Cervical cancer is the leading cause of cancer death in women in the developing countries.The treatment based on surgery,radiotherapy and chemotherapy is often accompanied by intolerable complications.Clinical practice has proved that TCM therapy has a positive effect on the complications related to the treatment of cervical cancer,but there is still a lack of scientific and standardized application reference opinions.Based on Delphi method,our research group constructed and formulated an expert consensus study on the complications related to the treatment of cervical cancer with TCM therapies,so as to provide a reference for clinical treatment of such diseases.

Objective:To investigate the effect of recombinant lipoproteins of Brucella outer membrane protein 16, 19 (L16 and L19) on the expression of immune regulatory factors in human monocytic leukemia cell line (THP-1 cells). Methods:THP-1 cells activated with phorbol ester (PMA) were used as an in vitro experimental cell model, and a group design was used to co-culture L16, L19 and THP-1 cells (L16 stimulated group, L19 stimulated group), respectively. THP-1 cells activated with PMA were used as the control group. When co-cultured for 4 hours, immunofluorescence staining (IFS) and Western blotting were used to detect whether L16 and L19 entered the cells, respectively; when co-cultured for 12, 24 hours, real-time fluorescent quantitative PCR was used to measure the mRNA expression levels of interferon regulatory factor 1 (IRF-1) and trans activator protein of major histocompatibility complex class Ⅱ (CⅡTA); Western blotting was used to detect the protein expression levels of T cell immunoglobulin mucin-3 (Tim-3) and γ interferon receptor 1 (IFNGR1). Results:When co-cultured for 4 hours, L16 and L19 were observed entering THP-1 cells in the L16 stimulated group and L19 stimulated group, respectively. When co-cultured for 12 hours, the expression level of IRF-1 mRNA in the L16 stimulated group (0.16 ± 0.15) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 24 hours, the expression level of CⅡTA mRNA in the L16 stimulated group (0.17 ± 0.10) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 12 and 24 hours, there were no statistically significant differences in the expression levels of IRF-1 and CⅡTA mRNA between the L19 stimulated group and the control group ( P > 0.05). Western blotting results showed that there were statistically significant differences in the expression levels of INFGR1 and Tim-3 protein among the control group, L16 stimulated group, and L19 stimulated group after co-cultured for 12 and 24 hours ( F = 50.92, 6.80, 148.73, 156.57, P < 0.05). Among them, when co-cultured for 12 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were significantly lower than that in the control group, and the L19 stimulated group was higher than the L16 stimulated group ( P < 0.05), and the expression level of Tim-3 protein in the L19 stimulation group was higher than that in the control group ( P < 0.05). When co-cultured for 24 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were lower than that in the control group, and the L19 stimulated group was higher than that in the L16 stimulated group ( P < 0.05); and the expression level of Tim-3 protein in the L16 stimulated group was higher than that in the control group and L19 stimulated group ( P < 0.05). Conclusions:Brucella L16 can downregulate the expression levels of IRF-1 and CⅡTA mRNA in THP-1 cells. Both L16 and L19 can downregulate IFNGR1 and upregulate Tim-3 protein expression levels.

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8⁺ T cells and CD4⁺ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4⁺ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.
Humans ; CD8-Positive T-Lymphocytes ; RNA, Long Noncoding/genetics* ; Algorithms ; CD4-Positive T-Lymphocytes ; Down-Regulation ; Graves Ophthalmopathy/genetics* ; Gene Regulatory Networks ; MicroRNAs/genetics* ; Serine-Arginine Splicing Factors ; Phosphoproteins

Objective To investigate the infection status and epidemiological characteristics of viral pathogens in hospitalized patients with severe acute respiratory infection (SARI) in Guangdong Province from 2019 to 2021, so as to provide reference for clinical diagnosis and prevention. Methods The respiratory tract samples of SARI patients collected from 2019 to 2021 were detected and analyzed for respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus/enterovirus (HRV/EV), human metapneumonic virus (HMPV) and other common respiratory viruses using Luminex respiratory multi-pathogen detection technology. Results A total of 1 948 influenza-negative cases were collected, of which 24.28 % were positive detection of virus infection. HRV/EV was the highest (10.32%), followed by RSV (4.31%). The detection rates were statistically significantly different among different age groups (χ²=176.186，P<0.05), and the highest detection rate was found in the group aged at 0 to 4 years (41.50%). There was no statistically significant between the male virus detection rate and the female virus detection rate (χ²=0.042，P>0.05). The detection peaks of RSV were mainly concentrated in summer and autumn, while HMPV was prevalent in winter, and HRV/EV and ADV had no obvious seasonality. Mixed infection was found in 39 samples, and the mixed infection rate was 2.00%. In the mixed infection cases, HPIV and HRV/EV combined infection was the most common. Conclusion HRV/EV, RSV, HMPV and ADV are predominant viral pathogens in SARI influenza-negative hospitalized cases in Guangdong Province from 2019 to 2021. It is recommended to strengthen the surveillance of SARI cases in children under 5 years old.

