Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective:To explore the clinical application value of spiral computed tomography(CT)three-dimensional(3D)scanning reconstruction combined with 3D printing technique in surgery for acetabular fracture.Methods:A total of 71 patients with acetabular fractures admitted to Xinjiang Uiger Municipal People's Hospital from January 2018 to December 2020,who underwent surgical treatment,were selected as the research objects.According to different treatment methods,they were divided into observation group(38 cases)and control group(33 cases).The observation group adopted spiral CT 3D reconstruction,and 3D printing was used to assist the treatment of internal fixation,and the control group adopted conventionally surgical treatment.And then,the surgical effect and recovery situation of the two groups were compared.Results:The quality score(Malta)of fracture reduction and the hip score of sub-item percentile of observation group were significantly higher than those of the control group,and the intraoperative blood loss,the times of intraoperative fluoroscopy,the operation time and hospitalization time of observation group were significantly lower than those of control group(t=23.426,4.216,3.425,17.783,P<0.05),respectively.There was significant difference in the excellent rate of fracture reduction between two groups(x2=4.059,P<0.05).The pain,function and joint activity scores of hip joint function scores of patients in observation group were significantly higher than those of control group(t=-4.873,-5.776,-6.247,P<0.05),respectively.The incidence of complications in observation group was significantly lower than that in control group(x2=4.059,P<0.05).Conclusion:In the perioperative period,the application of spiral CT 3D reconstruction combined with 3D printing of acetabular fractures can further ensure the safety and feasibility of the operation,and improve the quality and efficiency of the surgery,and promote postoperative recovery.

Objective:To explore the imaging characteristics and clinical value of CT angiography (CTA) of the aorta in active arteritis.Methods:A retrospective analysis was conducted on the clinical data and laboratory examination results of 77 patients with Takayasu arteritis (TAK) admitted to the Rheumatology and Immunology Department of People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to October 2022. They were divided into two groups: 62 cases in the TAK active group and 15 cases in the TAK inactive group. Among them, 17 patients were followed up, 13 cases became inactive, and 4 cases remained active. A total of 94 aortic CTA imaging results were divided into 2 groups, with 66 cases in the TAK active group and 28 cases in the TAK inactive group.All patients underwent plain chest and abdominal CT scans, aortic CTA, and post-processing examinations, with 12 active TAK patients undergoing delayed aortic enhancement scans. The t-test, Mann Whitney U test, χ2 Testing, Fisher′s exact probability method and Pearson/Spearman correlation analysis were used for data analysis. The imaging features of the two groups were measured and compared, the correlation between imaging features and laboratory results, Kerr score were investigated. The diagnositic efficacy of imaging features were explored and imaging features before and after treatment were analyzed. Results:In the TAK active and inactive groups, course of disease[14 (1, 29) months vs 33(8, 69)months, Z=2.70, P=0.007], Physical malaise or weight loss[32.3%(20/62) vs 20.0%(3/15), χ2=4.08, P=0.043], increased ESR [98.4% (61/62) vs 13.3% (2/15)], χ2=64.69, P<0.001], CRP level[69.4% (43/62) vs 6.7%(1/15), χ2=29.94, P<0.001] were statistically significant. The vascular wall thickness of the two groups was significantly different [(4.2±1.4)mm vs (2.4±0.8)mm, t=7.81, P<0.001], CT mean value of the garterial wall [(81±8) Hu vs (70±13)Hu, t=2.82, P=0.011], CT max value of the arterial wall [(106±12)Hu vs (96±12)Hu, t=2.38, P=0.024], relative CT value 1 of the arterial wall (0.20±0.08 vs 0.14±0.04, t=2.56, P=0.016), relative CT value 2 of the arterial wall (1.23±0.18 vs 1.06±0.17, t=2.63, P=0.013), CT mean value of periaortic adipose tissue [(-31±12)Hu vs (-58±20)Hu, t=4.80, P<0.001)], CT max value of periaortic adipose tissue [-35(-45,-25)Hu vs -87(-95, -42)Hu, Z=4.27, P<0.001], CT mean value of adipose tissue around branches[-28(-33, -14)Hu vs -76(-83, -31)Hu, Z=3.37, P=0.001], CT max value of adipose tissue around branches[-7(-13,-1)Hu vs -59(-72, -14)Hu, Z=3.74, P<0.001], relative CT values of adipose tissue around the aorta (0.26 ± 0.09 vs 0.51 ± 0.19, t=4.47, P<0.001)], relative CT values of adipose tissue around branches (0.17 ± 0.09 vs 0.28 ± 0.18, t=2.35, P=0.025) were significant different. The wall thickness value, relative CT value of periaortic adipose tissue, and CT mean value of periaortic adipose tissue had high diagnostic efficacy, with cut-off values of 3.25 mm, 0.455, and -55 Hu, respectively. The AUCs were 0.911, 0.887, and 0.863, respectively. The Youden index was 0.687, 0.730, and 0.715, respectively. The sensitivity and specificity were 0.758 and 0.929, 0.909 and 0.821, 0.894 and 0.821, respectively. After treatment, 11 active TAK patients became inactive, with reduced wall thickening, enhancement, and density of perivascular adipose tissue. Thirteen patients with active TAK underwent delayed aortic enhancement scanning, and it was found that the low-density loop sign of the aortic intima was more clearly displayed during this period, and the enhancement amplitude of the vascular wall tended to be uniform. Conclusion:Aortic CTA is an effective method for qualitative evaluation of TAK activity.

