[Safety and efficacy of the early administration of levosimendan in patients with acute non-ST-segment elevation myocardial infarction and elevated NT-proBNP levels: An Early Management Strategy of Acute Heart Failure (EMS-AHF)].

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.

[Establishment of morphological reference values for the differential count of white blood cells in peripheral blood smear, as well as nucleated cells and megakaryocytes in bone marrow smear].

Objective: To establish the morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear. Methods: From April 2012 to June 2020, 4 221 healthy donors for hematopoietic stem cell transplantation in Hebei Yanda Lu Daopei Hospital were selected. The median age was 36 (3-72) years old, including 2 520 males and 1 701 females. They were divided into four groups according to age: children group, with age≤14 years old [n=334, 11 (3-14) years old], youth group, with age >14 years old and <45 years old [n=2 855, 33 (15-44) years old], middle-aged adult group, with age ≥45 years old and < 60 years old [n=929, 49 (45-59) years old], and older adult group, with age ≥60 years old [n=103, 62 (60-72) years old]. Gender subgroups were established in each age group. According to different hematopoietic characteristics, the children group were divided into two subgroups: children group 1 [n=48, 6 (3-7) years old] and children group 2 [n=286, 11 (8-14) years old]. According to the clinical routine, 100 white blood cells in peripheral blood, 200 nucleated cells in bone marrow, and cell numbers/4.5 cm2 for megakaryocytes were classified and counted. The results of cell count in different age and gender groups were compared, and the reference values of morphological classification were established for different groups with statistical or clinical significance. Results: Due to the existence of statistically significant differences between children and adult groups and different gender subgroups in adults (all P<0.05), the reference values were established for children group and adult gender subgroups. The counts of segmented neutrophils and lymphocytes in peripheral blood were 46.65(43.97-49.32)% and 44.00(10.60-65.10)% in children group 1, 50.73(49.50-51.96)% and 39.55 (38.36-40.74)% in children group 2, and 57.00 (39.00-75.23) % and 33.00 (17.00-52.00) % in adult group, respectively. Bone marrow segmented neutrophils, orthochromatic erythroblasts, and mature lymphocytes were 11.54 (10.68-12.41)%, 14.20 (13.19-15.21)%, and 23.99 (22.06-25.92)% in children group 1, 12.50 (7.00-21.50)%, 15.00(9.50-25.50)%, and 21.02 (20.24-21.81)% in children group 2, 13.50 (7.50-21.00)%, 16.50 (10.50-26.00)%, and 15.50 (7.50-26.00)% in adult male group, and 14.50 (8.00-24.50)%, 14.50 (9.00-23.00)%, and 17.50 (8.50-29.00)% in adult female group, respectively. The myelopoiesis/erythropoiesis ratio in children group, adult male group and adult female group was 1.86∶1 (1.14∶1-3.23∶1), 1.96∶1 (1.12∶1-3.19∶1), 2.22∶1 (1.30∶1-3.69∶1), respectively. The numbers of granular megakaryocytes and thromocytogenic megakaryocytes were 138 (25-567) cells/4.5cm2 and 86 (13-328) cells/4.5 cm2 in children group, and 92 (13-338) cells/4.5 cm2 and 38 (3-162) cells/4.5 cm2 in adult group, respectively. Conclusion: The morphological reference values for the differential count of white blood cells in peripheral blood smear as well as nucleated cells and megakaryocytes in bone marrow smear are successfully established, which is helpful to improve the application of morphological examination in disease screening, diagnosis and monitoring.

Intrinsic Spin Susceptibility and Pseudogaplike Behavior in Infinite-Layer LaNiO_{2}.

