Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Qiling Tongluo Prescription Improves Renal Injury in Rats with Idiopathic Membranous Nephropathy by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Qiling Tongluo prescription against idiopathic membranous nephropathy （IMN） in rats based on Toll-like receptor 4/myeloid differentiation factor 88/nuclear transcription factor-κB （TLR4/MyD88/NF-κB） signaling pathway. MethodSixty male SD rats were randomly divided into the normal group， model group， benazepril hydrochloride （10 mg·kg-1） group， and low-，medium-， and high-dose （6.48， 12.95， and 25.9 g·kg-1） Qiling Tongluo prescription groups. The IMN rat model was established by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After the model was successfully prepared， the rats were gavaged with the corresponding drugs， once a day， for four consecutive weeks. After the treatment， the pathological changes in rat kidneys were observed by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-silver metheramine （PASM） staining， followed by the detection of 24 h urinary total protein （24 h UTP）， plasma albumin （ALB）， total serum protein （TP）， serum creatinine （SCr）， urea nitrogen （BUN）， and uric acid （UA） levels. The levels of interleukin-1β （IL-1β） and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of TLR4， MyD88， and NF-κB in the kidney tissue were assayed by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry （IHC）， and Western blot. ResultCompared with the normal group， the model group exhibited elevated 24 h UTP and serum SCr， BUN， UA， IL-1β， and IL-6 （P<0.05， P<0.01）， decreased ALB and TP （P<0.01）， up-regulated TLR4， MyD88， and NF-κB p65 mRNA and protein expression in kidney tissue （P<0.05， P<0.01）， obvious inflammation， disordered glomerular structure with enlarged volume， irregularly thickened basement membrane， inflammatory cell infiltration in the renal interstitium， reduced renal tubular epithelial cells due to shedding and apoptosis， and some vacuolar degeneration. Compared with the model group， benazepril hydrochloride and Qiling Tongluo prescription at the high dose remarkably lowered the serum SCr and UA （P<0.05） and increased ALB and TP （P<0.05）. Benazepril hydrochloride and Qiling Tongluo prescription at the low， medium， and high doses down-regulated the 24 h UTP， serum IL-1β and IL-6 levels， and renal TLR4， MyD88， and NF-κB p65 mRNA and protein expression to varying degrees （P<0.05， P<0.01）， alleviated IMN inflammatory reaction， glomerular swelling， and volume increase， slightly dilated glomerular capillaries， proliferated mesangial matrix， and relieved pathological and morphological damages in rat kidney， with inflammatory cell infiltration occasionally observed. ConclusionQiling Tongluo prescription may reduce the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to inhibit the inflammatory response in IMN rats， ameliorate proteinuria and kidney damage， and protect kidney function.

Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin a1 in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice / 神经科学通报·英文版

A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Characteristics of individuals positive for SARS-CoV-2 nucleic acid in a centralized isolation site for people entering China / 预防医学

Objective@#To analyze the characteristics of individuals positive for SARS-CoV-2 nucleic acid in a centralized isolation site for people entering China in Huzhou City of Zhejiang Province from December 18, 2021 to January 12, 2022, so as to provide insights into the prevention and control of overseas imported COVID-19. @*Methods@#The basic characteristics, nucleic acid detection and epidemiological investigations were collected from individuals positive for SARS-CoV-2 nucleic acid in a centralized isolation site for people entering China from December 18, 2021 to January 12, 2022, and the temporal distribution, population distribution, source of importation, and virus typing were descriptively analyzed.@*Results @#From December 18, 2021 to January 12, 2022, a total of 2 974 individuals in 19 flights were recorded in this centralized isolation site, and 33 cases were tested positive for SARS-CoV-2 nucleic acid, including 21 confirmed cases with common type, 9 confirmed cases with mild type, and 3 cases with asymptomatic infections. There were 11 cases with Omicron infections ( 33.33% ), 5 cases with Delta infections ( 15.15% ), and 17 cases with infection of unidentified types ( 51.52% ). The median interval ( interquartile range ) from the time of entry to the time of a positive test was 4.0 ( 7.0 ) days among all positive cases, 0 ( 4.0 ) day among cases with Omicron infections and 4.5 ( 8.5 ) days among cases with infections of Delta and unidentified types. The positive cases had a mean age of ( 36.97±8.58 ) years, and included 27 men (81.82%). There were 30 cases ( 90.91% ) receiving two and more doses of COVID-19 vaccines, and 7 cases ( 21.21% ) with a previous history of SARS-CoV-2 infections. There were 19 cases ( 57.58% ) from African countries, and 7 of 11 cases with Omicron infections were imported from African countries.@*Conclusion@#Omicron infection was predominant among individuals positive for SARS-CoV-2 nucleic acid in this centralized isolation site for people entering China from December 18, 2021 to January 12, 2022, with no severe cases detected, and most positive cases were imported from African countries.

