In the general population, obesity (high BMI) is often considered as an important risk factor for many diseases and premature death. However, in patients with a certain disease, the risk of death in people with obesity was lower than that in people with normal weight. This abnormal correlation has caused widespread discussion, and different explanations have been given by physiology and epidemiology. Based on causal inference theory, this study used directed acyclic graphs to introduce the collision bias (also called collision-stratification bias). Through example demonstrations, this study explored whether and why the abnormal correlation between obesity and higher survival rates in patients with hyperglycemia exists. Finally, it was concluded that this abnormal correlation among patients with a certain disease (e.g., hyperglycemia in the current analysis) was partly or even totally caused by collider bias.

Objective To investigate the effect of Remazolam(RZ)on intestinal injury in burn sepsis rats by regulating the Notch-1/hairy and enhancer of split homolog(Hes)signaling pathway.Methods Sixty SPF grade SD male rats were randomly separated into Normal group,Model group,low-dose RZ group(RZ-L group,3 mg/kg RZ),high-dose RZ group(RZ-H group,6 mg/kg RZ)and high-dose RZ+Notch-1 activator Jagged1 group(RZ-H+Jagged1 group,6 mg/kg RZ+0.67 mg/kg Jagged1),with 12 rats in each group.A burn sepsis model was prepared by establishing a 20%total surface area(TBSA)third-degree burn(burn)model on the back of rats,followed by injection of Pseudomonas aeruginosa.HE staining was applied to observe rat ileum tissue's pathological changes and assess intestinal mucosal damage score(Chiu's score).ELISA method was used to detect the levels of serum endotoxin,D-lactate,diamine oxidase(DAO),interleukin(IL-6),tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)in rats.RT-qPCR method was applied to detect the expression of Notch-1 and Hes mRNA in rat ileum tissue,and Western Blot was used to detect the expression of Notch-1/Hes signaling pathway-related proteins in rat ileum tissue.Results Compared with the Normal group,the intestinal mucosal injury score(5.30±0.48 vs 1.00±0.52),serum endotoxin(135.69±16.24 pg/ml vs 62.48±3.23 pg/ml),D-lactate(1403.58±68.97 pg/ml vs 752.06±25.29 pg/ml)and DAO levels(137.55±12.37 pg/ml vs 58.52±4.43 pg/ml),ileal tissue IL-6(186.45±16.37 ng/ml vs 21.32±3.66 ng/ml),TNF-α(163.37±11.40 ng/ml vs 15.52±1.03 ng/ml)and MPO levels(8.94±0.92 U/ml vs 2.35±0.33 U/ml),Notch-1 mRNA(1.86±0.19 vs 1.00±0.10)and protein(0.79±0.08 vs 0.21±0.02),Hes-1 mRNA(2.13±0.21 vs 1.00±0.12)and protein(0.88±0.09,0.32±0.03)expression levels in the Model group were greatly increased,and the differences were statistically significant(t=14.294～47.368,all P<0.05).Compared with the Model group,the corresponding indicators of the RZ-L and RZ-H groups showed opposite changes,and the differences were statistically significant(tRZ-L=5.650～21.448,tRZ-H=4.435～42.403,all P<0.05).The Notch-1 activator Jagged1 weakened the therapeutic effect of RZ on intestinal injury in burn sepsis rats.Conclusion RZ may alleviate intestinal injury in burn sepsis model rats by inhibiting the Notch-1/Hes signaling pathway.

In the general population, obesity (high BMI) is often considered as an important risk factor for many diseases and premature death. However, in patients with a certain disease, the risk of death in people with obesity was lower than that in people with normal weight. This abnormal correlation has caused widespread discussion, and different explanations have been given by physiology and epidemiology. Based on causal inference theory, this study used directed acyclic graphs to introduce the collision bias (also called collision-stratification bias). Through example demonstrations, this study explored whether and why the abnormal correlation between obesity and higher survival rates in patients with hyperglycemia exists. Finally, it was concluded that this abnormal correlation among patients with a certain disease (e.g., hyperglycemia in the current analysis) was partly or even totally caused by collider bias.

Objective To investigate the effect of Remazolam(RZ)on intestinal injury in burn sepsis rats by regulating the Notch-1/hairy and enhancer of split homolog(Hes)signaling pathway.Methods Sixty SPF grade SD male rats were randomly separated into Normal group,Model group,low-dose RZ group(RZ-L group,3 mg/kg RZ),high-dose RZ group(RZ-H group,6 mg/kg RZ)and high-dose RZ+Notch-1 activator Jagged1 group(RZ-H+Jagged1 group,6 mg/kg RZ+0.67 mg/kg Jagged1),with 12 rats in each group.A burn sepsis model was prepared by establishing a 20%total surface area(TBSA)third-degree burn(burn)model on the back of rats,followed by injection of Pseudomonas aeruginosa.HE staining was applied to observe rat ileum tissue's pathological changes and assess intestinal mucosal damage score(Chiu's score).ELISA method was used to detect the levels of serum endotoxin,D-lactate,diamine oxidase(DAO),interleukin(IL-6),tumor necrosis factor-α(TNF-α)and myeloperoxidase(MPO)in rats.RT-qPCR method was applied to detect the expression of Notch-1 and Hes mRNA in rat ileum tissue,and Western Blot was used to detect the expression of Notch-1/Hes signaling pathway-related proteins in rat ileum tissue.Results Compared with the Normal group,the intestinal mucosal injury score(5.30±0.48 vs 1.00±0.52),serum endotoxin(135.69±16.24 pg/ml vs 62.48±3.23 pg/ml),D-lactate(1403.58±68.97 pg/ml vs 752.06±25.29 pg/ml)and DAO levels(137.55±12.37 pg/ml vs 58.52±4.43 pg/ml),ileal tissue IL-6(186.45±16.37 ng/ml vs 21.32±3.66 ng/ml),TNF-α(163.37±11.40 ng/ml vs 15.52±1.03 ng/ml)and MPO levels(8.94±0.92 U/ml vs 2.35±0.33 U/ml),Notch-1 mRNA(1.86±0.19 vs 1.00±0.10)and protein(0.79±0.08 vs 0.21±0.02),Hes-1 mRNA(2.13±0.21 vs 1.00±0.12)and protein(0.88±0.09,0.32±0.03)expression levels in the Model group were greatly increased,and the differences were statistically significant(t=14.294～47.368,all P<0.05).Compared with the Model group,the corresponding indicators of the RZ-L and RZ-H groups showed opposite changes,and the differences were statistically significant(tRZ-L=5.650～21.448,tRZ-H=4.435～42.403,all P<0.05).The Notch-1 activator Jagged1 weakened the therapeutic effect of RZ on intestinal injury in burn sepsis rats.Conclusion RZ may alleviate intestinal injury in burn sepsis model rats by inhibiting the Notch-1/Hes signaling pathway.

