Abstract:Tumor is a dynamic pseudoorgan，which contains a variety of cell types，and the interaction between them produces a unique network. In this network，the survival of malignant cells faces many challenges and their metabolic characteristics are reprogrammed accordingly. This change can be experienced and carried out by itself through interaction with other cells in the tumor，especially immune cells. The reconstruction of tumor microenvironment can cause pathophysiological reactions and promote metabolic reprogramming. This metabolic interaction between different cells is used to support tumor metabolism and growth. The importance and universality of these processes and their role in tumor development and progression are being used to design new drug targets and cancer treatments. Therefore，the analysis of the characteristics of different intercellular metabolic reprogramming in tumor microenvironment will help to provide new immunotherapy schemes and strategies，and lay the foundation for individualized precision medical treatment.

Abstract:The coronavirus disease 2019（COVID-19）has now caused a global pandemic since it appeared in December 2019. According to the latest Diagnosis and Treatment Protocol for COVID-19 in China，the possibility of aerosol transmission exists under the condition of prolonged exposure to high concentrations of aerosol in a relatively closed environment. Aerosols are suspensions in air of solid or liquid particles. Due to their small aerodynamic diameter，bioaerosols are prone to deposit in the lower respiratory tract and are more likely to cause severe diseases such as pneumonia than droplets. This review will brush up on the literature on bioaerosols and expound its implications for the protection of COVID-19.

Abstract:Objective：The aim of this study was to analyze the expression of coronavirus-associated genes［angiotensin-converting enzyme 2（ACE2），transmembrane protease serine 2（TMPRSS2），dipeptidyl peptidase 4（DPP4），aminopeptidase N（ANPEP）］in the intestinal mucosa of patients with inflammatory bowel disease（IBD）. Methods：The occurrence of diarrhea in patients with corona virus disease 2019（COVID-19）were collected，and the IBDMDB database was used to analyze the expression of ACE2，TMPRSS2，DPP4 and ANPEP in the intestinal mucosa of IBD patients. Results：The occurrence of diarrhea in COVID-19 patients was 5.8%（136/2 350）. Compared with the rectal mucosa，the difference expression fold of ACE2，TMPRSS2，DPP4 and ANPEP in the terminal ileum were 9.800，0.571，5.318 and 11.127，respectively，with statistical differences（P < 0.05）. However，the expression of these 4 genes did not show significant differences between IBD and non-IBD patients（P > 0.05）. The GO classification showed that these genes were involved in the biological process of the virus entering the host cell，and there was a network interaction between these genes. Conclusion：There is no significant difference in the expression of coronavirus-related genes（ACE2，TMPRSS2，DPP4，ANPEP） in the intestinal mucosa of IBD and non-IBD. We speculate that IBD patients do not have a significantly increased risk of COVID-19.

Abstract:Objective：The aim of this study was to investigate the role of curcumin in promoting browning of white adipocytes and its underlying mechanisms through in vitro experiments. Methods：The subcutaneous primary adipocytes were extracted from mice and induced to differentiate into mature. Intervention with different concentrations of curcumin（10，20，40 μmol/L）for 48 h. Lipid droplet morphology was observed by oil red O staining. Intracellular mitochondria were detected with mitochondrial green fluorescent probe（Mito Tracker Green）. Mitochondrial superoxide indicator（Mito SOX Red） was used to determine the level of mitochondrial reactive oxygen species（ROS）. Intracellular ATP content was detected by the ATP assay kit. The expression of the browning-related marker gene was detected by real-time PCR. Finally，the mechanism was explored by using β3 adrenergic receptor（β3-AR） antagonist（SR59230A）. Results：In mouse subcutaneous primary adipocytes，curcumin markedly alleviates intracellular lipid accumulation. And more mitochondria were observed after curcumin treatment（P < 0.001）. Otherwise，curcumin of low dose（10，20 μmol/L） also reduced the production of ROS（P < 0.01），but increased the intracellular ATP content（P < 0.05）. In addition，curcumin can up-regulate the mRNA expression of the brown fat marker genes［β3-AR，uncoupling protein 1（UCP1），PPARγ coactivator-1α（PGC1α）］（P < 0.05）. However，β3-AR antagonist can antagonize the function of curcumin. Conclusion：Curcumin has the potential to promote mitochondrial biogenesis，improve their function and evoking white adipocyte browning through regulating β3-AR-dependent signaling pathway.

