Incidence of radiodermatitis and factors associated with its severity in women with breast cancer: a cohort study

Abstract Background: One of the main adverse reactions of adjuvant radiotherapy for breast cancer is radiodermatitis. Objective: To assess the incidence of radiodermatitis in women with breast cancer, identify factors associated with its severity and determine the time at which this event occurs. Methods: Prospective cohort study in 113 women with breast cancer who were evaluated before radiotherapy and at every fifth session until the end of treatment. Logistic regression and Cox proportional regression model were used for the assessment of risk factors; P values < 0.05 were considered significant. Results: The incidence rate of radiodermatitis was 98.2% and it was demonstrated that for each additional point of the Body Mass Index (BMI), the chance of occurrence of grades II to IV radiodermatitis increases by 14% (OR = 1.14 [95% CI 1.04-1.26]; p = 0.004) and statin use increases the risk of more severe skin lesions by four-fold (OR = 4.27 [95% CI 1.11-16.42]; p = 0.035). The exclusive use of hydrogel for skin hydration was an independent factor in delaying the onset of radiodermatitis (HR = 0.55 [95% CI 0.36-0.82]; p = 0.004). Study limitations: The main limitation of this study was its external validity. The identified factors should be considered for services and populations similar to those in this study. Conclusions: There was a high incidence of radiodermatitis and its severity was related to higher BMI, statin use; there was a protective effect of hydrogel use.

Progress in research on novel BC adjuvant system / 中国生物制品学杂志

@#Vaccines with novel adjuvants have been listed abroad,while in China,except for aluminum adjuvants widely used in vaccine research and production,few other novel adjuvants have been successfully listed. This paper briefly summarized the source,development history,research progress on biological activity and immune mechanism as well as safety evaluation of the novel BC adjuvant system with independent intellectual property right which has been applied to the vaccine in clinical research stage,so as to provide theoretical support for selection of the adjuvant in the development of novel vaccine.

Development and verification of a high performance liquid chromatography method for determination of aluminium adjuvant content in vaccine / 中国生物制品学杂志

@#Objective To develop a high performance liquid chromatography(HPLC)method for determination of aluminium adjuvant content in vaccine,and verify and preliminarily apply the method.Methods The 8-hydroxyquinoline derivatization method was used for determination. The chromatographic column was phenyl-hexyl column[Luna 5u PhenylHexyl(250 mm × 4. 6 mm)],and the mobile phase was composed of ammonium acetate solution-acetonitrile(with 8-hydroxyquinoline)(60 ∶ 40)containing 20 mg/L ascorbic acid,while eluted at a flow rate of 1. 0 mL/min with the isocratic eluent. The excitation wavelength and the emission wavelength of the fluorescence detector were 380 nm and 520 nm respectively. The column temperature was 40 ℃,and the sample injection was 50 μL. The developed method was verified for the specificity,linear range,accuracy,repeatability,stability and durability,and used to determine the aluminum content in 12 batches of vaccines. The results were compared with those determined by titration in general principle 3106of Chinese Pharmacopoeia(VolumeⅢ,2020 edition).Results No interference peaks appeared in the sample chromatogram,and the non-aluminum adjuvant vaccine components and phosphate buffer had no interference with the determination. The linearity of aluminum standard was good in the concentration range of 6. 25 ～ 100 μg/mL,r = 0. 999 6. The average results of spike recoveries of aluminum content in inactivated hepatitis A vaccine,recombinant hepatitis B vaccine,adsorbed acellular DTP vaccine and inactivated enterovirus 71 vaccine were 98. 32%,100. 85%,101. 09% and 99. 31%,respectively in the verification for accuracy. The relative standard deviations(RSDs) of the determination results of aluminum content in the solution of six samples of the four vaccines in the same batch were 1. 09%,1. 42%,0. 97% and1. 30%,respectively. The RSDs of aluminum content of four vaccine samples stored at room tempe-rature for 0,2,4,6 and8 h were 0. 82%,0. 73%,0. 40% and 0. 48%,respectively. When the ratio of ammonium acetate solution to 8-hydroxyquinoline acetonitrile solution in mobile phase changed within 5%,the fluctuation range of aluminum content of four vaccines was less than 2%. There was no significant difference between the developed HPLC method and the titration method of Chinese Pharmacopoeia(VolumeⅢ,2020 edition)for determination of aluminum content in the 12 batches of vaccine samples.Conclusion A HPLC method for determination of aluminum adjuvant content in vaccines has been successfully established with good specificity,linearity,accuracy,repeatability,stability and durability,simple operation,high degree of automation and less interference of manual factors. It can realize the determination of aluminium content in single dose,which provides an effective means for the rapid and large-scale determination of aluminum content in vaccine products and monitoring the dispensing of semi-final products in the production process.

