Objective To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. Methods We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2,4,6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. Results The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P<0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P<0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P<0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P<0.05). Conclusion KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

Objective To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. Methods We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2,4,6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. Results The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P<0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P<0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P<0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P<0.05). Conclusion KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

Objective To study the effects of different types of fluid resuscitation on mesenteric microcirculation and inflammatory factors in rabbits with hemorrhagic shock.Methods The model of hemorrhagic shock rabbits was established by reducing the basic mean arterial pressure by 40%through draining the blood from the common carotid artery.Animals were randomly divided into control group,saline group,lactate Ringer group,acetic acid Ringer group,hydroxyethyl starch group and succinyl gelatin group with 8 animals in each group.Mesenteric microcirculation was monitored with microcirculation monitor.Mean arterial pressure(MAP),heart rate(HR),microvascular perfusion ratio(PPV)and microvascular blood flow index(MFI)were recorded before bleeding(T0),at hemorrhagic shock(T1),at the beginning of fluid resuscitation(T2),at the completion of fluid resuscitation(T3),and at the end of the experiment(T4).The contents of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1)and lactic acid(Lac)were measured at T0,T2 and T4.Results Compared with hydroxyethyl starch group,there were statistically significant differences in T3 MAP(P<0.05),except for succinyl gelatin group,hydroxyethyl starch group had higher MAP at T4 than other groups,the difference was statistically significant(P<0.05).The differences in MAP between experimental control group and other groups were statistically significant at T4(P<0.05).PPV and MFI of hydroxyethyl starch group and succinyl gelatin group were higher than those of normal saline group,lactic acid Ringer group and acetic acid Ringer group at T4(P<0.05),and the lactic acid value of hydroxyethyl starch group at T4 was the lowest,compared with lactic acid Ringer group and normal saline group,the difference was statistically significant(P<0.05).There were statistical significances between all groups and experimental control group at T4(P<0.05).There were no significant differences in TNF-αand IL-1 in T0,T2 and T4 among all groups(P<0.05).Conclusion Hydroxyethyl starch solution and succinyl gelatin solution can improve the microcirculation of rabbits with hemorrhagic shock,but can not improve the level of inflammatory factors.

OBJECTIVE There are serious hazards in depression,and the precise mechanism underlying the delayed onset of clinical antidepressants remains unclear.The purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I)function balance in the mechanism of antidepressant action.METHODS Based on the previous study,we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC)here and used its excitability to represent the establishment of a new E/I functional balance.We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times,including fluoxetine(SSRI),duloxetine(SNRI),vilazodone[serotonin 1A receptor(5-HT1A)ago-nist and SSRI],ketamine[N-methyl-D-aspartate(NMDA)receptor antagonist],and hypidone hydrochloride(YL-0919,new antidepressant with sigma-1 receptor ago-nist and SSRI).We first examined the initial onset time of activation of pyramidal neurons using multichannel elec-trophysiological recordings and tested the antidepressant behavioral effects using the FST.We then selected three antidepressants(fluoxetine,ketamine,and vilazodone)to explore its effects on the BDNF-mTOR pathway by West-ern blotting.In addition,we disrupted the E/I function bal-ance using chemogenetics to investigate the antidepres-sant-like effects of YL-0919 and ketamine in the FST and TST.RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST.Similarly,it took duloxetine for 10 d,vilazodone for 4 d,YL-0919 for 3 d and ketamine for 24 h,to exert such effects.Meanwhile,Western blotting results sug-gested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased.How-ever,haloperidol,a classic antipsychotic(without antide-pressant effects),exerted no such effects on the firing activities of pyramidal neurons.In addition,disrupting the E/I function balance(via activating the GABA neurons and inhibiting the glutamate neurons)blocks out the antidepressant-like effects of YL-0919 and ketamine in the FST and TST.CONCLUSION Taken together,our findings suggest that the commencement of antide-pressant effects may be accompanied by the increase in the firing activity of pyramidal neurons and the activation of the BDNF-mTOR pathway,which may be a necessary and rate-limiting process.The re-establishment of the E/I balance may be a landmark event for the onset of antide-pressant effects.

Objective:To assess the effect of serum heat inactivation on the detection of 2019 novel coronavirus (2019-nCoV) specific IgM and IgG antibodies by colloidal gold method.Methods:The serum specimens were collected from a total of 106 Coronavirus Disease 2019 (COVID-19) patients and 52 control subjects. Both the fresh serum and the heat inactivated serum samples from the same patient were detected simultaneously with the 2019-nCoV IgM and IgG antibodies detection kit (colloidal gold method). According to the patient′s onset time, the positive rates of antibodies production profile were calculated. The influence of heat inactivation on the detection rates of antibodies at different stages of disease after onset was analyzed.Results:The test results of the specimens of the healthy control group before and after inactivation were all negative. For the 106 specimens of COVID-19 patients, the detection rates of 2019-nCoV specific IgM and IgG antibodies were reduced after heating at 56 ℃ for 30 min. The positive rates of IgM antibodies significantly decreased from 66.04% (70/106) to 43.40% (46/106) ( χ2=22.042, P=0.000), while the positive rates of IgG antibodies slightly decreased from 81.13% (86/106) to 76.42% (81/106) ( χ2=0.800, P=0.063). Further analysis revealed that there was a significant difference in the positive rates of IgM antibodies before and after heat inactivation in the 3rd, 5th and 6th week after onset. However, there was no statistically significant difference in the detection rates of IgG antibodies before and after serum heat inactivation in different periods of onset. Conclusions:Heat inactivation significantly decreased the detection rates of 2019-nCoV specific IgM antibodies, which may lead to serological false negative results.

