OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

Objective:To evaluate the effect of social media based behavioral intervention on promoting joint testing of HIV and syphilis in young men who have sex with men (MSM).Methods:After the recruitment, the participants who met the inclusion criteria were randomly divided (1∶1) into two groups, i.e. social media intervention group and control group. The control group was given routine voluntary counseling and testing (VCT) services. The intervention group was also given VCT services, besides; the comprehensive strategies through social media, including regular health education message and testing information sending, were given to them to strengthen the behavioral intervention. Follow up was conducted for the participants for 12 months after the intervention. The number and the proportion of young MSM receiving HIV and syphilis testing, and the reported proportion of the young MSM with sexually transmitted diseases (STD) symptoms between the intervention group and the control group were compared to evaluate the effect of the intervention.Results:A total of 315 young MSM were recruited (158 in the intervention group and 157 in the control group), in whom 248 young MSM completed the follow up. The follow-up rate was 78.7%. There was no significant difference in baseline characteristics between the intervention group and the control group (all P>0.05). The proportion of young MSM receiving more than one joint testing in the intervention group was slightly higher than that in the control group (53.2% vs. 48.4%, rate difference (RD): 4.8%, 95% CI: -7.5%-17.0%, P=0.448) without significant difference. However, in the young MSM who used condoms in the last anal sex, the proportion of those receiving more than one joint testing in the intervention group was higher than that in the control group (63.8% vs. 46.1%, RD: 17.7%, 95% CI: 1.5%-32.6%, P=0.035). In addition, the reported proportion of young MSM with STD symptoms in the intervention group was significantly lower than that in the control group (6.3% vs. 18.0%,RD: -11.7%, 95% CI: -20.6%- -3.0%, P=0.005). Conclusion:Compared with routine VCT, social media based behavioral intervention might promote joint HIV and syphilis testing in the young MSM who used condom in the study. It could significantly reduce the reporting proportion of STD symptoms, suggesting that this method can promote the AIDS and STD prevention related behaviors in young MSM.

OBJECTIVES: The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification. METHODS: The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model. RESULTS: This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm. CONCLUSIONS The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.
Artificial Intelligence ; Diabetes Mellitus ; Diabetic Foot ; Humans

Objective:To investigate the epidemiological characteristics and late diagnosis of suspected occupational diseases in Guangzhou from 2006 to 2018.Methods:The cases of suspected occupational diseases reported in Guangzhou from January 1, 2006 to December 31, 2018 were collected and followed up to the end of 2018. The cases of suspected occupational diseases were analyzed statistically.Results:A total of 1502 suspected occupational cases were reported in Guangzhou from 2006 to 2018, including suspected occupational otorhinolaryngological and oral diseases (58.59%, 880/1502) , suspected occupational chronic poisoning (25.03%, 376/1502) and suspected occupational pneumoconiosis (11.72%, 176/1502) . The key reporting areas were Huangpu District (27.50%, 413/1502) and Panyu District (20.91%, 314/1502) . The key reporting industries were manufacturing industry (80.36%, 1207/1502) , among which railway, ship, aerospace and other transportation equipment manufacturing industry (13.26%, 160/1207) , automobile manufacturing industry (12.51%, 151/1207) and general equipment manufacturing industry (10.19%, 123/1207) were the main industries. The main type of reported economy was private economy (39.95%, 600/1502) . The scale of the key reporting enterprises was medium and small-sized enterprises (31.09%, 467/1502 and 34.62%, 520/1502) . As of December 31, 2018, 263 cases were diagnosed with occupational diseases, and the diagnosis rate was 17.51%.Conclusion:The number of suspected occupational diseases reported in Guangzhou from 2006 to 2018 is large, and the overall diagnosis rate of suspected occupational diseases is low. It is necessary to strengthen the supervision and management of key diseases, key regions, and key industries of suspected occupational diseases. It is suggested that the reporting system of suspected occupational diseases should be standardized as soon as possible.

