Objective:This study explored the effect of nanoparticle-encapsulated curcumin on the highly expressed multidrug resistance gene 1 （MDR1） in a human low-differentiated nasopharyngeal carcinoma cell line （CNE2）. Methods:Curcumin/chitosan deoxycholic acid nanoparticles were prepared, and the cells were subjected to different treatments: radiotherapy, empty carriers, curcumin, and curcumin-loaded nanoparticles. Cell survival was analyzed using the clonogenic assay, and assessments of apoptosis, MDR1 levels, and miR593 levels were conducted. Results:The cell survival fractions in the curcumin group and the curcumin-loaded nanoparticles group were significantly reduced. Notably, higher apoptosis rates were observed in cells treated with curcumin or curcumin-loaded nanoparticles compared to those that received only radiotherapy. Moreover, a decreased MDR1 level was noted in both the curcumin group and the curcumin-loaded nanoparticles group, with further reduction in MDR1 expression observed in the nanoparticle group （P<0.05）. Enhanced expression of miR593 was found in the curcumin group and the curcumin-loaded nanoparticles group, with a relatively higher level in the nanoparticle group （P<0.05）. Curcumin encapsulated in nanoparticles exhibited a stronger radiosensitizing effect. The combination of curcumin and radiotherapy effectively inhibited nasopharyngeal carcinoma （NPC） tumor growth, suppressed MDR1 expression, and enhanced miR593 levels. After inhibiting miR593, MDR1 expression increased. The radiosensitizing effect of curcumin-loaded nanoparticles was regulated by miR593 rather than being triggered by MDR1. Conclusion:Curcumin-loaded nanoparticles mediated enhanced expression of miR593, which in turn inhibited the transcription and translation of the MDR1 gene, thereby reducing the radioresistance of NPC and effectively restraining its growth.
Humans ; Curcumin/pharmacology* ; Nasopharyngeal Neoplasms/pathology* ; Nasopharyngeal Carcinoma ; Nanoparticles ; Cell Line, Tumor ; Apoptosis/drug effects* ; MicroRNAs ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism* ; Cell Survival

OBJECTIVE To investigate the improvement effect and mechanism of triptolide （TP） on sciatica rats. METHODS Sciatica rat model was prepared and then randomly divided into model group （normal saline）， indomethacin group （positive control， 7.5 mg/kg）， TP low-dose and high-dose groups （TP-L group and TP-H group， 50， 100 μg/kg TP）， and high-dose TP+ stimulator of interferon gene （STING） activator group （TP-H+DMXAA group， 100 μg/kg TP+25 mg/kg DMXAA）， with 12 rats in each group. Another 12 unligated rats were selected as sham operation group （normal saline）. After 14 days of intraperitoneal administration， the paw mechanical withdrawal threshold （PWT） and paw withdrawal thermal latency （PWL） were detected； the pathological changes， morphology of sciatic nerve and the number of microglia in sciatic nerve were observed. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， mRNA and protein expression levels of cyclic guanosine monophosphate- adenosine monophosphate synthase （cGAS） and STING in sciatic nerve were detected. RESULTS Compared with sham operation group， PWT and PWL of rats in model group were obviously reduced and shortened， the number of Nissl bodies was obviously decreased， while the number of microglia， sciatic neuropathology score， the levels of IL-1β and TNF-α， mRNA and protein expressions of cGAS and STING were obviously increased （P＜0.05）， and sciatic nerve injury was serious. Compared with model group， the changes of various indexes in indomethacin group， TP-L group and TP-H group were opposite to the above （P＜0.05）， and sciatic nerve injury was reduced. STING activator DMXAA weakened the inhibitory effect of TP on the activity of microglia and inflammatory response in sciatica rats （P＜0.05）. CONCLUSIONS TP may reduce the activity of microglia and inflammatory response by down-regulating the cGAS/STING signaling pathway， thus alleviating sciatica in rats.

