Objective To Identify alternative indicators related to the risk of osteoporosis fractures in postmenopausal women through metabolomics and attempting to determine the predictive value of candidate metabolites.Methods From December 2018 to August 2021,158 postmenopausal women with non-traumatic hip fracture(fracture group)were enrolled in our hospital,and 197 postmenopausal women without fracture(non-fracture group)were enrolled.Quantitative analysis of serum metabolites was performed using AbsoluteIDQTM p180 kit and targeted metabolomics approach.Univariate and Multivariate Logistic regression were used to analyze the influencing factors of osteoporotic fracture in postmenopausal women,and Spearman and Pearson analysis were used to analyze their correlation.Results Compared with the non-fracture group,Only serum arginine[(105.2±22.4)μmol/L vs.(96.3±23.5)μmol/L],leucine[(180.9±50.0)μmol/L vs.(156.7±39.5)μmol/L)and spermine[(1.03± 0.67)μmol/L vs.(0.51±0.12)μmol/L]were significantly increased in the fracture group(P＜0.05).Logistic regression analysis showed that only serum spermidine concentration was significantly associated with hip fracture risk after adjustment for age,BMI,complications,and smoking status(HR=1.35,95％CI=1.03 to 1.65,P=0.020).According the receiver operating characteristic,serum spermidine level predicted hip fracture in postmenopausal women with an area under the curve of 0.882(95％CI:0.847 to 0.916).Spearman analysis showed that T value of hip was negatively correlated with serum spermidine level(r=-0.192,P＜0.001).The levels of serum spermine and putrescine in patients of low spermine level group were increased than those in high spermine level group.Pearson correlation analysis showed that serum spermidine level was negatively correlated with spermidine(r=-0.237,P＜0.001)and putrescine(r=-0.189,P=0.004)in fracture group.Univariate and multivariate Logistic regression analysis showed that serum spermidine ≥0.58 μmol/L was an independent risk factor for an increased risk of fragility hip fracture in postmenopausal women(P＜0.001).Conclusion Elevated baseline serum spermidine level are associated with increased risk of hip fracture in postmenopausal women and may be useful in predicting fragility fracture in postmenopausal women.

Objective:To investigate the activation of ubiquitin proteasome system (UPS) and autophagy in brain tissues of rats after severe traumatic brain injury (sTBI) and the role of autophagy in secondary traumatic brain injury.Methods:(1) Twenty-five SD rats were randomly divided into sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI ( n=5). Only bone window was opened in sham-operated group, and controlled cortical impact (CCI)-induced sTBI models were established in the other 4 groups. Western blotting was used to detect the expressions of free ubiquitin, ubiquitinated protein, vacuolar protein sorting 34 (VPS34), P62, microtubule-associated protein-light chain 3-II, and Mature-cathepsin D (CTSD). (2) One hundred SD rats were randomly divided into normal control group, sTBI group, lactacystin group and SAR405 group ( n=25). Ten μL lactacystin or SAR405 were stereotactically injected into the lateral ventricle of lactacystin group and SAR405 group, respectively; 30 min after that, CCI-induced sTBI models were established in the sTBI group, lactacystin group and SAR405 group. Three d after modeling, the expressions of ubiquitinated protein, LC3-II, P62, and Caspase-3 were detected by Western blotting; percentage of brain water content was determined by dry/wet weight ratio; neurological functions were assessed by modified neurological deficit scale (mNSS); degrees of brain tissue damage were detected by HE staining; and cerebral blood perfusion was detected by laser scattering hemodynamic imaging system. Results:(1) Compared with sham-operated group, group of 3 h after sTBI, group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly decreased free ubiquitin, and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased ubiquitinated protein in the brain tissues surrounding the injury lesions ( P<0.05). Compared with sham-operated group, group of 3 d after sTBI and group of 7 d after sTBI had statistically increased VPS34 and Mature-CTSD and significantly decreased P62 and group of 1 d after sTBI, group of 3 d after sTBI and group of 7 d after sTBI had significantly increased LC3-II in the brain tissues surrounding the injury lesions ( P<0.05). (2) The ubiquitinated protein relative expressions in the brain tissues surrounding the injury lesions of normal control group, sTBI group, lactacystin group and SAR405 group were 4.78±2.63, 10.62±0.73, 13.45±1.22 and 8.50±0.83, respectively, with significant differences ( P<0.05). Compared with the normal control group, the sTBI group, lactacystin group and SAR405 group had significantly higher LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the lactacystin group had significantly higher LC3-II, ubiquitinated protein, and cleaved caspase-3/pro-caspase-3, and significantly lower P62 in the brain tissues surrounding the injury lesions ( P<0.05); compared with the the sTBI group, the SAR405 group had significantly lower LC3-II, ubiquitinated protein and cleaved caspase-3/pro-caspase-3, and significantly higher P62 in the brain tissues surrounding the injury lesions ( P<0.05). Compared with the normal control group([67.60±2.51]%、[0±0] scores、[333.41±46.86] PU), the sTBI group, lactacystin group and SAR405 group had statistically higher percentage of brain water content and mNSS scores ([80.2±1.30]%, [87.0±1.58]% and [71.60±1.81]%; 13.8±1.10, 16.4±0.55 and 10.40±1.14) and signficantly lower cerebral blood perfusion volume ([53.98±5.99] PU, [21.71±2.62] PU and [87.97±6.75] PU, P<0.05); compared with the sTBI group, the lactacystin group had significantly higher brain water content and mNSS scores, and significantly lower cerebral blood perfusion volume ( P<0.05); compared with the sTBI group, the SAR405 group had significantly lower brain water content and mNSS scores, and significantly higher cerebral blood perfusion volume ( P<0.05). HE staining showed that the cortical tissues were most severely damaged in the lactacystin group, followed by the sTBI group; the least damage was noted in the SAR405 group, and no significant damage in the normal control group was noted. Conclusion:After sTBI, UPS activation is earlier than autophagy; autophagy inhibition helps to alleviate UPS dysfunction, reduce Caspase-3-induced apoptosis, and is beneficial to the recovery of neurological function.

