Analysis of Lymph Node Metastases of 1,526 Cases with Thoracic Esophageal and Cardiac Carcinomas: A Random Sampling Report froni the Fourth Hospital of Hebei Medical University from 1996 to 2004

OBJECTIVE To summarize the regular pattern and state oflymph node metastasis of patients with esophageal and cardiaccarcinomas,so as to analyze factors influencing lymph nodemetastasis.METHODS Clinical data collected from 1,526 thoracicesophageal and cardiac carcinoma patients who were admitted inthe Fourth Hospital of Hebei Medical University during a periodfrom January 1996 to December 2004,were randomly selectedand an Access Database of the patient's information was set up.Eight clinico-pathologic factors,including the patient's age,tumorlocation and size,pathological classification,the depth of tumorinvasion,vascular tumor embolus (VTE),the state of surroundingorgan encroachment and the status of tumor residues,wereidentified.A correlation between these factors and metastases wasstatistically analyzed using SPSS13.0 software.RESULTS Lymph node metastatic sites from esophagealcarcinomas included the thoracic and abdominal cavity.Lymphnode metastasis from the superior esophageal carcinomasmainly occurred in the neck and thoracic cavity.There was atwo-way lymph node metastasis in the patients with the middleesophageal carcinoma.The inferior esophageal carcinomas mainlymetastasized to the paraesophageal,paragastric cardia,and leftgastric artery lymph nodes.The rate and degree of the metastasisfrom the inferior esophageal carcinomas were significantly highercompared to those of the superior and the middle esophagealcarcinomas (P<0.0125).The degree of abdominal lymph node metastasis fromcarcinomas of the gastric cardia was significantly higher comparedwith that of esophageal carcinomas.In the group with carcinomaof the gastric cardia,the rate and degree of the lymph nodemetastases in the paragastric cardia and left gastric artery weresignificantly higher compared to the group with esophagealcarcinoma (P<0.05).Paraesophageal lymph node metastasis fromcarcinomas of the gastric cardia in the thoracic cavity frequentlyoccurred,too,and the degree of the metastasis was similar to thatof esophageal carcinoma.There was no significant difference inthe rate and degree of the paraesophageal lymph-node metastasisbetween the group with carcinoma of the gastric cardia comparedto those with esophageal carcinoma (P>0.05).Multifactoriallogistic regression analysis showed that the tumor size,depth oftumor encroachment,VTE,and tumor residues could all bringabout obvious impact on lymph-node metastases (P<0.05).CONCLUSION Lymph node metastasis from superioresophageal carcinomas mainly occurs in the neck and thoraciccavity.The middle esophageal carcinomas presented a two-waylymph-node metastasis (both the upwards and the downwards),and the lymph node metastasis from inferior esophagealcarcinomas mainly occurred in the thoracic and abdominal cavities.The metastases of carcinoma of the gastriccardia were most commonly found in the abdominalcavity,with frequent paraesophageal lymph-nodemetastasis.The sufficient attention should be paidto neck lymph node clearance in cases of esophagealcarcinoma.What is of the greatest concern is theclearance of the left gastric artery lymph nodes,andalso in cases of gastric cardia carcinoma,clearance,the paraesophageal lymph nodes.With an increasein the tumor size and depth of tumor encroachment,and occurrence of VTE and tumor residual cells,therisk of lymph node metastasis is significantly raised (P<0.05).

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

A Genetic Epidemiological Study on Esophageal Cancer and Carcinoma of the Gastric Cardia in Cixian County of Hebei Province

OBJECTIVE To investigate the role of family aggregation and genetic factors of esophageal cancer （EC）, including carcinoma of gastric cardia （CGC）, in Cixian county, and to calculate the segregation ratio and heritability of first-degree relatives （FDR） in EC cases.METHODS A case control study was conducted, and each of 285 esophageal cancer cases and FDR＇s case history and family medical history of EC in 1415 controls was carried by home visits to compare the incidence of EC in the crowds. The family aggregation of EC was found by X2 test for goodness of fit test according to binomial distribution. Li-Mantel-Gart method was used to calculate the segregation ratio and Falconer method was employed to compute the heritability （h2）.RESULTS The incidence rate of the FDR in the index case of EC （12.80%） was higher than that in the controls （7.52%）. There were significant differences between the 2 groups （X2= 44.34, P = 0.000）. The distribution of EC in the family did not agree with the binomial distribution, which presented a conspicuous familial aggregation （X2= 288.19, P 〈 0.0001）. The heritability of EC was （29.67 ±4.32）%, and segregation ratio was 0.1814 （95%CI = 0.1574-0.2054）, which is lower than 0.25, and can be regarded as a disease of multi-factorial inheritance.CONCLUSION The occurrence of EC in the Cixian County is the outcome of the mutual effect of genetic and environmental factors. The family history of upper gastrointestinal cancers increases the risk of EC in late generations.