Objective:To analyze the identification and antibiotics susceptibility of Herbaspirillum in catheter-related bloodstream infection, and improve the awareness and attention of the rare pathogenic microorganisms for clinicians and microbiologists. Methods:The bacterium was isolated from a positive blood culture of a hemodialysis patient with chronic renal failure. The smear of isolate was prepared, stained and observed by microscope. The single colonies were identified by mass spectrometry and VITEK 2 Compact identification and antibiotics sensitivity analysis system, respectively. Then, 16S ribosomal DNA (rDNA) was amplified and sequenced, and bacterial genome was sequenced.Results:The gram-negative bacilli was found in the positive blood culture bottle. After incubated on blood agar for 16 hours, milky white, bulging and non-haemolytic colonies were observed. The identification result was Burkholderia cepacian by VITEK 2_Compact and antimicrobial susceptibility testing showed resistance to aztreonam and polymyxin but sensitive to other drugs in N335 card. The isolate could not be identified by VITEK MS with clinical database. However, it was identified as Herbaspirillum huttiense/Herbaspirillum aquaticum with research database. The 16S rDNA of the strain was consistent with Herbaspirillum huttiense and Herbaspirillum aquaticum (more than 99%). High-throughput bacterial genome sequencing revealed that the isolate in this case shared 100% homology with Herbaspirillum huttiense subsp putei IAM 15032 in Genbank database, which confirmed that the isolate was Herbaspirillum huttiense. Conclusions:There are more and more environmental microorganisms evolved into human pathogenic bacteria. Herbaspirillum species are easy to be misidentified because its biochemical characteristics are similar to other strains.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection. Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded. Results:A total of 218 patients(98.2％)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6％),and 221/222(99.6％)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4％),and in patients with decompensated cirrhosis it was 8/22(36.4％).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events. Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.

Objective To study the efficiency and accuracy of artificial intelligence (AI) system based on fundus photograph in diabetic retinopathy(DR)screening,and evaluate the clinical application value of AI system. Methods A diagnostic trial was adopted. Total of 13683 color fundus photos were collected in Zhaoqing Gaoyao People's Hospital from March,2017 to November,2018. The AI system for DR (ZOC-DR-V1) was established,based on transfer learning + NASNet algorithm,by training 4465 precisely labeled fundus images (2510 normal,and 1955 with any stage of DR). One thousand confirmed fundus images (300 normal and 700 with any stage of DR),diagnosed by AI ( AI group ) and doctors ( 3 ophthalmologist doctors and 3 endocrinologist doctors ) ( doctor group ) , respectively. Ophthalmologist group and endocrinologist group were both composed of primary,intermediate and senior physicians. The mean reading time of each image and the total time of 1000 images were recorded. The accuracy and efficiency of AI system and doctor groups were compared. The reading process was divided into two stages. The diagnostic coincidence rate and the average reading time of each group between the two parts were calculated and compared. This study protocol was approved by Ethic Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No. 2017KYPJ104). Results After training,the diagnostic coincidence rate of AI system (ZOC-DR-V1) in test set was 94. 7％,AUC was 0. 994. In this "man-machine to war",the diagnostic coincidence rate of primary,intermediate and senior endocrinologist was 94. 0％,91. 4％ and 93. 4％;the diagnostic coincidence rate of primary,intermediate and senior ophthalmologist was 92. 7％,94. 4％ and 95. 6％;the diagnostic coincidence rate of AI system was 95. 2％. There was no difference in the diagnostic coincidence rate between AI system and senior ophthalmologist ( P = 0. 749 ) . The mean reading time of each image of primary, intermediate and senior endocrinologists was (4. 63±1. 87),(3. 74±3. 47) and (5. 71±3. 47) seconds,and the total time of 1000 images of primary,intermediate and senior endocrinologists was 1. 29,1. 04 and 1. 58 hours;the mean reading time of each image of primary,intermediate and senior ophthalmologists was ( 7. 25 ± 6. 58 ) , ( 5. 18 ± 5. 01 ) and ( 5. 18 ± 3. 47 ) seconds,and the total time of 1000 images of primary,intermediate and senior endocrinologists was 2. 02,1. 44 and 1. 44 hours;the mean and total time of AI system was (1. 62±0. 67) seconds and 0. 45 hours,and the reading time of AI system was significantly shorter than that of the doctor groups (all at P=0. 000). The diagnostic coincidence rates between previous and posterior part of primary endocrinologist, primary and intermediate ophthalmologist were significantly different (χ2=11. 986,6. 517,10. 896;all at P<0. 05),and the mean reading time in the posterior part was significantly shorter than that in the previous part of intermediate and senior endocrinologist and primary ophthalmologist (t=4. 175,8. 189,5. 160;all at P<0. 01). While the reading time of AI system remained stable throughout the process(χ2=3. 151,P=0. 103;t=0. 038,P=0. 970). Conclusions The ophthalmic AI system based on fundus images has a good diagnostic efficiency,and its diagnostic coincidence rate can compare with senior ophthalmologist,providing a new method and platform for large-scale DR screening.