Neutrophil extracellular traps (NETs) are compounds composed of depolymerized DNA fibers and antimicrobial peptides released by neutrophils. NETs formation not only plays a role in pathological process of non-infectious diseases such as cystic fibrosis, systemic lupus erythematosus, diabetes and cancer, but also is closely related to many central nervous system diseases. In recent years, a large number of studies have found the presence of neutrophils and NETs in perivascular space of the infarcted lesions in patients with ischemic stroke (IS) and corresponding animal models. This article provides a review on NETs formation and clearance process, characteristics of NETs changes after IS, pathological processes involved in NETs after IS, and effects of NETs on neurons, to provide some references for IS.

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, β-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.
Abdominal Pain/complications* ; Adult ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Anticoagulants ; Arrhythmias, Cardiac/complications* ; China/epidemiology* ; Diuretics ; Dizziness/complications* ; Dyskinesias/complications* ; Electrocardiography ; Europe/epidemiology* ; Female ; Humans ; Hypotension/complications* ; Middle Aged ; Platelet Aggregation Inhibitors ; Stroke Volume ; Takotsubo Cardiomyopathy/etiology* ; Ventricular Function, Left

OBJECTIVE：To investigate the effects of rabepr azole on the pharmacokinetic characteristics of clopidogrel and its active metabolite in healthy volunteers with different CYP2C19 genotypes. METHODS ：Healthy volunteers were selected as subjects，and then randomly divided into extensive metabolizer （EM）group，intermediate metabolizer （IM）group，and poor metabolizer（PM）group with 8 subjects in each group ，according to their CYP2C19 genotypes by random number table. In single-dose，randomized，open，two-cycle-crossover design ，each group was given Clopidogrel bisulfate tablets 300 mg or Clopidogrel bisulfate tablets 300 mg+Rabeprazole sodium enteric-coated tablets 20 mg. UPLC-MS/MS method was adopted to detect the concentration of clopidogrel and its active metabolite derivative （MP-H4）. The pharmacokinetic parameters were calculated and compared by DAS 2.0 software. RESULTS ：There was no statistical significance in clinical data as age ，height， body weight ，liver enzymes and serum creatinine among 3 kinds of metabolism subjects （P＞0.05）. Compared with subjects receiving clopidogrel alone ，cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in EM group were increased by 36％ and 27％，while those of MP-H 4 were decreased by 34％ and 28％（P＜0.01）；cmax and AUC 0－t of clopidogrel of subjects combined with rabeprazole in IM group were increased by 19％ and 18％，while those of MP-H 4 were decreased by 19％ and 16％ （P＜0.05 or P＜0.01）；there was no statistical significance in cmax and AUC 0－t of clopidogrel and MP-H 4 in PM group after receiving rabeprazole additionally as well as tmax of clopidogrel and MP-H 4 in all metablism subjects ，compared with clopidogrel alone（P＞0.05）. CONCLUSIONS ：Among CYP2C19 EM and IM subjects ，combined use of rabeprazole can significantly increase the exposure of clopidogrel and decrease the exposure of its active metabolite MP-H 4，but has no significant impact on clopidogrel and its active metabolite in CYP2C19 PM subjects.