Prevalence of myopia among primary and middle school students in Longkou City, Shandong Province / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To investigate the prevalence of myopia among primary and middle school students aged 7 to 18 in Longkou City, Shandong Province, and to provide a scientific basis for prevention and control of myopia. ·METHODS: The students aged 7 to 18 were enrolled through the method of stratified random and cluster sampling by the unit of schools and were investigated in Longkou, Shandong Province in 2015. A total of 58 schools were selected and 61 036 students were effectively sampled. All the subjects were divided into three- tiers based on geographical location: urban, rural-urban continuum, and rural areas. All the subjects were examined with the visual acuity and non -cycloplegic objective fraction. Microsoft Excel worksheet was used to establish a database, and SPSS 21. 0 software was used for statistical analysis. ·RESULTS: The prevalence of total myopia in the sample population of students of Longkou in 2015 was 49. 81% from 7 to 18 years old. The overall prevalence of myopia increased fastest from 11 to 12 years old. And the prevalence of mild myopia of students aged 13 was highest. The prevalence of total myopia were 46. 41% for boys and 53. 39% for girls, which showed the prevalence of girls was higher than the boys'. The prevalence of myopia in urban, rural- urban continuum, and rural areas were 55. 18% , 49. 75% , 44. 47% , respectively, and the prevalence of myopia in urban areas was the higher than the rural-urban continuum and the rural areas. The prevalence of total myopia gradually increased with age (rs=0. 943, P<0. 05). ·CONCLUSION: The results of the investigation showed a high prevalence of myopia among primary and middle school students in the city of Longkou, and gradually increased with age. The overall myopia prevalence for girls was higher than boys, and the prevalence was highest in urban areas.

Combined Let-7a and H19 Signature: A Prognostic Index of Progression-Free Survival in Primary Breast Cancer Patients / 한국유방암학회지

PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.

Predictive and prognostic value of monitoring lymphocyte subsets in peripheral blood before and after chemotherapy in patients with metastatic breast cancer / 北京大学学报(医学版)

Objective:To detect the proportion of lymphocyte subsets in peripheral blood of the ad-vanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa,as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prog-nosis.Methods:The proportions of lymphocyte subsets (CD3 +T cell,CD3 +/CD4 +T cell,CD3 +/CD8 +T cell,CD3 -/CD16 +56 +NK cell,CD3 +/CD16 +56 +T cell,CD19 +B cell,CD4 +/CD25 +T cell,CD8 +/CD28 -T cell,CD8 +/CD28 +T cell)in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy.The result was analyzed in combination with clinico-pathological data.Results:The proportion of regulatory T cells (Treg)after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034).The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survi-val (OS).The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg,which was 23.5 and 9.4 months respectively (P<0.05). Conclusion:The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

Analysis of correlation between hypokalemia and sudden death in young and middle-aged people / 中国医师进修杂志

