction prior to or in 2012. The TyG index was calculated as ln [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)/2], and the TyG index trajectories during 2006-2012 were identified by latent mixture modeling. Cox proportional hazards models were used to examine the associations between TyG index trajectories and incident CVD.Results We identified five distinct TyG index trajectories according to TyG index range and changing pattern over time: low-stable (n=9,806; mean TyG index 7.84-7.93), moderate-stable (n=22,066; mean TyG index 8.43-8.52), elevated-decreasing (n=1,469; mean TyG index 9.83-8.75), moderate-increasing (n=5,842; mean TyG index 8.98-9.26), and elevated-stable (n=1,290; mean TyG index 9.91-10.07). During 6.74 years of follow-up, we documented 1,577 incident CVD events. Compared with the low-stable pattern, the highest risk of CVD was observed in the elevated-stable pattern (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.73-2.90), followed by the moderate-increasing pattern (HR, 1.70; 95% CI, 1.43-2.04), the elevated-decreasing pattern (HR, 1.45; 95% CI, 1.11-1.89), and the moderate-stable pattern (HR, 1.25; 95% CI, 1.08-1.44). Similar results were also observed for stroke and myocardial infarction. Consistently, annual increment of the TyG index during 2006-2012 also predicted future risk of CVD.ConclusionsDistinct TyG index trajectories were significantly associated differently subsequent risk of CVD in normal-weight individuals. These observations suggested that long-term trajectories of TyG index may be useful for predicting CVD among normal-weight adults.

Background: The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the triglyceride-glucose (TyG) index (a simple surrogate of insulin resistance) seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity is mediated by the TyG index.Methods: A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. The TyG index was calculated as ln [fasting triglyceride (mg/dL)×fasting glucose (mg/dL)/2]. Mediation analysis using a newly proposed 2-stage regression method for survival data was to explore the mediating effects of the TyG index on the association between obesity and CVD.Results: During a median follow-up of 13.01 years, we identified 7,327 cases of CVD. Mediation analyses showed that 45.60% of the total association (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.18-1.31) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.10; 95% CI, 1.08-1.11), and the proportion mediated was 38.30% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 33.76%, 37.10%, and 33.10% for obesity, taken normal weight as reference. Similar results were observed for stroke and myocardial infarction.Conclusions: This study found that the association between obesity and CVD was mediated by the TyG index, suggesting proper control of insulin resistance can be effective to significantly reduce the effects of general and central obesity on CVD.

Background Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all‐cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all‐cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all‐cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow‐up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10–1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06–2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18–2.11). Similar associations persisted for all‐cause mortality. Conclusions The risk of MI and all‐cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all‐cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

Background Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and subsequent cardiovascular disease (CVD). However, the effect of longitudinal changes in TyG index on the risk of CVD remains uncertain. This study aimed to investigate the association between change in TyG index and the risk of CVD in the general population. Methods The current study included 62,443 Chinese population who were free of CVD. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and change in TyG index was defined as the difference between the TyG index in 2010 and that in 2006. Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to examine the association between change in TyG index and the risk of CVD. Results During a median follow-up of 7.01 years, 2530 (4.05%) incident CVD occurred, including 2018 (3.23%) incident stroke and 545 (0.87%) incident myocardial infarction (MI). The risk of developing CVD increased with the quartile of change in TyG index, after adjustment for multiple potential confounders, the hazard ratios for the Q4 group versus the Q1 group were 1.37 (95% confidence interval [CI], 1.21–1.54) for the overall CVD, 1.38 (95% CI, 1.19–1.60) for stroke, and 1.36 (95% CI, 1.05–1.76) for MI. Restricted cubic spline analysis also showed a cumulative increase in the risk of CVD with increases in the magnitude of change in TyG index. The addition of change in TyG index to a baseline risk model for CVD improved the C-statistics (P = 0.0097), integrated discrimination improvement value (P P Conclusions Substantial changes in TyG index independently predict the risk of CVD in the general population. Monitoring long-term changes in TyG may assist with in the early identification of individuals at high risk of CVD.

Background: The relationship between baseline triglyceride-glucose (TyG) index and cardiovascular disease (CVD) has been confirmed by former studies. However, the effect of longitudinal changes in TyG index on CVD remains uncertain. This study aimed to investigate the association of changes in TyG index with CVD in the general population. Methods: The current study included 62,443 Chinese population who were free of CVD. TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], changes in TyG index was defined as the difference in TyG index between 2010 and 2006. Cox proportional hazard model and restricted cubic spline was used to examine the association between changes in TyG index and CVD.Results: During a median follow-up of 7.01 years, 2,530 (4.05%) incident CVD occurred, including 2,018 (3.23%) stroke and 545 (0.87%) MI. Risk of CVD was increased with quartiles of changes in TyG index, the adjusted hazard ratio (HR) in Q4 group versus Q1 group was 1.37 (95% confidence interval [CI], 1.21-1.54) for the overall CVD, 1.38 (95% CI, 1.19-1.60) for stroke, and 1.36 (95% CI, 1.05-1.76) for MI. Restricted cubic spline also showed cumulative increased risk of CVD with increasing changes in TyG index. Furthermore, the addition of changes in TyG index to a baseline risk model for CVD improved the C-statistics (P=0.0097), the integrated discrimination improvement (PPConclusions: Substantial changes in TyG index can independently predict the risk of CVD in the general population. Monitoring long-term changes in TyG may be helpful in the early identification of individuals at high risk of CVD.

