Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

Background Arsenic exposure has been demonstrated to induce apoptosis. The fibronectin type III structural domain 3B protein (FNDC3B) has been shown to promote cancer cell proliferation; however, its role in arsenic-induced apoptosis remains to be elucidated. Objective To investigate the effects of sodium arsenite (NaAsO₂) and its metabolites on the expression of FNDC3B gene in A549 cells and to understand the function of FNDC3B gene in A549 cells. Methods (1) A549 cells were exposed to varying final concentrations of NaAsO₂ and their optical density at 450 nm values were measured by Cell Counting Kit-8 (CCK-8) after 48 h. Survival curves were plotted, and a final exposure dose was selected according to the survival rate. Total protein and RNA were extracted by exposing A549 cells to high (30 µmol·L⁻¹), medium (20 µmol·L⁻¹), and low (10 µmol·L⁻¹) NaAsO₂ concentrations, high (30 µmol·L⁻¹) monomethylarsinic acid (MMA), and high (30 µmol·L⁻¹) dimethylarsinic acid for a period of 48 h. mRNA expression and the protein expression of the FNDC3B gene was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB), while the protein ubiquitination expression of the FNDC3B gene was detected by co-immunoprecipitation (CO-IP) and WB assay. (2) Knockdown of FNDC3B gene expression was achieved in A549 cells by siRNA interference. The si-FNDC3B fragment was transfected in A549 cells for 48 h. The mRNA and protein expression of FNDC3B gene was then detected by qRT-PCR and WB assay. Cell viability was determined through CCK-8 assay. Hoechst 33342/propidium iodide (PI) double staining and JC-1 mitochondrial membrane potential assay were employed to detect both early and late apoptosis, while cleaved caspase3 protein and P53 signalling pathway related protein expressions were evaluated by WB. Results (1) The CCK-8 results demonstrated a decline in the viability of A549 cells with an increase in NaAsO₂ concentration, with an inhibitory concentration at 50% of 38.12 µmol·L⁻¹. The qRT-PCR results demonstrated that compared to the control group, varying concentrations of NaAsO₂ (10, 20, and 30 µmol·L⁻¹) significantly upregulated the mRNA expression of FNDC3B gene (P<0.01). In contrast, MMA and DMA showed no significant effect on FNDC3B mRNA expression (P>0.05). The WB analysis revealed that the protein expression of FNDC3B was reduced in the NaAsO₂-treated group compared to the control, accompanied by elevated ubiquitination levels of FNDC3B protein, particularly at the K48 ubiquitination site. MMA and DMA exhibited no impact on FNDC3B protein expression. (2) Following the specific knockdown of FNDC3B expression in A549 cells, the CCK-8 assay demonstrated a significant reduction in cell viability in the silenced FNDC3B group (si-FNDC3B) compared to the control group. The JC-1 assay demonstrated that the mitochondrial membrane potential was diminished in the si-FNDC3B group relative to the control group. The Hoechst 33342/PI staining assay revealed that the si-FNDC3B group exhibited a notable degree of apoptosis. The si-FNDC3B group also displayed substantial apoptosis. The WB analysis indicated that the relative expressions of cleaved caspase3, P53, MDM2, Bad, and Bax proteins were elevated in the si-FNDC3B group in comparison to the control group. Conclusion The presence of NaAsO₂ is observed to promote the ubiquitination expression of the FNDC3B protein, which in turn reduces the expression of FNDC3B protein. However, the main metabolites DMA and MMA have no effect on the expression of FNDC3B. Furthermore, the silencing of FNDC3B is observed to inhibit the viability of A549 cells and promote apoptosis, a phenomenon related to the activation of P53 signaling pathway.