Reflux esophagitis （liver-stomach disharmony， Spittoon-Qi interties， Qi and blood stasis syndrome， turbid poison intrinsic） and nonalcoholic fatty liver disease （liver depression， spleen deficiency， phlegm and blood stasis syndrome， hot and humid embodiment， phlegmy wet resistance） and functional dyspepsia （liver depression syndrome， liver stomach with spleen deficient， spleen deficiency cold syndrome， in a word， fever） is a common disease and frequently encountered disease of digestive system. The course of disease is prolonged and the prevalence is high. The successful establishment of animal model combining disease and syndrome is the premise of exploring the mechanism of traditional Chinese medicine（TCM） effect and the foundation of the development of new preparations. At the same time， mastering the complex relationship network among disease， syndrome and prescription is the prerequisite of effective treatment. When the same syndrome occurs between different diseases， the concept of "treating different diseases with the same treatment" in TCM suggests that methods can be cross-referenced for the shortage of some syndrome models. TCM intervention of digestive diseases has the characteristics of multi-path， multi-target， multi-dimension and multi-level. Therefore， this article through the literature review， summarizes the reflux esophagitis， nonalcoholic fatty liver disease and functional dyspepsia is a common disease such as the combined operation method of the model and the intervention mechanism of TCM， so as to diseases of the digestive system of different syndrome types provides the theory basis for the objective of research， and the basic research of TCM prescription and achievements provide methodological guidance.

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
Adenocarcinoma of Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Retrospective Studies

Objective: To analyze the related factors of the onset of vasovagal syncope (VVS) in children, and to provide basis for the early prevention, early diagnosis and early treatment of VVS. Methods: A total of 126 children with syncope admitted to Department of Pediatric Cardiology, Second Hospital of Lanzhou University from October 2018 to September 2019 were invited in the study. Totally 73 cases of children diagnosed with VVS by HUTT were selected as VVS group, and 53 HUTT negative children were selected as control group. Related factors were retrospectively investigated, and risk factors for VVS were analyzed by univariate and multivariate regression. Results: The VVS group showed statistically significant difference in age distribution with the control group ( χ 2=19.22, P <0.05). The VVS group showed statistically significant differences of proportion in family history, syncope history, prolonged standing, electrocardiogram abnormalities, and vitamin D deficiency (43.84%，31.51%，47.95%，34.25%， 30.14 %) compared with the control group (15.09%，13.21%，20.75%，15.09%，9.43%) ( χ 2=11.71,5.67,9.79,5.83,7.82, P < 0.05 ). Multivariate Logistic regression analysis showed that age and family historywere risk factors for VVS( χ 2=3.13, 11.06, P < 0.05 ). Conclusion Age and family history may be risk factors for the onset of VVS. Active attention should be paid to the high risk factors of child patient, early identification and diagnosis can prevent the occurrence and development of VVS in children.