Objective To explore the correlation between hypokalemia and sudden death in young and middle-aged people. Methods One hundred and twenty-nine young and middle-aged patients with sudden death during treatment were selected as observation group. Then 100 cases of healthy volunteers were randomly selected as control group. The incidence of cardiovascular disease, incidence of hypokalemia and intake of potassium were compared between 2 groups. Results The incidences of hypertension, arrhythmia, myocardial infarction, heart failure and hypokalemia in observation group were significantly higher than those in control group: 17.05% (22/129) vs. 5.00%(5/100), 13.18% (17/129) vs. 2.00% (2/100), 26.36% (34/129) vs. 9.00% (9/100), 9.30% (12/129) vs. 1.00% (1/100) and 55.04% (71/129) vs. 12.00% (12/100), and there were statistical differences (P<0.01). The ratios of higher, common, lower intake of potassium in observation group were 1.55%(2/129), 27.91% (36/129) and 70.54%(91/129), in control group were 15.00% (15/100), 58.00% (58/100) and 27.00% (27/100), and there was statistical difference (P<0.01). Logistic regression analysis result showed that hypertension, arrhythmia, myocardial infarction, heart failure, hypokalemia and lower intake of potassium were the risk factor for sudden death (P<0.01). The incidences of hypertension, arrhythmia, myocardial infarction and heart failure in hypokalemia patients were significantly higher than those in normokalemia patients: 28.92% (24/83) vs. 2.05% (3/146), 19.28% (16/83) vs. 2.05% (3/146), 44.58%(37/83) vs. 4.11% (6/146) and 13.25% (11/83) vs. 1.37% (2/146), and there were statistical differences (P<0.01). The incidence of hypokalemia in people with lower intake of potassium was significantly higher than that in people with higher and common intake of potassium: 56.78% (67/118) vs. 2/17 and 14.89%(14/94), and there was statistical difference (P<0.01). Conclusions There is a significant correlation between hypokalemia and sudden death in young and middle-aged people. Preventive measures of sudden death should be made according to serum potassium level in clinic. People should pay attention to the uptake of potassium in daily life.

Research Progress in Acupuncture Treatmentfor Male Infertility / 上海针灸杂志

The incidence of male infertility increased year by year, which seriously affects family welfare and social development. This article reviews and sorts out recent years’ studies on acupuncture treatment for male infertility. The results show that acupuncture treatment has produced a good clinical effect on this disease. Some progresses have been made in clinical acupuncture point selection, operating methods, complex treatment and therapeutic mechanism. The clinical effect and the mechanism of action of acupuncture treatment for this disease have been deeply explored from symptom differentiation and classification, acupoint selection and prescription, acupoint stimulation mode, and combined acupuncture and moxibustion therapy so as to provide new ideas for clinical acupuncture treatment and basic study.

Effects of Scalp Acupuncture on Cognition in Patients after Traumatic Brain Injury / 中国康复理论与实践

Objective To observe the effects of scalp acupuncture on cognitive impairments after traumatic brain injury (TBI). Methods 42 cases of TBI were randomized into experiment group (n=23) and control group (n=19). The control group accepted cognitive training and Donepezil, and the experiment group accepted scalp acupuncture in addition for 3 months. They were assessed with event related potential P300 and Montreal Cognitive Assessment (MoCA) before, 1 and 3 months after treatment. Results The results of P300 and MoCA improved significantly 3 months after treatment (P<0.001) in both groups, and improved more in the experiment group than in the control group (P<0.001). Conclusion Scalp acupuncture could improve outcomes of cognitive impairments after TBI.

