Objective To investigate the NAD+ - dependent protein deacetylase SIRT1 expression in the cochlea of C57BL/6 mice ,a mouse model of age - related hearing loss(AHL) .Methods A total of 46 C57BL/6 mice were used ,and were divided into 2 groups ;according the age ,there were young group (1 ~ 2 months old ,23 mice) and old group (12 ~ 16 months old ,23 mice) .ABR measurements were performed on young and old C57BL/6 mice . The expression of SIRT1 in the cochlea was detected by qRT - PCR and immunofluorescence .Results The ABR thresholds in the old mice(4 kHz :82 .7 ± 7 .32 dB SPL ,8 kHz :80 .9 ± 7 .8 dB SPL ,16 kHz :89 .3 ± 5 .5 dB SPL ,32 kHz :89 .9 ± 4 dB SPL) were significantly higher than those in the young C57BL/6 mice(4 kHz :52 .1 ± 8 .3 dB SPL ,8 kHz :40 .5 ± 6 .1 dB SPL ,16 kHz :50 .7 ± 9 .4 dB SPL ,32 kHz :57 .6 ± 11 .9 dB SPL)(P < 0 .001) .SIRT1 mRNA expression was significantly decreased in the cochlea of old C57BL/6 mice in comparison with young mice ( P <0 .01) .SIRT1 protein was abundantly expressed in the inner hair cells ,outer hair cells ,supporting cells ,strial marginal cells ,strial intermediated cells ,and spiral ganglion neurons .The positive area and the average flourescence intensity of SIRT1 protein were reduced in old C57BL/6 mice(P< 0 .001) .Conclusion The down - regulation of SIRT1 mRNA and protein expression in the older C57BL/6 mouse cochlea may be correlated with the pathogenesis of AHL .

AIM:To investigate the role of mesenchymal stem cell-induced regulatory dendritic cells ( MSC-DCregs) in mouse acute graft-versus-host disease( aGVHD) model.METHODS: Bone marrow cells from BALB/c ( H-2 d ) mice were isolated and were induced to differentiate into DCs.The DCs were selected by flow cytometry, and after 10 d co-culture with MSCs, they were induced to be MSC-DCregs.Male 8-week-old C57BL/6 (H-2b) mice were used as do-nor mice.The female 8-week-old BALB/c (H-2d) mice, who had received 100 cm source-skin distance, 30 cm ×30 cm radiation field, 700 cGy total body irradiation (TBI) pretreatment were used as recipient mice.The recipients were divided into 5 groups:control group, TBI group ( injected with medium only) , bone marrow transplantation group ( injected with 1 ×107 bone marrow cells), aGVHD group (injected with 1 ×107 bone marrow cells and 1 ×107 spleen cells), and MSC-DCregs group (injected with 1 ×107 bone marrow cells, 1 ×107 spleen cells and 1 ×106 MSC-DCregs).The white blood cell count, recipients’ chimerism, clinical evaluation of aGVHD, survival analysis and pathological changes were deter-mined.RESULTS:Hematopoieic recovery was seen at 10 d after transplantation.The recipients’ chimerism was parallel to the donors’ at 30 d.The median survival time of the mice in aGVHD group and MSC-DCregs group was 27 d and 33 d, and the survival rates at 30 d were 20% and 100% (P<0.01), respectively.The clinical scores of the mice in MSC-DCregs group were lower than those in aGVHD group ( P<0.01) .Moreover, the pathological changes in the skin and liver of the mice in MSC-DCregs group were less serious than those in aGVHD group.CONCLUSION: The MSC-DCregs in-duce an aGVHD tolerance in vivo, and further research of its mechanism is still in great necessary.