Abstract:Objective：This study aims to investigate the synergistic effects of mild elevation of free fatty acid and lipopolysaccharide（LPS）on apoptosis and insulin secretion in rat pancreatic β-cell line INS-1 and its mechanism. Methods：The INS-1 cells were cultured with palmitate（0.125 mmol/L）and different concentrations of LPS（1，10，50 ng/mL）for 24 h alone or together. Apoptosis rate was detected by flow cytometry. Western blot was used to detect the expression of Cleaved caspase-3. Neutral ceramidase（NCDase）activity was investigated by HPLC after INS-1 cells were treated with palmitate and LPS（50 ng/mL） alone or together. Insulin secretion was detected by ELISA. After transfected with recombinant plasmids pEGFP-C3-NCDase，the changes of apoptosis rate and insulin secretion of INS-1 cells stimulated by palmitate and LPS were observed. Results：Compared with the control，palmitate alone or LPS（50 ng/mL）alone had no significant effect on apoptosis or insulin secretion. However，the combination of palmitate and LPS significantly increased the apoptosis rate and up-regulated the expression of Cleaved caspase-3（P < 0.05）. Intracellular insulin content or glucose-stimulated insulin secretion was not altered while basal insulin secretion was significantly inhibited by palmitate and LPS for 24 h（P < 0.01）. In addition，NCDase activity was not affected by stimulation with palmitate or LPS alone while its activity was markedly inhibited by combination of palmitate and LPS（P < 0.01）. NCDase overexpression markedly ameliorated the apoptosis induced by palmitate and LPS in INS-1 cells and increased basal insulin secretion（P < 0.05）. Conclusion：Mild elevation of free fatty acid and LPS could synergistically promote β-cell apoptosis and decrease basal insulin secretion through inhibition of the activity of NCDase，a key enzyme of the sphingolipid metabolism.

Abstract:This study aims to investigate the role of sphingosine⁃1⁃phosphate receptor 2（S1PR2），proprotein convertase subtilisin/kexin type 9（PCSK9）in nonalcoholic steatohepatitis（NASH）. Methods：Twelve C57BL/6J mice were randomly assigned to control group and experimental group. After NASH models were successfully established by methionine choline deficiency diet（MCD） diet for six weeks，biochemical indices and inflammatory factors in serum and liver，including alanine aminotransferase（ALT）， aspartate aminotransferase（AST），glutamyl transferase（GGT），tumor necrosis factor alpha（TNF⁃α），interleukin⁃6（IL⁃6）and interferon ⁃γ（IFN⁃γ）were detected by ELISA．HE staining，oil red O staining and sirius red staining were used to observe liver inflammatory damage，lipid deposition and fibrosis. In vitro，the primary hepatocytes of C57BL/6J mice and HepG2 cells were challenged with palmiticacid and/or JTE⁃013（S1PR2 specific inhibitor），respectively；the lipid deposition was observed by oil red O staining，and the protein expression of S1PR2，PCSK9 and low ⁃density lipoprotein cholesterol receptor（LDLR）was detected by Western blot. HepG2 cells were transfected with S1PR2 interference or overexpression plasmids to find potential related genes by gene chip technology，and genes with significant expression differences were screened out in NASH mice. Results：Compared with the control group，expression level of liver S1PR2 was decreased and PCSK9 increased in experimetal group. In mouse primary hepatocytes and HepG2 cells，JTE⁃013 could increase lipid deposition，and increase the expression of phosphorylated ERK and PCSK9，while the expression of LDLR was decreased. A total of 343 genes were changed in HepG2 cells transfected with S1PR2 knockdown and overexpression plasmids. The levels of early growth response protein 1（Egr1）increased when S1PR2 was overexpressed and decreased when S1PR2 was interfered， and decreased in NASH model mice. Conclusion：S1PR2 is involved in the lipid metabolism and inflammatory injury of NASH，which may be related to the suppression of S1PR2 in inflammatory state，increaseing the expression of PCSK9 and decreaseing the expression of LDLR.

