Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

The biological clock(also known as the circadian rhythm)is the fundamental reliance for all organisms on Earth to adapt and survive in the Earth's rotation environment.Circadian rhythm is the most basic regulatory mechanism of life activities,and plays a key role in maintaining normal physiological and biochemical homeostasis,disease occurrence and treatment.Recent studies have shown that the biologi-cal clock plays an important role in the development of oral tissues and in the occurrence and treatment of oral diseases.Since there is cur-rently no guiding literature on the research methods of biological clock in stomatology,researchers mainly conduct research based on pub-lished references,which has led to controversy about the research methods of biological clock in stomatology,and there are many confusions about how to rationally apply the research methods of circadia rhythms.In view of this,this expert consensus summarizes the characteristics of the biological clock and analyzes the shortcomings of the current biological clock research in stomatology,and organizes relevant experts to summarize and recommend 10 principles as a reference for the rational implementation of the biological clock in stomatology research.

Redox-sensitive cysteine(RSC)thiol plays an important role in many biological processes such as photosynthesis,cellular metabolism,and transcription.Therefore,it is necessary to identify red-ox-sensitive cysteine accurately.However,traditional redox-sensitive cysteine identification is very ex-pensive and time-consuming.At present,there is an urgent need for a mathematical calculation method to identify sequence information and redox-sensitive cysteines quickly and accurately.Here,we devel-oped an effective predictor called iRSC-PseAAC,which used the dimension reduction algorithm LDA combined with the support vector machine to predict redox-sensitive cysteine sites.In the cross-validation results,the specificity(Sp),sensitivity(Sn),accuracy(Acc)and Matthews correlation coefficient(MCC)were 0.841,0.868,0.859 and 0.692 respectively.In the independent dataset results,the Sp,Sn,Acc and MCC were 0.906,0.882,0.890 and 0.767 respectively.compared with existing prediction methods,iRSC-PseAAC had obvious improvement effect.The method proposed for this study can also be used for many problems in computational proteomics.

The application of robots in thoracic surgery is mainly based on the da Vinci general surgery robot. With the popularization of artificial intelligence (AI) application scenarios, the combination of AI and robots is more closely, and there is a strong clinical demand and huge application space for the development of specialized disease-specific robotic systems for thoracic surgery. This article aims to systematically describe the history of the rise of specialized surgical robots and the status of the localization of surgical robots in China, propose the concept of applying AI to the research and development of integrated specialized disease-specific robots in thoracic surgery, and clarify the ethics and prospects that intelligent specialized disease-specific surgical robots will face.

Objective: : A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. Methods: : Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. Results: : Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference−0.33×10-3 mm2/s [95% CI, −0.44 to −0.23]; p<0.00001). Conclusion : DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

Objective: : A role of diffusion-weighted imaging (DWI) in the diagnosis of cerebral venous thrombosis (CVT) is not wellunderstood. This study evaluates the effectiveness of DWI in the diagnosis of CVT. Methods: : Literature search was conducted in electronic databases for the identification of studies which reported the outcomes of patients subjected to DWI for CVT diagnosis. Random-effects meta-analyses were performed to achieve overall estimates of important diagnostic efficiency indices including hyperintense signal rate, the sensitivity and specificity of DWI in diagnosing CVT, and the apparent diffusion coefficient (ADC) of DWI signal areas and surrounding tissue. Results: : Nineteen studies (443 patients with 856 CVTs; age 40 years [95% confidence interval (CI), 33 to 43]; 28% males [95% CI, 18 to 38]; symptom onset to DWI time 4.6 days [95% CI, 2.3 to 6.9]) were included. Hyperintense signals on DWI were detected in 40% (95% CI, 26 to 55) of the cases. The sensitivity of DWI for detecting CVT was 22% (95% CI, 11 to 34) but specificity was 98% (95% CI, 95 to 100). ADC values were quite heterogenous in DWI signal areas. However, generally the ADC values were lower in DWI signal areas than in surrounding normal areas (mean difference−0.33×10-3 mm2/s [95% CI, −0.44 to −0.23]; p<0.00001). Conclusion : DWI has a low sensitivity in detecting CVT and thus has a high risk of missing many CVT cases. However, because of its high specificity, it may have supporting and exploratory roles in CVT diagnosis.

