ObjectiveTo study the effect of Wulingsan on cerebral edema after intracerebral hemorrhage （ICH） in mice and explore the treatment mechanism. MethodsThe mouse model of ICH was established by injection of collagenase into the caudate nucleus. Mice were randomly assigned into the following groups： sham， ICH， intervention before modeling with low-dose and high-dose （3.69， 11.07 g·kg^-1， respectively） Wulingsan， and intervention after modeling with high-dose Wulingsan. The modified neurological severity score （mNSS） was recorded， and the small animal MRI T2 sequential scanning was performed to measure the volume of cerebral hemorrhage after the modeling of ICH in each group. The Y-maze test， open field test， and Morris water maze test were conducted to evaluate the neurological behaviors of mice in each group. Hematoxylin-eosin staining was employed to observe the pathological changes in the brain tissue. Immunohistochemistry was employed to observe the expression of aquaporin 4 （AQP4）， neuronal nuclei （NeuN）， and glial fibrillary acidic protein （GFAP） in the brain tissue. Western blot was employed to determine the protein levels of AQP4， Claudin-5， and zonula occludens-1 （ZO-1） in the hematoma area. ResultsCompared with the sham group， the ICH group showed increases in the mNSS， the cerebral hemorrhage volume， and the escape latency in the Morris water maze test （P<0.01）， decreases in the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， and reductions in the spontaneous alternation rate in the Y-maze test and the ratio of distance of center travel to total travel distance in the open field test （P<0.01）. Moreover， pathological changes such as cell disarrangement， cell space enlargement， and cell swelling were observed in the ICH group. Immunohistochemistry results showed that the ICH group had higher proportions of AQP4- and GFAP-positive cells and lower proportion of NeuN-positive cells than the sham group （P<0.01）. Compared with the sham group， the ICH group showed an up-regulated protein level of AQP4 and down-regulated protein levels of Claudin-5 and ZO-1 （P<0.01）. Compared with the ICH group， the intervention with Wulingsan decreased the mNSS， the volume of cerebral hemorrhage， and the escape latency in the Morris water maze test （P<0.05， P<0.01）， while increasing the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， the spontaneous alternation rate in the Y-maze test， and the ratio of distance of center travel to total travel distance in the open field test （P<0.05， P<0.01）. Furthermore， the intervention with Wulingsan alleviated the pathological changes in the brain tissue after ICH， decreased the proportion of AQP4- and GFAP-positive cells （P<0.01）， increased the proportion of NeuN-positive cells （P<0.01）， down-regulated the protein level of AQP4 （P<0.01）， and up-regulated the protein levels of Claudin-5 and ZO-1 （P<0.01）. ConclusionThe intervention with Wulingsan could reduce the neural function score and the cerebral hemorrhage volume， up-regulate the expression of Claudin-5 and ZO-1， and down-regulate the expression of AQP4 to ameliorate the neurological function defect and cerebral edema after ICH， thereby protecting the brain.