Objective To analyze the intraoperative and postoperative common complications of Enterprise stent-assisted embolization of intracranial aneurysms and the causes and preventive measures. Methods One hundred forty-three patients with intracranial aneurysm treated with Enterprise stent-assisted embolization at the Department of Neurosurgery,Yijishan Hospital,the First Hospital Affiliated to Wannan Medical College from January 2012 to March 2014 were analyzed retrospectively. The common intraoperative and postoperative complications and its possible causes,as well as the appropriate management were analyzed,and the prognoses were observed. Results A total 143 patients(205 aneurysms)with intracranial aneurysm were enrolled,included 43 with unruptured aneurysm,12 with recurrent aneurysm,and 88 with ruptured aneurysm. A total of 170 Enterprise stents were used. Twenty-two patients (15. 4%)had complications. Among them,2 had intraoperative aneurysm rupture,and they recovered well and discharged after active treatment. Thirteen patients had acute thrombosis,11 of the patients completely restored blood flow immediately after tirofiban and/or urokinase,microcatheter and guidewire-contact thrombolysis. The thrombolysis failed in 1 patient,and the blood flow was slow in 1 patient. Six patients had different degrees of cerebral infarction after procedure,and 1 died (peroperative Hunt-Hess grade Ⅳ). Three patients had vasospasm and they were improved after reducing blood vessel wall irritation and papaverine infusion. The introperative stent guidewire was broken and the stent in place was difficult in 1 case. The last coil packed difficultly during the procedure,and it protruded into the parent artery in 1 case. Two patients had non-aneurysmal hemorrhage after procedure. After conservative treatment,one left unilateral limb muscle strength decline and the other was stable after craniotomy,but leaving aphasia and hemiplegia. Conclusion When using the Enterprise stent-assisted embolization for complex aneurysms,grasping the indications strictly,strengthening the perioperative management and improving the operative skills may reduce or avoid the occurrence of complications.

Timely reporting, effective analyses and rapid distribution of surveillance data can assist in detecting the aberration of disease occurrence and further facilitate a timely response. In China, a new nationwide web-based automated system for outbreak detection and rapid response was developed in 2008. The China Infectious Disease Automated-alert and Response System (CIDARS) was developed by the Chinese Center for Disease Control and Prevention based on the surveillance data from the existing electronic National Notifiable Infectious Diseases Reporting Information System (NIDRIS) started in 2004. NIDRIS greatly improved the timeliness and completeness of data reporting with real time reporting information via the Internet. CIDARS further facilitates the data analysis, aberration detection, signal dissemination, signal response and information communication needed by public health departments across the country. In CIDARS, three aberration detection methods are used to detect the unusual occurrence of 28 notifiable infectious diseases at the county level and to transmit that information either in real-time or on a daily basis. The Internet, computers and mobile phones are used to accomplish rapid signal generation and dissemination, timely reporting and reviewing of the signal response results. CIDARS has been used nationwide since 2008; all Centers for Disease Control and Prevention (CDC) in China at the county, prefecture, provincial and national levels are involved in the system. It assists with early outbreak detection at the local level and prompts reporting of unusual disease occurrences or potential outbreaks to CDCs throughout the country.