OBJECTIVE: To explore the association between the abnormal root morphology and bone metabolism or root development related gene polymorphism in patients with generalized aggressive periodontitis. METHODS: In the study, 179 patients with generalized aggressive periodontitis were enrolled, with an average age of (27.23±5.19) years, male / female = 67/112. The average number of teeth remaining in the mouth was (26.80±1.84). Thirteen single nucleotide polymorphisms (SNPs) of nine genes which related to bone metabolism and root development were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Root abnormalities were identified using periapical radiographs. The abnormal root morphology included cone-rooted teeth, slender-root teeth, short-rooted teeth, curved-rooted teeth, syncretic-rooted molars, and molar root abnormalities. The number of teeth and incidence of abnormal root morphology in different genotypes of 13 SNPs were analyzed. RESULTS: The constituent ratio of root with root abnormality in GAgP patients was 14.49%(695/4 798). The average number of teeth with abnormal root morphology in GAgP was (3.88±3.84). The average number of teeth with abnormal root morphology in CC, CT and TT genotypes in vitamin D receptor (VDR) rs2228570 was (4.66±4.10), (3.71±3.93) and (2.68±2.68). There was significant difference between TT genotype and CC genotype (t = 2.62, P =0.01). The average number of root morphological abnormalities in CC, CT and TT genotypes of Calcitotin Receptor (CTR) gene rs2283002 was (5.02±3.70), (3.43±3.95), and (3.05±3.12). The incidence of root morphological abnormalities in CC genotype was higher than that in the patients with CT and TT, and the difference was statistically significant(87.86% vs. 65.26% & 63.64%, P=0.006, adjusted OR =3.71, 95%CI: 1.45-9.50). There was no significant difference in the incidence of abnormal root morphology between CT and TT genotypes. CONCLUSION VDR rs2228570 and CTR rs2283002 may be associated with the occurrence of abnormal root morphology in patients with generalized aggressive periodontitis, which is worthy of further research.
Adult ; Aggressive Periodontitis/genetics* ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/genetics* ; Young Adult

OBJECTIVE: To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL). METHODS: Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019. RESULTS: All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways. CONCLUSION Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.
Aminopyridines ; Benzamides ; Child ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; Transplantation, Homologous

Objective: : Covered stenting is an optional strategy for traumatic carotid pseudoaneurysm, especially in malignant conditions of potential rupture, but the long-term outcomes are not clear. Our aim was to determine if covered stenting is an effective option for traumatic carotid pseudoaneurysm with promising long-term outcomes. Methods: : Self-expanding Viabahn and balloon-expandable Willis covered stents were separately implanted for extra- and intracranial traumatic carotid pseudoaneurysm. The covered stent was placed across the distal and proximal pseudoaneurysm leakage under roadmap guidance. Procedural success was defined as technical success (complete exclusion of the pseudoaneurysm and patency of the parent artery) without a primary end point (any stroke or death within 30 days after the procedure). Longterm outcomes were evaluated as ischemic stroke in the territory of the qualifying artery by clinical follow-up through outpatient or telephone consultation and as the exclusion of the pseudoaneurysm and patency of the parent artery by imaging follow-up through angiography. Results: : Five patients with traumatic carotid pseudoaneurysm who underwent covered stenting were enrolled. The procedural success rate was 100%. No ischemic stroke in the territory of the qualifying artery was recorded in any of the five patients during a mean clinical follow-up of 44±16 months. Complete exclusion of the pseudoaneurysm and patency of the parent artery were maintained in all five patients during a mean imaging follow-up of 39±16 months. Conclusion : Satisfactory procedural and long-term outcomes were obtained, suggesting that covered stenting is an effective option for traumatic carotid pseudoaneurysm.

Objective To analyze the resistance of influenza virus to neuraminidase inhibitors (NAI) in Henan province during 2017-2018. Methods Virus were collected from the Henan Influenza Surveillance Network during 2017-2018. 36 confirmed influenza virus(with 15 H1pdm09，6 H3N2 and 15 B) were selected to test resistance to oseltamivir and zanamivi with fluorescence(FL). The NAI sensitive reference viruses were A/California/12/2012(H1pdm09)-275H,A/Beijing Haidian/1942/2014(H3N2)-119E and B/Rochester/02/2001-198D. The NAI resistant reference viruses were A/ Texas/23/2012(H1pdm9)-H275Y, A/Texas/12/2007(H3N2)-E119V and B/Rochester/02/2001-D198N. Results The half maximal inhibitory concentration(IC50) of A/California/12/2012(H1pdm09)-275H, A/Beijing-Haidian/1942/2014(H3N2)-119E and B/Rochester/02/2001-198D for oseltamivir were 0.29 nmol/L (nM),0.10 nM and 12.71 nM, and for zanamivir were 0.2 nM, 0.49 nM and 0.33 nM respectively. The IC50 for oxastatin of H1pdm09 and H3N2 ranged from (0.28-1.37 nM) and (0.08-0.17 nM) respectively, the IC50 for zanamivir ranged from (0.15-0.49 nM) and (0.12-0.22 nM), all was within 10 fold IC50 of the reference virus(corresponding type); the IC50 value of type B for oseltamivir and zanamivir ranged from (11.83-24.59 nM) and (0.48-1.25 nM), all was within 5 fold IC50 of the reference virus. Conclusion All the tested influenza strains isolated in Henan province during 2017-2018 were sensitive to NAI.