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA repair.Among the elements that lead to DDP resistance,O6-methylguanine(O6-MG)-DNA-meth-yltransferase(MGMT),a DNA-repair enzyme,performs a quintessential role.In this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in vivo.Conversely,in cancer cells,MGMT overexpression abolishes their sensi-tivity to DDP treatment.Mechanistically,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of CDK1.Meanwhile,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy drugs.Our transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant cells.In summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

This study deeply analyzes the common problems of three military medical universities in the management of undergraduate extracurricular scientific research, such as lack of communication means, limited online resources, backward laboratory opening and low utilization rate of equipment. We have built a cloud platform management system for undergraduate extracurricular scientific research. This system firstly sets up a teaching resources storage module including videos, PPTs, documents, pictures, electronic materials, question bank, etc. Then four subsystems for different roles of students, mentors, experimental teaching staff and administrators are constructed. Finally, this system realizes independent experiments by students, real-time evaluation by mentors, instrument sharing and efficient management through the seamless connection with the user terminal equipment. And the study also makes evaluation on the present usage.

Objective:To explore the molecular mechanism of Guchang-Zhixie pill in the treatment of ulcerative colitis based on network pharmacology. Methods:Retrieve the TCMSP database to get the effective components and target genes of each drug in Guchang-Zhixie pill, and then retrieve the OMIM database Disgenet database to get disease genes, and then intersect the drug genes and disease genes to get the core genes. Used STRING database to build gene function association network, and used DAVID database to analize go enrichment and pathway enrichment of the core genes. Results:A total of 77 active ingredients and 211 targets of Guchang-Zhixie pill were obtained by TCMSP database, 914 genes of ulcerative colitis were obtained by retrieving disease gene database, 72 core genes were obtained by intersection of drug gene and disease gene. Topology analysis showed that the core targets were IL6, IL1B, MAPK1, VEGFA, MMP9, etc; Twelve enriched biological process clusters were obtained. The biological processes with more contact targets were positive regulation of RNA polymerase Ⅱ promoter transcription and positive regulation of DNA template transcription; A total of 14 enriched pathway clusters were obtained by pathway enrichment analysis, among which TNF signaling pathway and PI3K/Akt signaling pathway were closely related to inflammation and associated with more targets. Conclusion:The target and pathway of Guchang-Zhixie pill in the treatment of ulcerative colitis are preliminarily obtained through database analysis, which has provided the reference for clarifying its mechanism.

Objective:To master the current status of iodine nutrition of residents in Tongchuan City and provide basis for policy adjustment of relevant department.Methods:In 2019, the cross-sectional survey method was used to divide 5 sampling areas in the 4 districts (counties) of Tongchuan City according to the east, west, south, north, and middle, and each area sampled 1 township (street, including at least 1 street), each township (street) selected one elementary school, each elementary school selected 42 non-boarding students aged 8 - 10, and each township (street) selected 21 pregnant women as the survey subjects. Home salt samples and urine samples were collected, salt iodine and urinary iodine were monitored, and thyroid examinations were performed on students.Results:A total of 1 260 salt samples were collected, including 2 non-iodized salt and 1 240 qualified iodized salt; the median salt iodine was 24.32 mg/kg; the coverage rate of iodized salt, the qualified rate of iodized salt, and the edible rate of qualified iodized salt were 99.84% (1 258/1 260), 98.57% (1 240/1 258) and 98.41% (1 240/1 260), respectively. A total of 840 urine samples were collected from students, the median urinary iodine was 196.19 μg/L. The medians urinary iodine of students aged 8, 9, and 10 were 182.59, 222.16, and 190.36 μg/L, respectively. The median urinary iodine of male and female students were 211.27 and 186.76 μg/L. A total of 840 students were tested for thyroid, thyroid rate was 1.79% (15/840) by B-ultrasound. A total of 420 urine samples were tested of pregnant women. The median urinary iodine was 155.05 μg/L. The medians urinary iodine of pregnant women in the first, second and third trimester of pregnancy were 166.79, 176.11 and 129.82 μg/L, respectively. There was a statistically significant difference in urine iodine content of pregnant women in different pregnancy periods ( H = 9.317, P < 0.05). Conclusions:The iodine nutrition level of residents in Tongchuan City is generally suitable. Pregnant women's urinary iodine shows iodine deficiency in the third trimester. Monitoring of iodine nutrition of pregnant women should be strengthened, classified guidance and scientific iodine supplementation should be adhered, to ensure the appropriate level of iodine nutrition for pregnant women.