Objective:To investigate the role and mechanism of astrocyte (AS) derived exosomes in protecting brain microvascular endothelial cells (bEnd. 3) from cerebral ischemia reperfusion injury by establishing an oxygen-glucose deprivation/re-oxygenation (OGD/R) model in vitro. Methods:(1) Dual-luciferase reporter gene assay was used to confirm the regulating effect of miR-193b-3p on transient receptor potential cation channel, subfamily M, member 2 (TRPM2). OGD/R model was established by OGD 8 h followed by reoxygenation 24 h in bEnd. 3 cells after being transfected miR-193b-3p mimics/negative sequence (OGD/R+miR-193b-3p mimics group or OGD/R+miR-193b-3p negative sequence group); real-time quantitative PCR (RT-qPCR) was used to detect the miR-193b-3p expression, Western blotting (WB) was used to detect the expressions of TRPM2, cleaved caspase-3, Bax, Bcl-2, ZO-1 and Claudin-5, and flow cytometry was used to detect the apoptosis. (2) AS was extracted from the cerebral cortex of C57BL/6 suckling mice and identified; modeling time was determined by CCK-8 and AS-derived exosomes were extracted by ultracentrifugation from cell supernatant and identified by electron microscopy, particle size analysis, and WB for marker proteins. RT-qPCR was used to detect the miR-193b-3p expression in AS and AS-derived exosomes. Low-expressed miR-193b-3p exosomes were extracted from AS after being transfected miR-193b-3p inhibitory sequence and co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived inhibitory sequence exosomes); exosomes were extracted from AS transfecting with miR-193b-3p negative sequence, and co-incubated with OGD/R bEnd.3 cells (group of OGD/R+AS-derived negative sequence exosomes); and normal exosomes were co-incubated with OGD/R bEnd. 3 cells (group of OGD/R+AS-derived exosomes). The miR-193b-3p expression in these 3 groups was detected by RT-qPCR, expressions of TRPM2, cleaved-caspase-3, Bax, Bcl-2, ZO-1, and Claudin-5 were detected by WB, cell apoptosis was detected by flow cytometry, and cell migration ability was detected by scratch test.Results:(1) Dual-luciferase reporter gene assay showed that miR-193b-3p could bind to TRPM2 mRNA. The miR-193b-3p can improve the TRPM2-mediated apoptosis and tight junction reduction in bEnd.3 cells during OGD/R: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased TRPM2, cleaved-caspase-3, and Bax protein expressions, and statistically increased Bcl-2, ZO-1 and Claudin-5 protein expressions ( P<0.05). Flow cytometry further verified the above results: compared with OGD/R group, OGD/R+miR-193b-3p mimics group had significantly decreased cell apoptosis rate (21.34% vs. 13.93%, P<0.05). (2) The extracted exosomes exhibited lipid bilayer cup-like structure with particle size of 126.5 nm (exosome marker proteins: negative Cal and positive CD81 and SG101), indicating successful exosome extraction. After modeling, miR-193b-3p expression in AS and AS-derived exosomes was significantly decreased compared with that in the Control goup ( P<0.05). Compared with the OGD/R group, the group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased miR-193b-3p expression, statistically decreased TRPM2, cleaved-caspase-3 and Bax protein expressions, and significantly increased ZO-1, Claudin-5 and Bcl-2 expressions ( P<0.05); while compared with those in the OGD/R group, no significant changes in the above protein expressions in group of OGD/R+AS-derived inhibitory sequence exosomes were noted ( P>0.05). Compared with the OGD/R group (18.22%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly decreased apoptosis rate (14.09% and 13.79%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (18.41%, P>0.05). Compared with the OGD/R group (13.55%), group of OGD/R+AS-derived exosomes and group of OGD/R+AS-derived negative sequence exosomes had significantly increased migration ability (43.01% and 40.59%, P<0.05), while group of OGD/R+AS-derived inhibitory sequence exosomes had no significant change (16.26%, P>0.05). Conclusion:AS-derived exosomes can suppress TRPM2 protein expression in brain microvascular endothelial cells distantly by miR-193b-3p to improve the brain microvascular endothelial cell injury caused by OGD/R, and then improve OGD/R injury.

Objective:To analyze whether patients with myasthenia gravis (MG) have cognitive impairment and changes of brain structure, and explore the possible mechanisms of cognitive impairment in MG patients from the perspective of brain structure.Methods:Twenty-eight patients with MG admitted to Department of Neurology, First Affiliated Hospital of Soochow University from July 2019 to December 2021 were selected as MG group, and 30 family members from MG patients or healthy subjects who underwent physical examination in Physical Examination Center during the same period were selected as healthy control group. Neuropsychological test was used to evaluate the cognitive function. VBM was used to analyze the changes of brain structure on structural MRI (sMRI). Correlations of gray matter volumes of different brain regions with cognitive function between the two groups were analyzed.Results:Compared with the healthy control group, the MG group had significantly decreased scores of Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clock Painting Test (CDT), and Verbal Fluency Test (VFT), and significantly decreased Rey Auditory Verbal Learning Test (RAVLT) immediate memory and delayed memory scores, while statistically increased time consuming in Making Track Test Part A (TMT-A), and Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) scores ( P<0.05). Compared with healthy control group, MG group had significantly decreased gray matter volumes of the left orbital superior frontal gyrus, right orbital middle frontal gyrus, right triangular inferior frontal gyrus, left insula, left middle frontal gyrus, right superior limbic gyrus, right anterior cingulate gyrus, right lateral cingulate gyrus, left medial cingulate gyrus, left lateral cingulate gyrus, left medial superior frontal gyrus, and left dorsalateral superior frontal gyrus ( P<0.05). Correlation analysis showed that gray matter volume in the left insula was negatively correlated with time consuming in Stroop Color-Word Test-A ( r=-0.407, P=0.035). Conclusion:Patients with MG may have cognitive decline and gray matter cortical atrophy of some brain regions, and brain areas with gray matter cortical atrophy correspond to areas of cognitive impairment.