Abstract:Objective：This study aims to investigate the role of max action protein 1-0（Mxi1-0） in SH-SY5Y cell apoptosis induced by oxygen-glucose deprivation（OGD）. Methods：The expression levels of Mxi1-0 and mitophagy related proteins LC3-Ⅱ，p62，Tom20 in SH-SY5Y cells under OGD conditions were detected by Western blot. Mxi1-0 siRNA was tranfected into SH-SY5Y cells. The expression of Mxi1-0 and mitophagy related proteins（LC3-Ⅱ，p62，Tom20） were detected in SH-SY5Y cells under OGD using Western blot. The role of Mxi1-0 in OGD-induced apoptosis was detected using CCK-8 method and Annexin V/PI staining. Results：The expression of Mxi1-0 increased firstly and then decreased in SH-SY5Y cells after OGD treatment. The expression of mitophagy related protein LC3-Ⅱ increasesed and the expression of p62 and Tom20 proteins decreased after OGD treatment. Under OGD conditions，Mxi1-0 silence reduced mitophagy in SH-SY5Y induced by OGD，and increase the apoptosis of SH-SY5Y induced by OGD. Conclusion：Mxi1-0 antagonizes OGD induced apoptosis of SH-SY5Y cells by enhancing mitochondrial autophagy.

Abstract:Objective：This study aims to modify the transcardial perfusion method to improve the effects of brain fixation in canines. Methods：Seven beagle dogs were randomly divided into three groups：control group（n=1），transcardial perfusion group（n=3），and improved perfusion group（n=3）. Canines in the improved perfusion group were anaesthetized and heparin was administrated. The femoral artery access was achieved，then a catheter was inserted into internal carotid artery under fluoroscopic guidance and constituted the inflow，and the right auricle was opened to act as an outflow access. After the ligation of inferior vena cava and abdominal aorta，the brains were perfused with saline followed by paraformaldehyde. Once the perfusion was accomplished，the brains were harvested for HE staining and transmission electron microscopy. Results：Compared with the transcardial perfusion method，the improved perfusion method can significantly reduce the occurrence of cell autolysis，and it is liquid-saving and time-saving. Conclusion：The improved perfusion method is more effective than transcardial perfusion in canine brain tissue fixation，and it is feasible for brain fixation in large animals.

Abstract:Objective：This work aimed to explore the feasibility of establishing ex vivo animal model of segmentectomy. Methods：The animal model of segmentectomy was established by ex vivo porcine lungs. Six different segments were separated by electrotome，and their intersegmental planes were completely removed in order to evaluate and analyze the degree of air leakage and modeling time between different segmentectomy. Results：We identified the normal anatomy of segments of pig lungs firstly，and all animal models of segmentectomy were successfully established，which could achieve a satisfying effect of the identification and separation of intersegmental plane. There was no significant difference in the level of air leakage among the six various segments（P > 0.05）. The modeling time of the a segment of right cranial lobe（RS1a）segment［（880±83）s］ was shorter than other segments［the b segment of right cranial lobe（RS1b）：（1 531±79）s，the a segment of left cranial lobe（LS1a）：（1 384±75）s，the b segment of left cranial lobe（LS1b）：（1 207±56）s，the levo-a segment of left caudal lobe（LS2La）：（1 273±94）s，the dextro-a segment of left caudal lobe（LS2Da）：（1 179±108）s］，and there were significant differences among them（P < 0.01），and RS1a also got a lower sample rejection rate（11.11%）compared to the average level（26.24%）. Conclusion：The RS1a in ex vivo porcine lung can be utilized as an ideal model of segmentectomy for experiments.

Abstract:Objective：This study aims to analyze the correlation between the expression of integrin α5（ITGA5） and prognosis of head and neck squamous cell carcinoma（HNSCC）. Methods：The RNA-seq data and relevant clinical follow-up information of HNSCC in TCGA database were used to establish mRNA spectrum for variation analysis，further verification was conducted in GEO databases. Results：The mRNA expression of ITGA5 was found significantly higher in tumor tissues compared to normal tissues，and the overall survival of patients by Kaplan-Meier analyses in ITGA5 high-expression group was notably shortened（P < 0.05）. The expression level of ITGA5 could be treated as an independent prognostic indicator since it was verified in GEO databases to be sensitive and specific for patient survival and prognosis. Conclusion：ITGA5 is closely related to the survival and prognosis of HNSCC patients and may serve as a novel prognostic biomarker.