Correction to:High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer

This is an erratum to the published paper titled,“High expression of autophagyrelated gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer.”We have removed the citations to certain articles in subsequent revisions of the manuscript.However,owing to our oversight,the citation marker in the upper right corner was not removed.We apologize for any confusion this may have caused.

Incidence and mortality rate of esophageal cancer has decreased during past 40 years in Hebei Province,China

Background： Hebei province is located in North of China with of approximately 6% of whole national population. It is known as a high-risk area for esophageal cancer in China and worldwide. The aim of our study was to estimate the esophageal cancer burden and trend in Hebei Province. Methods： Eight cancer registries in Hebei Province submitted cancer registry data to the Hebei Provincial Cancer Registry Center. All data were qualified and compiled for cancer statistics in 2011. The pooled data were stratified by gender and age group （0, 1-4, 5-9, 10-14...80＋）. Incidence and mortality rates were age-standardized to World Segi＇s population standard and expressed per 100,000 persons. In addition, proportions and cumulative incidence/mortality rates for esophageal cancer were calculated. Esophageal cancer mortality data during the periods 1973-1975, 1990-1992, and 2004-2005 were extracted from the national death surveys. Mortality and incidence rate data from Cixian and Shexian were obtained from population-based cancer registries in each county. Results： The estimated number of newly diagnosed esophageal cancer cases and deaths in 2011 in Hebei Province was 24,318 and 18,226, respectively. The crude incidence rate of esophageal cancer was 33.37/100,000 （males, 42.18/100,000 and females, 24.31/100,000）. The age-standardized rate by world standard population （ASRW） was 28.09/100,000, ranking third among all cancers. The esophageal cancer mortality rate was 25.01/100,000 （males, 31.40/100,000 and females, 18.45/100,000）, ranking third in deaths among all cancers. The mortality rates of esophageal cancer displayed a significant decreasing trend in Hebei Province from 1973-1975 （ASRW =48.69/100,000） to 2004-2005 （ASRW =28.02/100,000）, with a decreased rate of 42.45%. In Cixian, the incidence of esophageal cancer decreased from 250.76/100,000 to 106.74/100,000 in males and from 153.86/100,000 to 75.41/100,000 in females, with annual percentage changes （APC） of 2.13 and 2.16, while the mortality rates declined with an APC of 2.46 for males and 3.10 for females from 1988 to 2011. In Shexian, the incidence rate decreased from 116.90/100,000 to 74.12/100,000 in males and from 46.98/100,000 to 40.64/100,000 in females, while the mortality rates declined, with an APC of 4.89 in males from 2003 to 2011. Conclusions： Although the incidence and mortality rates of esophageal cancer remain high, an obvious decreasing trend has been observed in Hebei Province, as well as in high-risk regions, such as Cixian and Shexian, over the past 40 years.

Importance of SALL4 in the development and prognosis of hepatocellular carcinoma

AIM: To detect the expression of sal-like protein 4 (SALL4) and to explore its relationship with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC).METHODS: One hundred and twenty-six samples of HCC tissue, 44 of adjacent noncancerous cirrhotic tissue and 10 of liver hemangioma tissue, were obtained from patients who underwent hepatectomy for HCC at the Fourth Hospital of Hebei Medical University. None of the patients had received any form of treatment before the operation. After resection, all the tissues were fixed in 10% neutral formaldehyde and embedded in paraffin. Expression of SALL4 was detected by immunohistochemistry. Patients were followed up for postoperative survival until February 2014. The relationships between SALL4 expression level and clinicopathological data and prognosis of HCC were analyzed.RESULTS: SALL4 expression was negative in the 10 samples of tissue from liver hemangioma, was weakly positive in the two samples from adjacent noncancerous cirrhotic tissue, and positive in 58 samples of HCC tissues. The differences were statistically significant (P &#x0003c; 0.05). Expression of SALL4 was higher in patients with higher &#x003b1;-fetoprotein (AFP) levels, portal vein tumor thrombus, and later clinical stage based on the Barcelona Clinic Liver Cancer classification (P &#x0003c; 0.05). Among patients with negative expression, weakly positive expression, positive expression, and strongly positive expression of SALL4, the median survival time was 39, 25, 23, and 9 mo, respectively (P &#x0003c; 0.001). When both AFP and SALL4 were detected, patients who were negative for both AFP and SALL4, SALL4-positive only, AFP-positive only, and positive for both AFP and SALL4, had a median survival time of 41, 38, 31, and 12 mo, respectively (P &#x0003c; 0.001).CONCLUSION: Expression of SALL4 is relevant to the prognosis of HCC patients. Patients with higher expression levels of SALL4 and AFP have worse prognosis.