Chronic obstructive pulmonary disease (COPD) with increased morbidity and mortality is a worldwide healthcare challenge closely associated with cigarette smoking (CS). Currently, there is no effective therapeutic strategy to control inflammation in COPD patients. The present study tested the protective effects of (−)-Epicatechin (EC), a type of flavonoid, on CS-induced COPD and the underlying mechanism. Also, EC repressed the production of reactive oxygen species (ROS) and improved human bronchial epithelial cell viability after cigarette smoke extract (CSE) treatment. Further studies demonstrated that EC promotes ubiquitin-mediated Keap1 degradation by upregulating tripartite motif-containing protein 25 (TRIM25) expression and enhances the nuclear localization of Nrf2 protein. Also, EC dramatically inhibits the activation of NLRP3 inflammasome and reduces the CSE-induced pyroptosis, as indicated by decreasing lactate dehydrogenase release and the number of caspase-1-positive cells. Importantly, Nrf2 knockdown reversed the protective effect of EC on human bronchial epithelial cells, at least partially. Consistent with the results in vitro, EC inhibits the activation of NLRP3 inflammasome and relieves the CS-induced lung inflammation, as evident from decreased interleukin (IL)-1β and IL-18 secretion in a COPD rat model. In conclusion, this study revealed the protective effect of EC on experimental COPD rats and elucidated the mechanism of EC promoting Nrf2 activity, which might provide a novel therapeutic strategy for COPD.

BackgroundTriglyceride-glucose (TyG) index was recently suggested to be a reliable surrogate marker of insulin resistance. We aim to investigate the associations between baseline and long-term TyG index with subsequent stroke and its subtypes in a community-based cohort.MethodsA total of 97,653 participants free of history of stroke in the Kailuan Study were included. TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). Baseline TyG index was measured during 2006–2007. Updated cumulative average TyG index used all available TyG index from baseline to the outcome events of interest or the end of follow up. The outcome was the first occurrence of stroke, including ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage. The associations of TyG index with outcomes were explored with Cox regression.ResultsDuring a median of 11.02 years of follow-up, 5122 participants developed stroke of whom 4277 were ischemic stroke, 880 intracerebral hemorrhage, and 144 subarachnoid hemorrhage. After adjusting for confounding variables, compared with participants in the lowest quartile of baseline TyG index, those in the third and fourth quartile were associated with an increased risk of stroke (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12–1.33, and adjusted HR 1.32, 95% CI 1.21–1.44, respectively,Pfor trend ConclusionsElevated levels of both baseline and long-term updated cumulative average TyG index can independently predict stroke and ischemic stroke but not intracerebral hemorrhage in the general population during an 11-year follow-up.

Background: Triglyceride-glucose (TyG) index, as a simple surrogate marker of insulin resistance, has been suggested to be associated with arterial stiffness. However, there is limited data regarding the effect of the TyG index on intra- and extra-cranial artery stenosis (ICAS and ECAS). This study aimed to assess the cross-sectional and longitudinal associations of the TyG index with ICAS and ECAS in Chinese adults.Methods: Participants were recruited from the Asymptomatic Polyvascular Abnormalities Community study, 5,381 participants were enrolled in the cross-sectional analysis, and then 3,447 and 1,853 participants were enrolled in the longitudinal analysis for incident ICAS and ECAS, respectively. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Multivariable logistic analysis was used to assess the association of the TyG index with the outcomes by calculating odds ratio (OR) and 95% confidence interval (CI). Results: The results of cross-sectional and longitudinal analysis were basically the same, as the fully adjusted OR comparing participants in the highest tertile versus lowest tertile of the TyG index was 1.34 (95% CI, 1.13-1.59) for prevalence of ECAS and 1.85 (95% CI, 1.26-2.71) for incident ECAS, respectively. The addition of TyG index to a conventional model had an incremental effect on the predictive value for ECAS, the integrated discrimination improvement and category-free net reclassification was 0.20% (P=0.0011) and 9.14% (P=0.0008) in the cross-section analysis, 0.30% (P=0.0315) and 20.03% (P=0.0042) in the longitudinal analysis. However, we did not observed any significant association between the TyG index and ICAS. Conclusions: Elevated TyG index was significantly associated with a higher risk of ECAS, but not with ICAS in Chinese adults. This conclusion lends support to the clinical significant for the TyG index for the assessment of artery stenosis, especially for ECAS.