The recent discovery of superconductivity in doped infinite-layer nickelates has stimulated intensive interest, especially for similarities and differences compared to that in cuprate superconductors. In contrast to cuprates, although earlier magnetization measurement reveals a Curie-Weiss-like behavior in undoped infinite-layer nickelates, there is no magnetic ordering observed by elastic neutron scattering down to liquid helium temperature. Until now, the nature of the magnetic ground state in undoped infinite-layer nickelates was still elusive. Here, we perform a nuclear magnetic resonance (NMR) experiment through ^{139}La nuclei to study the intrinsic spin susceptibility of infinite-layer LaNiO_{2}. First, the signature for magnetic ordering or freezing is absent in the ^{139}La NMR spectrum down to 0.24 K, which unambiguously confirms a paramagnetic ground state in LaNiO_{2}. Second, a pseudogaplike behavior instead of Curie-Weiss-like behavior is observed in both the temperature-dependent Knight shift and nuclear spin-lattice relaxation rate (1/T_{1}), which is widely observed in both underdoped cuprates and iron-based superconductors. Furthermore, the scaling behavior between the Knight shift and 1/T_{1}T has also been discussed. Finally, the present results imply a considerable exchange interaction in infinite-layer nickelates, which sets a strong constraint for the proposed theoretical models.

[Analysis of the self-conscious health status and influencing factors of greenhouse agricultural workers in Beijing suburb].

Objective: To explore the self-conscious health status and related influencing factors of greenhouse agricultural workers in Beijing suburb, so as to provide scientific basis for developing strategies to improve and promote the occupational health conditions of those workers. Methods: According to the production characteristics and scale of the main agricultural districts or counties in the suburb of Beijing, 182 agricultural production personnel were randomly selected to investigate the general situation, occupational situation and self-conscious health status during June 2018 to December 2019. The relevant factors which may affect the self-conscious health conditions were also analyzed by statistical methods. Results: The detection or reported rate of self-conscious health problems was 51.6% (94/182) , among which 29.1% (53/182) workers reported musculoskeletal disorder diseases and 21.4% (39/182) workers reported nervous system diseases. And the self-conscious health status of greenhouse agricultural workers were statistically different in household registration, gender, marital status, working years, mixing or spraying pesticides, smoking or eating in the greenhouse (P<0.05) . Moreover, gender, mixing or spraying pesticide, eating and smoking behavior in the workplace all had an impact on the risk of self-conscious health status of greenhouse agricultural workers (P< 0.05) . Specifically, male is the protective factor to reduce the occurrence of self-conscious symptoms of greenhouse agricultural workers (OR=0.447, 95%CI: 0.234~0.852) , while mixing or spraying pesticides and smoking or eating behaviors in the workplace are the risk factors (OR=1.055, 2.524; 95%CI: 0.503~2.210, 1.107~5.755) . Conclusion: Reducing pesticide use from the source thus minimize related exposure opportunities, strengthening occupational health education thus foster good hygienic habits and improve individual protection consciousness are of great significance for the health protection of greenhouse agricultural workers in Beijing suburb.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.

[Clinical analysis of 43 cases of retroperitoneal laparoscopic renal biopsy].

Objective: Percutaneous renal biopsycurrently is the most important and widely used method of renal biopsy. However, there still are some patients in whom a percutaneous approach may be considered a major risk. In these patients, renal biopsy under direct vision is a reliable alternative. We described our personal technique and experience in a series of Chinese patients who underwent retroperitoneal laparoscopic renal biopsy. Methods: We retrospectively reviewed the patients who had performed retroperitoneal laparoscopic renal biopsy over a 4-year period (Jan 2013 to Jan 2017).Forty-three patients with renal dysfunction were involved inour center.Especially some patients showed atrophic kidney and poor visualization on ultrasonography. The patients' abnormal conditions includeddialysis (10 cases), morbid obesity (5 cases), deaf-mutes (2 cases) and uncontrolled severe hypertension. The kidney was approached via alaparoscopic retroperitoneal route using athree-ports technique. Then biopsies were performed bya 16-gaugebiopsy needle, and hemostasis was achieved by compression.In less cases, a topical spray hemostatic gel was required. Results: Biopsy was performed successfully in all cases and adequate renal tissue was acquired.Mean operative time was 59.4 minutes, mean blood loss was 36.5 ml.Under general anesthesia, no anesthetic accidents and related complications were recorded. Forty-onepatients were discharged within 24 h after operation. Onepatient occurred disseminated intravascular coagulationduring operation. Red blood cell transfusion and fresh-frozen plasma infusion were performed. Injury at hilum of kidney was detected in another patient. And extrapyelogenic repair surgery was performed. Conclusions: The retroperitoneallaparoscopic renal biopsy is a safe, reliable, minimallyinvasive alternative renal biopsy method with better haemostasis, fewer complications and a rapid recovery. As the helpful supplement of percutaneous renal biopsy, this technique may have to be used more often in the future.

