【Objective】 To investigate the mechanism of pristane inducing autophagy in macrophages. 【Methods】 Pristane was used to stimulate NR8383， a rat macrophage cell line. The changes in signaling pathways of AMPK， mTOR， and endoplasmic reticulum （ER） stress pathways including eIF2α and IRE1α in the cell model， as well as the expression of transcriptional factor TFEB and its translocation to the nucleus， were detected by using Western blotting. ER stress pathways were intervened by using an inducer DTT or an inhibitor 4-PBA to determin its effect on mTOR expression and autophay. 【Results】 In pristane-stimulated NR8383 cell model， ER stress pathway eIF2α was activated at 0.5 h after stimulation， and then mTOR expression was decreased at 1 and 3 h after stimulation. There was no change for AMPK and IRE1α pathways. With 4-PBA treatment， pristane-reduced mTOR expression and increased LC3-II were reversed， while with DTT treatment， mTOR expression decreased and LC3-II expression increased even more. Pristane induced the expression and activation of TFEB in NR8383 cells. 【Conclusion】 Pristane induces ER stress and leads to autophagy enhancement in rat macrophages.

Objective:To investigate the role of survival motor neuron ( SMN) gene knockout in mice with cisplatin-induced acute kidney injury (AKI). Methods:A mouse model (C57BL/6) of cisplatin-induced AKI was constructed. Twenty male wild type (WT) and SMN+/- mice weighing 22-24 g were randomly divided into four groups: WT mice with saline injection group (WT vehicle, n=5), SMN+/- mice with saline injection group ( SMN+/- vehicle, n=5), WT mice with cisplatin injection group (WT cisplatin, n=5) and SMN+/- mice with cisplatin injection group ( SMN+/- cisplatin, n=5). Mice were injected intraperitoneally with 20 mg/kg cisplatin or 0.9% saline. 72 hours later, the mice were sacrificed, and serum and kidney tissues were collected. The real time PCR and Western blotting were used to measure the expression levels of SMN mRNA and protein. The sarcosine oxidation and urease method were used to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal pathologic changes were observed by PAS staining. TUNEL immunofluorescence assay was used to detect the level of apoptosis. Western blotting and immunohistochemistry were used to detect the protein expression levels of apoptosis index poly (ADP-ribose) polymerase (PARP) and endoplasmic reticulum stress index CHOP. Results:Compared with WT mice, SMN mRNA and protein expression levels were lower in SMN+/- mice, and the expression level of SMN mRNA and protein was further decreased after intraperitoneal cisplatin injection (all P<0.05). Compared with WT mice with saline injection group, WT mice with cisplatin injection group had higher levels of Scr, BUN, tubular damage scores, TUNEL positive cell numbers, PARP and CHOP, while the expression levels of above indexes in the SMN+/- mice with cisplatin injection group were higher than those in the WT mice with cisplatin injection group (all P<0.05). Conclusions:SMN gene knockout can aggravate renal pathological damage and apoptosis of renal tubular epithelial cell in cisplatin-induced AKI mice. SMN may be a potential therapeutic target of AKI.

Objective:To explore the sex-based heterogeneity in demographic and pathological trends of lung cancer during the past 30 years.Methods:Patients with primary lung cancer who received surgical treatment in the Department of thoracic surgery, Shanghai Pulmonary Hospital Tongji University from 1989 to 2018 were retrospectively analyzed. The differences between male and female patients in age, smoking history, pathological stage and type were compared. Mann- Kendall trend test was performed for trend analysis. Results:A total of 58 433 patients were included in this study, encompassing 30 729(52.6%) men and 27 , 704(47.4%) women. Compared with male patients, female patients were younger(56.0 years old vs. 59.7 years old), and had a higher proportion of non-smokers(98.3% vs. 52.3%), stage Ⅰ lung cancers(60.6% vs. 49.3%), and adenocarcinoma(93.7% vs. 56.1%, all P-values <0.001). Trend analyses revealed that the proportion of female patients increased year by year, and surpassed males in 2015, with the current ratio of male to female being 1∶1.5. After 2013, the age of onset in females was getting younger, and the average age decreased from 58.7 years old to 54.7 years old( P=0.02). The decrease in the proportion of smoking patients was mainly reflected by male patients(from 68.5% to 31.1%, P<0.01). Stage Ⅰ lung cancers in male and females outnumbered advanced stage in 2012 and 2010, respectively, with a much higher proportion in female patients. Among male patients, adenocarcinoma has replaced squamous cell carcinoma as the most common pathological type since 2012, while in female patients adenocarcinoma remained the most common pathological type of lung cancer, and its proportion continued to increase reaching over 98%. Conclusion:A dramatic change in gender distribution was noticed during the past 30 years. Female patients became the primary population in surgically-treated lung cancers, with a trend of getting younger. The proportion of smokers and squamous cell carcinoma decreased significantly in male patients, and adenocarcinoma has become the most common pathological type of lung cancer. The proportion of stage Ⅰ lung cancers was on a dramatic rise, with the popularization of CT screening for lung cancer.