Objective: To analyze the association between the occurrence of menarche and the exposure to artificial light at night (ALAN) in female Han nationality girls aged 9-18 in China, so as to provide a reference for the research on the disturbance mechanism of ALAN on puberty, as well as provide a scientific evidence for controlling ALAN and making public sanitary policy. Methods: A total of 74 483 Han girls aged 9-18 with complete records of menarche, height, and weight were included in the 2014 Chinese National Surveys on Students Constitution and Health. Pearson correlation was used to explore the correlation between the incidence of menarche and the exposure to artificial light at night in 11-year-old Han girls, and the third quantiles of the area covered by outdoor night lights (0.16, 0.60) and the third quantiles of the average night light intensity [0.97, 5.91 nw/(sr ·cm) 2] were used respectively to divide the study subjects into 3 groups, and the multifactor Logistic regression model was used to analyze the effect of artificial light at night exposure on menarche. Results: In 2014, the median age of menarche of Chinese Han girls was 12.18 years old, and the incidence of menarche in the 11-year-old group was 26.31%. After controlling for body mass index, local population and the logarithmic values of per capita GDP, the incidence of menarche of 11-year-old Han girls was positively correlated with the local outdoor average night light coverage area ratio and the night average light intensity logarithmic adjustment value( r =0.29, 0.30, P <0.05).The higher the local outdoor night light coverage area ratio ( OR =1.28, 1.52) and the average night light intensity ( OR =1.47, 1.58), the higher the incidence of menarche in 11-year-old Han girls( P <0.05). Conclusion There is a positive correlation between artificial light at night exposure and the menarche rate of 11-year-old Han girls. Research on artificial light at night exposure may provide scientific evidence on puberty onset and its effects on population health.

Objective:To evaluate the effect of goal-directed fluid therapy (GDFT) based on permissive high stroke volume variation (SVV) guidance on residual liver function in elderly patients undergoing laparoscopic hepatectomy.Methods:A total of 100 elderly patients of either sex, aged 65-80 yr, with body mass index of 18.5-24.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with Child-Pugh grade A or B, scheduled for elective laparoscopic hepatectomy, were divided into 2 groups ( n=50 each) by the random number table method: SVV-guided GDFT group (group SG) and CVP-guided fluid replacement group (group C). Intraoperative fluid management was divided into 2 stages.The first stage was from the start of surgery to the completion of liver resection, the SVV was maintained at 13%-20% in group SG, and the low CVP was maintained at 0-5 cmH 2O in group C. The second stage was from completion of liver resection to the end of the operation, SVV was maintained at 9%-13%, additional hydroxyethyl starch 3 ml/kg was given or repeatedly administered when SVV>13% (for 5 min) or when the response to previous fluid replacement was positive (SVV increased by more than 10%), and the infusion rate was slowed down when the SVV was 9%-13% in group SG, and CVP was maintained at 5-12 cmH 2O in group C. Mean arterial pressure and heart rate were recorded on admission to the operating room, at skin incision (T 1), at the start of liver resection (T 2), at completion of liver resection (T 3) and at the end of operation (T 4). The operation time, intraoperative blood loss, transfusion volume, urine volume and levels of serum lactic acid before operation and at the end of operation were recorded.Blood samples from the median cubital vein were collected at T 0-4 to measure blood glucose and cortisol concentrations.The concentrations of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and albumin were measured before operation, at 1, 3 and 5 days after operation, and prothrombin time, activated partial thromboplastin time, thrombin time and Fib were recorded.The concentrations of serum interleukin-6, tumor necrosis factor-alpha and C-reactive protein were measured by enzyme-linked immunosorbent assay before operation and at the end of operation, and the postoperative complications and length of hospital stay were recorded. Results:Compared with group C, mean arterial pressure and heart rate were significantly decreased at T 2, 3, blood loss was reduced, transfusion volume and urine volume were increased, prothrombin time and activated partial thromboplastin time were shortened at the end of operation, serum concentrations of interleukin-6 and lactic acid and concentrations of aspartate aminotransferase and alanine aminotransferase in serum at 5 days after operation were decreased, and the length of hospital stay was shortened in group SG ( P<0.05). Conclusions:GDFT based on permissive high SVV guidance can improve residual liver function in elderly patients undergoing laparoscopic hepatectomy.