Controversias en radioterapia adyuvante en cáncer de próstata localizado

La elección del momento más adecuado para realizar radioterapia en el tratamiento del cáncer de próstata es controversial ya que puede ser realizada inmediatamente posterior a la prostatectomía o como tratamiento de rescate ante una recaída. En este artículo, se realiza una búsqueda del tema, se seleccionan los ensayos clínicos con mayor evidencia y se analizan los resultados. Si bien existe beneficio en la radioterapia adyuvante, este resultado no se encuentra en todos los pacientes y sí se asocia a mayor toxicidad genitourinaria tardía, por lo tanto, la clave está en la selección del tratamiento según el paciente específico.

The choice of the most appropriate time to perform radiotherapy in the treatment of prostate cancer is controversial since it can be performed immediately after prostatectomy or as rescue treatment in case of relapse. In this article, a search for the topic is carried out, the clinical trials with the greatest evidence are selected and the results are analyzed. Although there is benefit in adjuvant radiotherapy, this result is not found in all patients and it is associated with greater late genitoutinary toxicity, therefore, the key is in the selection of treatment according to the specific patient.

Postoperative radiotherapy with an electron beam on keloid scar: epidemiological evaluation in a teaching hospital / Radioterapia pós-operatória com feixe de elétrons sobre cicatriz queloideana: avaliação epidemiológica em hospital de ensino

Introduction: Keloids are one of the most aggressive spectrums of healing disorders. They have a unique pathophysiology and multiple specific genetic and cellular factors, which have not yet been fully elucidated. So far, literature reviews have found the influence of genetics, injury site, and ethnicity on the incidence and rate of recurrence. Furthermore, the need to associate an adjuvant method with surgical excision has already been verified, but the best therapy has yet to be defined. Method: A retrospective analysis of medical records was carried out to assess the profile of patients who underwent postoperative radiotherapy with an electron beam to treat keloids at the Hospital das Clínicas da Faculdade de Medicina de Botucatu between 2015 and 2019. Results: Data from 131 patients were evaluated, with 269 keloid scars treated. The average duration of treatment was 51 days, and the number of sessions was 17. White patients were predominant (78%) and women (70%), with surgical incision being the main cause of formation (49%) and ear the most identified location (33%). Women were more likely to complete the proposed treatment (p=0.04), while non-literates completed less than those who had at least completed primary or secondary education (p<0.0001). Conclusion: Postoperative radiotherapy for keloid scars is a well-established treatment in the literature and an important tool for plastic surgeons. Knowing the profile of patients who need this therapy is essential to create methods that improve adherence and results.

Introdução: Os queloides correspondem a um dos espectros mais agressivos dos distúrbios da cicatrização. Possuem fisiopatologia ímpar e múltiplos fatores genéticos e celulares específicos, ainda não totalmente elucidados. Até o momento, revisões literárias encontraram influência da genética, local da lesão e etnia sobre a incidência e taxa de recorrência. Ademais, já foi constatada a necessidade de associação de um método adjuvante com a excisão cirúrgica, mas ainda sem definição da melhor terapia. Método: Realizada uma análise retrospectiva de prontuários para avaliação do perfil dos pacientes submetidos a radioterapia pós-operatória com feixe de elétrons para o tratamento de queloides no Hospital das Clínicas da Faculdade de Medicina de Botucatu, entre 2015 e 2019. Resultados: Foram avaliados os dados de 131 pacientes, com um total de 269 cicatrizes queloideanas tratadas. A média da duração do tratamento foi de 51 dias e do número de sessões, de 17. Houve predominância de pacientes brancos (78%) e de mulheres (70%), sendo incisão cirúrgica a principal causa de formação (49%) e a orelha a localização mais identificada (33%). As mulheres tiveram mais chance de completar o tratamento proposto (p=0,04), enquanto os não alfabetizados completaram menos do que aqueles que tinham pelo menos ensino fundamental ou médio completo (p<0,0001). Conclusão: A radioterapia pós-operatória em cicatrizes queloideanas é um tratamento consagrado na literatura e uma importante ferramenta do cirurgião plástico. Conhecer o perfil dos pacientes que necessitam desta terapia é fundamental para criar métodos que melhorem a adesão e o resultado da mesma.