[Safety and efficacy of transarterial embolization combined with octreotide LAR on reducing tumor burden for neuroendocrine tumor liver metastasis].

Objective: To evaluate the tumor burden reducing efficacy and safety of transcatheter arterial embolization (TAE) combined with octreotide LAR on neuroendocrine tumor liver metastasis (NETLM). Methods: Twenty-nine NETLM patients treated in the First Affiliated Hospital of Sun Yat-sen University from October 2014 to August 2018 were retrospectively recruited, including 12 males and 17 females. The mean age was 25-69(50±11) years. All patients were histologically proved as well-differentiated NET liver metastasis. Seventeen patients underwent combined treatment of TAE plus octreotide LAR (combined group) and 12 patients treated with only octreotide LAR (control group). Response of hepatic lesions were assessed according to RECIST 1.1. Objective response rates (ORR) of two groups were compared and analyzed. Safety and tolerance to TAE were also evaluated. Results: There were 13 PR and 4 SD in combined group, but only 1 PR and 9 PD in the control group. The ORR between the two groups were significantly different (13/17 vs 1/12, P<0.01).The main complication post TAE was post embolization syndrome, including abdominal pain (12/17), vomiting (6/17), fever (4/17), elevated transaminase (8/17) and bilirubinemia (3/17). Tumor lysis syndrome was observed in one patient. Conclusion: Compared to administration of octreotide LAR, TAE combined with octreotide LAR can effectively reduce tumor burden in patients with NETLM. TAE is safe and well-tolerated.

[Screening of optimal siRNA interference sequence of CIT gene and its inhibition expression in hepatoma SK-Hep-1].

Objective: To construct and screen optimal siRNA interference sequence of CIT gene and to detect its interference efficiency as well as proliferation effect in human hepatoma cell line SK-Hep-1. Methods: Three siRNA target spots were designed and synthesized according to the CIT gene sequence. SK-Hep-1 HCC cells were transfected by liposome transfection. The knockdown efficiency of the target CIT gene was detected by real-time PCR and Western blot. Expressional change of CIT in SK-Hep-1 cells after 48 hours of siRNA interference were observed by immunohistochemistry and confocal microscopy. The proliferation of SK-Hep-1 cells after 48 hours of siRNA interference was detected by EdU cell proliferation assay. A t-test was used to compare the mean of two samples, and one-way ANOVA was used to compare the mean of multiple samples. Results: Western blot results showed that the three interference sequences were targeted at different target spots. The expression level of CIT protein in KD-1,-2, and-3 groups were decreased (P < 0.01) than control, while the protein expression level of KD1 group was the lowest. Real-time PCR results showed that compared with the control group, the expression level of CIT mRNA in KD-1, -2, and -3 groups decreased (P < 0.01), while that in KD1 group was the lowest. Laser confocal microscopy also confirmed that the morphological expression of CIT attenuated significantly after transfection with siRNA. The results of EdU proliferation assay showed that siRNA transfected with CIT significantly attenuated the proliferation of SK-Hep-1 hepatoma cells (P < 0.05). Conclusion: The successful construction and screening of siRNA fragments can effectively inhibit the expression and proliferation of CIT gene in hepatoma SK-Hep-1.

Antidamping-Torque-Induced Switching in Biaxial Antiferromagnetic Insulators.