Objective:To investigate the epidemiological characteristics and late diagnosis of suspected occupational diseases in Guangzhou from 2006 to 2018.Methods:The cases of suspected occupational diseases reported in Guangzhou from January 1, 2006 to December 31, 2018 were collected and followed up to the end of 2018. The cases of suspected occupational diseases were analyzed statistically.Results:A total of 1502 suspected occupational cases were reported in Guangzhou from 2006 to 2018, including suspected occupational otorhinolaryngological and oral diseases (58.59%, 880/1502) , suspected occupational chronic poisoning (25.03%, 376/1502) and suspected occupational pneumoconiosis (11.72%, 176/1502) . The key reporting areas were Huangpu District (27.50%, 413/1502) and Panyu District (20.91%, 314/1502) . The key reporting industries were manufacturing industry (80.36%, 1207/1502) , among which railway, ship, aerospace and other transportation equipment manufacturing industry (13.26%, 160/1207) , automobile manufacturing industry (12.51%, 151/1207) and general equipment manufacturing industry (10.19%, 123/1207) were the main industries. The main type of reported economy was private economy (39.95%, 600/1502) . The scale of the key reporting enterprises was medium and small-sized enterprises (31.09%, 467/1502 and 34.62%, 520/1502) . As of December 31, 2018, 263 cases were diagnosed with occupational diseases, and the diagnosis rate was 17.51%.Conclusion:The number of suspected occupational diseases reported in Guangzhou from 2006 to 2018 is large, and the overall diagnosis rate of suspected occupational diseases is low. It is necessary to strengthen the supervision and management of key diseases, key regions, and key industries of suspected occupational diseases. It is suggested that the reporting system of suspected occupational diseases should be standardized as soon as possible.

Objective To evaluate the in vitro antifungal activity of osthole against Talaromyces marneffei (TM) in yeast phase,in order to provide an experimental reference for the clinical treatment of TM infection with Chinese medicine.Methods There were 20 TM strains,including 1 standard strain,2 fluconazole-spontaneously resistant strains,11 clinical isolates,and 6 isolates from wild bamboo rats.A microdilution method was used to prepare 96-well antifungal sensitivity test plates containing osthole,fluconazole,amphotericin B,itraconazole and voriconazole at different concentrations,which were incubated with (1-5) × 103 CFU/ml of tested TM strain suspensions at 37 ℃ for 48 hours.Meanwhile,TM strains cultured in the media without antifungal drugs served as positive (growth) control group,and culture media served as negative group.The minimum inhibitory concentrations (MICs) of antifungal drugs against yeasts were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution susceptibility method (M27-A2 Document).Fluconazole MIC was defined as the lowest drug concentration that resulted in ≥ 80％ growth inhibition,and MICs of other antifungal drugs were the lowest drug concentrations that resulted in 100％ growth inhibition,compared with growth control wells.Results The MICs among the quality control strains were all within the reference range,and TM grew well in the positive control wells.The MIC ranges of fluconazole,amphotericin B,itraconazole and voriconazole against TM strains were 2.0-8.0 mg/L,1.0-4.0 mg/L,0.03-0.25 mg/L and 0.06-0.25 mg/L respectively,and the MIC of fluconazole against fluconazole-spontaneously resistant strains was 128 mg/L.The MICs of osthole against the TM standard strain (FRR2161),fluconazole-spontaneously resistant strains and 1 isolate from wild bamboo rats were 16,32 and 128 mg/L respectively,and the MIC range of osthole against other 16 TM strains was 16-64 mg/L.The MICs of osthole at which 90％ and 50％ of the TM strains were inhibited were 64 and 32 mg/L respectively.Conclusion Osthole exhibits the antifungal activity against the yeast form of TM.