Background Arsenic is a human carcinogen. Arsenic and its metabolites affect the expression of p53, but whether there are any changes of p53 phosphorylation and ubiquitination levels in human bronchial epithelium cells (BEAS-2B) are not clear after exposure to arsenic and its metabolites. Objective To study the effects of arsenic and its metabolites monomethylarsic acid (MMA) and dimethylarsinic acid (DMA) on the expression of tumor suppressor gene p53 in BEAS-2B cells. Methods Different concentrations of sodium arsenite (NaAsO₂) were used to infect BEAS-2B cells, and the cell viability was detected with CCK-8 reagent to determine the dose and time of NaAsO₂ used for the following study. Based on the results of cell viability, the cells were divided into two panels: a sodium arsenide panel and an arsenic methylation metabolite penal. The doses of sodium arsenite were 0, 2, 4, and 6 μmol·L⁻¹ NaAsO₂; the arsenic methylation metabolite panel consisted of 0 μmol·L⁻¹ NaAsO₂ group (control), 6 μmol· L⁻¹ MMA group, 6 μmol· L⁻¹ DMA group， and 6 μmol· L⁻¹ NaAsO₂ group. The cells were collected after 48 h treatment, and the total protein and total RNA were extracted. The relative levels of p53 mRNA expression were determined by quantitative real-time polymerase chain reaction (qRT-PCR), the relative expression levels of p53 protein, p53 Ser9 and Ser15 phosphorylated proteins were determined by Western blot, and the level of p53 ubiquitination was detected by co-immunoprecipitation (CO-IP). Results Compared with the control group, the cell viability rates in all BEAS-2B cells treated by NaAsO₂ were significantly reduced (P<0.05), and the 50% cell viability was observed at 6 μmol·L⁻¹. Compared with the control group, the relative expression level of p53 mRNA gradually decreased after NaAsO₂ (2, 4, 6 μmol·L⁻¹) treatment (P<0.05), the relative expression levels of p53 protein and Ser9 phosphorylated protein induced by NaAsO₂ also decreased gradually (P<0.05), and the relative expression level of p53 Ser15 phosphorylated protein induced by NaAsO₂ followed the same pattern, but it was only lower than that of the control group in the 6 μmol·L⁻¹ NaAsO₂ group (P<0.05). Compared with the control group, there were no significant effects on the relative expression levels of p53 mRNA, p53 protein, Ser9 and Ser15 phosphorylated proteins in the MMA group and the DMA group. Compared with the control group, the expression level of p53 ubiquitination was significantly decreased and the expression of K48 ubiquitination decreased significantly after NaAsO₂ infection. Conclusion Arsenic causes a decrease in the expression of the p53 protein in BEAS-2B cells, largely due to inhibition of the phosphorylated pathway and a decrease in mRNA expression, and protein changes caused by a decrease in p53 ubiquitination do not play a dominant role. MMA and DMA do not affect p53 gene expression.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective To investigate the expression of circular ribonucleic acid carnitine palmitoyltrans-ferase 1A(circRNA CPT1A)in patients with diabetic retinopathy(DR)and its mechanism of action on neuropathy.Methods To-tally 80 patients(102 eyes)with type 2 diabetes admitted to our hospital from January 2019 to January 2022 were selected,including 22 patients(28 eyes)with no DR(NDR group),38 patients(48 eyes)with non-proliferative DR(NPDR group),and 20 patients(26 eyes)with proliferative DR(PDR group).Optical coherence tomography angiography was used to measure the thickness of the peripapillary retinal nerve fiber layer(pRNFL)and macular ganglion cell complex(GCC),the level of phosphatase and tensin homolog(PTEN)in peripheral blood was detected by Western blot,and the circRNA CPT1A level in peripheral blood was detected by fluorescence quantitative polymerase chain reaction.The levels of circRNA CPT1A and PTEN in peripheral blood,as well as the thickness of pRNFL and GCC,were compared among three groups,and Pearson correlation analysis was used to investigate the correlation between circRNA CPT1A and PTEN,pRNFL and GCC thickness.Results The circRNA CPT1A in the peripheral blood of the PDR group was higher than that in the NDR group and NPDR group;the PTEN in the peripheral blood of the PDR group was lower than that in the NDR group and NP-DR group(all P＜0.05).There was no statistically significant difference in the expression of circRNA CPT1A and PTEN be-tween NDPR group and NDR group(all P＞0.05).The Pearson correlation analysis showed that the expression level of cir-cRNA CPT1A in peripheral blood was negatively correlated with PTEN(P＜0.05).With the increase in disease severity,the thickness of pRNFL and GCC showed a decreasing trend;the thickness of pRNFL and GCC in the whole,upper and lower parts of eyes in the NDR group were higher than those in the NPDR group(all P＜0.05),while those in the NPDR group were higher than the PDR group(all P＜0.05).Pearson correlation analysis showed that the expression level of cir-cRNA CPT1A in peripheral blood was negatively correlated with the thickness of pRNFL and GCC in the whole,upper and lower parts of the observed eyes(all P＜0.05).Conclusion With the increase in the severity of DR,circRNA CPT1A in the peripheral blood of DR patients shows an increasing trend and is negatively correlated with peripheral blood PTEN lev-el,as well as macular pRNFL and GCC thickness.The mechanism of action may be that circRNA CPT1A negatively regu-lates the expression of PTEN and thus participates in the occurrence and development of DR.

ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

Objective:To establish a method for rapid detection of OXA and par C resistance genes of Acinetobacter baumannii(Ab)by double nucleic acid colloidal gold strip and to develop kit.Methods:DNA of Ab was extracted by heating and boiling method.OXA and par C genes sequences of Ab were selected as target gene fragments based on NCBI.Primers were designed and labeled with 6-FAM,digoxin and biotin,respectively.Drug resistance gene detection reagents were developed,and nucleic acid gold test strips were used for rapid and visual detection.Molecular cloning and sequencing techniques were used to clone positive control samples and evaluate specificity,sensitivity and stability of kit.Results:DNA concentration and purity of Ab extracted by boiling method were good.Homology between cloned and sequenced plasmid DNA and gene sequence in GenBank database was 100%,respectively.Speci-ficity of kit was good,with only Ab showing positive results and other bacterial genera showing negative results;DNA concentration of Ab in double nucleic acid colloidal gold test strip decreased to 10-3 ng/μl,a red line still appeared,whose sensitivity was 10 times higher consistent with minimum detection limit of electrophoresis 10-2 ng/μl;test kits were tested at 3rd,6th and 9th months,and showed good stability.Conclusion:Double resistance detection kit established in this study can simultaneously detect OXA and par C resis-tance of Ab,who has advantages of high sensitivity,strong specificity,rapid and simple,and provides a new method for detection of carbapenem and quinolone antibiotic resistance of Ab.

Objective To evaluate the clinical efficacy and safety of preoperative endovascular embolization of Solid Hemangioblastomas.Methods The data bases including Wan Fang,CNKI(China National Knowledge Infrastructure),VIP Database,PubMed、Medline、Springer were searched for the related studies.Two independent surgeons assessed trails for eligibility and quality,and all data marching the standards were abstracted for Meta-analysis by RevMan 5.3.Results 8 randomized controlled trails(RCT)were included.Selected analysis of embolized and non-embolized groups of Solid Hemangioblastomas were observed for variables of clinical efficacy in surgery time,number of blood loss and transfusions,complete resection,there were statistical difference.(P＜0.000 01,WMD=-1.18,95％CI[-1.16,-0.71];P＜0.000 01,WMD=-464.17,95％CI[-492.17,-437.24];P＜0.000 01,WMD=-238.81,95％CI[-282.84,-194.77];P＜0.006,RR=1.17,95％CI[1.05,1.31]).Conclusion The preoperative endovascular embolization is beneficial for Hemangioblastomas because it can shorten the time of surgery,diminish the necessity of intra-operative blood loss and transfusion,it also raises the ratio of complete resection of Solid Hemangioblastomas.

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

Objective:To summarize the clinical data and experience of pure single-port lumpectomy non-lipolysis breast-conserving surgery (PSLN-BCS) in patients with early-stage breast cancer.Methods:A retrospective analysis was conducted on 400 patients who underwent breast-conserving surgery for early-stage breast cancer in the Second Department of Breast Surgery at Harbin Medical University Cancer Hospital from Jan. 2022 to Jan. 2023. Patients were divided into two groups: PSLN-BCS group ( n=200) and conventional breast-conserving surgery (C-BCS) group ( n=200). The surgical time, intraoperative blood loss, postoperative drainage within three days, and short-term (3 months to 6 months after surgery) complications, including the incidence of residual fluid after drain removal and incision infection were observed. Long-term (6 months after surgery) complications, including the incidence of skin and pectoralis major muscle adhesions in the surgical area and cosmetic results after breast-conserving surgery, were also evaluated. Statistical analysis was performed using R language, and quantitative data were expressed as mean ± standard deviation ( ± s) and analyzed using t-test, while count data were analyzed using χ2 test. A p-value less than 0.05 was considered statistically significant. Results:PSLN-BCS had a longer average surgical time than C-BCS (198.341min vs 62.961min, P<0.001, 95% CI:132.028 vs 138.732). PSLN-BCS had less intraoperative bleeding (18.824 ml vs 22.627 ml, P=0.003, 95% CI: -6.294 vs -1.311) and lower postoperative drainage volume (346.157 ml vs 406.191 ml, P<0.001, 95% CI: -70.571-a-49.496). There were no significant differences in short-term postoperative complications such as subcutaneous fluid accumulation ( χ2=2.33, P=0.127) or incisional infection ( χ2=0.14, P=0.708) between the two groups. The incidence of skin and muscle adhesions in the surgical area was lower in patients who underwent PSLN-BCS at 6 months postoperatively ( χ2=11.58, P<0.001). Patients who received PSLN-BCS achieved better cosmetic outcomes, with a statistically significant difference ( χ2=273.00, P<0.001) compared to those who received C-BCS. Conclusion:Pure single-port lumpectomy non-lipolysis breast-conserving surgery is a safe and effective treatment option for early-stage breast cancer and can be considered as a surgical option for patients with cosmetic requirements.