Hospitalization costs of pediatric community-acquired pneumonia in Shanghai / 中华儿科杂志

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ2 test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ2=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ2=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.

Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer / 中华肿瘤杂志

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury / 中国应用生理学杂志

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

Application of Embodied Cognition in Speech Therapy (review) / 中国康复理论与实践

Embodied cognition is an important research direction in current psycholinguistics. Perceptual symbols theory, indexical hypothesis, immersed experiencer framework, symbol interdependency hypothesis and mirror neuron system are important research achievements of embodied cognition in the field of language, which may light a way for the further development of speech therapy.

Fluorescence assay for the detection of apurinic/apyrimidinic endonuclease 1 (APE1) activity in human blood samples / 北京大学学报(医学版)

OBJECTIVE@#To develop a simple, sensitive and robust method for rapid detection of human apurinic/apyrimidinic endonuclease 1 (APE1) in various biological samples.@*METHODS@#An abasic site-containing DNA probe with a sequence of 5'-T*T*C*C*T*C*T(ROX)AGAGXCGTT (BHQ2)C*A*C*T*G*T*AGTTTATA*C*A*G*T*GAATCTCTCTAG*T*C*T-3' ["X" represents AP site; The phosphorothioated nucleotides (at 3' side) are indicated with an asterisk after the nucleotides; ROX is 6-carboxy-X-rhodamine and BHQ2 is Black Hole quencher 2] was synthesized and used for the detection. In the presence of APE1, the DNA probe could be specifically hydrolyzed by the enzyme and release the fluorophore, resulting in strong fluorescence emission. The activity of APE1 was determined according to the rate of increase in fluorescence intensity. In this work, we modified the reaction buffer and significantly improved the performance of the method. Moreover, the method was further extended to measure the contents of APE1 in the protein extraction from peripheral blood mononuclear cells (PBMCs) extracted from human whole blood samples by density gradient centrifugation. The assay was also applied to measure the activity of APE1 in human serum samples.@*RESULTS@#With a new reaction buffer composed of 0.04% (V/V) Triton X-100, 50 mmol/L KAc, 20 mmol/L Tris-Ac, 10 mmol/L Mg(Ac)2 and 1 mmol/L dithiothreitol (DTT), the method achieved a detection limit of 0.005 U/mL (3 pg/mL) and a linear response ranging from 6 pg/mL to 1.2 ng/mL. The contents of APE1 in the protein extraction from PBMCs of eight blood samples were measured to be in the range from 0.061 to 0.40 ng/μg protein, with an average of 0.16 ng/μg protein. The recovery was 98%±5% (n=3). The levels of APE1 in the sera from 102 normal individuals (51 male and 51 female, age range: 59-75 years) were observed to be from 0.13 to 0.34 ng/mL, with a recovery of 96%±15% (n=3).@*CONCLUSION@#The new fluorescence assay was simple, rapid and sensitive, providing a practical tool to measure the activity of APE1 in serum samples and cell extracts. It also holds great potential in measurement of APE1 in many other biological samples for clinical test and laboratory research.

A new method on investigate chemical constituents which have anti-thrombin effect by HPLC / 中国中药杂志

An in vitro anti-thrombin bioassay was developed to investigate the chemical constituents which have anti-thrombin effect from the water soluble components of Salvia miltiorrhiza. Using Chromozym TH as a probe combined with ethyl acetate Semi-micro extraction was applied to measure p-nitroaniline by HPLC. According to the results, the inactivationrate of thrombin by sodium danshensu, salvianolic acid A and salvianolic acid B under a given set of conditions were 3.06%, 77.77% and 2.35%, respectively. In the water-soluble components, salvianolic acid A has a direct inhibition of thrombin, while sodium danshensu and salvianolic acid B have no significant effect on thrombin. The method is sensitive and low consumption. It can eliminate the interference absorbed for the sample itself which can be used for screening single or multiple direct antithrombin active ingredient of herbal extract.