We investigate the current-induced switching of the Néel order in NiO(001)/Pt heterostructures, which is manifested electrically via the spin Hall magnetoresistance. Significant reversible changes in the longitudinal and transverse resistances are found at room temperature for a current threshold lying in the range of 10^{7} A/cm^{2}. The order-parameter switching is ascribed to the antiferromagnetic dynamics triggered by the (current-induced) antidamping torque, which orients the Néel order towards the direction of the writing current. This is in stark contrast to the case of antiferromagnets such as Mn_{2}Au and CuMnAs, where fieldlike torques induced by the Edelstein effect drive the Néel switching, therefore resulting in an orthogonal alignment between the Néel order and the writing current. Our findings can be readily generalized to other biaxial antiferromagnets, providing broad opportunities for all-electrical writing and readout in antiferromagnetic spintronics.

[The effect of tri-modality therapy on the treatment of muscle-invasive bladder cancer].

Objective: To explore the effect of radical TURBT combing with concomitant chemo-radiotherapy for muscle-invasive bladder cancer (MIBC). Methods: From 2010 to 2015, 73 patients were diagnosed as MIBC, in which 28 patients (TMT Group) received tri-modality bladder sparing treatment, including 21 males and 7 females, mean age (68.9±8.9) yr. There were 16 cases of T(2), 12 cases of T(3). 45 patients (RC Group) received radical cystectomy (RC), including 32 males and 13 females, mean age (66.3±9.6) yr. There were 25 cases of T(2), 18 cases of T(3) and 2 cases of T(4a). The effect of two treatment modality and influence for patient's life quality were retrospective analysis. Results: The overall survival (OS) rate of TMT group was 64.3%, cancer specific survival (CSS) rate was 78.6%. And the OS rate of RC group was 66.7%, CSS rate was 82.2%. There was no statistical difference between two groups. The life quality of TMT group was better than that of RC group. Conclusion: In strict control of indication criterion, rigorous postoperative follow-up and timely salvage radical cystectomy, tri-modality therapy can be used as a new option of muscle-invasive bladder cancer.

[Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma].

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

[Downregulation of large conductance calcium-activated potassium channels in paraventricular nucleus contributes to sympathoexcitation in rats with chronic heart failure].

Objective: To elucidate the association between large conductance calcium-activated potassium channels (BKCa) in the paraventricular hypothalamic nucleus (PVN) and sympathetic outflow in rats with chronic heart failure (CHF) . Methods: Male Wistar rats (6-7 weeks old) were randomized to sham operated group and CHF group (coronary artery ligation) . Two weeks after operation, BKCa inhibitor Iberiotoxin (IBTX) was infused into PVN by osmotic minipumps, rats were divided into following groups: sham+aCSF, CHF+aCSF, sham+low dose IBTX (0.125 nmol/nl) , CHF+low dose IBTX, sham+moderate dose IBTX (1.25 nmol/nl) , CHF+moderate dose IBTX, sham+ high dose IBTX (12.5 nmol/nl) , and CHF+high dose IBTX (n=6 each) . Additional rats were grouped as follows: sham+vehicle, sham+KCNMB4 knockdown (by rAAV2-KCNMB4 shRNA virus injection in PVN) , CHF+vehicle, CHF+ KCNMB4 knockdown group (n=6 each) . The cardiac function was determined by echocardiography, left ventricular hemodynamics were measured invasively, renal sympathetic nerve activity (RSNA) was recorded at 6 weeks after coronary artery ligation or sham operation. The contents of norepinephrine (NE) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in plasma were determined by enzyme-linked immunosorbent assay. The protein and mRNA expression of KCNMB4 in PVN were measured by immunofluorescence staining, Western blot, and real-time PCR, mRNA expression of BKCa in PVN was detected by real-time PCR. Results: Compared with the sham operation group, the cardiac function of the heart failure group was significantly reduced (P<0.05) , and the plasma NE and the serum NT-proBNP were significantly elevated (P<0.05) . The protein and mRNA expression of KCNMB4 in PVN were obviously down-regulated in CHF rats (P<0.05) . After perfusion of IBTX or KCNMB4 knockdown by microinjection of rAAV2-KCNMB4 shRNA virus,right ventricular weight/body weight and lung weight/body weight ratio as well as left ventricular end-diastolic diameter were increased and left ventricular ejection fraction was decreased (all P<0.05) , the sympathetic driving indexes was increased in sham rats, changes of these parameters further aggravated in CHF rats (P<0.05) . KCNMB4 knockdown further downregulated protein expression in PVN of CHF rats. Conclusion: Downregulation and blunted function of BKCa in PVN may contribute to sympathoexcitation and deterioration of cardiac function in rats with chronic heart failure.