EPIDEMIC STRENGTH OF CARDIA AND DISTANT STOMACH CANCER IN THE HIGH RISK REGION OF ESOPHAGEAL CANCER AND THEIR IMPLICATION TO EDOSCOPIC SCREENING

Objective： To discuss the epidemic strength of cardia and distant stomach cancers in the high risk region of esophageal cancer along the south Taihang mountain such as in Shexian, Linxian, and Cixian Counties, and to clarify the tasks for the control of upper gastrointestinal tract cancer as a whole in the region. Methods： Comparisons of incidence and mortality rates of esophageal, cardia and stomach cancers were made between Cixian, Linxian and Shexian Counties with reference to detection rates of cancer in situ and precancerous lesions of the three upper gastrointestinal cancers by endoscopic screening. The screening was performed from 1999 through 2004 in the three adjacent counties including a total of 6233 local residents aged 40 to 69 years old. Results： The incidence rates for cardia cancer for the male and female from 2000 through 2004 were 69.9 and 41.5, and the mortality rates were 54.3 and 33.2 respectively in Shexian County. Esophageal, cardia, and stomach cancers constitute about 70～80 percent of all malignant disease by incidence or mortality rates. Endoscopic survey with iodine staining can effectively detect squamous cell precancerous lesions in the esophagus, but the method is inadequate for the detection of adeno precancerous lesions of the cardia and stomach. Conclusion： The south Taihang mountain region is a high risk area not only for esophagus cancer, but also for cardia and stomach cancers. To control upper gastrointestinal tract cancers as a whole in the region, special attention should be paid to the control of cardia and stomach cancers. Presently, to find effective screening methods for detecting cardia and stomach precancerous lesions is especially important.

Role of the Chinese Herbal Medicine Xianhuayin on the Reversal of Premalignant Mucosal Lesions in the Golden Hamster Buccal Pouch

Aim To investigate the role of the Chinese herbal medicine Xianhuayin on the reversal of 7,12-dimethylbenz[a]anthracene （DMBA）-induced premalignant mucosal lesions in the oral buccal pouch of golden hamsters. Methodology The animals were randomly divided into a non-diseased control group （n=5） and an experimental group including 50 animals in which the buccal mucosa had been painted with DMBA （0.5% in acetone） to generate an oral mucosa premalignant lesion. Animals in the experi- mental group were further divided into Xianhuayin-treated group （n=30）, untreated prem＇alignant lesion group （n=10） and normal saline （NS）-treated group （n=10）. The cheek （buccal） pouch mucosa of the golden hamsters in each group was observed with light and electron microscopy eight weeks after intragastric administration with NS or Xianhuayin. Results In the non-diseased control group, the buccal mucosa was keratinized and stratified squamous epithelium under a light microscope. In the untreated premalignant lesion group, variable degrees of epithelial dysplasia was observed. The irregular epithelial mucosa gradually became distinct in the Xianhuayin-treated group. Scanning electronic microscopic （SEM） analysis showed that surface of the cells exhibited honeycomb structures in the hamster of untreated- group. The cells were morphologically irregular, overlapped and loosened in the untreated premalignant lesion group. Most of the cell surface exhibited honeycomb structure in the Xianhuayin-treated group. Transmission electronic micro- scopic （TEM） analysis showed that buccal mucosal epithelial cells were morphologically regular in the non-diseased control group. Desmosomes and tonofibrils were reduced and the nucleus was morphologically irregular in the untreated premalignant lesion group. In the Xianhuayin-treated group, the widening intercellular gap was gradually reduced, desmosomes and the cells becoming morphologically regular. No significant difference was observed between the hamsters in NS-treated group and those in the untreated premalignant lesion group. Significant therapeutic efficacy was observed in the group receiving Xianhuayin. Conclusion Xianhuayin is effective in the reversal of DMBA-induced premalignant lesions in the buccal pouch of golden hamsters.

