To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

Objective To investigate the protective effect and mechanism of heat acclimation(HA)on electromagnetic field(EMF)induced hippocampus neuron injury in mice.Methods Forty healthy BALB/c male mice(18～22 g,7 weeks old)were randomly divided into 4 groups(n=10):Control group(Con),HA group(34℃,30 d),EMF group(2 450 MHz,20 min/d,4 weeks)and HA+EMF group(HA preconditioning+EMF).Sucrose preference test was performed to evaluate sucrose preference levels of mice in each group.Tail suspension test and forced swimming test were utilized to observe the immobility time.Morris water maze test was conducted to determine the learning and memory capabilities.Pathological changes in the hippocampus were observed with HE staining.Immunohistochemical assay for Iba1(marker of microglia),CD68(marker of pro-inflammatory phenotype)and CD206(marker of anti-inflammatory phenotype)were used to detect the number and activation phenotype of microglia in the hippocampus.ELISA was applied to measure the levels of TNF-α,IL-1β,TGF-β and IL-10 in the hippocampus of each group.Western blotting was performed to determine the protein levels of HSP70 in the hippocampus.Results As compared with the Con group,the EMF group showed a decreased preference for sucrose(P<0.05),prolonged immobile time in the tail suspension test(P<0.01)as well as in the forced swimming test(P<0.01),extented escape latency on the 7th day(P<0.01),and a decreased time of crossing the platform(P<0.05).EMF exposure resulted in that the hippocampal neurons were in disordered arrangement,loose structure and irregular morphology,with swollen cytoplasm and condensed nuclei,swollen and more microglial cells in the hippocampus(P<0.01),and enhanced relative fluorescence intensity of CD68(P<0.01),but not in CD206 fluorescence intensity(P=0.885).All these findings suggested that activated microglia predominantly exhibited a pro-inflammatory M1 phenotype during this phase.In the hippocampus,the levels of TNF-α and IL-1β were significantly increased,while the levels of IL-10 and TGF-β were significantly decreased(P<0.01).HA treatment reversed the conditions induced by EMF exposure,including better preference for sucrose(P<0.01),shorten immobile time in tail suspension test(P<0.05)and forced swimming test(P<0.01),less escape latency on the 7th day(P<0.01),and improved hippocampal cell injuries.Compared with the Con group,there were more microglial cells in the hippocampus in the HA+EMF group,with increased relative fluorescence intensity of M2 phenotype marker CD206(P<0.01)and decreased CD68 fluorescence intensity(P<0.01).HA treatment also significantly decreased the expression of TNF-α and IL-1β levels(P<0.01),increased the expression of IL-10 and TGF-β(P<0.01),and elevated the protein level of HSP70(P<0.01)when compared with the EMF group.Conclusion HA may ameliorate EMF-induced hippocampus neurons injury in mice by altering the phenotype of activated microglia and inhibiting inflammatory responses.

Objective:To investigate the association of peripheral blood inflammatory markers and lymphocyte subsets with different severities of acute ischemic stroke(AIS).Methods:A total of 128 AIS patients who were admitted to Department of Neurology,The First Affiliated Hospital of Chongqing Medical University,from January to December 2022 were enrolled as subjects,and according to the National Institutes of Health Stroke Scale(NIHSS)score,the patients were divided into mild AIS group(67 patients with an NIHSS score of<4)and moderate-to-severe AIS group(61 patients with an NIHSS score of≥4).The two groups were compared in terms of baseline clinical data,blood biochemical parameters,and peripheral[MLR],neutrophil-to-lymphocyte ratio[NLR],and platelet-to-lymphocyte ratio[PLR]).Flow cytometry was used to measure the number and percentage of lymphocyte subsets.Results:Compared with the mild AIS group,the moderate-to-severe AIS group had a significantly higher proportion of patients with hyperlipidemia blood inflammatory markers(C-reactive protein[CRP],systemic immune-inflammation index[SII],monocyte-to-lymphocyte ratio(47.761%vs.67.213%,P=0.032),with relatively high values of low-density lipoprotein(LDL)/high-density lipoprotein(HDL)ratio(P=0.025)and total cholesterol(TCHO)/HDL ratio(P=0.020),as well as significantly higher levels of the peripheral blood inflamma-tory markers CRP(P<0.001),platelet count(P=0.001),MLR(P<0.001),and NLR(P<0.001),significantly higher numbers of periph-eral blood CD3 T cells(P=0.006),CD4 T cells(P=0.009),CD8 T cells(P=0.032),and CD3-/CD16+/CD56+NK cells(P=0.002),and a significantly higher proportion of T helper cells(P=0.041).The binary logistic regression analysis showed that platelet count(odds ratio[OR]=1.035,P=0.004),CRP(OR=2.016,P<0.001),NLR(OR=2.585,P=0.030),the proportion of total lymphocytes(OR=1.169,P<0.001),and the number of lymphocytes(OR=1.008,P<0.001)were significantly associated with moderate-to-severe AIS.The receiver operating characteristic(ROC)curve analysis showed that NLR,CRP,and the proportion of total lymphocytes had an area under the ROC curve of 0.760,0.812,and 0.777,respectively.Conclusion:Patients with moderate-to-severe AIS tend to have high levels of the peripheral blood inflammatory markers NLR and CRP,a high lymphocyte count,and a high proportion of lymphocytes.NLR,CRP,and the proportion of lymphocytes are independent risk factors for the development of moderate-to-severe AIS.

BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

Diabetic retinopathy(DR)is one of the common serious microvascular complications in diabetic patients,with the main pathological features of retinal vascular injury,oxidative stress and chronic inflammatory re-sponse.In recent years,more and more studies have shown that mitophagy plays an important role in maintaining the func-tional homeostasis of retinal cells and preventing oxidative damage,and nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)is a key regulator of pro-inflammatory response in DR.Mitophagy can reduce the excessive pro-duction of reactive oxygen species(ROS)by removing damaged mitochondria,thereby inhibiting the activation of NLRP3 inflammasome.In contrast,mitochondrial dysfunction can lead to excessive activation of NLRP3 inflammasome,which further aggravates the inflammatory response and apoptosis of the retina.Therefore,this article reviews the independent role of mitophagy and NLRP3 inflammasome in DR and their mutual regulatory mechanisms,so as to provide reference for the study of mitophagy and NLRP3 inflammasome as targets.

Diabetic retinopathy(DR)is one of the common serious microvascular complications in diabetic patients,with the main pathological features of retinal vascular injury,oxidative stress and chronic inflammatory re-sponse.In recent years,more and more studies have shown that mitophagy plays an important role in maintaining the func-tional homeostasis of retinal cells and preventing oxidative damage,and nucleotide-binding oligomerization domain-like re-ceptor protein 3(NLRP3)is a key regulator of pro-inflammatory response in DR.Mitophagy can reduce the excessive pro-duction of reactive oxygen species(ROS)by removing damaged mitochondria,thereby inhibiting the activation of NLRP3 inflammasome.In contrast,mitochondrial dysfunction can lead to excessive activation of NLRP3 inflammasome,which further aggravates the inflammatory response and apoptosis of the retina.Therefore,this article reviews the independent role of mitophagy and NLRP3 inflammasome in DR and their mutual regulatory mechanisms,so as to provide reference for the study of mitophagy and NLRP3 inflammasome as targets.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

Objective:To investigate the relationship between sleep quality and slow-flow in patients with acute coronary syndrome during percutaneous coronary intervention(PCI) and its impact on clinical prognosis.Methods:200 patients with ACS hospitalized in the cardiology department of Guangzhou First People's Hospital from January 2017 to October 2018 were selected. The Pittsburgh Sleep Quality Index (PSQI) was measured before elective PCI, and the sleep breathing of patients was monitored by micro motion sensitive mattress sleep monitoring system (MSMSMS). The patients were divided into normal sleep group (68 cases, PSQI≤7 points) and sleep disorder group (132 cases, PSQI>7 points). The levels of plasma endothelin-1 (ET-1) and nitric oxide (NO) were measured. The " slow-flow" that took place during PCI were also recorded. Major cardiac adverse events (MACE) of patients took placed during 12 months follow-up periods were recorded and compared between two groups.Results:Compared with normal sleep group, patients in sleep disorder group had higher ratio of sleep apnea-hypopnea syndrome (SAHS), hypoxemia and lower deep sleep (25.00% vs 10.29%, 25.76% vs 11.76%, 66.67% vs 48.53%, all P<0.05); lower level of NO and higher level of ET-1 [(28.65±3.26)μmol/L vs (30.24±4.08)μmol/L; (21.17±3.08)pg/ml vs (18.90±2.95)pg/ml, P<0.05]; more slow-flow events took place during PCI in sleep disorder group than normal sleep group (16.67 vs 5.88%, P<0.05); After 12 months of follow-up, Kaplan-Meier survival analysis showed patients of the two groups had significantly different cumulative non-events survival rates (19.70% vs 7.35%, Log rank=5.06, P=0.025). Conclusions:Sleep disorder increase the slow-flow phenomenon during PCI in patients with ACS and affect the clinical prognosis.