Objective:To understand the characteristics and diagnosis and treatment of brucellosis with joint pain as the first clinical manifestation, and summarize the clinical classification of brucellosis complicated with joint pain, so as to provide reference for clinical diagnosis and treatment.Methods:Cases of brucellosis with first symptom of joint pain diagnosed in the 940th Hospital of PLA Joint Logistic Support Force from January 2015 to January 2020 were selected. The main clinical features, laboratory examination, diagnosis and treatment were analyzed.Results:A total of 82 patients with joint pain of the first symptom were selected, including 61 males and 21 females. Joint pain was the main complaint of the patients, 63.4% (52/82) of the patients visited spine surgery department, 17.1% (14/82) visited minimally invasive orthopedics department, 12.2% (10/82) visited rheumatic immunology department, and 7.3% (6/82) visited traditional Chinese medicine department. Brucellosis patients with cervical lesions accounted for 22.0% (18/82), combined with lumbar lesions accounted for 51.2% (42/82). The patients with elevated C-reactive protein accounted for 68.3% (56/82), abnormal liver function accounted for 52.4% (43/82), anti "O" positive accounted for 3.7% (3/82), abnormal autoantibodies accounted for 6.1% (5/82), and human leukocyte antigen-B27 (HLA-B27) positive accounted for 12.2% (10/82). Four patients with HLA-B27 positive had sacroiliac arthritis. All patients were cured after standard and full course therapy.Conclusion:Joint pain may be the first symptom of brucellosis, and the lumbar spine and cervical spine are the most vulnerable parts.

Objective To investigate the rehabilitation needs and technical support for people with disabilities in rural areas. Methods From October, 2017 to February, 2018, 800 persons with disabilities, aged five to 80 years, from 23 villages in five township, Xi'an, Shaanxi, were surveyed with self-designed questionnaire and interview, including the basic situation, disability and training plan, rehabilitation support and skills maintained. Results The persons were mainly aged 50 to 80 years (58.37%), male (65.37%), accepting middle school education or less (46.63%), married (70.63%), living with their family (77.38%), income less than 2000 Yuan (66%), mainly from their family labor (62.62%). Their disabilities were mainly of grade 3 (40.63%), from hemiplegia (30.63%), dependence in living (45.38%), and no systematic rehabilitation program (55.25%). Most of them needed rehabilitation of self-care (40%), accessible guidance (30.63%) and reimbursement from medicare of Rural Cooperative Medical Scheme (50.63%), and hoped to participate social activities (41.87%). The rehabilitation supports were as that: the rehabilitation services were mobile or none (67.58%), the guiders of rehabilitation were few or none (48.88%), knew some or less rehabilitation knowledge (64.25%), the professionals accepted no continue education training (40%).Conclusion It is important to improve the rehabilitation technical support system for rural people with disabilities.

Objective To evaluate the hemostatic effect of hemocoagulase agkistrodon on surgical wound in breast cancer surgery. Methods Totally 60 patients undergoing breast cancer surgery were enrolled in this prospective,randomized,double-blinded,and controlled study. All the patients met the inclusion and exclusion criteria and signed the informed consent. Hemocoagulase agkistrodon (2 U) was injected 20 minutes before surgery and 4 and 24 hours after surgery in the intervention group (n=30),whereas normal saline was used instead in the control group (n=30). The volume of intraoperative bleeding,wound drainage volume 1-3 days after surgery,and total drainage volume were recorded. Meanwhile,the change of blood coagulation function,treatment safety,and clinical outcomes were observed. Results The intra-operative hemorrhage volume of the intervention group [(95.0±48.3)g] was significantly lower than that of the control group [(144.8±105.4)g] (t=-2.07,P=0.044). The volume of total drainage of the intervention group [(166.7±71.2)g] was significantly lower than that of the control group [(251.4±166.3)g] (t=-2.29,P=0.029). The hemoagglutination indicators were similar in the two groups and no complication such as thrombosis occurred. The length of hospital stay of the intervention group [(15.00±3.53)d] was similar to that of the control group [(15.92±2.32)d] (t=-1.057,P=0.297). No research drug-related adverse event was occurred in our study. Conclusion Hemocoagulase agkistrodon has good hemostatic effect for patients undergoing breast cancer surgery without increasing the risk of thrombosis.