Abstract:Objective：This study aims to investigate the expression of fibroblast growth factor receptor 1（FGFR1），basic fibroblast growth factor（bFGF） and phosphatase and tensin homolog deleted on chromosome ten（PTEN） in lung squamous cell carcinoma（SCC）and its correlation with clinicopathological features and prognosis. Methods：All of 149 cases of lung SCC with complete clinicopathological data from 2011 to 2013 were collected from the First Affiliated Hospital of Nanjing Medical University to produce tissue microarrays. The expression of FGFR1，bFGF and PTEN was detected by MaxVision immunohistochemical method. Postoperative follow-up of patients was taken by telephone and outpatient service. Results：①In lung SCC，the positive rate of FGFR1，bFGF were 51.7%（77/149）and 61.7%（92/149）respectively. The expression of FGFR1 was significantly associated with smoking（P=0.019），lymph node metastasis（P＜0.001） and differentiation of tumor（P＜0.001）. The expression of bFGF was correlated with lymph node metastasis and T stage（P＜0.05）. The negative rate of PTEN was 57.0%（85/149）. The loss of PTEN expression was related to differentiation（P＜0.05）. In addition，FGFR1 expression was significantly associated with bFGF expression or PTEN expression（P < 0.05）. ②Univariate survival analysis showed that the expression of bFGF and FGFR1 were significantly correlated with the relapse free survival（RFS）and overall survival（OS）（P < 0.05）. There was no significant correlation between the loss expression of PTEN and RFS/OS. ③The Cox multi-factor survival analysis showed that FGFR1 expression was an independent prognostic factor for RFS and OS（P < 0.05）. Conclusion：The expression of FGFR1 in lung SCC was significantly correlated with poor differentiation，lymph node metastasis，smoking history，bFGF expression and loss of PTEN expression. Patients with FGFR1 positive expression had shorter survival time than those without FGFR1 expression. FGFR1 was an independent prognostic factor for SCC.

Abstract:Objective：This study aimed to investigate the prognostic factors affecting the radioiodine refractory-differentiated thyroid cancer（RAIR-DTC）and the predictive index. Methods：Differentiated thyroid cancer（DTC） patients who received total thyroid resection were retrospectively collected，with 131I treatment and follow-up in the First Affiliated Hospital of Nanjing Medical University from January 2009 to December 2017. The clinical characteristics，dynamic risk stratification and prognosis stratification were analyzed. The prognostic factors affecting the RAIR-DTC were explored，and the area under the receiver operating characteristic（ROC）curve and 95% confidence interval（CI），sensitivity and specificity of important intercept points were calculated. Results：①A total of 318 DTCs，272（85.5%）had no distant metastasis，46（14.5%）had distant metastasis；32（10.1%）patients were RAIR，286（89.9%）were non-radioiodine refractory（NRAIR）. Comparing with those of NRAIR patients，age and male proportion of RAIR patients was higher，the longest diameter of thyroid lesions of RAIR patients was larger，and the 131I treatment frequency，the distant metastasis rate，the dynamic risk stratification and prognosis stratification of RAIR patients were higher. There was no significant difference in the incidence of nodular lesions，lesions on the left and right，and multifocal lesions between RAIR and NRAIR patients. ②Binary logistic regression analysis showed that males，131I treatment frequency，cervical lymph node reaction were prognostic factors affecting RAIR-DTC. ③The area under the ROC（AUC）indicated that 131I treatment frequency was a major prognostic factor. When DTC patients receiving ≥3 131I treatment，the AUC of predicting RAIR was 0.861（95%CI 0.817-0.897），the sensitivity was 78.12% and the specificity was 88.85%（P＜0.001）. Conclusion：It is suggested to assess the probability of RAIR in ≥ 55 years DTC patients who received ≥3 131I treatment still with at least 1 metastasis without 131I uptake or progressive disease. Once diagnosed as RAIR，molecular targeted therapy should be taken as soon as possible.