Objective:To preliminarily investigate the effect of circIGF2BP3 on autophagy in photoaged dermal fibroblasts.Methods:Human dermal fibroblasts were isolated from circumcised foreskin tissues from 6 children in the Department of Urological Surgery, Third Affiliated Hospital of Sun Yat-sen University. An ultraviolet A (UVA) -induced photoaged human dermal fibroblast model (UVA radiation group) was established by repeated UVA radiation at a dose of 10 J/cm 2 for 14 consecutive days, and human dermal fibroblasts receiving no treatment served as control group. The photoaged cell model was verified by β-galactosidase staining, Western blot analysis for determining P21 protein expression, and cell counting kit-8 (CCK8) assay for evaluating cell viability. Moreover, Western blot analysis was performed to determine the protein expression of autophagy-related proteins P62, microtubule-associated protein 1 light chain 3 (LC3) -Ⅰand LC3-Ⅱ in photoaged human dermal fibroblasts, and real-time quantitative RCR (qRT-PCR) to verify the differential expression of circIGF2BP3 between photoaged and normal human dermal fibroblasts. Furthermore, circIGF2BP3 was biologically annotated. Some cultured primary human dermal fibroblasts were divided into 4 groups: empty vector group transfected with an empty vector, UVA + empty vector group transfected with an empty vector followed by repeated UVA radiation, circIGF2BP3 group transfected with a circIGF2BP3-overexpressing lentiviral vector, UVA + circIGF2BP3 group transfected with a circIGF2BP3-overexpressing lentiviral vector followed by repeated UVA radiation. Western blot analysis was performed to determine the expression of autophagy-related proteins. Statistical analysis was carried out by using t test, one-way analysis of variance and least significant difference- t test. Results:Compared with the control group, the UVA radiation group showed significantly increased proportions of β-galactosidase-positive cells (61.33% ± 5.78% vs. 6.37% ± 0.32%, t = 9.49, P < 0.01) and P21 expression (1.25 ± 0.03 vs. 1.00 ± 0.05, t = 4.26, P < 0.05), but significantly decreased cell viability (74.33% ± 3.48% vs. 100%, t = 7.38, P < 0.01). Moreover, the P62 expression and LC3-Ⅱ/Ⅰ ratio were significantly higher in the UVA radiation group than in the control group (both P < 0.05). The relative expression of circIGF2BP3 was 0.72 ± 0.04 in the photoaged human dermal fibroblasts, which was significantly lower than that in the normal human dermal fibroblasts (1.00 ± 0.03, t = 5.46, P < 0.01). The P62 expression and LC3-Ⅱ/Ⅰ ratio were significantly lower in the circIGF2BP3 group (0.60 ± 0.01, 0.71 ± 0.01, respectively) than in the empty vector group (1.00 ± 0.02, 1.00 ± 0.01, t = 16.25, 2.75, P < 0.01, < 0.05, respectively), and lower in the UVA + circIGF2BP3 group (1.05 ± 0.02, 2.04 ± 0.05, respectively) than in the UVA + empty vector group (1.31 ± 0.02, 2.72 ± 0.14, t = 10.493, 6.472, respectively, both P < 0.01) . Conclusion:circIGF2BP3 can regulate autophagy in UVA-induced photoaged dermal fibroblasts, which provides a new potential therapeutic target for the prevention and treatment of skin photoaging.

OBJECTIVETo analyze the implement performance of China Infectious Diseases Automated-alert and Response System (CIDARS) of 31 provinces in mainland China, and to provide the evidences for further promoting the application and improvement of this system.

METHODSThe amount of signals, response situation and verification outcome of signals related to 32 infectious diseases of 31 provinces in mainland China in CIDARS were investigated from 2011 to 2013, the changes by year on the proportion of responded signals and timeliness of signal response were descriptively analyzed.

RESULTSA total of 960 831 signals were generated nationwide on 32 kinds of infectious diseases in the system, with 98.87% signals (949 936) being responded, and the median (the 25(th) percentile to the 75(th) percentile (P25-P75) ) of time to response was 1.0 (0.4-3.3) h. Among all the signals, 242 355 signals were generated by the fixed-value detection method, the proportion of responded signals was 96.37% (62 349/64 703), 98.75% (68 413/69 282) and 99.37% (107 690/108 370), respectively, and the median (P25-P75) of time to response was 1.3 (0.3-9.7), 0.8(0.2-4.9) and 0.7 (0.2-4.2) h, respectively. After the preliminary data verification, field investigation and laboratory test by local public health staffs, 100 232 cases (41.36%) were finally confirmed.In addition, 718 476 signals were generated by the temporal aberration detection methods, and the average amount of signal per county per week throughout the country were 1.53, and 8 155 signals (1.14%) were verified as suspected outbreaks. During these 3 years, the proportion of signal response was 98.89% (231 149/233 746), 98.90% (254 182/257 015) and 99.31% (226 153/227 715), respectively, and the median (P25-P75) of time to response was 1.1 (0.5-3.3), 1.0 (0.5-2.9) and 1.0 (0.5-2.6) h, respectively.

CONCLUSIONFrom 2011 to 2013, the proportion of responded signals and response timeliness of CIDARS maintained a rather high level, and further presented an increasing trend year by year. But the proportion of signals related to suspected outbreaks should be improved.