The Assessment of the Clinical Effect of the Drug Compatibility and Course of Treatment to the Brucellar Spondylitis

Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.

The Comparison of the Manifestation of the Clinical Imageology and Pathology between the Brucellar Spondylitis and the Spine Turberculosis

Objective: To improve the clinical differential diagnosis level, the clinical manifestation of the brucellar spondylitis and the spine turberculosis were discussed in this paper. Method: The study was completed in the No. 1 Affiliated Hospital of Hebei North University in Zhangjiakou City, Hebei Province, China, from January 2001 to December 2013 by Analyzing the X-ray, CT scanning and MRI of 257 cases of the brucellar spondylitis retrospectively and comparing with the clinical imageology and pathology 332 cases of turberculosis of the spine diagnosed finally. Results: The brucellar spondylitis: The focuses usually locate in the lumbar vertebra and L4, 5 has the highest occurrence rate. The focuses are often small but multiple, and limited to the edge of the vertebra. Hyperostosis and osteoscterosis are usually found in the tissuses around the focuses. There are often new focuses in the newborn bones, and the destruction of intervertebral discs is usually slight. Hyperostosis and osteoscterosis might be found in the surfaces of the joints. The densites of the bones close to the focuses become high. There were less or no paravertebral abscesses but inflammational granuloma can be found frequently. Turberculosis of the spine: The focuses are usually located in the thoracic and lumbar vertebra, and are characterized by the destruction of the vertebra and the intervertebral discs, accompanied by the appearance of dead bones. In most cases, paravertebral abscesses and osteoporosis might be found. Conclusions: The specific manifestation of the clinical imageology can help to differentiate the brucelar spondylitis from the turberculosis of the spine.

The Use of Zein and Shuanghuangbu for Periodontal Tissue Engineering

Aim Tissue engineering is a promising area with a broad range of applications in the fields of regenerative medicine and human health. The emergence of periodontal tissue engineering for clinical treatment of periodontal disease has opened a new therapeutic avenue. The choice of scaffold is crucial. This study was conducted to prepare zein scaffold and explore the suitability of zein and Shuanghuangbu for periodontal tissue engineering.Methodology A zein scaffold was made using the solvent casting/particulate leaching method with sodium chloride （NaC1） particles as the porogen. The physical properties of the zein scaffold were evaluated by observing its shape and determining its pore structure and porosity. Cytotoxicity testing of the scaffold was carried out via in vitro cell culture experiments, including a liquid extraction experi- ment and the direct contact assay. Also, the Chinese medicine Shuanghuangbu, as a growth factor, was diluted by scaffold extract into different concentrations. This Shuanghuangbu-scaffold extract was then added to periodontal ligament cells （PDLCs） in order to determineits effect on cell proliferation. Results The zein scaffold displayed a sponge-like structure with a high porosity and sufficient thickness. The porosity and pore size of the zein scaffold can be controlled by changing the porogen particles dosage and size. The porosity was up to 64.1%-78.0%. The pores were well-distributed, interconnected, and porous. The toxicity of the zein scaffold was graded as 0-1. Furthermore, PDLCs displayed full stretching and vigorous growth under scanning electronic microscope （SEM）. Shuanghuangbu-scaffold extract could reinforce proliferation activity of PDLCs compared to the control group, especially at 100 μg.mL^-1 （P〈0.01）. Conclusion A zein scaffold with high porosity, open pore wall structure, and good biocompatibility is conducive to the growth of PDLCs. Zein could be used as scaffold to repair periodontal tissue defects. Also, Shuanghuangbuscaffold extract can enhance the proliferation activity of PDLCs. Altogether, these findings provide the basis for in vivo testing on animals.