Posterior capsule releasing in total knee arthroplasty for patients with rheumatoid arthritis with stiff knees in flexion / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the correct method of bone resection and posterior capsular soft tissue releasing in total knee arthroplasty (TKA) for the patients with rheumatoid arthritis with stiff knee in flexion.</p><p><b>METHODS</b>From November 2009 to January 2012,15 patients with rheumatoid arthritis with stiff knee in flexion underwent primary TKA and releasing of the posterior soft tissues. There were 7 males and 8 females,aged 22 to 75 years old (58.7 years old on average). The preoperative range of movement(ROM) was (3.2 ± 1.7)°. According to Knee Society score (KSS) criterion, the preoperative clinical score was 23.3 ± 12.5 and functional score was 35.2 ± 9.8. Based on the correct osteotomy, effective releasing of posterior structures was used for different degrees of flexion contracture during the TKA procedure.</p><p><b>RESULTS</b>All the patients were followed up, and the average duration was 2.3 years (1.6 to 3 years). At the latest follow-up,the KSS clinical score was 81.7 ± 6.5 and functional score was 82.8 ± 9.3. The flexion and extension ROM of the knee joint was (103.5 ± 13.1). Three knees remained 50 flexion contracture deformity, but the function of the affect knees was good.</p><p><b>CONCLUSION</b>The effective releasing of the soft tissue of posterior capsule is a major management for correction of the flexion contracture in TKA. The correct releasing of posterior structure can not only achieve fundamental gap of TKA but also effectively avoid bone over-resection.</p>

Effects of Scalp Acupuncture on Cognition in Patients after Traumatic Brain Injury / 中国康复理论与实践

@#Objective To observe the effects of scalp acupuncture on cognitive impairments after traumatic brain injury (TBI). Methods 42 cases of TBI were randomized into experiment group (n=23) and control group (n=19). The control group accepted cognitive training and Donepezil, and the experiment group accepted scalp acupuncture in addition for 3 months. They were assessed with event related potential P300 and Montreal Cognitive Assessment (MoCA) before, 1 and 3 months after treatment. Results The results of P300 and MoCA improved significantly 3 months after treatment (P<0.001) in both groups, and improved more in the experiment group than in the control group (P<0.001). Conclusion Scalp acupuncture could improve outcomes of cognitive impairments after TBI.

The relationship between microstructure of vertebral cancellous bone and fixation strength of pedicle screws / 医用生物力学

Objective By measuring the microstructure parameters of cancellous bone in vertebral bodies with different bone mineral density (BMD) levels, to study the correlation between such parameters and the corresponding maximum pullout strength (MPS) when fixed by pedicle screws, so as to understand if the microstructure parameters are related with screw stability and further to reveal the cause of screw loosening. Methods Based on the BMD detection results, fresh human cadaver spines were stratified into four levels: normal, osteopenia, osteoporosis and severe osteoporosis, according to diagnosis criteria in clinic. The corresponding vertebral specimens were then instrumented with pedicle screws, and screw pullout tests were conducted to measure the MPS of such screws. All the vertebral specimens were collected subsequently, and the cancellous bone cylinders were drilled from the center of each vertebra for micro CT scanning. Microstructure parameters of the vertebral trabecular bone at different BMD levels were obtained to investigate the interrelationships in between, and the relationships between the microstruture parameters and corresponding MPS of pedicle screws with osteoporosis severity were then compared. Results With the decline of BMD from normal to severe osteoporosis level, the corresponding MPS of pedicle screws was significantly declined. With the severity of osteoporosis increasing, the progressive bone volume loss, mechanical incompetence and microstructure deterioration also appeared evidently. Significant differences were found in microstructure parameters at different BMD levels. Strong correlations were extensively observed among BMD, microstructure parameters and MPS of screws. The MPS of pedicle screws was highly correlated with bone volume over total volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) from micro-CT scanning. Conclusions Significant deterioration would occur in bone tissues with the decline of BMD level, and the MPS of pedicle screws was highly correlated with some microstructure parameters.