Objective:To investigate the effects of estimated dose of radiation to immune cells (EDRIC) on overall survival (OS), local progression-free survival (LPFS) and distant metastasis-free survival (DMFS) in limited-stage small-cell lung cancer (LS-SCLC) with different tumor burdens.Methods:Clinical data of 216 patients with LS-SCLC who initially received conventional fractionated radiotherapy of the chest for radical treatment in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were retrospectively analyzed. EDRIC was calculated based on the model developed by Jin et al. and tumor burdens were assessed by gross tumor volume (GTV) or clinical stage. The study endpoints were OS, LPFS and DMFS, which were calculated from the date of diagnosis. The optimal cut-off value of EDRIC was calculated by R language. The correlation between EDRIC and tumor burdens was analyzed using Spearman's correlations. Survival analysis was performed by Cox proportional hazards regression model and Kaplan-Meier curve. Results:The median follow-up time for the whole group was 47.8 months, and the median OS and DMFS was 34.6 months and 18.5 months, respectively, while the median LPFS did not reach. The optimal cut-off value of EDRIC was 6.8 Gy. Cox multivariate analysis showed that EDRIC was an independent prognostic factor affecting OS and DMFS. EDRIC was weakly correlated with GTV or clinical stage. Stratified by the median GTV, OS ( P=0.021) and DMFS ( P=0.030) were significantly shortened and LPFS had a tendency of shortening ( P=0.107) when EDRIC>6.8 Gy compared with those when EDRIC ≤ 6.8 Gy in the GTV ≤ 34.6 cm 3 group; EDRIC had little effect on OS, LPFS, and DMFS ( P=0.133, 0.420, 0.374) in the GTV>34.6 cm 3 group. Stratified by clinical stage, OS ( P=0.003) and DMFS ( P=0.032) were significantly shortened and LPFS ( P=0.125) tended to shorten when EDRIC>6.8 Gy in stage I, II and IIIA groups; EDRIC exerted slight effect on OS, LPFS, and DMFS ( P=0.377, 0.439, 0.484) in stage IIIB and IIIC groups. Conclusion:EDRIC is an important factor affecting prognosis and exerts more significant impact on prognosis in patients with smaller tumor burden.

ObjectiveTo investigate the current status and development needs of evidence-based medicine （EBM） capability in ethnic minority medicine， and explore effective strategies to enhance EBM capability in this field. MethodsThe questionnaire survey was conducted in various ethnic minority medical institutions and research organisations. The questionnaire covered three dimensions， firstly， perceptions and attitudes towards evidence-based medicine； secondly， advantages and challenges in the development of ethnic minority medicine； thirdly， demands and recommendations for enhancing evidence-based medicine capability in ethnic minority medicine. ResultsA total of 501 valid questionnaires were collected， of which 103 questionnaires were collected by re-sending to minority medicine regions with insufficient participation. The questionnaires included 354 responses （70.66%） from practitioners of minority medicine， including Tibetan medicine， Mongolian medicine， Uyghur medicine， Zhuang medicine， and Korean medicine. Among the 501 questionnaires， 146 respondents （29.14%） indicated that they knew about EBM， 355 respondents （70.86%） had either a "general understanding" or had "not heard about" EBM before， and 469 respondents （93.61%） believed that introducing ECM could promote the development of ethnic minority medicine. The primary challenge in promoting EBM in the field of ethnic minority medicine is the lack of professionals in EBM and a lack of understanding of how to apply it into clinical practice （442 respondents， 88.22%）. In the 9-point importance rating for enhancing evidence-based abilities， high scores were achieved in standardization of clinical practice guidelines （7.50±1.90） and methods for sample sizes in clinical research （7.45±1.90）. Regarding the demand for improving clinical research literacy， expert academic lectures， and experience sharing （404 respondents， 80.64%） and evidence-based methodology monographs on ethnic minority medicine （401 respondents， 80.04%） were emphasized. ConclusionsPractitioners in ethnic minority medicine hold a positive attitude towards integrating EBM. However， there remains substantial room for the education and dissemination of EBM. Enhancing evidence-based capabilities can be achieved through specific measures such as cultivating or recruiting talents in EBM， establishing evidence-based support platforms for clinical research， organizing regular academic lectures and exchanges， and strengthening the construction of theoretical frameworks and evaluation systems tailored to ethnic minority medicine， thereby following a path of evidence-based practices aligned with the unique characteristics of ethnic minority medicine.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.