Effect of Neoadjuvant CAF Regimen on the Expression of BCSG1 in Breast Cancer

Objective： To evaluate the efficacy of neoadjuvant chemotherapy and explore a sensitive and objective way in the evaluation of neoadjuvant chemotherapy, the pathological changes and BCSG1 expression were studied by pathological and immunohistochemical method in breast cancer patients with CAF neoadjuvant chemotherapy （Cyclophosphamide, Adriamycin and Fluorouracil, CAF） and those without at the same period. Methods： Specimens were obtained from 34 breast cancer patients receiving neoadjuvant CAF regimen chemotherapy （CAF group） and 110 breast cancer patients not receiving neoadjuvant chemotherapy （control group）. The BCSG1 expression was detected by SP immunohistochemistry. Correlation between BCSG1 expression and pathological response to CAF neoadjuvant chemotherapy was analyzed. Results： Overall response rate to neoadjuvant chemotherapy was 79.4%. The strong cytoplasm expression of BCSG1 was significantly lower in CAF group than in control group （29.4% vs. 64.5%, P〈0.01）. In CAF group, the positive cytoplasm expression in partial response （PR） （grade Ⅱ） cases was significantly lower than that in no response （NR） （grade Ⅲ） cases （P=0.002）. Conclusion： Neoadjuvant chemotherapy of CAF regimen could decrease the nuclear expression of BSCG1 in breast cancer.

Multicenter phaseⅡstudy of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis

Objective:Breast cancer(BC)with chest wall metastasis(CWM)usually shows rich neovascularization.This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2(HER2)-negative advanced BC involving CWM.Methods:This trial involved four centers in China and was conducted from September 2016 to March 2020.Patients received apatinib 500 mg/d[either alone or with endocrine therapy if hormone receptor-positive(HR+)]until disease progression or unacceptable toxicity.Progression-free survival(PFS)was the primary endpoint.Results:We evaluated 26 patients for efficacy.The median PFS(mPFS)and median overall survival(mOS)were4.9[range:2.0-28.5;95%confidence interval(95%CI):2.1-8.3]months and 18(range:3-55;95%CI:12.9-23.1)months,respectively.The objective response rate(ORR)was 42.3%(11/26),and the disease-control rate was76.9%(20/26).In the subgroup analysis,HR+patients compared with HR-negative patients had significantly improved mPFS of 7.0(95%CI:2.2-11.8)months vs.2.3(95%CI:1.2-3.4)months,respectively(P=0.001);and mPFS in patients without or with chest wall radiotherapy was 6.4(95%CI:1.6-19.5)months vs.3.0(95%CI:1.3-4.6)months,respectively(P=0.041).In the multivariate analysis,HR+status was the only independent predictive factor for favorable PFS(P=0.014).Conclusions:Apatinib was highly effective for BC patients with CWM,especially when combined with endocrine therapy.PFS improved significantly in patients with HR+status who did not receive chest wall radiotherapy.However,adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.

A multi-center,open-label,randomized,parallel-controlled phase II study comparing pharmacokinetic,pharmacodynamics and safety of ripertamab(SCT400)to rituximab(Mab Thera?)in patients with CD20-positive B-cell non-Hodgkin lymphoma

Objective:This multi-center,open-label,randomized,parallel-controlled phaseⅡstudy aimed to compare the pharmacokinetics(PK),pharmacodynamics(PD)and safety profile of ripertamab(SCT400),a recombinant antiCD20 monoclonal antibody,to rituximab(MabThera^(■))in patients with CD20-positive B-cell non-Hodgkin lymphoma(NHL).Methods:Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab(375mg/m^(2))or rituximab(MabThera^(■),375 mg/m^(2)).PK was evaluated using area under the concentration-time curve(AUC)from time 0 to d 85(AUC_(0-85d)),AUC from time 0 to week 1(AUC0-1 w),AUC from time 0 to week 2(AUC_(0-2 w)),AUC from time 0 to week 3(AUC_(0-3 w)),AUC from time 0 to week 8(AUC_(0-8 w)),maximum serum concentration(C_(max)),terminal half-life(T_(1/2)),time to maximum serum concentration(T_(max))and clearance(CL).Bioequivalence was confirmed if the 90%confidence interval(90%CI)of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%.PD,immunogenicity,and safety were also evaluated.Results:From December 30,2014 to November 24,2015,a total of 84 patients were randomized(ripertamab,n=42;rituximab,n=42)and the PK analysis was performed on 76 patients(ripertamab,n=38;rituximab,n=38).The geometric mean ratios of ripertamab/rituximab for AUC_(0-85d),ATC_(0-inf),and Cmaxwere 96.1%(90%CI:87.6%-105.5%),95.9%(90%CI:86.5%-106.4%)and 97.4%(90%CI:91.6%-103.6%),respectively.All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%.For PD and safety evaluation,there was no statistical difference in peripheral CD 19-positive B-cell counts and CD20-positive B-cell counts at each visit,and no difference in the incidence of anti-drug antibodies was observed between the two groups.The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.Conclusions:In this study,the PK,PD,immunogenicity,and safety profile of ripertamab(SCT400)were similar to rituximab(MabThera^(■))in Chinese patients with CD20-positive B-cell NHL.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Tuning the intensity statistics of random speckle patterns