Supervivencia a dos años en pacientes con cáncer gástrico localmente avanzado en una institución de Popayán entre 2018 y 2020 / Two-year survival in patients with locally advanced gastric cancer at an institution in Popayán between 2018 and 2020

Introducción. El tratamiento oncológico perioperatorio en pacientes con cáncer gástrico localmente avanzado está indicado; aun así, no siempre es posible. El objetivo de este estudio fue evaluar la supervivencia de los pacientes según la administración de quimioterapia perioperatoria. Métodos. Estudio observacional, tipo cohorte ambispectivo, incluyendo pacientes con cáncer gástrico localmente avanzado quienes recibieron o no quimioterapia perioperatoria. Resultados. Se incluyeron 33 pacientes, 90,9 % pertenecían al régimen subsidiado de salud y el 78,8 % en estadio T4. El grupo que recibió quimioterapia perioperatoria, que solo tuvo 5 pacientes (15,1 %), presentó mayor supervivencia global a 2 años (100 %), seguido del grupo de quimioterapia postoperatoria (58,8 %) y del grupo sin quimioterapia, que alcanzó una supervivencia global a 2 años de 54,5 %. Discusión. La supervivencia global fue mayor en el grupo de quimioterapia perioperatoria, consonante a lo descrito a nivel internacional, aunque los pacientes se encontraban en un estadío localmente más avanzado, la mayoría con T4 y N+ según AJCC VIII edición. Conclusiones. El estadío clínico es un factor pronóstico importante y, en nuestro medio, la mayoría de los pacientes consultan en estadíos localmente más avanzados. A eso se suman las dificultades en el acceso a la atención en salud. Aun así, la quimioterapia perioperatoria mostró una supervivencia mayor en pacientes con cáncer gástrico localmente avanzado

Introduction. Perioperative cancer treatment in patients with locally advanced gastric cancer is indicated; even so, it is not always possible. The objective was to evaluate survival according to time and receipt of perioperative chemotherapy. Methods. Observational study, ambispective cohort type, including patients with locally advanced gastric cancer who received or did not receive perioperative chemotherapy. Results. Thirty-three patients were included, 90.9% belonged to the subsidized regimen and 78.8% with TNM T4. The perioperative chemotherapy group, which only had five patients (15.1%), had a higher overall survival at 2 years (100%), followed by the postoperative chemotherapy group and by the group without chemotherapy, with an overall survival at 2 years of 58.8% and 54.5%, respectively. Discussion. Overall survival was higher in the perioperative chemotherapy group, consistent with what has been described internationally, although the patients were in a more advanced stage, most being with T4 and N+ according to the AJCC VIII edition. Conclusions. The clinical stage is an important prognostic factor and in our environment, most patients consult in more advanced stages, coupled with difficulties in accessing health care. Even so, perioperative chemotherapy showed a longer survival in patients with locally advanced gastric cancer, the data should not be extrapolated since the number of patients in each group is significantly different

Argon Beam Coagulation as an Adjuvant for Extended Curettage for Giant Cell Tumors of the Bone: A Study of 50 Cases / Coagulação por plasma de argônio como adjuvante à curetagem estendida em tumores de células gigantes do osso: Um estudo de 50 casos