Genome sequencing and the molecular evolutionary analysis of a SFTSV isolated from Zhejiang province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To sequence the whole genome and to analyze the molecular and evolutionary of Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) isolated from Zhejiang province.</p><p><b>METHODS</b>Viral RNA was extracted from the specimens and detected by quantitative real-time RT-PCR. SFTSV strain was isolated. A total of 17 overlapping fragments covering the whole genome were amplified by RT-PCR. And the entire genomes were formed by sequencing and assembly the fragments. The SFTSV sequence of Zhejiang strain was compared with the sequences of SFTSV that have been published to generate the phylogenetic tree. And the SFTSV sequence of Zhejiang strain was compared with the sequences of strains of the genus phlebovirus in the Bunyaviridae family and analysis of homology.</p><p><b>RESULTS</b>SFTSV strain was isolated from SFTSV infection positive serum successfully. The genomic fragments were amplified by RT-PCR. A total of 3 cDNA sections were formed by sequencing and assembly the fragments. The S segment contained 1 745 nucleotides. The M fragment contained 3 378 nucleotides, and the L segment contained 6 368 nucleotides. Molecular phylogenetic analysis result showed SFTSV Zhejiang strain had the highest similarity with Japan/SPL004A/2013 strain. The similarity of the S segment was 98%. The similarity of the M fragment was 97%. And it was 98% that of the L fragment. Meanwhile, the comparison results also confirmed the Zhejiang strain belonged to the genus phlebovirus.</p><p><b>CONCLUSION</b>SFTSV Zhejiang strain of isolated from SFTSV infection positive serum successfully. And the genome sequencing was complete molecular evolution analysis shows SFTSV Zhejiang strain has the maximum similarity with SFTSV Japan strain.</p>

Effect of yanggan yishui granule on collagen I, III, and IV, and FN in spontaneously hypertensive rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Yanggan Yishui Granule (YGYSG) on collagen protein I, III, and IV, as well as fibronection (EN) in spontaneously hypertensive rats (SHR), and to explore its possible renal protective mechanisms.</p><p><b>METHODS</b>Fourty SHR were randomly divided into four groups, i.e., the model group, the Benazepril group, the low dose YGYSG group, and the high dose YGYSG group, 10 in each group. A normal control group was set up with recruited Wistar-Kyoto (WKY) rats. After 6 weeks of treatment, the expression of collagen protein I, III, and IV, as well as FN in the 5.1 image analysis system.</p><p><b>RESULTS</b>In the WKY-control group, there was only a small amount of brown particles in the mesenchymal region, the glomerular basement membrane, or the mesangial region. The expression of collagen I, Ill, and IV, as well as EN significantly increased more in the model group than in the normal control group (P < 0.01). After treatment, the expression of collagen I, III, and IV, as well as FN significantly decreased in each treated group, showing statistical difference when compared with the model group (P < 0.01). Besides, decresed expression of collagen I, III, and IV was shown in the low dose YGYSG group and the Benazepril group (P > 0.05). The expression of collagen I, III, and IV could be further reduced in the high dose YGYSG group, showing statistical difference when compared with the Benazepril group and the low dose YGYSG group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>YGYSG might play an important role in the renal protective effect through reducing the synthesis of renal collagen I, III, and IV, as well as FN, increasing the degradation of renal collagen I, III, and IV, as well as FN, thereby reducing excessive deposition of renal extracellular matrix (ECM).</p>

Albumin-bound paclitaxel for treatment of patients with refractory metastatic breast cancer / 中国癌症杂志

Background and purpose:Nab-paclitaxel (Abraxane) is an albumin-bound form of paclitaxel that utilizes the natural properties of albumin to improve paclitaxel delivery to the tumor. It has recently been approved for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within short time after adjuvant chemotherapy. The purpose of this study was to evaluate the efifcacy and safety of albumin-bound paclitaxel in patients with aggressive and refractory metastatic breast cancer (MBC).Methods:A total of 58 patients with MBC were enrolled into this study from Jul. 2009 to Jan. 2014. All patients received albumin-bound paclitaxel-based chemotherapy. The adverse reactions were evaluated every cycle, and the short-term response was evaluated every two cycles. The patients were followed-up, and the survival was analyzed.Results:58 patients with refractory MBC were evaluable for response, 67.2% of patients received multiple line (≥3 lines) chemotherapy, 32.8% of patients with first and second line of chemotherapy were involved metastasis within one year after adjuvant chemotherapy, 84.5% of patients with visceral metastasis and 93.1% with prior taxane treatment. The objective response rate (ORR) was 13.8%, and disease control rate (DCR) was 60.3%, the median progression free survival (PFS) was 4.0 months, and the overall survival (OS) was 10.1 months. For 23 patients with triple negative breast cancer, ORR was 13.0% and DCR was 56.5%, the median PFS was 4.1 months, and OS was 6.6 months. The main toxicity was myelosuppression (grades 3 and 4 neutropenia, anemia and thombocytopenia were seen in 34.5%, 12.1% and 6.9% of patients, respectively), gastrointestinal reactions, sensory neuropathy, myodynia/arthragia, fatigue, alopecia and so on.Conclusion:The albumin-bound paclitaxel-based chemotherapy can be used in aggressive and refractory MBC. It also showed antitumor activity in taxanes-resistance patients and triple negative patients with good safety and tolerance.