[Correlation between expression of long non-coding RNA ZXF1 and prognosis of lung adenocarcinoma and its potential molecular mechanism].

Objective: To investigate the correlation between expression of long non-coding RNA (lncRNA) ZXF1 and clinicopathological characteristics, as well as prognosis of lung adenocarcinoma; and to explore its potential molecular mechanism. Methods: A total of 83 lung adenocarcinoma tissue samples and 83 paracancerous lung tissue samples from lung adenocarcinoma patients were collected. The mRNA expression of ZXF1 in the tumors and the corresponding adjacent non-tumor tissues were determined by real-time fluorescence quantitative PCR. The correlation between ZXF1 level and clinicopathological characteristics such as age, gender, smoking history, tumor size, tumor differentiation and lymph node metastasis was evaluated. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression, based on the data of a 12-56 months follow-up after surgery. In vitro ZXF1 was over-expressed in lung adenocarcinoma A549 cells, and then the proteins functionally related to ZXF1 were identified by protein array analysis. Results: Of the 83 cases of lung adenocarcinoma, the ZXF1 mRNA levels in the tumor and adjacent non-tumor tissues were 8.32±3.05 and 1.05±0.47, respectively (P<0.05), and a high-level the high expression of ZXF1 in the tumor tissues was detected in 56 cases. The expression status of ZXF1 was closely correlated with the tumor differentiation and lymph node metastasis (P<0.05), but was not significantly related to age, gender and tumor size. Based on a 12-56 months follow-up, the patients with high level ZXF1 expression had a shorter disease free survival (DFS) and overall survival (OS) than that of the group with low level ZXF1 (all P<0.05). Multivariate analysis showed that ZXF1 expression, tumor size and lymph node metastasis were independent risk factors to DFS; and ZXF1 expression, tumor size, lymph node metastasis and tumor differentiation were independent risk factors to OS. The protein array data revealed that expressions of bone morphogenetic protein 5 (BMP-5)and stem cell factor receptor (SCFR)were upregulated upon overexpression of the ZXF1 in A549 cells. Conclusions: lncRNA ZXF1 is overexpressed in lung adenocarcinoma, and is closely correlated with tumor differentiation and lymph node metastasis. As an independent risk factor, a high expression of ZXF1 indicates a poor prognosis for the patients. ZXF1 may influence the biological behavior of lung adenocarcinoma by enhancing the protein expression of BMP-5 and SCFR.

[Risk factors for lower extremity amputation in patients with diabetic foot].

Objective: To explore the risk factors for lower extremity amputation in patients with diabetic foot. Methods: The clinical data of 1 771 patients with diabetic foot at the Air Force General Hospital of PLA from November 2001 to April 2015 were retrospectively analyzed. The patients were divided into the non-amputation and amputation groups. Within the amputation group, subjects were further divided into the minor and major amputation subgroups. Binary logistic regression analyses were used to assess the association between risk factors and lower extremity amputation. Results: Among 1 771 patients with diabetic foot, 323 of them (18.24%) were in the amputation group (major amputation: 41; minor amputation: 282) and 1 448 (81.76%) in the non-amputation group. Compared with non-amputation patients, those in the amputation group had a longer hospital stay and higher estimated glomerular filtration rate(eGFR)levels. Fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), C-reaction protein (CRP), ESR, ferritin, fibrinogen and WBC levels of the amputation group were higher, while hemoglobin albumin, transferrin, TC, TG, HDL-C and LDL-C were lower than those of the non-amputation group (all P<0.05). The proportion of hypertension(52.48% vs 59.98%), peripheral vascular disease (PAD)(68.11% vs 25.04%), and coronary heart disease(21.33% vs 28.71%)were different between the amputation and non-amputation groups (all P<0.05). Multivariable logistic regression analyses showed that Wagner's grade, PAD and CRP were the independent risk factors associated with lower extremity amputation in hospitalized patients with diabetic foot. Conclusion: Wagner's grade, ischemia of lower limbs and infection are closely associated with amputation of diabetic foot patients.

