BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

The incidence and detection rates of benign and low-grade malignant pancreatic tumors have risen yearly.For patients with such tumors,traditional radical resection procedures often result in excessive loss of normal pancreatic parenchyma,leading to complications such as postoperative insufficiency of both exocrine and endocrine functions.Studies have shown that functional-preserving surgeries,such as minimally invasive enucleation or partial resection surgeries,can maximize the protection of patients'pancreatic function and improve long-term quality of life.However,for some tumors deep within the pancreatic parenchyma,accurately locating the tumor and protecting the pancreatic duct pose challenges.Intraoperative ultrasound(IOUS)has become an ideal intraoperative imaging tool,often referred to as the surgeon's"third eye"because of its portability,ability to provide real-time high-resolution information,non-reliance on ionizing radiation,and the fact that it does not require special patient preparation.With advancements in technology,the application scope of IOUS has expanded beyond its initially limited diagnostic role to various surgical applications,including identifying non-palpable lesions,guiding surgical strategies,and staging tumors.In the current era of minimally invasive and precision surgery,the proficiency of surgeons in using IOUS has become an important issue.This article reviews the history of IOUS applications,summarizes the advantages and basic usage methods of robotic IOUS,and shares techniques for applying IOUS in robot-assisted precise resection of pancreatic tumors.

A retrospective data collection was conducted on 16 patients who underwent secondary resection of bladder cancers using β-knife resection. The postoperative follow-up period is 12(10, 15)months, and no perioperative complications were detected. Among them, there were 3 cases of tumor recurrence, 2 cases continued to undergo β-knife resection, and 1 case underwent radical cystectomy. The safety of β-knife secondary electric cutting is high, and it can correct the insufficient first TURBT.

A retrospective data collection was conducted on 16 patients who underwent secondary resection of bladder cancers using β-knife resection. The postoperative follow-up period is 12(10, 15)months, and no perioperative complications were detected. Among them, there were 3 cases of tumor recurrence, 2 cases continued to undergo β-knife resection, and 1 case underwent radical cystectomy. The safety of β-knife secondary electric cutting is high, and it can correct the insufficient first TURBT.

ObjectiveTo summarize the modeling methods, test indicators, and evaluation methods of the animal models of urticaria and provide a basis for the subsequent research on urticaria models. MethodWith the keywords of "urticaria" and "animal model" and the time interval from inception to July 13, 2022, relevant articles were retrieved from CNKI, Wanfang Data, VIP, CBM, Web of Science, Embase, and PubMed. Two evaluators independently screened the articles and extracted the publishing time, sources, animal conditions, modeling methods, modeling time, and test indicators from the articles meeting the inclusion criteria to establish a data library for quantitative statistics and analysis. ResultA total of 116 articles were included, involving 129 animal experiments (102 in Chinese and 27 in English) of urticaria. In the last three years, the studies about the animal models of urticaria presented an obvious upward trend, and the articles were dominated by dissertations. KM mice and SD rats of both females and males were mainly used for the modeling of urticaria, and the models were mainly established by passive sensitization of skin for 14-16 days. The models were mainly evaluated based on apparent indicators such as blue-stained lesion area and ear swelling, supplemented by the pathological indicators of the skin and serum. ConclusionAlthough the experimental studies of urticaria are increasing, the modeling methods lack unified modeling standards and have low coincidence with clinical symptoms. Therefore, this paper analyzed the modeling elements and evaluation criteria of urticaria animal models, and proposed that both male and female KM mice (6-8 weeks old) or SD rats (8-10 weeks old) of SPF grade should be preferentially selected for modeling. Active and passive sensitization can be combined for the modeling, and the specific modeling elements such as modeling time and sensitization times need to be further explored. The model evaluation should include four aspects of behavior, appearance, pathology, and immunity.