Absorption characteristics of liposome encapsulated Centella asiatica total glucosides / 中草药

Objective: To study the intestinal absorption characteristics of the liposome encapsulated Centella asiatica total glucosides in vitro. Methods: Dialysis method was adopted to study the stability of the liposome encapsulated C. asiatica total glucosides in both PBS and Tyrode solution. RP-HPLC was adopted to detect the chromatographic profile of the sample solutions. To research the in vitro intestinal absorption properties of C. asiatica total glucosides and its liposome in isolated everted intestine model, the cumulative absorptive percentages of them in the different intestines are calculated and the cumulative absorption curve of them are drawn, in which the cumulative absorptive percentages of them are calculated by the amount of asiaticoside, and the intestinal absorption effects of them are compared. Results: The results show that the lipsome encapsulated C. asiatica total glucosides could exist stably in the PBS and Tyrode solution. C. asiatica total glucosides and its liposome could be absorbed in the small intestine and have no significant absorption site. The uptake of asiaticoside in ileum increased with time prolonging, and there was no absorptive saturation within 120 min. During the ileum absorption, the liposome encapsulated C. asiatica total glucosides have a higher percentage and a higher quantity of cumulative absorption than the drug of C. asiatica total glucosides, which showed that apparent permeation coefficient was higher significantly. Conclusion: The encapsulated C. asiatica total glucosides could promote the absorbtion of C. asiatica total glucosides in the ileum of rats, which provides the experimental evidence for the development of the oral dosage forms of C. asiatica total glucosides.

Progress on PI3K/Akt signaling pathway regulating self-renewal and pluripotency of embryonic stem cells / 生理学报

The phosphatidylinositol 3-kinase (PI3K) and its downstream target protein kinase B (Akt/PKB) can be activated by a variety of extracellular and intracellular signals. They are important signaling molecules and key survival factors involved in cell proliferation, differentiation, apoptosis and other cellular processes. Recently, many reports demonstrate that type I PI3K/Akt signaling pathway plays an important role in maintenance of self-renewal and pluripotency of embryonic stem (ES) cells. Further studies with regard to the self-renewal and pluripotency of ES cells and underlying molecular mechanisms are crucial to its application in cell replacement therapy, regenerative medicine and tissue engineering. The present review focuses on the recent progress on the mediation of PI3K/Akt signaling pathway on the maintenance of self-renewal and pluripotency of ES cells.

Clinical value of trastuzumab in the treatment of lapatinib-resistant HER2-positive metastatic breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Retrospective and prospective studies have shown that continuous administration of trastuzumab with different chemotherapy regimens resulted in better clinical outcomes than the administration of chemotherapy alone in women with HER2-positive, trastuzumab-refractory metastatic breast cancer (MBC). However, there are limited data to evaluate the activity of trastuzumab in patients progressed after other anti-HER2 therapies, e.g. lapatinib. The aim of the present study was to evaluate retrospectively the clinical value of trastuzumab in patients with lapatinib-resistant HER2-positive advanced breast cancer treated in our center.</p><p><b>METHODS</b>Patients with HER2-positive MBC who experienced progression after first-line lapatinib-based regimens were assigned to receive either conventional treatment without trastuzumab or in combination with trastuzumab as second-line therapy. The efficacy end points included progression-free survival (PFS) and overall survival (OS).</p><p><b>RESULTS</b>Thirty-five eligible patients progressed after treatment with lapatinib-based regimens were collected. None of the patients had received prior trastuzumab in either the adjuvant or metastatic setting. Twenty-two patients were assigned to receive conventional treatment without trastuzumab as second-line therapy (non-T arm) and 13 patients received conventional treatment combined with trastuzumab (T arm). There were no significant differences in the main clinical factors between the two arms, such as age, PS status, ER/PR, metastatic status, etc. Both the two cases with no disease progression after the second-line therapy were trastuzumab-treated patients, and all the other 33 cases were patients with progression despite the second-line therapy. Twenty-seven patients died due to disease progression, and eight survived (six cases of the T-arm and two cases of the non-T arm). The median PFS was 3.3 months in the non-T arm and 10.0 months in the T arm (P = 0.001). The median OS was 7.0 months in the non-T arm and 31.1 months in the T arm (P = 0.015).</p><p><b>CONCLUSIONS</b>Trastuzumab plus conventional treatment is superior to conventional treatment in women with lapatinib-resistant HER2-positive metastatic breast cancer. Continuous anti-HER2 management can provide survival benefit to patients with HER2-positive breast cancer.</p>