Speckle patterns are a fundamental tool in a variety of physical and optical applications. Here, we investigate a method of precisely tuning the intensity statistics of random speckle patterns into a desirable pattern that possesses the same spatial correlation length and similar statistics distribution. This tuning mechanism relies on the derivation of the transform function and transmission matrix, which achieves different contrasts while maintaining the same average value or energy level. The statistics properties of the generated speckle patterns are further investigated by analyzing the standard deviation under different fitting parameters. Precisely tuning the intensity statistics of random speckle patterns could be useful for both fundamental research and practical applications, such as microscopy, imaging, and optical manipulation.

Mucosa-associated lymphoid tissue lymphoma of the trachea treated with radiotherapy:A case report

BACKGROUND Mucosa-associated lymphoid tissue(MALT)lymphoma originates in the marginal zone of lymphoid tissue.lung is one of the most frequent non-gastrointestinal organs involved,here known as bronchus-associated lymphoid tissue(BALT)lymphoma.BALT lymphoma of unknown etiology,and most patients are asymptomatic.The treatment of BALT lymphoma is controversial.CASE SUMMARY A 55-year-old man admitted to hospital had a three-month history of progressively coughing up yellow sputum,chest stuffiness,and shortness of breath.Fiberoptic bronchoscopy revealed mucosal visible beaded bumps 4 cm from the tracheal carina at 9 o'clock and 3 o'clock,the right main bronchus,and the right upper lobe bronchus.Biopsy specimens showed MALT lymphoma.Computed tomography virtual bronchoscopy(CTVB)showed uneven main bronchial wall thickening and multiple nodular protrusion.BALT lymphoma stage IE was diagnosed after a staging examination.We treated the patient with radiotherapy(RT)alone.A total dose of 30.6 Gy/17 f/25 d was given.The patient had no obvious adverse reactions during RT.The CTVB was repeated after RT and showed that the right side of the trachea was slightly thickened.CTVB was repeated 1.5 mo after RT and again showed that the right side of the trachea was slightly thickened.Annual CTVB showed no signs of recurrence.The patient now has no symptoms.CONCLUSION BALT lymphoma is an uncommon disease and shows good prognosis.The treatment of BALT lymphoma is controversial.In recent years,less invasive diagnostic and therapeutic approaches have been emerging.RT was effective and safe in our case.The use of CTVB could provide a noninvasive,repeatable,and accurate method in diagnosis and follow-up.

Regulatory effect of vascular endothelial growth factor on blood spinal cord barrier in presyrinx state of experimental syringomyelia