Objective:To investigate the influencing factors, periprocedural complications, and long-term outcomes of successful recanalization after endovascular treatment in patients with non-acute symptomatic internal carotid artery occlusion.Methods:Patients with non-acute internal carotid artery occlusion received endovascular treatment in the Nanjing Stroke Registration System between January 2010 and December 2021 were retrospectively enrolled. Clinical endpoint events were defined as successful vascular recanalization, periprocedural complications (symptomatic embolism and symptomatic intracranial hemorrhage), neurological function improvement, and recurrence of ipsilateral ischemic events. Multivariate logistic regression analysis was used to investigate the independent influencing factors of successful vascular recanalization. Cox proportional hazards regression analysis was used to investigate the correlation between endovascular treatment outcomes and neurological function improvement, as well as ipsilateral ischemic cerebrovascular events. Results:A total of 296 patients were included, of which 190 (64.2%) were successfully recanalized. Multivariate logistic regression analysis showed that symptoms manifest as ischemic stroke (odds ratio [ OR] 3.353, 95% confidence interval [ CI] 1.399-8.038; P=0.007), the time from the most recent symptom onset to endovascular therapy within 1 to 30 d ( OR 2.327, 95% CI 1.271-4.261; P=0.006), proximal conical residual cavity ( OR 2.853, 95% CI 1.242-6.552; P=0.013) and focal occlusion (C1-C2: OR 3.255, 95% CI 1.296-8.027, P=0.012; C6/C7: OR 5.079, 95% CI 1.334-19.334; P=0.017) were the independent influencing factors for successful vascular recanalization. Successful recanalization did not increase the risk of symptomatic intracranial hemorrhage within 7 d after procedure (3.2% vs. 0.9%; P=0.428). The median follow-up time after procedure was 38 months. Cox proportional hazards regression analysis showed that after adjusting for confounding factors, successful recanalization was significantly associated with postprocedural neurological improvement (hazard ratio 1.608, 95% CI 1.091-2.371; P=0.017), and significantly reduced the risk of recurrence of long-term ischemic events (hazard ratio 0.351, 95% CI 0.162-0.773; P=0.010). Conclusion:In patients with non-acute internal carotid artery occlusion, successful endovascular recanalization can effectively reduce the risk of long-term ischemic events without increasing the risk of symptomatic intracranial hemorrhage.

Objective:To investigate predictive factors for successful endovascular recanalization in patients with non-acute symptomatic internal carotid artery occlusion (SICAO), to develop a decision tree model using the Classification and Regression Tree (CART) algorithm, and to evaluate the predictive performance of the model.Methods:Patients with non-acute SICAO received endovascular therapy at 8 comprehensive stroke centers in China were included retrospectively. They were randomly assigned to a training set and a validation set. In the training set, the least absolute shrinkage and selection operator (LASSO) algorithm was used to screen important variables, and a decision tree prediction model was constructed based on CART algorithm. The model was evaluated using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and confusion matrix in the validation set.Results:A total of 511 patients with non-acute SICAO were included. They were randomly divided into a training set ( n=357) and a validation set ( n=154) in a 7:3 ratio. The successful recanalization rates after endovascular therapy were 58.8% and 58.4%, respectively. There was no statistically significant difference ( χ2=0.007, P=0.936). A CART decision tree model consisting of 5 variables, 5 layers and 9 classification rules was constructed using the six non-zero-coefficient variables selected by LASSO regression. The predictive factors for successful recanalization included fewer occluded segments, proximal tapered stump, ASITN/SIR collateral grading of 1-2, ischemic stroke, and a recent event to endovascular therapy time of 1-30 d. ROC analysis showed that the area under curve of the decision tree model in the training set was 0.810 (95% confidence interval 0.764-0.857), and the optimal cut-off value for predicting successful recanalization was 0.71. The area under curve in the validation set was 0.763 (95% confidence interval 0.687-0.839). The accuracy was 70.1%, precision was 81.4%, sensitivity was 63.3%, and specificity was 79.7%. The Hosmer-Lemeshow test in both groups showed P>0.05. Conclusion:Based on the type of ischemic event, the time from the latest event to endovascular therapy, proximal stump morphology, the number of occluded segments, and the ASITN/SIR collateral grading constructed the decision tree model can effectively predict successful recanalization after non-acute SICAO endovascular therapy.

Chronic Urticaria(CU)is a common skin disease involving autoimmunity and allergies,which brings a heavy burden to patients and society.The theory of traditional Chinese medicine"the Lung is combined with the Large Intestine,and the symptoms of large intestine can be reflected from the skin"has long shown that there is a close physiological and pathological relationship between the function of the Large Intestine and the skin.With the modern advancement of the"gut-skin axis"theory,the correlation between gut microbiome and CU has gradually become an emerging focus of research.Adjusting the imbalance of gut microbiome would be a new trend in the clinical treatment of CU.Acupuncture has a beneficial effect of regulating the gut microbiome,and the definite curative effect on CU.Therefore,this article summarized the research progress between the gut microbiome and CU in recent years,in order to discuss the feasibility of acupuncture to treat CU by regulating the gut microbiome,and provide a new idea for the mechanism research of acupuncture in the treatment of CU from the perspective of"treating skin from intestine".