Clinical analysis of 34 patients with adrenal metastasis from breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis.</p><p><b>METHODS</b>Thirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis.</p><p><b>RESULTS</b>During the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P < 0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005).</p><p><b>CONCLUSIONS</b>The incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.</p>

Clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases: a report of 17 cases / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases.</p><p><b>METHODS</b>Seventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed.</p><p><b>RESULTS</b>The frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P < 0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P < 0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P < 0.05).</p><p><b>CONCLUSIONS</b>The prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.</p>

Association of genetic variantions of circadian clock genes and risk of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between genetic variantions of circadian clock genes and risk of breast cancer.</p><p><b>METHODS</b>A case-control study including 406 breast cancer patients and 412 controls was conducted and genes Clock (rs2070062) and Per2 (rs2304672, rs2304669, rs934945) were genotyped by TaqMan real-time PCR. Unconditional logistic regression model was used to analyze the association between the genetic polymorphisms and breast cancer.</p><p><b>RESULTS</b>Individuals with the rs2304669-TT genotype showed significantly increased breast cancer risk with the OR of 2.33 when compared with the individuals with rs2304669-CC and CT genotypes (P = 0.001). In addition, the three haplotypes containing the risk T allele of rs2304669 were identified to be associated with increased breast cancer risk. However, it was found that rs2304672, rs2070062 and rs934945 polymorphisms were not related with breast cancer risk.</p><p><b>CONCLUSIONS</b>The locus rs2304669 on Per2 gene is associated with breast cancer risk. Genetic variation of circadian clock genes may increase the susceptibility to breast cancer. Therefore, it may become an important biomarker of susceptibility to breast cancer.</p>

Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer / 华中科技大学学报（医学）（英德文版）

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer / 华中科技大学学报（医学）（英德文版）

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Research on human enterovirus 71 infectivity assay based on a real-time cell analysis / 病毒学报

This research aims to evaluate the application of Real - time cell assay (RTCA) based on microelectronics sensor technology in the detection of HEV71 induced cell lesion. Growth indexes of RD cells at different stages were observed dynamically, appropriate cell concentration was selected to test HEV71 infectivity and to determine the HEV71 neutralizing antibody titer in serum. The traditional microplate test was used as methodology comparison and results validation at the same time. Cell impedance was transformed to cell index (CI) value and visual dynamic curve through software, and the result showed that the observation of HEV71 infectivity was more than 5d when the RD cells concentration was 1. 5 X 10(4) hole on the 96 electronic orifice plate. Compared with the traditional cytopathic effect (CPE) through microscope observation method, the end point judgment results were consistent between these two methods at 132h (about 5. 5d) post virus inoculation. In the neutralization tests, three CI values of neutralizing antibody titers against HEV71 in human serum were correspond to those obtained from traditional 96 microplate microscopy. RTCA also suggested that the presentation time of CPE induced by the i virus could be different even the end point judgment was the same with the same neutralization antibody titer. Compared with the traditional microplate monitoring method, RTCA can save labor and eliminate the hands-on error in the monitoring HEV71 infectivity and antibody titer detection in serum. RTCA can be served as one of the supplementary methods of traditional detection method, with the advantages of dynamically observing the occurrence and development of cell pathological changes, and the variation of virus infectivity and serum neutralizing antibodies.