OBJECTIVE:To provide reference for drug consultation of Chinese patent medicine(CPM)in pregnancy. METH-ODS:Package inserts of CPM in our hospital during Jan.-Jun. 2016 were collected. Referring to the prohibited,contraindicated and caution materials and decoction pieces in Chinese Pharmacopoeia(part 1,2015 edition),based onnoteitem in Chinese Pharma-copoeia and Clinical Application Guidelines(2010 edition),problems existing in pregnancy contraindication labeling of package in-serts were compared and analyzed. RESULTS:There were 99 kinds of prohibited,contraindicated and caution materials and decoc-tion pieces in Chinese Pharmacopoeia. There were 210 package inserts of CPM except for the special medicine for children,in which 32 contained prohibited materials,61 contained caution materials,only 21 were in line with the contained materials. Among the package inserts of 93 CPM containing prohibited or caution materials,27 were included in Chinese Pharmacopoeia,13 in Clini-cal Application Guidelines only,17 in both,but only 6 had the same contraindication labeling. Among the package inserts of 32 CPM containing prohibited materials,6 were explicitly labeled prohibited,17 labeled contraindicated or caution,and 9 labeled none. Among the package inserts of 61 CPM containing caution materials,29 were labeled prohibited or contraindicated,15 la-beled caution,and 17 labeled none. Among the package inserts of 117 CPM containing no prohibited,contraindicated or caution materials,8 were labeled contraindicated in pregnancy,and 18 labeled prohibited in pregnancy. CONCLUSIONS:The pregnancy contraindications of most CPM are not normative,showing poor consistency with Chinese Pharmacopoeia or Clinical Application Guidelines. Except for providing drug consultation by complying with Chinese Pharmacopoeia,Clinical Application Guidelines and package insert,pharmacists can judge the CPM without labeled pregnancy contraindication by analyzing its classification of con-tained materials. Using TCM does not indicate safety drug use,in addition,some CPM contain western medicine ingredients. There-fore,pharmacists should conduct medication education for patients who used CPM in pregnancy. Considering the new and severe adverse reactions of TCM injections are more,its adverse reactions exist unpredictability,so that pregnant patients should be sug-gested to avoid using TCM injections by pharmacists.

Objective To investigate the clinical manifestations and pathogenic characteristics of nosocomial bacterial infection in children with infectious mononucleosis (IM).Methods A retrospective analysis was performed for IM children from January to December 2015 in West China Second University Hospital.According to whether there was the process of secondary bacterial infection,the patients were divided into the secondary infection group and the non-infection group.The clinical manifestations and pathogenic bacteria were analyzed.Results Two hundred and sixteen children with IM were enrolled,of whom,177 cases (81.9％) were in the non-infection group,and 39 cases (18.1％) were in the secondary infection group.The patients in non-infection group were (4.7 ± 3.2) years old,and the patients in secondary infection group were (7.0 ± 3.8) years old,and the difference was statistically significant (t =3.066,P ＜ 0.05).The secondary infection group included bacterial tonsillitis in 17 cases,bronchial pneumonia in 11 cases,otitis media in 5 cases,cervical bacterial lymphadenitis in 3 cases,periorbital cellulitis in 2 cases,and sepsis in 1 case.Meanwhile,3 cases of concomitant thrush were observed in the secondary infection group.The rate of nosocomial bacterial infection in IM children [18.1％ (39/216 cases)] was significantly higher than the incidence of nosocomial infection [1.53％ (644/41 992 cases)] in the same period,and the difference was statistically significant (x2 =368.474,P ＜ 0.01).The patients with secondary bacterial infection were treated with antibiotics,and the pathogenic bacteria were mainly gram-negative bacteria,which was consistent with pharyngeal tonsil colonization bacteria on admission.In 212 cases (98.1％) with IM,variant lymphocytes increased,and there was no significant difference between 2 groups in the variation of lymphocyte composition (x2 =2.087,P ＞ 0.05).C-reactive protein (CRP) level of IM children on admission was (11.3 ± 17.4) mg/L,while the secondary infection group was (10.2 ±9.7) mg/L and the non-infection group was (11.5 ± 18.1) mg/L,and there was no significant difference between the 2 groups (t =1.309,P ＞ 0.05).CD3 +,CD4+,CD8 + lymphocytes in the secondary infection group were 0.877 6 ± 0.031 8,0.079 0 ± 0.032 5 and 0.682 1 ± 0.053 5,compared with the non-infection group,while CD3 + lymphocytes (t =12.652,P ＜ 0.01) and CD8 + lymphocytes (t =-9.723,P ＜ 0.01) increased significantly,but the proportion of CD4+ lymphocytes decreased significantly (t =18.341,P ＜0.01).Conclusions The IM children are susceptible to nosocomial bacterial infection,which is more obvious in school-age children.Secondary respiratory tract infections are the most common type,and pathogenic bacteria may be caused by the dissemination of colonization bacteria in the pharyngeal tonsils.The CRP and variant lymphocytes on admission could not be used as the marker for predicting noscoomial bacterial infection in IM.