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

This paper reviewed the concept of organizational silence, elaborated on the content, evaluation methods, reliability, validity, characteristics, and other aspects of nurse organizational silence assessment tools, and compares the basic characteristics, content, and application of each tool. The aim was to provide reference for selection of appropriate assessment tools to identify nurse organizational silence, as well as for the development of comprehensive assessment tools and the early formulation of management strategies.

Objective:To evaluate the relationship between spinal cord cytoplasmic activation/proliferation-associated protein-1 (Caprin-1)-mediated expression of calmodulin-dependent protein kinase Ⅱ alpha(CaMKⅡα) and pain perception in mice.Methods:Nestin CreERT2 mice and Caprin-1 flox/flox mice were hybridized to obtain Nestin CreERT2; Caprin-1 flox/flox homozygous mice. The mice were divided into 2 groups ( n=5 each) using a random number table method: Nestin CreERT2; Caprin-1 flox/floxsolventcontrol group (SC group) and Caprin-1 gene knockout group (KO group). Tamoxifen 100 mg/kg was intraperitoneally injected for 5 consecutive days to generate inducible knockout of the Caprin-1 gene in KO group. The mechanical paw withdrawal threshold was measured at day 1 before and day 5 after the end of administration. Then the mice were sacrificed, and L 4-6 segments of the spinal cord were removed for determination of the expression of Caprin-1 and CaMKⅡα protein and mRNA (by Western blot or real-time quantitative polymerase chain reaction) and co-expression of Caprin-1 with CaMKⅡα (by immunofluorescent double staining). Results:Compared with SC group, the mechanical paw withdrawal threshold was significantly increased at 5 days after the end of tamoxifen administration, the expression of Caprin-1 and CaMKⅡα protein and mRNA was down-regulated ( P<0.05), and the co-localization expression of Caprin-1 and CaMKⅡα in the spinal dorsal horn was down-regulated in KO group. Conclusions:Caprin-1 is involved in the development of pain perception by promoting CaMKⅡα expression.

Objective:To investigate the correlation between sleep duration, sleep timing and the risk of osteoporosis in postmenopausal women, to identify contributing mechanisms and guide the prevention and treatment of osteoporosis.Methods:A total of 5 449 postmenopausal women were included in this study. All participants completed questionnaires, medical examinations, blood test and the measurement of bone mineral density using calcaneal quantitative ultrasonography. After adjusting for potential confounders, logistic regression model was used to assess the association of sleep duration, sleep timing with the risk of osteoporosis. Results:In postmenopausal women, there were significant differences in sleep duration and timing among groups with different risk of osteoporosis( P<0.05). After controlling ages, BMI, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption and physical activity, sleep duration was correlated with the risk of osteoporosis, long sleep duration(≥9 h)increased the risk of osteoporosis( OR=1.39, 95% CI 1.17-1.65, P<0.05)compared with the group with sleep duration of 7~8 hours. In analysis of the combined effect of sleep duration and sleep time on the risk of osteoporosis, compared with normal sleep duration(7-8 h)and normal sleep timing(22: 00-23: 00), long sleep duration(≥9 h)and normal sleep timing(22: 00-23: 00)increased the risk of osteoporosis( OR=1.38, 95% CI 1.01-1.87, P<0.05), which was higher in the group of long sleep duration(≥9 h)and late sleep timing(≥23: 00; OR=1.43, 95% CI 1.01-2.01, P<0.05). Conclusion:Long sleep duration(≥9 h)and late sleep timing(≥22: 00)are risk factors for the increased risk of osteoporosis in postmenopausal women, the late sleep timing leads to the higher risk.

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

Objective To establish the HPLC fingerprints of petroleum ether parts from five traditional medicine (Alpinia officinarum Hance, Alpinia galangal ( L.) Wild, Alpinia galanga Will., Alpinia katsumadai Hayata, and Alpinia oxyphylla Miq), and to explore the similarities and differences of chemical composition,as well as the correlation between the genetic relationship and the chemical composition. Methods HPLC method was used to analysis the five traditional medicines. The data were evaluated by using the"similarity evaluation system for chromatographic fingerprint of TCM" software. Results The similarity chemical composition from Alpinia officinarum Hance,Alpinia galangal(L.) Wild,Alpinia galanga Will.,Alpinia katsumadai Hayata,and Alpinia oxyphylla Miq in ethyl acetate were 0.741,0.855,0.610,0.510, 0.680,respectively. Conclusion Though there were differences of fingerprint peak of petroleum ether parts between five the traditional Chinese medicines, similarities were also observed among them.