Abstract Objective Extended curettage with adjuvants of giant cell tumors of bone is associated with a lower rate of recurrence of the tumor while preserving the adjacent joint. The present study was conducted to estimate the recurrence rate and functional outcome after using argon beam as an adjuvant for extended curettage. Methods We selected 50 patients with giant cell tumors, meeting all the inclusion criteria, who underwent extended curettage using high speed burr and argon beam photocoagulation between July 2016 to January 2019. On their follow-up visit, they were assessed for any complaints of pain and signs like tenderness, locally raised temperature, and decreased range of motion of the adjacent joint. Radiologically, the patients were assessed for any increased lucency around the cement mantle and uptake of the subarticular graft. Musculoskeletal Tumor Society Score (MSTS) was administered to the patients, and range of motion of the adjacent joint was compared with the contralateral joint. Results Recurrence was found in 4 patients, that is, an 8% recurrence rate. Twenty-six out of 28 patients with a tumor in the lower limb had a grade-5 weight bearing status 6 months from the surgery, and their range of motion was comparable to contralateral healthy joint with an average MSTS score of 27 (18-30). Conclusion Extended curettage of giant cell tumors using argon beam coagulation is associated with low recurrence rates of the tumor and is an effective modality in the treatment of these tumors besides having a functional outcome comparable to the healthy limb.

Resumo Objetivo A curetagem estendida com adjuvantes de tumores de células gigantes do osso está associada a uma menor taxa de recidiva da neoplasia e à preservação da articulação adjacente. Este estudo foi feito para estimar a taxa de recidiva e o resultado funcional após o uso de plasma de argônio como adjuvante à curetagem estendida. Métodos Cinquenta pacientes com tumores de células gigantes que atendiam a todos os critérios de inclusão foram selecionados para o estudo e submetidos à curetagem estendida com broca de alta velocidade e fotocoagulação com plasma de argônio entre julho de 2016 e janeiro de 2019. À consulta de acompanhamento, os pacientes foram avaliados quanto a quaisquer queixas de dor e sinais como sensibilidade, aumento local da temperatura e diminuição da amplitude de movimento da articulação adjacente. Radiologicamente, os pacientes foram avaliados quanto à presença de qualquer aumento de radiotransparência ao redor do manto de cimento e incorporação do enxerto subarticular. O questionário Musculoskeletal Tumor Society Score (MSTS) foi administrado aos pacientes e a amplitude de movimentação da articulação adjacente foi comparada à articulação contralateral. Resultados Quatro pacientes apresentaram recidiva, o que corresponde a uma taxa de 8%. Seis meses após a cirurgia, 26 de 28 pacientes com tumor no membro inferior tinham capacidade de sustentação de peso de grau 5 e amplitude de movimento comparável à articulação saudável contralateral, com pontuação MSTS média de 27 (intervalo de 18 a 30). Conclusão A curetagem estendida de tumores de células gigantes com coagulação por plasma de argônio está associada a baixas taxas de recidiva da neoplasia; é uma modalidade eficaz no tratamento desses tumores e o resultado funcional é comparável ao do membro saudável.

Re-engineering of bicistronic plasmid pGPD/IFN to construct fusion gene co-expressing Glyceraldehyde 3-phosphate dehydrogenase gene (GAPDH) of Edwardsiella tarda and Interferon-gamma (IFN-?) gene of Labeo rohita (Hamilton) and its in vitro functional analysis

Edwardsiella septicemia disease in the cultured Indian major carps is caused by the fish pathogen Edwardsiella tarda and it is preventable by DNA vaccination. Here, we tried to develop a bicistronic DNA vaccine pGPD/IFN expressing the Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene of Edwardsiella tarda and Interferon-gamma (IFN-?) gene of Labeo rohita. The vaccine showed high protective efficiency in our previous studies; however as a limitation of bicistronic construct the expression of gene cloned in second frame (B) is poor. To overcome this limitation we re-engineered the construct and designed a fusion gene co-expressing the GAPDH and IFN-? genes as one frame with an aim to get the optimum expression of both the genes. For this purpose, a fusion insert comprising GAPDH and IFN-? coding sequences was cloned in to pcDNA3.1(+) plasmid vector. The fusion genes' in vitro expression was confirmed in the striped snakehead fish cell line (SSN-1). Successful expression of the re-engineered fusion gene DNA vaccine in the cell line was achieved at 48h post-transfection, which was confirmed by amplifying the expression transcripts of GAPDH and IFN-? genes. Thus, the study concludes that the re-engineered fusion vaccine pcGPD/IFN (pcDNA3.1(+) plasmid having fusion GPD/IFN) is functional and can be effectively utilized to vaccinate rohu (Labeo rohita) as it contains the species-specific immune gene (IFN-?) as an adjuvant