Endobronchial metastases from breast cancer: a clinicopathological and survival analysis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Endobronchial metastases (EBM) secondary to extrapulmonary solid malignant tumors are rare but may occur. The most common extrathoracic malignancies associated with EBM are colorectal, renal and breast cancer. This study aimed to evaluate the clinicopathological aspects of EBM from breast cancer and the prognosis of the patients.</p><p><b>METHODS</b>Clinicopathological data of 11 cases diagnosed as EBM from breast cancer treated in our hospital from 2003 to 2010 were re-evaluated. Their symptoms, recurrence interval, radiological features, histopathological properties, and prognosis were assessed.</p><p><b>RESULTS</b>Eleven cases were diagnosed by bronchoscopic bronchial biopsy. The median interval from diagnosis of breast cancer was 57 months (range: 11 - 189 mo). All patients had other proven metastases when the EBM was diagnosed. The most frequently observed symptoms were cough (8 cases). Interestingly, two patients were asymptomatic. Hilar mass (5 cases) was a common radiological finding. No disaccordance between the hormone receptor status in the primary and metastatic lesions in these patients was found. The median survival after EBM diagnosis was 21 months (range: 6 - 36) with four patients still alive and one of these four patients was surviving more than 7 years.</p><p><b>CONCLUSIONS</b>On average, EBM is diagnosed about 5 years after the diagnosis of breast cancer, which is a relatively long lead time, but the median survival time is short, as 21 months in our group. The treatment plan must be individualized, because in some cases, long-term survival can be expected.</p>

Docetaxel plus carboplatin versus EC-T as adjuvant chemotherapy for triple-negative breast cancer: safety data from a phase III randomized open-label trial / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Triple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for ∼ 15% of overall breast cancer and associated with a poor prognosis. There is a short of standard adjuvant chemotherapy regimens for TNBC. A number of studies have shown that TNBC might be sensitive to cisplatin and carboplatin on the basis that dysfunction of BRCA1 and its pathway is associated with a specific DNA-repair defect, but data of adjuvant setting about this is limited.</p><p><b>METHODS</b>From January 2010 to September 2011, 95 early triple-negative breast cancer patients confirmed by pathology were randomly assigned to receive TP (docetaxel 75 mg/m², carboplatin AUC = 5, day 1, 21 days a cycle for 6 cycles) or EC-T (epirubicin 90 mg/m², cyclophosphamide 600 mg/m², d1, 21 days a cycle for 4 cycles, followed by docetaxel 80 mg/m², d1, 21 days a cycle for 4 cycles) chemotherapy. Adjuvant radiation therapy was given selectively after chemotherapy. Here we report a preliminary safety analysis with the chi-square test.</p><p><b>RESULTS</b>Seventy-six out of the 95 patients had completed the chemotherapy and could be assessed for the safety profiles of the regimens. Thirty-seven of them were in the EC-T group with a median age of 47 years, and 21 out of these 37 patients were premenopausal (56.8%). Another 39 patients came from the TP group with a median age of 46 years, and 22 out of these 39 patients were premenopausal (56.4%). All of the 37 patients in EC-T group completed the planned treatment whereas 2 patients of the 39 cases in TP group did not because of bone marrow suppression. During the treatments, 9 patients had dose adjustment in each group. Adverse events of grade 1/2 were common. Specific incidence of adverse events with grade 3/4 in each group was as follows: alopecia, 29.7% vs. 10.3% (P = 0.033), vomiting 21.6% vs. 7.7% (P = 0.085), leukopenia 54.1% vs.25.6% (P = 0.011) and neutropenia 51.4% vs. 35.9% (P = 0.174). Other grade 3/4 toxicities were rare. All the adverse events (except peripheral neuropathy and pigmentation) recovered within 1 month after the chemotherapy.</p><p><b>CONCLUSION</b>Both EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the treatment of triple-negative breast cancer patients, while the TP regimen has advantages with less grade III/IV alopecia and leukopenia.</p>

Phase II clinical trial of neoadjuvant therapy with carboplatin plus paclitaxel for locally advanced triple-negative breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.</p><p><b>METHODS</b>Patients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.</p><p><b>RESULTS</b>Overall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.</p><p><b>CONCLUSIONS</b>As a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.</p>