【Objective】 To explore the correlation of preoperative fibrinogen-to-albumin ratio （FAR） with the clinicopathological characteristics and prognosis of patients with rectal cancer so as to clarify the role of coagulation function and nutritional status in the occurrence and progression of tumors. 【Methods】 We retrospectively analyzed the clinicopathological data of 647 patients with rectal cancer who underwent radical resection in The First Affiliated Hospital of Xi’an Jiaotong University from January 1， 2013 to December 31， 2016. According to the optimal cut-off point value of FAR determined by receiver operating characteristic curve， 647 rectal cancer patients were divided into high FAR level group and low FAR level group. The correlation between different preoperative FAR levels and clinicopathological characteristics of rectal cancer patients was analyzed. Multivariate Cox regression analysis was used to analyze the independent risk factors for the prognosis of rectal cancer patients. R software was used to construct the nomogram， and C index and calibration chart were used to evaluate the prediction efficiency of the nomogram. 【Results】 Preoperative FAR levels had a good predictive value for the prognosis of rectal cancer patients. The area under ROC curve was 0.771， the optimal cut-off point was 0.092， and the Youden index was 0.446. There were statistically significant differences in age， T stage， N stage， TNM stage， preoperative CEA levels and preoperative CA19-9 levels between rectal cancer patients with different preoperative FAR levels （P<0.05）. The overrall survival and disease-free survival of rectal cancer patients with different preoperative FAR levels had statistically significant differences （P<0.05）. In the multivariate analysis， preoperative FAR levels （≥0.092， HR=3.298， 95% CI： 2.365―4.600， P<0.001）， age （≥60 years， HR=2.110， 95% CI： 1.479―3.012， P<0.001）， TNM stage （Ⅲ grade， HR=6.743， 95% CI： 2.771―16.771， P<0.001）， grade of differentiation （poor， HR=1.639， 95% CI： 1.104―2.432，P=0.014）， preoperative CA19-9 levels （≥37 U/mL， HR=2.205， 95% CI： 1.529―3.180， P<0.001） and not perform postoperative chemoradiotherapy（HR=1.792， 95% CI： 1.294―2.480，P<0.001） were independent risk factors of overall survival for patients with rectal cancer. OS and DFS nomograms of rectal cancer were established by the Rlanguage software， and the C-index was （0.781， 95% CI： 0.749―0.815； 0.754， 95% CI： 0.693―0.760）， respectively. The calibration curve of the nomogram showed high consistence between predictions and actual results for 1-year， 3-year， 5-year OS and DFS. 【Conclusion】 The preoperative high FAR level was an independent risk factor for the prognosis of patients with rectal cancer. It can be supplemented with pathological factors such as TNM stage as prognostic indicators for patients with rectal cancer， which may be helpful for clinicians to follow up or make beneficial treatment for rectal cancer patients.