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Abstract: To investigate the changes of cerebral blood flow(CBF) in patients with type 2 diabetes mellitus(T2 DM) and its correlation with cognitive function and olfactory impairment. Methods: Cognitive function assessment and smell identification test were performed on 83 patients with T2 DM and 62 healthy controls(HC). Three-dimensional pseudo-continuous arterial spin labeling(3 D-pcASL) head images were collected from the two groups. CBF values of the cerebral cortex were compared between the patients and HC after the postprocessing. Correlations between the CBF values and cognitive function assessment and between the CBF values and smell identification test scores were analyzed as well. Results: Compared to the HC, Chinese smell identification test(CSIT), montreal cognitive assessment(MoCA), digit span test(DST), verbal fluency test(VFT) scores were lower in T2 DM patients(P<0.05).The CBF of the bilateral middle frontal gyrus in T2 DM patients was higher than that in HC group(P<0.001). The CBF of the bilateral gyrus rectus and olfactory cortex in T2 DM patients was lower than that in HC group(P<0.001). Conclusion The cognitive and olfactory function of patients with T2 DM decreased. Patients with T2 DM have abnormal perfusion in the bilateral middle frontal gyrus, gyrus rectus and olfactory cortex, revealing that CBF changes in these brain regions may be one of the causes for cognitive impairment and olfactory dysfunction in T2 DM.

Objective:To explore the clinical characteristics and prognosis of metastatic sites symptom as the first manifestation in esophageal carcinoma patients with stage T 1 and T 2, and to provide a reference for clinical practice. Methods:The clinical data of 50 esophageal carcinoma patients with stage T 1 and T 2 who had lymph node or distant metastasis as the first symptom in Anyang Tumor Hospital of Henan Province from November 2007 to December 2019 were retrospectively analyzed. Survival analysis was performed by using Kaplan-Meier method. Univariate analysis was performed by using log-rank test. Results:Among 50 patients with esophageal carcinoma, lymph node metastases as the first symptom were found in 42 cases and distant organ metastases as the first symptom were found in 8 cases. The 1-, 3-, 5-year overall survival rates of patients with stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ were 58.7%, 49.0%, 16.3% and 56.1%, 12.2%, 0, respectively, and there was no statistically significant difference in OS of both groups ( P = 0.094). The 1-, 3-, 5-year overall survival rates of patients with stage N 1 and stage N 2-N 3 were 63.5%, 34.7%, 17.3% and 52.2%, 11.9%, 0, respectively, and there was no statistically significant difference in OS of both groups ( P = 0.083). The 1-, 3-, 5-year overall survival rates were 64.6%, 30.5%, 18.3%, respectively in radiotherapy group and 38.2%, 0, 0, respectively in non-radiotherapy group, and there was a statistically significant difference in OS of both groups ( P = 0.008); the progression-free survival in radiotherapy group was better than that in non-radiotherapy group ( P = 0.028). The 1-, 3-, 5-year overall survival rates were 70.8%, 35.5%, 21.3% and 33.3%, 0, 0 and 35.4%, 0, 0, respectively in concurrent chemoradiotherapy group, radiotherapy group and chemotherapy group, and there was a statistically significant difference in overall survival among three groups ( P = 0.004). The results of univariate analysis showed that radiotherapy ( χ2 = 7.112, P = 0.008) and concurrent chemoradiotherapy ( χ2 = 10.940, P = 0.004) were the main factors affecting the prognosis. Conclusions:Lymph node and distant metastasis could occur in esophageal carcinoma patients with stage T 1 and T 2. Radiotherapy can prolong the progression-free survival time and concurrent chemoradiotherapy could benefit overall survival of these patients.

Objective:To compare the prognosis of fluoroucil combined with cisplatin and paclitaxel combined with cisplatin regimens with concurrent radiotherapy in treatment of esophageal squamous cell carcinoma.Methods:A total of 120 patients with esophageal squamous cell carcinoma who were admitted to Anyang Tumor Hospital of Henan Province from December 2012 to November 2018 were randomly divided into group A and group B by using a random number generator. Group A was given cisplatin combined with 5-fluorouracil, and group B was given cisplatin combined with paclitaxel. Both groups had the same radiotherapy regimen, and both used intensity-modulated radiation therapy (IMRT). Completions of 50 Gy radiotherapy and at least one cycle of chemotherapy were considered to be in line with the plan. Survival data was analyzed in the term of intention-to-treat (ITT) and per-protocol (PP) set.Results:Of the 120 patients, 114 patients were treated and the adverse reactions could be evaluated, including 55 cases in group A and 59 cases in group B. The incidence of grade Ⅲ-Ⅳ leukopenia in group B was higher than that in group A [49.2% (29/59) vs. 25.5% (14/55)], and the difference was statistically significant ( χ2 = 6.805, P = 0.012), and there were no statistical differences in the other adverse reactions between the two groups (All P > 0.05). A total of 113 cases can be analyzed for survival. According to ITT analysis, the median progression-free survival (PFS) time in group A and group B was 28.0 months (95% CI 15.5-34.5 months) and 27.0 months (95% CI 17.0-41.0 months), the median overall survival (OS) time was 28.0 months (95% CI 15.8-34.2 months) and not reached, the differences were not statistically significant (both P > 0.05). According to PP analysis, the median PFS time in group A and group B was 28.0 months (95% CI 15.8-34.2 months) and 29.0 months (95% CI 14.9-45.1 months), the median OS time in group A and group B was 28.0 months (95% CI 3.7-52.3 months) and not reached, the differences were not statistically significant (both P > 0.05). Conclusions:The fluorouracil combined with cisplatin regimen and paclitaxel combined with cisplatin regimen with concurrent radiotherapy have similar PFS and OS time in treatment of esophageal squamous cell carcinoma, the adverse reactions are different, but they are all tolerable. In individualized clinical practice, the toxicities and costs of the two regimens can be comprehensively considered.