Objective To explore the effect of scenario simulation teaching method in the training of cardiopulmonary resuscitation (CPR) for junior surgical residents. Methods 133 junior residents (working life<3 years) in the author's hospital rotating Cardiac Surgery department were selected and divided into control group (n=65) and observation group (n=68), in which the control group adopted traditional classroom teaching: teacher explanation-demonstration-student practice-teacher counseling; the observation group adopted scenario simulation teaching: teacher explanation-demonstration-student practice-teacher counseling scenario simulation. Before and after training, two groups both received the CPR theory and double operation assessment , comparing the difference of assessment scores between groups before and after training . Results There was no statistically significant difference in the demographic characteristics between the two groups. The assessment scores of CPR theory and operation were improved in both groups after training, and there were significant differences (P=0.000). There were no statistically significant differences in the CPR theory and operation assessment scores between the two groups before training (P>0.05);compared with the scores of CPR operation between the two groups after training, the observation group [(84.62±3.94)] was significantly higher than that of the control group [(79.68±5.45)] and there were significant statistical differences (P=0.000), while there was no statistically significant difference in CPR theory assessment scores between the two groups (P>0.05). Conclusions Both traditional classroom teaching and scenario simulation teaching methods could improve the CPR theory and skill level of the surgical junior resident, but situa tional simulation teaching method is better than traditional classroom teaching method in improving students' CPR performance.

The Letournel-Judet classification system for acetabular fractures is widely used, but there are still some shortcomings, such as incomplete classification and confusion of classification concepts, which cannot effectively guide the treatment. Professor Hou Zhiyong proposed and elaborated an improved acetabular fracture classification system based on the concept of three columns of acetabulum. However, the credibility and repeatability of the classification still lacked validation from clinical data. In this regard, the author included 463 patients with relatively complete imaging data admitted to Third Hospital of Hebei Medical University and Honghui Hospital affiliated to Xi'an Jiaotong University Medical College in the past five years. Four trauma orthopedists classified the patients according to the modified classification method of acetabular fracture. After two months, the original sequence of imaging data was disrupted and re-classified by the same trauma orthopedists. The consistency of the classification was evaluated by Kappa test and compared with Letournel-Judet classification. The results showed that credibility and repeatability of the modified classification were higher than Letournel-Judet classification, suggesting the feasibility of clinical application.

Objective: To investigate the changes of cardiac sympathetic nerve function and susceptibility of ventricular arrhythmia at chronic stress condition in experimental rats.
Methods: A total of 30 SD rats were randomly assigned into two groups: Control group, the rats were fed with normal condition and Chronic stress group, the rats were fed with unpredictable chronic stimulus program.n=15 in each group and all animals were treated for 4 weeks. The behavior of rats was assessed by open ifeld test and sucrose intake test, the susceptibility of ventricular arrhythmia was measured by Burst stimulus program under narcosis condition, and the sign of cardiac sympathetic nerve reconstruction, tyrosine hydroxylase content was examined by immunohistochemistry.
Results: Compared with Control group, Chronic stress group had decreased ratio of sucrose favorite/open field test, P<0.05 and increased susceptibility of ventricular arrhythmia,P<0.05. Masson staining showed that the ventricular collagen score was similar between 2 groups,P>0.05. Immunohistochemistry presented that Chronic stress group had much higher tyrosine hydroxylase content (1397.8 ± 268.8) um2/mm2 than Control group (995 ± 232.3) um2/mm2,P<0.05.
Conclusion: Chronic stress may increase the susceptibility of ventricular arrhythmia in experimental rats, and the cardiac sympathetic nerve reconstruction might be an important mechanism.