Objective:To analyze the application effect of discharge planning based on enhanced recovery after surgery (ERAS) in patients with osteoporotic thoracolumbar fracture (OTLF).Methods:A retrospective cohort analysis was made on clinical information of 230 OTLF patients treated in Honghui Hospital of Xi′an Jiaotong University from January to December 2020, including 44 males and 186 females, aged 53-92 years [(72.0±9.9)years]. A total of 115 patients receiving conventional nursing intervention from January to June 2020 were enrolled in regular nursing group and 115 patients receiving discharge planning intervention based on ERAS from July to December 2020 were enrolled in discharge planning group. The length of hospital stay, readiness for hospital discharge scale (RHDS) at 4 hours before discharge, caregiver preparedness scale (CPS) on admission and at 4 hours before discharge, discharge rate before 12∶00, Chinese osteoporosis quality of life short questionnaire (COQOL) on admission and at 6 months after surgery, and re-fracture rate were compared in the two groups.Results:The patients were followed up for 6 months, except for 3 patients lost to follow up in discharge planning group and 4 patients in regular nursing group. The length of hospital stay was (2.8±0.6)days in discharge planning group and (2.6±0.7)days in regular nursing group ( P>0.05). The RHDS in discharge planning group was significantly greater at 4 hours before discharge when compared with regular nursing group [(103.0±8.3)points vs. (95.3±9.5)points] ( P<0.01). The two groups had no significant difference in CPS at admittance ( P>0.05), but a significantly greater CPS was found in discharge planning group at 4 hours before discharge when compared with regular nursing group [(28.9±3.5)points vs. (24.3±4.8)points] ( P<0.01). The discharge rate before 12∶00 in discharge planning group was significantly higher when compared with regular nursing group [27.7%(31/115) vs. 15.3%(17/115)] ( P<0.05). The COQOL was similar at admittance between the two groups ( P>0.05), but a significantly lower score was found in discharge planning group than that in regular nursing group [(21.6±6.2)points vs. (26.6±6.9)points] ( P<0.01). A significantly lower re-fracture rate was found in discharge planning group at 6 months after surgery when compared with regular nursing group [4.5%(5/112) vs. 12.6%(14/111)] ( P<0.05). Conclusion:For OTLF patients, discharge planning based on ERAS is superior to regular nursing in improving the readiness for hospital discharge, caregiver preparedness, quality of life and management of beds, and lowering re-fracture rate.

Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.

Objective:To investigate the correlation between gamma-glutamyl transferase/high-density lipoprotein cholesterol ratio (GHR), neutrophil/lymphocyte ratio (NLR) and coronary heart disease (CHD), and evaluated its pathogenic risk and predictive value for CHD.Methods:A total of 694 patients admitted to our hospital from December 2017 to December 2018 for suspected CHD and coronary angiography were selected. According to the results of coronary angiography,the patients were divided into CHD group ( n=527) and non-CHD group ( n=167). The clinical data of all patients were recorded. Gamma-glutamyl transferase (GGT), high-density lipoprotein cholesterol (HDL-C) and other biochemical indicators were recorded. Neutrophils, lymphocyte count and other hematological indicators were recorded. GHR, NLR and Gensini scores of the patients were calculated. Clinical data and GHR, NLR and other indicators were compared between the two groups. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of GHR, NLR in CHD, and to determine the optimal cut-off value; Logstic regression analysis was used to investigate the risk factors of CHD.Spearman correlation analysis was used to analyze the correlation between serum OPN, OPG and Gensini score in patients with CHD. Results:The GHR and NLR were 32.59(21.05, 48.24) and 3.53(2.18, 8.46) significantly higher in the CHD group than in the non-CHD group 16.56(10.07, 25.21) and 2.20(1.45, 3.28) respectively, with statistically significant differences ( Z=11.094, 9.055, P<0.05). ROC curve analysis showed that the AUC of NLR and MLR in diagnosing CHD was 0.785 and 0.732( P<0.05). When the critical values of GHR and NLR respectively were 19.805 and 2.678, respectively, the diagnostic efficiency of CHD was the highest, and the sensitivity and specificity were 79.30%, 62.90% and 63.80%, 68.30%, and the AUC of GGT in diagnosing CHD was 0.628. When the critical value was 19.500, the sensitivity and specificity were 80.50% and 39.50%, respectively,the AUC of GHR was greater than that of GGT ( Z=12.973, P<0.05). Multivariate Logistic regression analysis showed that Smoking ( OR=2.887, 95% CI:1.850-4.505, P<0.05), hypertension ( OR=2.009, 95% CI: 1.311-3.080, P<0.05), fasting plasma glucose ( OR=1.109, 95% CI:1.034-1.189, P<0.05), age ≥60 years ( OR=1.567, 95% CI:1.179-2.415, P<0.05), NLR ≥2.687 ( OR=3.152, 95% CI:2.066-4.808, P<0.05) and GHR ≥19.805 ( OR=4.768, 95% CI:3.131-7.262, P<0.05) was an independent risk factor for CHD. After gradually adjustment for risk factors such as smoking, hypertensive, fasting plasma glucose, age ≥60 years and NLR ≥2.687, GHR ≥19.805 was still an independent risk factor for coronary heart disease(OR and 95% CI were 4.620 (3.049-7.000), 4.768 (3.131-7.262), 6.567 (4.408-9.810), 4.768 (3.131-7.262), 4.768 (3.131-7.262), respectively; all P<0.001). Spearman correlation analysis showed that GHR and NLR were positively correlated with Gensini score ( r=0.312, 0.394; all P<0.05). Conclusion:GHR and NLR were positively correlated with the severity of coronary artery disease, which is of significance in the diagnosis of coronary heart disease. NLR ≥2.687 and GHR ≥19.805 were independent risk factors for CHD. GHR was superior to GGT and HDL-C alone in the diagnosis of CHD,and has certain clinical application value