Objective To investigate the effect of renal sympathetic denervation (RSD) on the activity of renalase in dogs with chronic heart failure (CHF).Methods After induced by abdominal aorta constriction,dogs were divided into three groups according to whether they underwent double renal artery ablation:2 dogs in control group,2 dogs in sham-operated group (no renal artery ablation),and 5 dogs in RSD group (renal artery ablation).Plasma noradrenaline (NE),B-type natriuretic peptide (BNP),and renalase were determined in 5 dogs with RSD (RSD group),2 control dogs (control group),and 2 shamoperated dogs (sham-operated group).Results NE,BNP and heart rate were significantly higher and renalase was lower in CHF group than those in control group (all P ＜ 0.05).Compared to the control dogs with CHF,the levels of renalase were significantly increased in 6 weeks after RSD [(1 948.78 ±49.19) ng/ml vs (1 847.35 ±20.72)ng/ml,P =0.029],and NE [(166.30 ±7.68)pg/ml vs (181.29 ±8.57)pg/ml],and BNP [(75.10 ± 5.58)lμg/ml vs (89.79 ± 2.04) μg/ml] were decreased in 8 weeks after RSD (all P ＜ 0.05).An decreased trend of the levels of renalase was observed in 8 weeks than in 6 weeks in CHF dogs after RSD,without significant difference (P ＞ 0.05).Conclusions The activity of renalase in dogs with CHF can be affected by RSD.

Objective To report our method to determine lateral needle insertion point (intersection point skin marker) in closed reduction and percutaneous Kirschner wire fixation for pediatric supracondylar fracture of humerus.Methods From May 2012 to June 2014,125 children with supracondylar fracture of humerus were treated with closed reduction and percutaneous Kirschner wire fixation.Of them,60 did not use the intersection point method to determine the lateral needle insertion point (group A),including 46 boys and 14 girls,with an average age of 6.3 ±0.6 years.According to Gartland classification,28 cases were type Ⅱ and 32 cases type Ⅲ.In the other 65 children,the intersection point method was used to determine the lateral needle insertion point (group B),including 50 boys and 15 girls,with an average age of 6.4 ± O.9 years.According to Gartland classification,29 cases were type Ⅱ and 36 cases type Ⅲ.The 2 groups were compared in terms of operation time,fluoroscopy times,hospital stay and hospitalization cost.The efficacy was evaluated at the final follow-ups using Flynn criteria.The 2 groups were compatible without significant differences in preoperative general data (P ＞ 0.05).Results All the 125 children obtained successful closed reduction and percutaneous pin fixation,and an average follow-up of 13 months (from 12 to 15 months)as well.There were significant differences between groups A and B in average operation time (23.1 ± 15.3 min versus 17.5 ± 10.3 min) and fluoroscopy times (9.2 ± 1.0 times versus 5.3 ± 1.3 times) (P ＜ 0.05).There was no statistically significant difference between the 2 groups either in Flynn excellent to good rate [(98.3％ (59/60) versus 98.5％ (64/65)] (P ＞ O.05).Needle irritation occurred in 2 cases and Kirschner wire shift in one in group A while tensile blistering occurred in one in group B.Conclusion In closed reduction and percutaneous Kirschner wire fixation for pediatric supracondylar fracture of humerus,the intersection point skin marker is a simple and reliable method to determine the lateral needle insertion point,leading to considerable reduction in radiographic exposure for both patients and doctors.