Pancreatic cancer induced by mutation KRAS exhibited a higher risk of incidence, recurrence and mortality. C-Myc is downstream of KRAS and can be involved in the regulation of multiple oncogenic pathways and signaling pathways in pancreatic cancer. Over expressing of C-Myc promotes glycolysis and glutamine uptake in pancreatic cancer cells, promotes cell metabolism and proliferation, is an important factor driving the progress and maintenance of pancreatic cancer, and is related to chemotherapy and immunotherapy drug resistance. C-Myc also interacts with cell cyclin-dependent kinase(CDK) and non-coding RNA to regulate the proliferation, development and metastasis of pancreatic cancer. Therefore, targeting C-Myc was regarded as an effective strategy for the treatment of pancreatic cancer. The activation of C-Myc depends on heterodimerization with its partner MAX and thereby paly a role through binding to the canonical E-Box sequence 5’-CACGTG-3’. Researches showed direct targeting of C-Myc can inhibit the growth of pancreatic carcinoma,such as promoting the degradation of C-Myc, inhibiting the binding of C-Myc/MAX and blocking the binding of C-Myc/MAX to E-box. However, direct targeting has been proved challenging because of its special protein structure. Indirect targeting of C-Myc provided a new strategy for the treatment of pancreatic cancer. C-Myc can be indirected targeting through inhibiting transcription and translation of C-Myc, C-Myc-MAX heterodimerization and promote the ubiquitination and degradation of C-Myc, thus affects the occurrence, development and metastasis of pancreatic cancer.

Objective To explore the effects of HPV16 E6 on genes and signaling pathways in cervical epithelial cells and to screen genes associated with oncogenic transformation.Methods HUCEC models infected with HPV16 E6 were constructed,and transcriptome sequencing was performed to screen for differentially expressed genes(DEGs),which were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment to analyze the differential signaling pathways.RT-qPCR was used to validate major differentially down-regulated expressed genes.After predicting the major differentially expressed proteins by molecular docking analysis,the expression of major differential genes in HUCEC cell model was verified by RT-qPCR and Western blotting.In addition,RT-qPCR and Western blotting were used to further verify the expression of major differential genes in cervical cancer cell lines,SiHa and CaSki.Results A total of 55 genes with more than two-fold differential expression were screened.The results centering on down-regulated genes showed that the negatively regulated differential gene was mainly enriched in redox processes;KEGG enrichment analysis revealed that it was mainly associated with carbohydrate metabolism and cancer.RT-qPCR results showed that the down-regulated differential expression trends of the selected 10 genes were basically consistent with the sequencing results.Molecular docking analysis predicted an interaction between DHRS2 and HPV16 E6,and RT-qPCR and Western blotting confirmed that HPV16 E6 down-regulated DHRS2 mRNA(P＜0.01)and protein(P＜0.05)and ETV5 protein expression(P＜0.01).In SiHa and CaSki cells,compared with the control group,the mRNA and protein expression of DHRS2 was downregulated and positively correlated with the trend of P53 protein expression(P＜0.05).Conclusion HPV16 E6 can mediate oncogenic transformation of cervical cells and promote cervical carcinogenesis through downregulating DHRS2 expression.

