The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.

ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.

Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy.Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for comple-mentary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diver-sity and caregiver self-efficacy for complementary feeding of infants and young children.Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56% (474/770)for all the infants and young children and 45.00% (108/240),69.16% (287/415),and 68.70% (79/115)for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respective-ly.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing fac-tor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR = 1.42,95% CI=1.17-1.73,P<0.001).Conclusion The dietary diversity for infants and young children in rural Nan-chong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.

Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.

Objective:To explore effects of the specialist nurse training program of based on the context, input, process, product (CIPP) evaluation model in the training of junior nurses in the Department of Otolaryngology.Methods:From April 2018 to May 2020, convenience sampling method was used to select 80 specialist nurses who received training in the Shandong ENT Hospital as research objects. A total of 40 nurses who received traditional training from April 2018 to March 2019 were divided into a control group. From April 2019 to May 2020, 40 nurses who were trained in a specialist nurse training program based on the CIPP evaluation model were divided into observation groups. This study compared nurses' core competence and training qualification rate.Results:After training, the core competence score of observation group was higher than that of control group, and the difference was statistically significant ( P<0.05) . The training qualification rate of observation group and control group was 92.50% (37/40) and 70.00% (28/40) respectively, also with a statistical difference ( P<0.05) . Conclusions:The training program for specialist nurses based on the CIPP evaluation model can improve the theoretical knowledge and practical ability of nurses, and then improve the quality of clinical care, and promote the long-term development of the hospital, which is worthy of promotion.

OBJECTIVETo analyze the status of maternal health behaviors and it's risk factors for Yi-nationality women in poor rural areas of Sichuan province.

METHODSIn 2012, multi-stage stratified cluster sampling method was used to select 14 villages of two poor counties in Liangshan Yi-nationality autonomous prefecture Sichuan province. At least 10 women who have infants aged 0-12 months were selected in each simple villages, a total of 284. The structured questionnaire was developed on the basis of the theory of reasoned action. Yi-nationality female college students were trained as investigators. Research indicators included prenatal care rate, hospital delivery rate, postpartum examination rate, socio-demographic characteristics, maternal health care knowledge. χ² test was used to compare the differences of above indicators among different groups. The structural equation model were used to statistical analyze.

RESULTSIn the 284 subject women, 51.7% (147/284) women owned more than 2 children, 41.6% (118/284) women were more than 30 years old, 87.3% (248/284) women were illiteracy. The prenatal care rate was 69.7% (197/284), the hospital delivery rate was 26.8% (76/284), and the postnatal check rate was 22.9% (65/284). The influence factors of maternal health behaviors included the number of children, age and education (χ² were 10.92, 13.24, 9.58; P values were 0.027, 0.004, 0.008, respectively).The structural equation model analysis results showed that the maternal health behaviors were directly or indirectly affected by subjective norms (β = 0.236, P < 0.001), women's cognition (β = 0.226, P = 0.020) and women's attitudes on maternal health behavior (β = 0.157, P = 0.001). Among subjective norms, women have high compliance to their husbands (β = 0.850, P < 0.001), their peers (β = 0.708, P < 0.001), and their mothers-in-law (β = 0.636, P < 0.001).

CONCLUSIONThere were still serious problems in maternal health behaviors for Yi-nationality women in poor rural areas. The main factors included not only the women's cognition and attitudes for maternal health, but also the attitudes of important social relationships.

Child ; China ; Ethnic Groups ; Family ; Female ; Health Behavior ; ethnology ; Humans ; Infant ; Maternal Health ; ethnology ; Maternal Health Services ; Postpartum Period ; Pregnancy ; Prenatal Care ; Risk Factors ; Rural Population

Objective To analyze the status of maternal health behaviors and it's risk factors for Yi-nationality women in poor rural areas of Sichuan province. Methods In 2012, multi-stage stratified cluster sampling method was used to select 14 villages of two poor counties in Liangshan Yi-nationality autonomous prefecture Sichuan province. At least 10 women who have infants aged 0-12 months were selected in each simple villages, a total of 284. The structured questionnaire was developed on the basis of the theory of reasoned action. Yi-nationality female college students were trained as investigators. Research indicators included prenatal care rate, hospital delivery rate, postpartum examination rate, socio-demographic characteristics, maternal health care knowledge. χ2 test was used to compare the differences of above indicators among different groups .The structural equation model were used to statistical analyze. Results In the 284 subject women, 51.7%(147/284) women owned more than 2 children, 41.6%(118/284)women were more than 30 years old, 87.3%(248/284)women were illiteracy. The prenatal care rate was 69.7%(197/284), the hospital delivery rate was 26.8%(76/284), and the postnatal check rate was 22.9%(65/284). The influence factors of maternal health behaviors included the number of children, age and education (χ2 were 10.92,13.24,9.58;P values were 0.027, 0.004, 0.008, respectively).The structural equation model analysis results showed that the maternal health behaviors were directly or indirectly affected by subjective norms (β= 0.236, P<0.001), women's cognition (β= 0.226,P=0.020) and women's attitudes on maternal health behavior (β=0.157, P=0.001). Among subjective norms, women have high compliance to their husbands (β=0.850, P<0.001), their peers (β=0.708, P<0.001), and their mothers-in-law (β=0.636, P<0.001). Conclusion There were still serious problems in maternal health behaviors for Yi- nationality women in poor rural areas. The main factors included not only the women's cognition and attitudes for maternal health, but also the attitudes of important social relationships.

Objective To analyze the status of maternal health behaviors and it's risk factors for Yi-nationality women in poor rural areas of Sichuan province. Methods In 2012, multi-stage stratified cluster sampling method was used to select 14 villages of two poor counties in Liangshan Yi-nationality autonomous prefecture Sichuan province. At least 10 women who have infants aged 0-12 months were selected in each simple villages, a total of 284. The structured questionnaire was developed on the basis of the theory of reasoned action. Yi-nationality female college students were trained as investigators. Research indicators included prenatal care rate, hospital delivery rate, postpartum examination rate, socio-demographic characteristics, maternal health care knowledge. χ2 test was used to compare the differences of above indicators among different groups .The structural equation model were used to statistical analyze. Results In the 284 subject women, 51.7%(147/284) women owned more than 2 children, 41.6%(118/284)women were more than 30 years old, 87.3%(248/284)women were illiteracy. The prenatal care rate was 69.7%(197/284), the hospital delivery rate was 26.8%(76/284), and the postnatal check rate was 22.9%(65/284). The influence factors of maternal health behaviors included the number of children, age and education (χ2 were 10.92,13.24,9.58;P values were 0.027, 0.004, 0.008, respectively).The structural equation model analysis results showed that the maternal health behaviors were directly or indirectly affected by subjective norms (β= 0.236, P<0.001), women's cognition (β= 0.226,P=0.020) and women's attitudes on maternal health behavior (β=0.157, P=0.001). Among subjective norms, women have high compliance to their husbands (β=0.850, P<0.001), their peers (β=0.708, P<0.001), and their mothers-in-law (β=0.636, P<0.001). Conclusion There were still serious problems in maternal health behaviors for Yi- nationality women in poor rural areas. The main factors included not only the women's cognition and attitudes for maternal health, but also the attitudes of important social relationships.