Abstract Human adenovirus (HAdV), which is characterized by infectivity, complex pathogenesis and multiple target organs, causes multiple organ infections in the respiratory system, gastrointestinal system and eyes, which seriously endangers human health. Various subspecies of HAdV has different tissue tropism, which presents diverse clinical symptoms and epidemiological characteristics. Based on the molecule biological characteristics of HAdV, this review summarizes the clinical symptoms and epidemiological characteristics of HAdV infections depending on tissue tropism, and describes the trends in HAdV epidemiology, so as to provide insights into prevention and control of HAdV infections.

OBJECTIVE: To study the genetic variants of a child with Autism Spectrum Disorder (ASD) combined with epilepsy, and explore its possible pathogenic mechanism. METHODS: Clinical data of the child were collected and evaluated, whole-exome sequencing (WES) technology was used to explore the genetic variants sites of the child and his parents and candidate genes were filtered out. Sanger sequencing were performed to verify the variants identified by WES and PolyPhen2 was utilized to predict the function of these variants. qPCR was carry out to determine the expression of the variant gene. RESULTS: The proband carried a compound heterozygous mutation in the SIK3 gene (Chr11 q23.3, NM_025164.6), which contains a missense mutation c.1295A>G (p.N432S) inherited from the father and a deletion [c.2389_2391del(p.797del)] inherited from the mother. Both mutation sites are highly conservative, and PolyPhen2 predicted (c.1295A>G [p.N432S]) to be harmful. Compared to the mother, expression of SIK3in mRNA level in the peripheral blood of the proband and his father were both significantly decreased; compared to normal child, SIK3 expression in the peripheral blood of the proband and two other children with ASD were all decreased significantly too. In addition, studies on mice found that Sik3 gene has a marked higher level of expression in the brain. CONCLUSION The SIK3 gene variants may probably be associated with ASD. The detailed mechanism needs to be studied further, which may involve lipid metabolism dysfunction in the brain.
Animals ; Autism Spectrum Disorder/genetics* ; Epilepsy/genetics* ; Male ; Mice ; Mutation ; Mutation, Missense ; Protein Kinases ; Protein Serine-Threonine Kinases/genetics* ; Whole Exome Sequencing

Objective:To explore the application of peritoneal dialysis routine examination in reducing the incidence of peritonitis associated with peritoneal dialysis.Methods:From July 2018 to June 2019, 191 patients with peritoneal dialysis who were followed up regularly in the nephrology department were selected as the study subjects.Using convenient sampling method, outpatient follow-up on Tuesday were selected as control group(95 cases) and fixed outpatient follow-up on Thursday were selected as observation group(96 cases). Routine follow-up was performed in the control group, and routine examination of peritonitis was performed in the observation group during the follow-up.Intervention was given immediately when the problems were found to the naked eye and the examination results were abnormal.The incidence of peritonitis in the two groups was compared.Results:Peritonitis occurred in 24 cases in the control group(25.26%), and 9 cases in the observation group(9.38%). The incidence of peritonitis in the observation group was lower than that in the control group, and the difference was statistically significant(χ 2=5.972, P<0.05). Conclusion:The occurrence of peritoneal dialysis-related peritonitis is related to a variety of factors.Paying attention to the routine examination of peritonitis and observing the color of peritonitis, strengthening the aseptic fluid exchange operation, and following up the patients can effectively reduce the occurrence of peritonitis and improve the quality of dialysis.