Abstract:Objective：This study aims to evaluate effects and mechanisms of laparoscopic sleeve gastrectomy（LSG）on the changes of sex hormone level in obese young men with acanthosis nigricans. Methods：The clinical data of 45 young male obesity patients［body mass index（BMI）≥30 kg/m2］who underwent LSG was collected. The obesity patients were divided into obesity without acanthosis nigricans group（OB group，n=23）and obesity with acanthosis nigricans group（AN group，n=22）. The anthropometries parameters（weight，BMI，waist circumference，and body fat percentage），glucose metabolic indices［plasma glucose，glycosylated hemoglobin（HbAlc），insulin，homeostasis model assessment-insulin resistance index（HOMA-IR）］，lipid profiles（total cholesterol，triglyceride，high density lipoprotein cholesterol，low density lipoprotein cholesterol），inflammatory factors（serum uric acid，interleukin-6，tumor necrosis factor α） and sexual hormones were evaluated and calculated. Changes of these variables before and after surgery were analyzed. Results：LSG can significantly improve the level of total testosterone（TT）in obese young men. Before operation，the TT of AN group was only（7.60 ± 4.43）nmol/L，which was lower than the normal level and significantly lower than that of OB group（P < 0.01）. TT of OB group was（10.42 ± 5.14）nmol/L，which was also lower than the normal level. At 6 months after operation，TT levels in OB group and AN group were significantly higher than those before operation（P < 0.05），TT level in OB group was（15.58 ± 5.32）nmol/L，was（21.13 ± 23.43）nmol/L in AN group，and TT level in AN group increased more significantly than that in OB group（P < 0.05）. At 6 months after operation，inflammatory factors，plasma insulin level and HOMA-IR decreased significantly in OB group and AN group（P < 0.05），especially in AN group. TT was negatively correlated with BMI，body fat ratio，HOMA-IR，fasting and 2 hours postprandial insulin（P < 0.05），but not with fasting and 2 hours postprandial blood glucose（P > 0.05）. Conclusion：LSG can not only effectively reduce the weight of obese patients，but also significantly alleviate the hypotestosterone of obese men with acanthosis nigricans by improving insulin resistance and inflammation.

Abstract:Objective：This study aims to evaluate the clinical value of the anthropometric waist-to-height ratio（WHtR） through the hyperinsulinemic-euglycemic clamp. Methods：A total of 154 subjects was included in the study. Lipid profiles and other biochemical markers were measured from the fasting blood sample. All the patients underwent hyperinsulinemic-euglycemic clamp，and the glucose metabolic rate，body mass index（BMI），waist circumference（WC），waist-to-hip ratio（WHR），WHtR and HOMA index were calculated. The ability of each index to predict the assessment of insulin resistance was compared. Results：Correlation analysis showed that WHtR（r=-0.730，P < 0.001），WHR（r=-0.651，P < 0.001），BMI（r=-0.717，P < 0.001），WC（r=-0.716，P < 0.001）were all significantly correlated with the glucose metabolic rate obtained in the hyperinsulinemic-euglycemic clamp. The area under ROC curve was HOMA-IR（0.860）> WHtR（0.850）> BMI（0.846）> WC（0.837）> WHt（0.749）. The best value of WHtR for the diagnosis of insulin resistance was 0.56，which showed the highest sensitivity（93.9%）and specificity（66.7%）in the ROC curve. Conclusion：WHtR has a significant correlation with the glucose metabolic rate obtained from the hyperinsulinemic-euglycemic clamp，and has a higher sensitivity and specificity than BMI，WC and WHR，suggesting that it could be widely used in epidemiological studies or some large-scale clinical trials.

Abstract:Objective：This study aims to evaluate the clinical efficacy about triamcinolone acetonide oral ointment on minor recurrent aphthous ulcer（RAU）. Methods：Patients were selected from the Department of Oral Mucosal Disease，the Affiliated Stomatological Hospital of Nanjing Medical University from July 2018 to March 2019，and they were randomly divided into 3 groups . Group A was given with triamcinolone acetonide oral ointment and Kouyanqing granule； group B was treated with recombinant bovine basic fibroblast growth factor and Kouyanqing granule，group C was treated with Guilin watermelon frost spray and Kouyanqing granule. The scores of the visual analog scale（VAS） and the area and exudation as well as hyperemia of the target ulcer of patients were recorded at the first visit，the 3rd，5th and 7th day of follow-up respectively. At the same time，the ulcer healing time and analgesic time were also recorded. Results：The average healing time and the analgesic time of group A were significantly shorter than that in other two groups（P < 0.05）. The average laxation score of VAS about the target ulcers on the 3rd and 7 th day in group A was significantly higher than that in other two groups（P < 0.05）. On the third day，the reduced area of target ulcer of group A was significantly better than that of other two groups（P < 0.05）. At the same time，the exudation score and hyperemia score of group A were significantly different from the other two groups（P < 0.05） only on the fifth day. Conclusion：Triamcinolone acetonide oral ointment has a significant effect on promoting ulcer healing and reducing pain of patients suffering in the treatment of minor recurrent aphthous ulcer.