Objective:To investigate the feasibility and safety of endovascular repair for traumatic thoracic aortic pseudoaneurysm.Methods:From Oct 2015 to Oct 2018, the clinical and followup data of 7 patients diagnosed as traumatic thoracic aortic pseudoaneurysm in Fuwai Hospital of Chinese Academy of Medical Sciences were analyzed retrospectively.Results:The patients average age was (51.2±11.0) years old. All patients underwent surgery in the hybrid operating room under general anesthesia. Two did thoracic endovascular aortic repair (TEVAR), three did TEVAR combined with chimney technique to reconstruct the left subclavian artery, and 1 had TEVAR combined with fenestration to reconstruct the left subclavian artery. One did TEVAR with left common carotid artery and left subclavian artery bypass. The mean operative time was (90.1±27.4) min, the mean postoperative hospital stay was (8.9±3.7) d, and the mean postoperative follow-up time was 42.4 months. All the patients received CTA reexamination of the aorta after 1, 6, 12 months and yearly thereafter. TypeⅠendoleak was found in one patient with chimney technique to reconstruct of left subclavian artery after operation. CT showed that the type Ⅰ endoleak disappeared 6 months after operation. There was no death, paraplegia or stroke during the perioperative period and follow-up period, and there was no aortic related reintervention.Conclusion:TEVAR is a safe and effective method for the treatment of traumatic pseudoaneurysm of thoracic aorta, and the early and mid-term results were satisfactory.

Objective:To evaluate the safety and feasibility of the in-situ needle fenestration combined with the in vitro physician modified fenestration technique to reconstruct supra-aortic branches during thoracic endovascular aortic repair (TEVAR) for aortic arch lesions requiring landing at Z0 and Z1.Methods:From Nov 2017 to Dec 2019, eighteen patients who underwent both the in-situ needle fenestration and the in vitro physician modified fenestration techniques to extend the proximal landing zone to Z0 and Z1 during TEVAR were included in our study.Results:Sixteen patients underwent in vitro physician modified fenestration ,two patients underwent in vitro physician modified fenestration to reconstruct both the left common carotid artery and the innominate artery. All eighteen patients received in-situ needle fenestration to preserve the left subclavian artery. Supra aortic branches were preserved in all patients (38/38, 100%). There was no Type Ⅰ endoleak. Type Ⅱ endoleak was found in four paitnets (4/18). Type Ⅲ endoleak occurred in one patient (1/18). Type Ⅳ endoleak in four patients (4/18). Type Ⅲ endoleak needed open aortic arch repair 6 months later. The median follow-up time was 12 months. One (1/18) died in 12 months and the other patients were doing well.Conclusions:The joint application of the in-situ needle fenestration and the in vitro physician modified fenestration to reconstruct supra-aortic branches during TEVAR for aortic arch pathologies requiring landing at Z0 and Z1 was satisfactory.