BACKGROUND： Vascular endothelial growth factor （VEGF） is able to regulate blood spinal cord barrier function as well as influence neovascularization and cause edema. OBJECTIVE： Through establishment of a rabbit model of syringomyelia, to explore the correlation between VEGF protein and mRNA expressions and function of blood spinal cord barrier and edema degree of spinal cord in presyrinx state. DESIGN, TIME AND SETTING： Randomized controlled animal study was performed in the Tumor Institute of the Fourth Hospital, Hebei Medical University from January to June 2007. MATERIALS： Atotal of 0.6 mL Kaolin solution （250 g/L, 37℃） was injected into the cisterna magna of 40 rabbits in the kaolin group to establish syringomyelia models. Goat anti-rabbit VEGF monoclonal antibody was provided by DIACLONE Company, USA; RT-PCR related reagents were provided by Huamei Bioengineering Co., Ltd., Beijing. METHODS： Sixty Chinese white rabbits were divided randomly into two groups： Kaolin group （n = 40） and control group （n = 20）. Physiological saline （0.6 mL at 37℃） was injected in rabbits of control group. On days 1,3, 7, 14 and 21 after kaolin injection, cervical cords samples were harvested after sacrifice of animal. MAIN OUTCOME MEASURES： VEGF protein and mRNA expressions were detected by immunohistochemistry and RT-PCR on days 1, 3, 7, 14, and 21 after kaolin injection. A quantitative analysis of blood spinal cord barrier function was performed by Evans blue technique. Water content of the spinal cord was measured by dry-wet weight technique. The correlation between the expression of VEGF protein and mRNA and the function of blood spinal cord barrier in the upper cervical cord of the presyrinx state was analyzed by linear correlation analysis. RESULTS： The water content and Evans blue content increased in the kaolin group on days 1 and 3 postoperatively compared with the control group （F = 7.387, 61.35, P 〈 0.05, 0.01）, and reached a peak on day 7 （F = 135.94, 528.35, P 〈 0.01）. They declined slowly to day 21 postoperatively, but both contents were still higher than the control group （F = 11.51, 58.63, P 〈 0.01）. VEGF protein expression increased on day 1, and stronger positive expression was seen on days 3, 7 and 14. It decreased on day 21. VEGF protein expression was higher than the control group at each time point （F = 137.4-468.5, P 〈 0.01 ）. VEGF mRNA expression showed the same pattern in the cervical cord at different time points. By statistical analysis, the expression of VEGF protein and mRNA had a significantly positive correlation with the structural and functional changes of the blood spinal cord barrier in the presyrinx state （r = 0.604-0.979, P 〈 0.05）. CONCLUSION： In the presyrinx state of syringomyelia, the expressions of VEGF protein and mRNA can influence the structure and function of the blood spinal cord barrier and play an important role in the formation and development of spinal cord edema and syringomyelia.

Gastrointestinal stromal tumor with multisegmental spinal metastases as first presentation:A case report and review of the literature

BACKGROUND Gastrointestinal stromal tumor(GIST)usually originates in the stomach,followed by the small intestine,rectum,and other parts of the gastrointestinal tract.The most common sites of metastasis are the liver and peritoneum,whereas spinal metastases from GIST are extremely rare.CASE SUMMARY We found a case of GIST with the first presentation of multilevel spinal metastases involving the thoracic and lumbar vertebrae.A 61-year-old Chinese man presented to our clinic because of pain in his lower back and hip for 10 d without cause.Subsequently,computed tomography(CT)and magnetic resonance imaging(MRI)revealed abnormal signals in the vertebral appendages of T12 and L4 accompanied by spinal canal stenosis,which was considered as tumor metastasis.As there were no metastases to vital organs,posterior thoracic and lumbar spinal decompression+adnexal mass resection+pedicle internal fixation was adopted to achieve local cure and prevent nerve compression.The results of histopathological studies were consistent with the metastasis of GIST.No local recurrence or new metastases were found at the 6-mo follow-up at the surgical site.The patient has no neurological symptoms at present.It is worth mentioning that a rectal mass was found and surgically removed 1 mo after the patient was discharged from hospital,and the pathological diagnosis of the mass was GIST.CONCLUSION By reviewing 26 previously reported cases of spinal metastasis in GIST,it was found that spinal metastasis of GIST has become more common in recent years,so the possibility of early spinal metastasis should be recognized.CT and MRI are of great value in the diagnosis of spinal metastatic tumors,and pathological biopsy is the gold standard for the diagnosis of metastatic tumors.It is safe and feasible to treat isolated spinal metastasis in GIST by excising metastatic masses,decompressing the spinal canal,and stabilizing the spine.

Leptin promotes proliferation and invasion of osteosarcoma cells by upregulating the expression of SIRT1

Osteosarcoma(OS)is a primary high-grade malignant bone neoplasm,and the prognosis ofOS remains poor due to early metastasis.Leptin plays an essential role in tumorigenesis,but the role of leptin in the development of OS is still not fully understood.In this study,we used a human osteosarcomaMG-63 cell line as an experimentalmodel.MG-63 cells were treated with leptin,and cell proliferation,apoptosis,adhesion,invasion,and gene expression,were evaluated.The results showed that leptin promoted proliferation,decreased adhesion,suppressed apoptosis,and promoted invasion,of MG-63 cells.Moreover,the expression of SIRT1 was upregulated in MG-63 cells exposed to leptin.Furthermore,MMP-2,8,and 9 were significantly upregulated by SIRT1,while SIRT1 knockdown inhibited the proliferation and invasion of MG-63 cells.In conclusion,our results suggest that leptin promotes OS cell proliferation and invasion by inducing the expression of SIRT1.