Abstract:Objective：This study aims to evaluate the short-term effects of different plasmas treatments on short-term bond strength of zirconia ceramic surface. Methods：Many pieces of zirconia ceramic slices were sandblasted and randomly divided into 5 groups based on different treatments. Group A，sandblast group；Group B，sandblast + oxygen（O2）plasma group；Group C，sandblast +argon（Ar）plasma group；Group D：sandblast +nitrogen（N2）plasma group；Group E：sandblast+Z-Prime plus group. The zirconia surface topography，contents of carbon and oxygen elements，roughness values，hydrophilicity were determined by scanning electron microscopy（SEM），energy dispersive spectrum（EDS），atomic force microscope（AFM）and water contact angle assay，respectively. And then composite resin columns were prepared and cemented on the pre-treated zirconia blocks with composite resin cement. Initial shear bond strengths（SBS） between zirconia and resin were measured after 24 h water storage. Failure modes were also analyzed. Results：There was no obvious difference in zirconia topography among testing groups. EDS showed that contents of carbon decreased and contents of oxygen increased after zirconia treated by different plasmas. Water contact angle test found that surface energy in groups treated with plasma was significantly improved comparing with group A. SBS test suggested that SBS in group C was similar as group E（P > 0.05），and SBS in both of them were significantly increased compared with other groups（P < 0.05）. Conclusion：The short-term bonding strength of zirconia can be significantly increased after treated by Ar plasma.

Abstract:Objective：The autoregressive integrated moving average（ARIMA）model was used to predict the number of registered tuberculosis cases in Changzhou and Yancheng in Jiangsu Province，in order to explore its feasibility for predicting tuberculosis epidemic situation in Jiangsu Province，and provide reference for future tuberculosis prevention and control work. Methods：The data on the number of registered tuberculosis cases in Changzhou and Yanchengof Jiangsu Province from January 2005 to December 2016 were collected，and the ARIMA models were established by the R3.5.2 software. The number of registered tuberculosis cases in January to December 2017 was predicted，with mean absolute percentage error（MAPE），root mean square error（RMSE）and mean absolute error（MAE）to evaluate the accuracy of ARIMA model predictions. Results：The optimal prediction models for Changzhou and Yancheng were ARIMA（0，1，1）（0，1，1）12 and ARIMA（1，1，1）（0，1，1）12，respectively. In the predicted number of registered tuberculosis cases in 2017，the MAPE values of the two cities were 8.718 6 and 16.787 8，the RMSE values were 14.061 7 and 39.487 2，the MAE values were 11.813 1 and 33.349 8，respectively. Conclusion：The ARIMA model has a relatively good fitting effect in predicting the monthly number of registered tuberculosis cases in Changzhou，so it is speculated that the model is suitable for short-term prediction and dynamic analysis of tuberculosis in the southern of Jiangsu.

Abstract:Cerebral small vessel disease（CSVD）is a series of age-related vascular disease that involves in a variety of pathologies. Increasing evidence has shown that CSVD is closely related to the occurrence of cognitive function. At present，the pathogenesis of CSVD and how it affects cognition are not yet fully understood，so there are no established treatment strategies for either preventing or treating CSVD. Combining the definition，classification，pathophysiology，and animal models of CSVD，this article reviews the clinical research and treatment of CSVD and related cognitive dysfunction.

Abstract:Under normal circumstances，Lactobacillus are the dominant bacterial flora in human vagina. Lactobacillus adhere to the vaginal mucosa and produce a series of metabolites，they can protect us from HPV infection and cervical lesions. The mechanism is various，including inhibiting the colonization of pathogen，inducing body immunity，playing cytotoxic effects on cancer cells，performing antimutagenic effect，regulating carcinogen metabolism and protecting DNA from oxidative damage. In his review，we discussed the progression in the protective mechanism of Lactobacillus on cervical lesions.