[Effects of chronic intermittent hypoxia on left ventricular myocardial contractibility in a rabbit model of obstructive sleep apnea].

Objective: To explore the effects of chronic intermittent hypoxia (CIH) on left ventricular myocardial contractibility in a rabbit model of obstructive sleep apnea (OSA). Methods: Based on random number table, twenty-four rabbits were randomly divided into three groups: operation, sham, and control groups, each with 8 rabbits. The rabbit model for OSA in operation group was established by repeatedly closing the airway and then reopening it. Upper airway obstructions were conducted on rabbits every day, which were alternately closed for 15 s and then reopened for 75 s in a 90 s-long cycle, for 8 h each day over 3 months. The sham rabbits were subjected to the same surgical procedure but no airway obstructions were applied. The control animals were subjected to no intervention. The blood pressure, left ventricular function parameters were assessed before and after the experiment. And the relative expressions of myosin heavy chain α/ß (α-MHC and ß-MHC) mRNAs in myocardium were observed for all rabbits by real time fluorescent quantitative polymerase chain reaction 3 months later. Results: After 3 months, all rabbits in the operation group manifested sleepiness and the blood pressure rose gradually [(114.25±4.20) vs (93.88±2.10) mmHg, P<0.01]. Compared with the sham operation and the control groups, the left ventricular end-systolic volume [(6.05±1.62) vs (2.83±0.49) and (2.74±0.32) ml, P<0.001] and the left ventricular end-diastolic volume [(1.61±0.78) vs (0.83±0.13) and (0.82±0.10) ml] in operation group were obviously higher, the left ventricular ejection fraction [(63.9±4.2) % vs (74.3±2.5) % and (75.8±3.8) %], left ventricular fractional shortening [(32.2±2.1) % vs (41.8±1.8) % and (42.1±1.8) %] and stroke volume [(1.46±0.13) vs (1.93±0.21) and (1.98±0.24) ml/s] were decreased (all P<0.001). Besides, the maximal rate of the increase of left ventricular pressure [(4 154±360) vs (6 802±492) and (6 759±206) mmHg/s], the maximal rate of the decrease of left ventricular pressure [(4 994±621) vs (6 330±314) and (6 591±225) mmHg/s] in the operation group decreased markedly, left ventricular end diastolic pressure (LVEDP) increased [(6.5±1.6) vs (3.3±0.8) and (3.2±0.9) mmHg] (all P<0.001). The relative expression of α-MHC mRNA in left ventricular myocardial tissue was lower and the relative expression of ß-MHC mRNA was higher in operation group than those in the sham operation and the control groups (P<0.05). There were no significant difference in the relevant indicators of cardiac function, and in the relative expressions of α-MHC mRNA and the ß-MHC mRNA between the control group and the sham operation group (P>0.05). Conclusions: Repeated intermittent hypoxia can induce hypertension and myocardial contractibility damage in OSA model rabbit simulating upper airway obstruction.

[Value of neutrophil-lymphocyte ratio in predicting hepatitis B-related liver failure].