The efficacy and safety of high-dose adjuvant chemotherapy with paclitaxel and thiotepa in postoperative breast cancer patients with high risk of recurrence / 肿瘤

Objective: Patients with high-risk breast cancer has a high recurrence rate. The clinical value of high-dose adjuvant chemotherapy supported by autologous HSCT (hematopoietic stem cell transplantation) for postoperative breast cancer patients with high risk of recurrence remains controversial. This study was to explore the efficacy and safety of high-dose adjuvant chemotherapy with paxlitaxel and thiotepa supported by autologous HSCT for postoperative breast cancer patients with high risk of recurrence. Methods: Twenty-four postoperative breast cancer patients (stages II-III) with high risk of recurrence were enrolled in this study. The patients received paclitaxel 175 mg/m2 and G-CSF (granulocyte colony-stimulating factor) 5 μg/kg for mobilization and collection of peripheral blood CD34+ stem cells. Then two cycles of high-dose adjuvant chemotherapy were given subsequently [11 patients: paclitaxel 175 mg/m2 + thiotepa 150 mg/m2 + carboplatin (area under curve = 6; 300 mg/m2 divided in two days); 13 patients: paclitaxel 175 mg/m2 + thiotepa 150 mg/m2) every 28 d]. The CD34+ stem cells were infused for an autologous HSCT on day 2 after chemotherapy, and the G-CSF was started on day 3 after chemotherapy and discontinued until the peripheral WBC (white blood cell) count reached over 10.0×109/L continuously for three days. The adverse effects of high-dose adjuvant chemotherapy were observed. The median DFS (disease-free survival) and the three-year DFS rate were calculated. Results: The median follow-up was 32 months (3-62 months). The median DFS was 32 months. The three-year DFS rate was 56.3%. High-dose chemotherapy had a good safety profile and no treatment-related death. Conclusion: High-dose chemotherapy with paclitaxel and thiotepa supported by autologous HSCT in postoperative breast cancer patients with high risk of recurrence has a good safety profile and can obtain a better benefit of DFS as compared with standard-dose chemotherapy. These results suggest that this treatment strategy deserves further exploration. Copyright © 2013 by TUMOR.

Effects of magnetic stimulation on apoptosis of nerve cells and the production of iNOS after spinal cord injury / 中华物理医学与康复杂志

Objective To investigate effects of magnetic stimulation on apoptosis of nerve cells and the production of inducible nitric oxidate synthase (iNOS) after spinal cord injury (SCI). Methods Thirty-two SpragueDawley male rats were randomly divided into a magnetic stimulation group (n = 16) and a control group (n = 16).SCI models were established by spinal cord transection in both groups. Rats were sacrificed at the 6th, 12th, 24th and 72nd hour post-injury, but the rats in the stimulation group received magnetic stimulation before being sacrificed.Apoptosis index (AI) and iNOS-positive cells rate were recorded at each time point. Results Apoptotic cells could be observed by the 6th hour post-injury, and were elevated from the 24th to the 72th hour. iNOS-positive cells were few at the first two time points, but had increased significantly at the 24th and 72nd hour post-injury. Compared with the control group, the apoptosis index of the stimulation group decreased a little at the 6th and 12th hour, but not significantly. The difference was quite significant at the 24th and 72nd hour, however, and the AI in the stimulation group decreased much more than that in the control group. There was little difference in the rate of iNOS-positive cells between the control and stimulation groups at any time point. Conclusions Magnetic stimulation could inhibit neural apoptosis and protect neurons from secondary SCI, but it has little effect on iNOS production.