Objective To observe the ultrastructure of dimorphic Penicillium marneffeiisolates from wild bamboo rats (Rhizomys pruinosus) in Guangxi region as well as from a patient with penieilliosis marneffei,and to compare their biological characteristics and anti-oxidative mechanisms.Methods Two Penicillium marneffei strains,including one isolated from wild bamboo rats (Rhizomys pruinosus) in Guangxi region and one from a patient with penicilliosis marneffei,were cultured with or without the presence of 2.0 mmol/L hydrogen peroxide in potato dextrose agar (PDA) at 25 ℃ and in brain-heart infusion (BHI) broth at 37℃ for seven days.The shape of colony and growth of both strains were observed.Light microscopy was carried out to study the morphology,and transmission electron microscopy to observe the ultrastructure,of both isolates.Results Ater incubation with hydrogen peroxide,there was a slowdown in the growth of both Penicillium marneffei isolates at both mycelial phase and yeast phase,with an increase in the production of pigment at mycelial phase at 25℃.No obvious changes were observed at 37 ℃ in the morphology of either the clinical isolate or the bamboo rat isolate when cultured with hydrogen peroxide compared with those cultured without hydrogen peroxide.Light microscopy showed attenuated spore formation by the clinical isolate when cultured at 25 ℃ with hydrogen peroxide,crenation of both isolates when cultured at 37 ℃ with hydrogen peroxide.Under a transmission electron microscope,the mycelial cells of both isolates exhibited smooth cell walls,intact cell membranes,with nuclei,mitochondria,endoplasmic reticulum,lipid body,vacuoles of various sizes in the cytoplasm at 25 ℃,and even microbodies at 37 ℃,when cultured without the presence of hydrogen peroxide.After incubation with hydrogen peroxide,the cell wall of both isolates became incomplete with defects in some areas and uneven thickness,the cell membrane discontinuous with shrinkages and projections,and the cytoplasm was inhomogeneous with obvious phagocytosis and numerous phagocytic vacuoles.Conclusions The clinical and bamboo rat isolates of Penicillium marneffei experience different biological and morphological changes under oxidative stress,hinting differences in antioxidative mechanism between them.

Both innate and adaptive immunity contribute to the pathogenesis of ischemia-reperfusion injury (IRI).During acute phase of kidney IRI,kidney endothelial cells promote inflammation after IRI by increasing adhesion molecule expression and vascular permeability,and tubular epithelial cells increase complement C3 binding and Toll-like receptor 2 and Toll-like receptor 4 expression.Early activation of kidney dendritic cells initiates a cascade of events leading to accumulation of neutrophils,macrophage,natural killer cells,CD4 + T cells and B cells in the early phase of renal IRI.Soluble components of the immune system,such as complement activation production,cytokines and chemokines,also are implicated in the injury and repair of post-ischemic kidneys.Foxp3 + regulatory T cells and alternatively activated macrophage participate in attenuating the inflammation and initiating the repair of kidney IRI,while B lymphocytes limit repair of kidney IRI.