Identification and validation of a novel prognostic model based on platinum resistance-related genes in bladder cancer

ABSTRACT Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.

Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer / 中华消化外科杂志

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.

Current situation and prospect in the clinical treatment of gallbladder cancer / 中华消化外科杂志

Gallbladder carcinoma is a tumor with poor prognosis and lack of effective comprehensive treatment. At present, surgical resection is still the main treatment for gallbladder carcinoma. Precise evaluation and adequate preparation before surgery, and safe, effective, standar-dized resection are the key points to successful treatment of gallbladder carcinoma. In clinic, there has been a growing appreciation of the prevention and reasonable treatment of incidental gallbladder carcinoma. Neoadjuvant and conversion therapy give full play to the effects of chemotherapy, targeted therapy, and immunotherapy agents on tumor cells, which can achieve the goal of downstage or conversion of tumors before surgery, increasing the radical resection rate, and improving the prognosis of patients.

New progress in the diagnosis and treatment of biliary tract tumors / 国际外科学杂志

Biliary tract cancers (BTC) is a type of digestive tract malignant tumors that originate from biliary epithelial cells, is characterized by strong occult and highly invasive, and has a high mortality rate. Early detection and diagnosis are considered to be the key to obtaining radical surgical treatment. R0 resection is an effective measure to benefit patients with BTC. However, most of the patients present with local progression or associated distant metastasis, making it impossible to undergo radical surgical treatment. With existing diagnosis and treatment methods, the 5-year survival rate of patients is still very low. Therefore, how to improve the level of diagnosis and treatment of BTC, prolong survival, and improve the quality of life has become an urgent problem to be solved. In view of the characteristics of BTC and the continuous deepening of clinical pathological molecular research, adjuvant therapy, precisely targeted therapy, immunotherapy, and comprehensive treatment are currently considered to be standardized diagnosis and treatment models and research directions beyond surgery. Therefore, this article systematically analyzes the current research progress of BTC both domestically and internationally, aiming to provide strategies for the diagnosis and treatment of patients with BTC.

Exploration of risk factors and establishment of nomograms model for postoperative adjuvant chemotherapy in stage Ⅰ gastric cancer / 国际外科学杂志

Objective:To identify the risk factors associated with postoperative adjuvant chemotherapy in patients with stage I gastric cancer and establish nomograms model based on risk factors.Methods:In this retrospective case-control study, 161 cases with stage Ⅰ primary gastric adenocarcinoma were included who underwent gastrectomy at the Department of General Surgery of the First Medical Center of Chinese PLA General Hospital from January to December in 2020, including 129 male cases and 32 females cases, with the average age of (59.90±0.80) years. Among them, 41 cases were treated with postoperative adjuvant chemotherapy (chemotherapy group), while 120 cases who did not receive postoperative adjuvant chemotherapy (no chemotherapy group). Univariate and multivariate Logistic regression analyses were used to identify the risk factors of adjuvant chemotherapy in stage Ⅰ gastric cancer patients and establish the nomograms predictive model. ROC curve and calibration curve were used to evaluate the performance of the model.Results:Multivariate analysis revealed that primary tumor site, tumor size, T stage, N stage lymph-vascular tumor embolus or perineural invasion were the independent risk factors of postoperative adjuvant chemotherapy for stage Ⅰ gastric cancer( P<0.05). The ROC curve indicated that area under the curve (AUC) of the multivariate model was 0.91(95% CI: 0.86-0.97). The calibration curve showed that probability predicted by nomograms was consistent with the actual situation(C-index: 0.91). Conclusions:The tumor located in the proximal stomach, tumor size>2 cm, T 2, N 1, lymph-vascular tumor embolus or perineural invasion maybe be the risk factors for chemotherapy decision in stage Ⅰ gastric cancer patients. The established model has good predictive ability for postoperative chemotherapy of stage Ⅰ gastric cancer patients, which might provide reference for the selection of clinical decisions in this part of patients.