Objective:To study whether aspirin has inhibitory effect on microglia activation induced by Poly-IC and its mechanism.Methods:Microglia cell line BV2 were cultured in vitro to establish a Poly-IC stimulation-induced microglia cell immune activation model. The experiment groups were divided into control group (no treatment), model group (Poly-IC 10 μg/ml), high dose aspirin group (1 mmol/L aspirin), low dose aspirin group (0.1 mmol/L aspirin), high dose aspirin pretreatment group (Poly-IC 10 μg/ml + 1 mmol/L aspirin) and low dose aspirin pretreatment group (Poly-IC 10 μg/ml + 0.1 mmol/L aspirin). The phagocytosis ability of microglia cells, reactive oxygen species (ROS) and Iba1 protein expression were detected by using immunofluorescence method. The expression of the inflammatory cytokines Il-1β, Il-6, Il-10, TNF-α and cox-2 mRNA in microglia cells were detected by real-time quantitative PCR (RT-qPCR).Results:Compared with the control group, the morphology of microglia cells in model group changed significantly, and the phagocytosis ability and production of reactive oxygen species (ROS) increased. At the meantime, the expression of Iba1 protein was strongly decreased. In the model group, The mRNA expressions of IL-1β(20.55±1.92), IL-6 (63.98±7.83), TNF-α (16.84±3.19), COX-2 (6.78±0.42) were higher than IL-1β(1.01±0.14), IL-6 (0.95±0.17), TNF-α (1.22±0.38), COX-2 (0.87±0.11) in the control group. (Il-1β ( t=26.14), Il-6 ( t=10.22), TNF-α ( t=17.06) and COX-2 ( t=37.07), all P<0.01). In the aspirin pretreatment group, the phagocytic ability of microglia cells was inhibited compared with the model group, and the production of reactive oxygen species (ROS) reduced. The expression of Iba1 protein was also partly recovered. Meanwhile, the effect of the high aspirin dose pretreatment group on pro-inflammatory factors IL-1β(9.95±0.52), IL-6 (39.64±6.89), TNF-α(1.57±0.42), COX-2 (2.47±0.14)were lower than those in the model group significantly.(IL-1β: t=14.18, IL-6: t=3.69, TNF-α: t=16.68, COX-2: t=27.03, all P<0.01). Conclusion:Aspirin has an inhibitory effect on microglial activation induced by Poly-IC, which may be related with inhibiting the expression of inflammatory factors.

Objective To establish an artificial intelligence deep learning model using clinical colonoscopy images and video to assist the diagnosis by colonoscopy. Methods More than 600000 colonoscopy images were collected in endoscopic center of the Second Affiliated Hospital of Zhejiang University School of Medicine from 2014 to 2018, and endoscopic experts recorded a large number of high-quality operation video of colonoscopy as analysis data. After repeated discussion by six experts, the classified intestinal sites and pathological features were determined, and fuzzy and confusable images were deleted. The final selection result was approximately 1 out of 4. And then the features of images were marked using an independently developed software. The deep learning algorithm was developed using TensorFlow platform of Google. Results After repeated comparison and analysis of the results of machine training and judgment results combined with pathology from endoscopic experts, the sensitivity of the model for some diseases ( such as colon polyps) was 99％ under laboratory conditions. In the clinical colonoscopy test, the sensitivity, specificity, and overall accuracy of this model for diagnosis of colon polyps were 98. 30％(4187/4259), 88. 10％ (17620/20000), and 92. 92％ [2×98. 30％×88. 10％/(98. 30％+88. 10％)], respectively. The sensitivity and specificity for ulcerative colitis were 78. 32％ ( 2671/3410) , and 67. 06％(13412/20000), respectively. The diagnosis time spent on a single image was 0. 5±0. 03 s, and it was the real time for application, including system recognition, text prompt in video image, background record and storage. Conclusion The artificial intelligence assisted diagnosis model developed by our team can identify colonic polyps, colorectal cancer, colorectal eminence, colonic diverticulum, ulcerative colitis, etc. The auxiliary diagnosis model of colon disease can guide beginners to carry out colonoscopy, and can improve lesion detection rate, reduce misdiagnosis rate, and improve the overall operating efficiency of endoscopic center, which is conducive to the quality control of colonoscopy.

As a potent collagenase activator,ocriplasmin is a recombinant truncated form of serine protease that retains the protease activity of plasmin.Pre-clinical animal experiments,clinical trials and recent clinical studies all indicated a promising outcome of intravitreal injection of ocriplasmin to treat vitreomacular interface diseases,including vitreomacular adhesion (VMA),vitreomacular traction (VMT) and full-thickness macular hole.Ocriplasmin was approved by the Food and Drug Administration of USA in the management of symptomatic VMA,and by the European Medicines Agency in treating VMT-associated macular hole with less than or equal 400 pm.Further randomized controlled clinical trials are needed for further comprehensive observation and evaluation on its efficiency,safety and other noteworthy issues.