Objective: To investigate the value of neutrophil-lymphocyte ratio (NLR) in predicting hepatitis B-related liver failure. Methods: A total of 349 subjects were enrolled, among whom 60 were healthy persons who underwent physical examination (group A), 111 had severe chronic hepatitis B (group B), 92 had decompensated hepatitis B cirrhosis (group C), and 86 had acute-on-chronic liver failure (ACLF) (group D). Routine blood test results, liver function parameters, and coagulation parameters were collected, and NLR was calculated. According to disease progression, group B was further divided into groups B1 (with progression to ACLF) and B2 (without progression to ACLF). NLR was compared between groups, and its prognostic value was evaluated. Results: NLR was 2.22(1.76-3.05) in group A, 2.54(1.78-3.49) in group B, 3.07(1.95-5.04)in group C, and 3.41(2.01-5.15) in group D, and NLR gradually increased with the aggravation of disease condition. The univariate and multivariate regression analyses of groups B1 and B2 showed that NLR and prothrombin activity were prognostic factors for disease progression. There was a significant difference in baseline NLR between groups B1 and B2 (3.87 ± 1.54 vs 2.71 ± 1.54, P = 0.004). There was a significant increase in NLR when severe hepatitis B in 16 patients progressed to ACLF (P = 0.042). The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of NLR for predicting the progression of severe hepatitis B to ACLF was 2.79, with an area under the ROC curve (AUC) of 0.739 (P = 0.002). NLR was also a reference index for judging end-stage liver disease with a cut-off value of 3.94 (AUC = 0.612, P = 0.001). Conclusion: Peripheral NLR can reflect disease progression and predict the development of liver failure.

[Transforming growth factor-ß1 small interfering RNA regulates platelet-derived growth factor and phosphorylated extracellular regulated protein kinase in rats with hepatic fibrosis: an experimental study].

Objective: To investigate the impact of transforming growth factor-ß1 (TGF-ß1) silencing by small interfering RNA (siRNA) on the expression of platelet-derived growth factor-ß (PDGF-BB) and its receptor (PDGF-ßR) in rats with hepatic fibrosis. Methods: A total of 40 male Sprague-Dawley rats were randomly divided into normal control group, model group, TGF-ß1 siRNA treatment group, and negative control group. All rats except those in the normal control group were given subcutaneous injection of 40% carbon tetrachloride to establish a rat model of hepatic fibrosis. The rats in the negative control group and the TGF-ß1 siRNA treatment group were given tail vein injection of negative control plasmid or TGF-ß1 siRNA plasmid twice a week at a dose of 0.25 mg/kg, and those in the normal control group and the model group were given the injection of sterile isotonic saline twice a week. The rats were sacrificed after 12 weeks and liver tissue samples were collected. Real-time PCR, immunohistochemistry, and Western blot were used to measure the expression of PDGF-BB, PDGF-ßR, and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) in liver tissue. A one-way analysis of variance, the q test, and the Kruskal-Wallis test were used for statistical analysis based on data type. Results: Compared with the model group and the negative control group, the TGF-ß1 siRNA treatment group had significantly inhibited mRNA and protein expression of PDGF-BB and PDGF-ßR (F = 24.785 and 22.92, P < 0.01), as well as significantly inhibited expression of p-ERK1/2 (P < 0.05). Conclusion: Targeted TGF-ß1 siRNA can effectively downregulate the expression of PDGF-BB, PDGF-ßR, and p-ERK1/2 in liver tissue and thus help to improve hepatic fibrosis.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aß) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aß and mediates Aß-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aß. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aß deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aß deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing ß-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aß toxicity and would be a novel therapeutic target and biomarker for AD.

Sunitinib modulates the radiosensitivity of esophageal squamous cell carcinoma cells in vitro.

This study aims to explore the radiosensitivity of sunitinib on esophageal cancer cell lines. For in vitro studies, human esophageal squamous cell carcinoma (ESCC) cell lines were treated with sunitinib 24 hours before irradiation. ESCC cell lines were treated with sunitinib with or without radiation. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis and cell cycle analysis were detected by flow cytometry. Deoxyribonucleic acid (DNA) double-strand breaks were performed by immunocytofluorescence analysis. Western blot analysis was used to determine the effect of sunitinib on radiation induced signal transduction. Sunitinib potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.13-1.72. Furthermore, sunitinib increased radiation induced DNA double-strand breaks, promoted the apoptosis of ESCC cells and induced the G2/M arrest. Radiosensitization was accompanied with enhanced apoptosis and regulated by the intrinsic pathway of apoptosis. Sunitinib sensitized ESCC cells to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in esophageal cancer.