Objective:To systematically analyze the clinical features of severe fever with thrombocytopenia syndrome (SFTS) and to provide evidence for the prevention and treatment of SFTS.Methods:Relevant studies of SFTS from six databases, including China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP, PubMed, Cochrane Library and Embase from January 2009 to May 2019 were systematically searched and identified. The literatures were screened and the data of patients′ epidemiology, clinical manifestations, laboratory examinations and prognosis were obtained. Revman 5.2 software was used for meta analysis.Results:Sixty-eight Chinese literatures and fourteen English literatures encompassing 6 780 patients with SFTS were included in the final analysis. Of these patients, 845 cases (12.46%) died. SFTS mostly occurred in mountainous and hilly areas, and farmers (3 637 cases) were the usual victims. The onset season was mostly in summer and the peak was from May to August each year. There were 1 434 patients had a clear history of tick bites, and 21 cases were human-to-human transmitted.There were 6 071 cases (89.54%) presented with fever, 5 407 cases (79.75%) presented with fatigue, 3 140 cases (46.31%) presented with muscle soreness, and 2 300 cases (33.92%) presented with chills.Using random effects model for meta analysis, the levels of creatine kinase (CK) (mean difference ( MD)=500.40, 95% confidence interval ( CI) 380.51-620.28, P<0.01) and lactic acid dehydrogenase (LDH)( MD=442.81, 95% CI 152.85-732.78, P=0.003) in severe patients were both higher than those in mild patients, and the difference were both statistically significant. The risk of death increased in patients aged>60 years( MD=8.19, 95% CI 4.03-12.36, P<0.01). The levels of CK( MD=530.92, 95% CI 29.27-1 032.56, P=0.040), LDH( MD=609.28, 95% CI 80.25-1 138.31, P=0.020), urea nitrogen ( MD=4.67, 95% CI 3.05-6.30, P<0.01) and creatinine ( MD=43.05, 95% CI 23.49-62.62, P<0.01) of patients in the death group were all higher than those in the survival group. The differences were all statistically significant. Conclusions:During the course of SFTS, the patients may show impaired blood system, heart, liver and kidney functions with high mortality. Clinicians should timely monitor the changes of blood routine, myocardial enzyme spectrum, liver and kidney functions and other indicators, so as to find cardiovascular and other system complications as early as possible. Timely treatment could not only reduce liver, heart and other organ injuries, but also reduce mortality.

Objective:To explore the mechanism of Cordyceps sinensis on chronic obstructive pulmonary disease (COPD) by means of network pharmacology.Methods:By searching in TCMSP database, extracted the active ingredients and targets of Cordyceps sinensis; by searching in GeneCards and OMIM database, extracted the disease targets of chronic obstructive pulmonary disease (COPD) , then constructed the drug-disease and protein interaction network, and analyzed GO enrichment and KEGG on the targets.Results:Seven effective components and 84 effective targets of Cordyceps sinensis were obtained from TCMSP database, 5 142 COPD-related genes were obtained from GeneCards and OMIM database, 31 key targets for Prunella vulgaris to treat non-small cell lung cancer were obtained from drug-disease network, and 31 PPI networks were established, with 31 nodes, 77 edges and rich GO. GO enrichment found that the moderate targets include CASP3, NOS3, PPARG and RELA. KEGG enrichment yields 64 biological processes involving 17 signaling pathways.Conclusions:This study preliminarily validates the role and mechanism of Cordyceps sinensis in the treatment of COPD, and provides a reference for further research on the selection of target genes and signal pathways.

AIM: To investigate the role of post-hemorrhagic shock mesenteric lymph (PHSML) in the enhancementof vascular permeability .METHODS: Eighteen Wistar rats were randomized into sham group , shock group,and shock plus mesenteric lymph drainage (shock +drainage) group.The rats in shock group and shock +drainagegroup were routinely subjected to hemorrhagic shock and hypotension [(40 ±2) mmHg] was maintained for 90 min, andthen the fluid resuscitation was performed.Mesenteric lymph was drained in the rats in shock +drainage group from resuscitationfinished to 6 h, for the observation of PHSML drainage on the vascular permeability in multiple tissues of hemorrhagicshock rats.Afterwards, human umbilical vein endothelial cells (HUVECs) were incubated with the PHSML in vitro to observethe effects of PHSML on the morphology and permeability of HUVECs .RESULTS: The degree of blue color and concentrationsof Evens blue in the lung, myocardium, kidney, liver, spleen and small intestine were significantly increased inthe shocked rats than that in sham group, while the ratios of the dry weight to the wet weight were decreased .The mesentericlymph drainage reversed these changes .Meanwhile, 4% and 10% of PHSML at 0 ~3 h and 3 ~6 h after resuscitation,and lipopolysaccharide (10 mg/L) all caused the damage of HUVECs, decreased the viability and trans-endothelial electricalresistance of HUVECs, and increased the permeability of HUVECs to fluorescein isothiocyanate -labeled albumin. CONCLUSION: PHSML is a vital factor in the enhancement of vascular permeability .