Risk Factors and Predictive Model for Severe Myelosuppression due to Chemotherapy in Triple-negative Breast Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer （TNBC）. MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2， 2016 to September 2， 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ2 test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic （ROC） curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients （51%） had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years （OR = 3.463， 95% CI： 1.144 to 10.486， P = 0.028）， age >60 years （OR = 3.474， 95% CI： 1.004 to 12.020， P = 0.049）， body mass index （BMI） 18.5 to 24.0 （OR = 1.445， 95% CI： 0.686 to 3.087， P = 0.328）， BMI <18.5 （OR = 3.582， 95% CI： 1.260 to 10.182， P = 0.017）， tumor TNM stage Ⅱ （OR = 1.698， 95% CI： 0.831 to 3.468， P = 0.146）， tumor TNM stage Ⅲ （OR = 2.943， 95% CI： 1.199 to 7.227， P = 0.019）， previous diabetes （OR = 2.441， 95% CI： 1.076 to 5.539， P = 0.033）， low pre-treatment albumin level （OR = 2.759， 95% CI： 1.141 to 6.669， P = 0.024） and low pre-treatment lymphocytes （OR = 3.428， 95% CI： 1.689 to 6.958， P = 0.001） were independent risk factors for severe myelosuppression due to chemotherapy. The χ2 value for the logistic regression model Hosmer-Lemeshow test was 11.507， P= 0.175， the area under the ROC curve was 0.763， standard error 0.033， 95% CI： 0.698-0.828， P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%； the kappa value was 0.679， standard error 0.081， P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.

Zanthoxylum bungeanum Aqueous Extract Treated Rheumatoid Arthritis by Inhibiting Synovial Cell Proliferation and Inducing Cell Apoptosis / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effect of the water extract of Zanthoxylum bungeanum aqueous extract（ZBAE）on rheumatoid arthritis. MethodThe sixty SD rats were divided into normal group， model group ［complete Freund's adjuvant （CFA）， 10 mg·kg-1］， methotrexate（MTX） group （0.25 mg·kg-1）， low -， medium -， and high-dose ZBAE groups （90， 180， 360 mg·kg-1）. The rats in MTX group were given intraperitoneal injection for two weeks， three times a week， and the rats in ZBAE group were administrated for 14 days. The swelling of the ankle joint and body weight were observed， and arthritis scores were also performed. Computed tomography （CT）， hematoxylin-eosin （HE） staining and safranine-O and fast green staining were used to observe the effect of ZBAE on synovial hyperplasia and bone protection. Cell counting kit-8（CCK-8）method was used to detect the proliferation of the RA-FLSs cells treated with ZBAE. According to the results of CCK-8 experiment， the optimal concentration and time of administration were determined， blank group， low -， medium -， and high-dose ZBAE groups （0.08，0.10，0.12 g·L-1） were set up. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry，the migration ability of RA-FLSs cells was examined by scratch test. Western blot was used to detect the effect of ZBAE on phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， cyclin-dependent kinase 2 （CDK2）， Cyclin A and phosphorylated PI3K， Akt （p-PI3K，p-Akt） protein expression in RA-FLSs cells. ResultCompared with the normal group，joint swelling index and arthritis score were increased in the model group （P<0.05），the bone of the ankle was seriously damaged， and there was obvious synovial hyperplasia. Compared with the model group， the ZBAE group could significantly reduce the joint swelling index （P<0.05）， inhibit synovial hyperplasia and cartilage destruction. In vitro study showed that compared with the blank group， ZBAE could inhibit the migration of RA-FLSs （P<0.05）， promoted cell apoptosis （P<0.05）， and acted on RA-FLSs cells in S phase to inhibit cell proliferation. Moreover， the result of Western blot showed that compared with the blank group， the expression of p-PI3K， p-Akt， CDK2 and Cyclin A proteins were significantly decreased in the high dose group of ZBAE （P<0.05）. ConclusionThese results suggest that ZBAE has a therapeutic effect on rheumatoid arthritis by inhibiting synovial hyperplasia， promoting synovial apoptosis and inhibiting its migration.