Objective:To observe the clinical features of high myopia domed-shaped macula (DSM) complicated with choroidal neovascularization (CNV) and the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF).Methods:A retrospective clinical study. A total of 23 eyes of 23 patients with high myopia DSM combined with CNV diagnosed by ophthalmology examination in Department of Ophthalmology of The Second People's Hospital of Foshan from January 2019 to December 2023 were included in the study.Best corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT) were performed in all eyes. BCVA tests are performed using the international standard visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. DSM height, central macular thickness (CMT) and choroidal thickness (ChT) were measured by OCT. According to OCT image features, DSM was divided into horizontal and vertical elliptic bulges and circular bulges. According to the literature standard, CNV was divided into subfoveal CNV and parafoveal CNV. All patients were treated with 0.05 ml intravitreal injection of ranibizumab or conbercept (IVR or IVC). The treatment regimen was 1+ on-demand treatment. The first IVR and IVC treatment were performed on 17 eyes and 6 eyes, respectively, and were divided into IVR group and IVC group. Follow-up time ≥1 month after treatment. The clinical features of the patients and the changes of BCVA, intraocular pressure, CMT and ChT after treatment were observed. Independent sample t test was used for comparison between groups. Results:There were 23 eyes in 23 cases, 7 males had 7 eyes and 16 females had 16 eyes. There were 11 and 12 eyes in the right and left eyes respectively. Age were (49±16) years old; logMAR BCVA was 0.94±0.39. Shapes of DSM were in 13 (56.52%, 13/23), 6 (26.09%, 6/23), and 4 (17.39%, 4/23) eyes, respectively. The dome height was (97.83±46.14) μm. CMT and ChT were (276.39±98.35) and (49.48±31.66) μm, respectively. There were 17 eyes in the IVR group, including 4 males and 13 females. There were 6 cases in the IVC group, 3 cases were male and 3 cases were female. At the last follow-up, logMAR BCVA and CMT were 0.60±0.39 and (209.96±71.38) μm, respectively. BCVA was significantly increased and CMT was significantly decreased compared with before treatment, with statistical significance ( t=2.98, 2.62; P=0.005, 0.010). One month after treatment and at the last follow-up, there were no significant differences in the degree of BCVA improvement ( t=1.47, 1.35), intraocular pressure change ( t=-0.20, -0.56) and ChT reduction thickness ( t=0.80, -0.62) between IVR group and IVC group ( P>0.05). At 1 month after treatment and last follow-up, the CMT of patients in IVR group and IVC group was decreased by (57.94±67.61), (83.17±78.37) μm and (13.33±9.73), (18.17±17.88) μm compared with that before treatment, respectively, and the differences were statistically significant ( t=2.64, 3.21; P<0.05). Conclusions:IVR or IVC in the treatment of high myopia DSM combined with CNV can effectively improve BCVA. The reduction of CMT with ranibizumab is better than conbercept.

Objective:To observe the characteristics of back scraping skin symptoms in sub-health people through diagnostic scraping, and explore the characteristics of back scraping skin symptoms in sub-health people with different constitutions.Methods:By adopting a cross-sectional study method, the Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine recruited volunteers through a combination of offline and online methods from March 2021 to September 2022. Totally 2 239 sub-health people were treated for TCM constitution identification and were diagnostic scraped with Wentong scraping cup. The differences of back scraping skin symptoms in the color, speed, amount, shape, nature of pain and feeling characteristics under scraping board were compared between sub-health people with different TCM constitutions and gentle constitution.Results:There were differences in the characteristics of Sha Xiang among sub-health individuals with different constitutions. Among them, 49.02% (351/716) of individuals with a gentle constitution had a bright red color, 90.64% (649/716) had a fast rate of appearance, 5.73% (41/716) had a large amount of sha, 3.35% (24/716) had a patchy shape, 3.35% (24/716) felt a stabbing pain, and 0 felt nodules under the scraping plate. Among individuals with a damp-heat constitution, 86.72% (457/527) had a bright red color, 95.64% (504/527) had a fast rate of appearance, 100.00% (527/527) had a large amount of sha, 88.80% (468/527) had a patchy shape, 95.64% (504/527) felt a stabbing pain and 97.72% (515/527) felt nodules under the scraping plate. There was a statistically significant difference between the two groups ( χ2 values were 11.27 to 1 243.00, all P<0.05). Conclusions:The characteristics of back scraping skin symptoms of sub-health people with different constitutions are different. It is expected that the type of TCM constitution of sub-health people can be judged according to the characteristics of scraping skin symptoms in the future, in order to guide patients in health management and improve their satisfaction with traditional Chinese medicine scraping treatment.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:To explore the application effect of global trigger tool (GTT) in detecting adverse events in ICU patients.Methods:According to contents of triggers in the GTT white paper, combined with the scope of domestic adverse event reporting and some ICU indexes, 16 triggers were established. A total of 1 683 medical records were collected from ICU of the Second People's Hospital of Liaocheng in Shandong Province from July 2018 to June 2019. According to the inclusion/exclusion criteria, 421 medical records of discharged patients were randomly selected according to the number of sampling intervals and 420 medical records were reviewed after eliminating repeated medical records. GTT method was used for retrospective analysis.Results:Of the 420 medical records actually used for review, 14 of the 16 triggers were positive, and the positive frequency of triggers was 128 cases, involving 62 patients. Adverse events were identified 51 times, involving 43 patients, with a detection rate of 10.24% (43/420) . Among the 51 cases of adverse events, 37 cases (72.55%) were Grade E, 13 cases (25.49%) were Grade F, and 1 case (1.96%) was Grade H. No Grade G or I was found. In the same year, 18 cases of adverse events were reported voluntarily in ICU, the reporting rate was 1.07% (18/1 683) .Conclusions:GTT can be effectively applied to the detection of adverse events in ICU patients, and a properly designed trigger can improve the detection rate.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective To analysis the relationship between of waist-to-height ratio(WHtR) and the non-alcoholic fatty liver disease(NAFLD).Methods A total of 7 896 were selected as observed subjects from the Kailuan Group in 2011-2012 health physical examination.A questionnaire survey,blood biochemical and abdominal ultrasound examination were finished by trained medical staff.According to previous study recommended cut points the observed subjects was divided into two groups:abdominnal obesity group(WHtR≥0.5,n=3 185) and non-abdominnal obesity group(WHtR<0.5,n=479).According to the WHtR and its quartile,the observed subjects was divided into four groups(first(WHtR<0.47),second(0.47≤WHtR<0.51),third(0.51≤WHtR<0.55) and forth(WHtR≥0.55) quartile groups).NAFLD detection rate of the four groups were Compared.Multiple Logistic regression analysis was used to analyze the influencing factors of the NAFLD.Results (1)The detection rate of NAFLD in abdominnal obesity group was higher than that in non-obesity group(62.7% vs.21.5%,P<0.01).Along with increasing WHtR level in the 4 quartile groups,the incidence of NAFLD was progressively increased,being 12.6 %,38.1%,57.5% and 72.5% respectively in the total population.After stratified by gender,15.1%,40.6%,59.6% and 75.0% in male,7.8%,31.5%,48.3% and 63.8% in female.In the same WHtR group,the NAFLD detection rate of male was higher than female,the differences were statistically significant(P<0.01).(2)Multiple logistic regression analysis showed that compared with the first quartile group,the second,third and forth quartile groups had increased risk of NAFLD after adjusting age,gender and other risk factors,the OR value being 3.19,5.93 and 9.81 in the total population.After adjusting above factors,the OR value being 3.12,6.02 and 10.45 in male,3.32,5.37 and 7.57 in female,respectively.Conclusion The incidence of NAFLD is increased along with the increasing the WHtR.