Oral etoposide monotherapy is effective for metastatic breast cancer with heavy prior therapy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment option for metastatic breast cancer (MBC) patients pre-treated with chemotherapy is limited. Oral etoposide has shown some promises in these patients. However, patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure. This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.</p><p><b>METHODS</b>MBC patients receiving at least two chemotherapy regimens prior to the enrollment were treated with repeated cycles of oral etoposide (60 mg×m(-2)×d(-1) on days 1-10, followed by 11 days of rest). The primary end point was the progression free survival (PFS). The secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and toxicity profiles.</p><p><b>RESULTS</b>Thirty-two patients received 230 cycles of oral etoposide with a median of 6 cycles (range, 2-20 cycles) per patient. Eight patients (25%) had partial response (PR) and 14 patients achieved stable disease (SD). The ORR was 25%. Nine patients achieved SD for more than 24 weeks and CBR was 53%. The median PFS and OS were 5 (range, 1.5-17.0 months) and 16 months (range, 3.0-51.0 months), respectively. The patients who achieved clinical benefit had longer survival time than those who did not (25.0 versus 11.0 months, P<0.01). Among the 16 patients who received more than four regimens prior to this study, four patients achieved PR and four achieved SD for more than 24 weeks, with a CBR of 50%. The most common hematologic adverse events were anemia (43.8%) and neutropenia (38.5%). Nausea/vomiting (75.0%) and alopecia (62.5%) were the most frequent non-hematologic toxicities.</p><p><b>CONCLUSION</b>Oral etoposide is effective and well tolerated in Chinese women with heavily pretreated MBC.</p>

Treatment outcomes and clinicopathologic characteristics of advanced triple-negative breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To characterize the sites of distant recurrence and clinical outcomes in a cohort of Chinese patients with metastatic triple-negative breast cancer (TNBC).</p><p><b>METHODS</b>One hundred and thirty-four patients with metastatic TNBC treated at Cancer Hospital of CAMS from January 1999 to December 2007 were included in this study. The clinicopathological features and long-term survival of the patients were retrospectively analyzed.</p><p><b>RESULTS</b>The median age of the patients was 45 years. Most patients (72.7%) had a higher predilection for visceral metastasis and early recurrence within the first two years of follow-up. Six patients (4.5%) presented with stage IV disease, 14 patients were diagnosed with locoregional recurrence after mastectomy, 75 patients with distant metastases, and 45 patients with both locoregional recurrence and distant metastasis. The most common site of first recurrence was the lung, and 62(51.7%)of the patients had more than two sites of metastasis. By July 30, 2009, 75 patients died of breast cancer (56.0%). The median overall survival (OS) was 26.5 months [95% confidence interval (CI), 20.5 - 32.6 months]. The 1-, 3- and 5-year overall survivals (OS) were 80.9%,37.1% and 30.1%, respectively. The median overall survival time of 58 patients with single site of metastasis was 28.5 months, longer than that of patients with more than two sites of metastases. Patients whose initial distant recurrence was bone metastasis only (7 patients) had better prognosis, with a median OS of 84.2 months. The median OS (28.5 vs. 12.6 months, P = 0.0001) differed significantly between patients who received first-line chemotherapy and those who did not. Forty-five of the 96 patients with measurable disease achieved complete/partial response (CR/PR), 39 patients had stable disease (SD), and 12 patients had disease progression (PD). The median OS was 36.1 months in patients with CR/PR, 20.8 months with SD, and 14 months with PD, respectively. The median OS of patients with CR/PR was significantly longer than that of patients with SD/PD (P = 0.0108). Distant metastasis, first-line chemotherapy and clinical response were significantly related with OS by univariate analysis. Furthermore, first-line chemotherapy and the clinical response were demonstrated to be an independent prognostic factor by multivariate analysis.</p><p><b>CONCLUSIONS</b>Recurrence risk and mortality are considerably higher in TNBC patients within the early years of follow-up. TNBC patients have a higher risk of multiple and visceral metastases, and poorer survival, which might attribute to its aggressive clinical behavior and lack of effective regimens. Our findings also suggest that chemotherapy can effectively improve the clinical outcome of those patients.</p>