Background Our study aimed to evaluate whether the effects on adverse clinical outcomes, defined as death, recurrent stroke, and poor functional outcomes, differed by leukocyte subtype in patients with acute ischemic cerebrovascular events, including both ischemic stroke and transient ischemic attack (TIA). Methods We derived data from the Third China National Stroke Registry (CNSR-III). The counts and percentages of each leukocyte subtype were collected within the first 24 hours after admission. Enrolled patients were classified into four groups by the quartiles of each leukocyte subtype count or percentage. Hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) of adverse clinical outcomes were calculated, with the lowest quartile group as the reference category. We used C statistics, integrated discrimination improvement (IDI), and the net reclassification index (NRI) to evaluate each leukocyte subtype's incremental predictive value beyond conventional risk factors. Results A total of 14,174 patients were enrolled. Higher counts of leukocytes, neutrophils, and monocytes were associated with elevated risks of adverse clinical outcomes. In contrast, higher counts of lymphocytes and eosinophils were related to reduced risks of adverse clinical outcomes. Meanwhile, basophil counts seemed to not correlate with adverse clinical outcomes. Furthermore, there were also significant associations between the percentages of leukocyte subtypes and adverse clinical outcomes. Conclusions Leukocyte subtypes had different relationships with adverse clinical outcomes at 3-month and 1-year follow-up in patients with acute ischemic cerebrovascular events and could slightly increase the predictive value compared with the conventional model.

Evidence is lacking about the role of serum uric acid (SUA) in the progression from prehypertension to hypertension. Herein, we aimed to investigate the association of both baseline and dynamic change in SUA with the risk of hypertension developing from prehypertension. The study enrolled 11,488 participants with prehypertension during 2006-2010 from the Kailuan study. Change in SUA was assessed as % change of SUA from 2006 (baseline) to 2010. Participants were categorized into four groups by quartiles of baseline and change in SUA, separately. Multivariable logistic regressions were used to calculation the odds ratio (OR) and 95% confidence interval (CI). During a median follow-up of 7.06 years, 2716 (23.64%) participants developed hypertension from prehypertension. In the multivariable-adjusted model, the OR for hypertension comparing participants in the highest versus the lowest quartile of baseline SUA were 1.18 (95% CI, 1.02-1.36). Increased SUA over time was also associated with elevated risk of hypertension (OR in the highest quartile was 1.41 [95% CI, 1.23-1.62] versus the lowest quartile), especially in those with baseline SUA ≥ median (OR, 1.48; 95% CI, 1.21-1.81). Moreover, the addition of SUA to a conventional risk model had an incremental effect on the predictive value for hypertension (integrated discrimination improvement 0.30%, P

BackgroundTo investigate the risk of incident arterial stiffness according to metabolically healthy obese (MHO) phenotype in Chinese population.Materials and methodsThe Kailuan study is an ongoing prospective cohort study, 37,180 participants with at least one-time measurement of branchial-ankle pulse wave velocity (baPWV) were included in the cross-sectional analysis, and 16,236 participants with repeated measurement of baPWV during the follow-ups were included in the longitudinal study from March 1, 2010, to January 31, 2020. Cross-classification of body mass index (BMI) categories and metabolic health status created six groups. Linear and logistic regression analyses were used to assess the association between BMI-metabolic status phenotypes and baPWV in mono-factor and multi-factor models. ResultsThe results of cross-sectional and longitudinal investigation were basically the same, as the abnormality of baPWV increased with BMI categories in metabolically healthy participants, while the increasing tendency disappeared in metabolically unhealthy participants. A 1.6-fold, 2.8-fold increased risk for the new occurrence of arterial stiffness were documented in MHO and metabolically unhealthy obese participants compared to metabolically healthy normal weight controls in the fully adjusted model. Further stratified analysis shown that metabolic health status was an interaction factor between BMI and arterial stiffness in either study population (PP=0.0003 for longitudinal study).ConclusionsMetabolic health status and BMI categories contribute to the progression of arterial stiffness, while BMI is positively associated with arterial stiffness only in metabolically healthy participants. Moreover, MHO is an intermediate stage between metabolically healthy and unhealthy status.Trial registration: ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050

To solve the problem of general search engine's inability to timely include information in campus network and time-lag, this paper proposes a perfect solution of campus network search engine based on Elasticsearch full-text search engine and Scrapy framework. This paper mainly analyzes the operation process of Elasticsearch, studies the search mechanism of Elasticsearch, and designs the system architecture of campus network search engine on this basis, and presents the key implementation technologies of web crawling module, index and query module and Front-end display module of the system. Finally, through experimental verification, compared with the traditional general search engine, the campus network search engine designed in this paper has better relevance and quantity of search results, and the inclusion of new information in the campus network is better.