Objective: To investigate the clinical and laboratory features of Aeromonas bacteremia in patients with hematological diseases, and provide evidence for the prevention and treatment of Aeromonas infection. Methods: A retrospective study of patients with bloodstream infection of Aeromonas in our hospital from January 2014 to December 2018 was carried out. The clinical characteristics, antimicrobial susceptibility, infection seasons, antimicrobial therapy and evolution were analyzed. Results: A total of 42 patients with hematological diseases had Aeromonas bloodstream infection within 5 years. Among them, 39 cases (92.9%) of bloodstream infection occurred in the stage of neutropenia. The median time of fever was 4 (1-27) d, 22 (52.4%) patients only had fever, 6 (14.3%) with gastrointestinal symptoms (abdominal pain, diarrhea, nausea, upper gastrointestinal bleeding) , 8 (19.0%) with pulmonary infection, 13 (31.0%) with skin and soft tissue infections. Seven patients (16.7%) died with skin and soft tissue infection. The resistance of Aeromonas to carbapenems was 68.3%-70.7%, while the resistance rate to cephalosporins, quinolones and aminoglycosides were less than 10%. Conclusions Aeromonas bacteremia in patients with hematological diseases mainly occur in the neutropenia stage, usually with symptom like fever. The mortality is increased when accompanied by skin and soft tissue infection. Antibiotic use should be based on susceptibility results, and avoid the use of carbapenems.

BACKGROUND:Schwann cells are important celllines in the process of repairing peripheral nerve injury, and human amniotic homogenate supernatant is shown to secrete a variety of cytokines, which could promote the proliferation of Schwann cells.
OBJECTIVE:To investigate the effect of different concentrations of human amniotic homogenate supernatant on the proliferation of rat Schwann cell96.
METHODS:Schwann cell96 was cultured with high-glucose DMEM containing 20%fetal bovine serum, and the second generation of Schwann cell96 was applied for experiments. The cultured cells were divided into five groups according to different volume fractions of human amniotic homogenate supernatant (0%, 10%, 15%, 20%, 25%) in the medium.
RESULTS AND CONCLUSION:The total protein concentration of human amniotic homogenate supernatant was 675μg/mL, in which the concentration of epidermal growth factor, basic fibroblast growth factor and vascular endothelial growth factor were respectively (470.625±2.546), (4.121±0.026) and (0.172±0.002) ng/L. At 1-7 days, the cellproliferation rate of the 10%and 15%concentration groups was greater than that in 20%and 25%concentration groups (P<0.05);10%and 15%concentrations promoted cellproliferation, while 20%and 25%concentrations inhibited cellproliferation. There were no significant difference in the viability of Schwann cell96 between the control group and the experimental group (P>0.05). Low concentrations (10%, 15%) of human amniotic homogenate supernatant promote the proliferation of Schwann cell96, while high concentrations (20%, 25%) of human amniotic homogenate supernatant inhibit cellproliferation.

OBJECTIVETo screen molecular markers in early breast cancer and establish gene subtyping-based diagnostic criteria for predicting the prognosis of early breast cancers.

METHODSTumor tissue specimens were obtained from 8 patients with early breast cancer for analysis of the differentially expressed genes using Agilent custom 8×15 000 chips in combination with the prognostic data of the patients. Another 42 tumor tissue specimens were used to validate the differential genes by real-time fluorescent quantitative PCR.

RESULTSGene microarray analysis identified 132 differentially expressed genes between the patients with favorable and poor prognosis, and 44 of these genes were significantly up-regulated (by over two folds) and 88 down-regulated in patients with poor prognoses.

CONCLUSIONThe gene expression profiles differ in early breast cancer tissues of the same pathological type but with different clinical stages and prognoses, and CD44, MKI67, NTRK2, Nek2, C16orf60, TOP2A, ANCCA, and RRM2 genes can be used as the prognostic markers for early breast cancer.

Adult ; Aged ; Biomarkers, Tumor ; analysis ; genetics ; Breast Neoplasms ; genetics ; pathology ; Carcinoma, Ductal, Breast ; genetics ; pathology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Oligonucleotide Array Sequence Analysis ; Prognosis