Comparing the effects of transcuataneous electrical nerve stimulation and fluoxetine on central pain in patients with spinal cord injury / 中华物理医学与康复杂志

Objective To compare the effects of fluoxetine and transcuataneous electrical nerve stimulation (TENS) on central pain after spinal cord injury (SCI) using a sham-controlled crossover method.Methods Ele-ven patients with central pain after SCI were randomly divided into two groups which were then subject to 2 phases of treatment.Patients in group 1 were treated by oral intake of fluoexetine for 4 weeks followed by TENS treatment for 4 weeks.Those in group 2 were treated in the reverse sequence.A fifteen day washout period was arranged between the two phases of treatment.The short-form McGill pain questionnaire (SF-MPQ) and the Beck depression inventory (BDI) were used to assess all patients pre-and post-treatment.Results SF-MPQ scores were reduced significantly after either fluoexetine or TENS treatment.After each phase of treatment there was no significant difference between the two groups.Significant improvement in terms of BDI scores was found with fluoxetin treatment in both phases of the trial,but not with TENS treatment.Conclusions Both fluoxetine and TENS can alleviate central pain after SCI,and fluoxetine can relief patients' depression at the same time.

Changes of gene expression profile in human myeloma cell line induced by thalidomide / 中国实验血液学杂志

The study was aimed to investigate the anti-myeloma molecular mechanism of thalidomide (TLD) by detecting gene expression profiles of human myeloma cell line RPMI8226 treated with thalidomide. cDNA microarray were used to detect thousands of gene expression in gene chip. Two cDNA probes were prepared through reverse transcription from mRNA of RPMI8226 cells untreated and treated with TLD. These two probes were labeled with Cy3 and Cy5 fluorescence dyes respectively, then hybridized with cDNA microarray containing 1152 different human genes. The genes with differential expression in RPMI8226 cells treated with TLD for 72 hours were screened by scanning and analysis of computer software, and their functions were explored. The results showed that after co-culture of RPMI 8226 cells with TLD in 100 micromol/L concentration for 72 hours, 22 genes with differential expression were screened. Among these genes, the expressions of 4 genes were down-regulated including rpl32 gene, scya3 gene, mmp1 gene and igbp1 gene. Eighteen genes were up-regulated including wars gene, tubb4q gene, ube1l gene, txnrd1 gene and fyb gene. The study indicated that (1) wars gene encoding tryptophanyl-tRNA synthetase was up-regulated by TLD, while mmp1 gene encoding matrix metalloprotein 1 was down-regulated, they may be related to the inhibition of angiogenesis caused by TLD. (2) scya3 gene encoding macrophage inflammatory protein-1alpha and igbp1 gene encoding immunoglobulin binding protein 1 were down-regulated by TLD, they may play a role in the inhibition of cell proliferation caused by TLD. (3) tubb4q gene encoding tubulin beta4, ube1l gene encoding ubiquitin-activating enzyme E1-like protein and txnrd1 gene encoding thioredoxin reductase 1 were up-regulated by TLD, they may involve in apoptosis of RPMI8226 cells induced by TLD. (4) fyb gene encoding Fyn-binding protein was up regulated by TLD which associated with killing MM cells. It is concluded that 22 differentially expressed genes are involved in protein synthesis and degradation, cell signal transduction, cytoskeletal movement, immune modulation, cell metabolism, regulation of anti-oncogene and cell apoptosis, which relate directly or indirectly to molecular mechanisms of anti-myeloma effects induced by TLD.