Objective To explore the change in anatomical volume during intensity?modulated radiotherapy (IMRT) for different stages of nasopharyngeal carcinoma (NPC) and its influence on dose distribution, and to assess the necessity to modify the IMRT plan. Methods Twenty?four patients with newly diagnosed NPC who received IMRT and chemotherapy were enrolled in the study, and were divided into early?intermediate group ( 12 cases ) and locally advanced group ( 12 cases ) according to the 2008 staging system for NPC. Each patient had a repeated CT scan at week 5 of radiotherapy, and target volume and organs at risk ( OAR) were contoured. The dose distribution of the original plan shown on CT was calculated. Changes in target volume, OAR anatomical volume, and dose distribution were analyzed, and paired t?test and Spearman correlation analysis were performed. Results In the early?intermediate group, gross target volume of neck positive lymph nodes (GTVnd) was reduced during radiotherapy (P=0. 059), and gross target volume of nasopharynx ( GTVnx ) , high?risk clinical target volume ( CTV1 ) , and parotid volume were reduced significantly during radiotherapy ( P= 0. 001, 0. 012, 0. 002, and 0. 000, respectively) . In locally advanced group, GTVnx , GTVnd , CTV1 , and parotid volume were significantly reduced during IMRT (P=0. 000, 0. 000, 0. 003, 0. 003, and 0. 000, respectively). Compared with the values before radiotherapy, the parotid dose increased significantly in the two groups during IMRT ( P=0. 044, 0. 026, 0. 033, and 0. 026, respectively;P=0. 024, 0. 016, 0. 030, and 0. 015, respectively) , and the increase in GTVnd dose was observed in the locally advanced group ( P= 0. 029 and 0. 049 ) . Conclusions It is recommended to perform another CT scan for patients with locally advanced NPC at week 5 of radiotherapy and formulate a new IMRT plan to maintain target volume dose and guarantee a safe parotid dose.

Objective To investigate the prognostic value of maximum diameter in axial plane of primary tumor (MDAPPT) on MRI in nasopharyngeal carcinoma (NPC).Methods From 2005 to 2007,333 patients with newly diagnosed and biopsy-proven NPC without distant metastasis,who underwent MRI scans of the nasopharynx and neck,were included in our study.MDAPPT was measured on MRI.The univariate analysis with the log-rank test and multivariate analysis with the Cox proportional hazards model were used to analyze the relationship between MDAPPT and prognosis.Results The median values of MDAPPT in patients with T1,T2,T3,and T4 NPC were 21.2,30.0,38.0,and 52.3 mm,respectively.For all patients with a MDAPPT of ≤30 mm,＞ 30-50 mm,and ＞ 50 mm,the 5-year overall survival (OS) rates were 81.3％,70.1％,and 51.5％,respectively (P =0.000) ; the 5-year progression-free survival (PFS) rates were 81.3％,70.0％,and 48.9％,respectively (P =0.000) ;the 5-year distant metastasisfree survival (DMFS) rates were 85.5 ％,86.5 ％,and 67.2 ％,respectively (P =0.000) ; the 5-year local relapse-free survival (LRFS) rates were 97.7％,91.5％,and 83.3％,respectively (P =0.013).The multivariate analysis showed that MDAPPT was a prognostic factor for PFS and DMFS.For the T3-T4 patients with a MDAPPT of ≤50 mm and ＞50 mm,the 5-year OS rates were 69.4％ and 52.2％ (P =0.004),the 5-year PFS rates were 68.0％ and 49.6％ (P =0.001),and the 5-year DMFS rates were 84.0％ and 66.8％ (P=0.001).In the patients with a MDAPPT ≤30 mm,the 5-year LRFS rates for those with T1,T2,T3,and T4 NPC were 10 0 ％,9 5.8 ％,9 6.3 ％,and 10 0 ％,respectively (P =0.6 4 3).Conclusions MDAPPT is a prognostic factor for PFS and DMFS in NPC,and it is an important prognostic factor in patients with T3-T4 NPC.In the NPC patients with a small MDAPPT,local control rate varies little in different T stages.