Objective To investigate the effects of waist-to-hip ratio (WHR) on the formation of carotid plaque in the middle-aged and elderly people.Methods A total of five thousand and ninety-nine participants who have taken physical examination in Tangshan Kailuan Company from June 2010 to October 2011(above 40 years old,no previous history of ischemic stroke,transient ischemic attack,myocardial infarction) were enrolled in this study.Questionnaire survey,blood biochemical and carotid artery ultrasound examination were used to examine the subjects.According to WHR,quartile division was used to divide the subjects into four groups.The detection rates of carotid plaque among the 4 groups were compared.Multivariate logistic regression analysis was used to analyze the factors effecting carotid artery plaques.Results (1) The detection rate of carotid artery plaque increased with the increase of WHR,the rates of the first,second,third and fourth group were 20.7% (571/2 753),21.9% (604/2 753),27.5% (758/2 753) and 29.8% (820/2 753) respectively.The difference was statistically significant(P=0.000).(2) Logistic regression model was used to analyze multiple factors affecting the detection rate of carotid plaque.After the correction of other factors,compared with the first group,the carotid artery plaque detection rate in the second,third,fourth group were all increased,the OR values were 1.23(95%CI:1.10~1.54),1.65(95%CI:1.52~2.13),1.67(95%CI:1.54~2.17),respectively.Conclusion The increased WHR in the middle-aged and elderly population may increase the risk of carotid plaque formation.

To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties. The cocrystal of 5-Fu-NCT was prepared through the cooling technology. PXRD, NMR, FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal. Solubility was measured by HPLC method. Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal, the inhibition effect was tested by MTT and HE staining, and cancer cell migration was determined by scratch test. According to PXRD, NMR, FTIR and DSC results, the cocrystal of 5-Fu-NCT had been synthesized successfully. The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4, 20.4, 22.3, 27.9 and 30.1. The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC. The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU, and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL, respectively. 5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows an enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.
Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Crystallization ; Fluorouracil ; chemistry ; Humans ; Liver Neoplasms ; Niacinamide ; chemistry ; Solubility