Research Progress on Postoperative Adjuvant Therapy for Completely Resected Stage ⅠB Non-small Cell Lung Cancer / 肿瘤防治研究

Lung cancer is considered as the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of primary lung cancer. Owing to the improved utilization of medical technological level and the popularization of health examinations, the detection rate of early-stage NSCLC is gradually increasing. The main treatment modalities for early-stage NSCLC are surgical resection and adjuvant chemotherapy. Platinum-based chemotherapy is recommended as the standard postoperative adjuvant treatment for patients with completely resected stageⅡ-ⅢA NSCLC. However, adjuvant therapy remains a controversial option in stageⅠB NSCLC. This review focuses on postoperative adjuvant therapy such as adjuvant chemotherapy, targeted therapy, and immunotherapy for completely resected stageⅠB NSCLC. Moreover, the biomarkers and prognostic factors of high-risk patients are discussed.

Current Situation of Postoperative Adjuvant Chemoradiotherapy for Extrahepatic Cholangiocarcinoma / 肿瘤防治研究

In recent years, the incidence of extrahepatic cholangiocarcinoma (ECC) has been increasing annually. As a result of frequently invading adjacent structures, such as hepatic artery, hepatic vein, and portal vein, and low radical resection rate, the prognosis is poor. Even if radical resection is completed early, the 5-year survival rate is still less than 30%. At present, whether postoperative adjuvant therapy can improve the prognosis of ECC remains a research hotspot and a controversial point. This article will combine the latest research results to discuss the plan and status of postoperative adjuvant therapy after ECC, as well as analyze the effect of postoperative adjuvant therapy on ECC.

Advances in Treatment of Locally Advanced Renal Cell Carcinoma / 肿瘤防治研究

Renal cell carcinoma (RCC) is the third most common malignant tumor of the genitourinary system. During disease progression, RCC can undergo local and/or distant metastasis, which seriously affects the prognosis of the patient. With the advancements in targeted therapy and immunotherapy for advanced RCC, treatment for locally advanced RCC has changed. Studies have focused on applying targeted therapy or immunotherapy in the perioperative period. This article aims to review progress on treatment of locally advanced RCC to offer references for novel treatment strategies.

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice / 中国生物制品学杂志

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice@#Objective To investigate the effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 crown protein vaccine in mice.Methods The amantadine dimer was synthesized by substitution reaction ligation,hydrolytic acidification reaction ligation and amide condensation reaction ligation,with which as adjuvant,female BALB/c mice were immunized with the receptor-binding domain(RBD).The mice were randomly divided into five groups,six for each as follows:R6A+RBD group[21 μg(0.033 μmol)amantadine dimer+10 μg RBD],Ada+RBD group[10 μg(0.066 μmol)amantadine+10 μg RBD],Alu+RBD group(35 μg aluminum adjuvant+10 μg RBD),RBD group(10 μg RBD)and Blank group(0.9% normal saline),which were immunized i.m.on day 0,14 and 28 respectively.Serum samples were collected from tail vein of mice 7 d after the second dose and 14 d after the last dose and determined for specific IgG antibody levels by ELISA.Results The amantadine dimer was purified by thin layer chromatography(TLC)and identified by electrospray ionization-MS(ESI-MS)positive/negative ion mode.After two times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all higher than those of Ada+RBD group,while lower than those of Alu+RBD group.However,after three times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all significantly higher than those of Ada+RBD and Alu+RBD groups(each F > 30,each P < 0.000 1 and each P < 0.01).Conclusion Amantadine dimer adjuvant enhanced humoral immune response induced by SARS-CoV-2 protein vaccine in mice with good adjuvant effect,which may be used as an alternative adjuvant.This strategy based on existing drug transformation provided a new idea for the development of novel adjuvants.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures / 中国医学科学杂志(英文版)

Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.