Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review.

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.

[Clinical Study of San Wei Sheng Huo Decoction in the Treatment of Refractory Chemotherapy-Induced Thrombocytopenia].

Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula. Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment. Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P<0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9L －1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9L －1 ( P<0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment. Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT.

Usage of Chinese Herbs in Cancer Patients in Southern China: A Survey.

OBJECTIVE: To study the use of Chinese medicine (CM) in cancer patients in southern China. METHODS: A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. RESULTS: The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. CONCLUSION: This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

[The Anti-virus Effect of AY358935 Gene on Vesicular Stomatitis Virus and the Mechanism Study].

OBJECTIVE: To explore the anti-virus effect of AY358935 gene cloned by our research team on vesicular stomatitis virus (VSV), and studytheanti-virus mechanism. METHODS: HEK293 cells were stably transfected by the AY358935 gene recombinant plasmid pcDNA3.1-AY358935 or pcDNA3.1 blank plasmid respectively. Then VSV was added into the cell wells to infect the above cells at the multiplicity of infection (MOI) of 0.001. The virus titers in the liquid supernatant of the above three groups of cells were detected on different time, and the mortality of cells of each group was tested with trypan blue exclusion test at 24 h post VSV infection. Total RNA was extracted from the cells that stably transfected with target gene for the whole genome-wide cDNA microarray analysis. RESULTS: ① Virus titer:The virus titer in the liquid supernatant of pcDNA-3.1-AY358935 transfection cells group was obviously lower than those in pcDNA-3.1 transfection cell group and blank control cell group at 12 h post infection. The virus titerin the liquid supernatant of three groups were (7.16±2.33)×105 PFU/mL, (6.25±2.05)×106 PFU/mL and (7.75±2.54)×106 PFU/mL respectively at 18 h post infection. At that time, the virus titerin the liquid supernatant of pcDNA3.1-AY358935 group was nearly 10 times lower than those of other two groups (P < 0.01). ②Mortality of cells:The cell mortality of pcDNA3.1-AY358935 group, pcDNA3.1 group and blank group were (35.00±6.68)%, (78.33±15.03)% and (83.34±14.98)% respectively at 24 h post infection.The cell mortality of pcDNA3.1-AY358935 group was significantly decreased comparing with other two groups (P < 0.01). ③Result of genes chip analysis: compared with pcDNA3.1 group, 30 cell genes were up-regulated by more than 3 times in pcDNA3.1-AY358935 group. Among them, the proportion of interferon-activating gene, interferon-effect gene, cytokine and chemokine was 27%, 17%, and 20%, respectively. CONCLUSION: AY358935 gene hasan anti-VSV effect, and its anti-virus mechanism may involve the interferon-associated natural immune response.

[Cohort Study of EGFR-TKIs Combined with Traditional Chinese Medicine and Single EGFR-TKIs for Advanced NSCLC (Non₋small Cell Lung Cancer)].

OBJECTIVE: To explore the curative effect of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) combined with Traditional Chinese Medicine (TCM) versus single EGFR-TKIs for Advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 59 NSCLC patients with EGFR mutation were divided (2:1) into treatment group and control group. Patients in treatment group (39 cases) take EGFR-TKIs plus TCM and control group (20 cases) take EGFR-TKIs. Analysis the progression-free survival (PFS), disease control rate (DCR) and treatment-related adverse events of two groups. RESULTS: The DCR of the treatment group and control group was 94.1% and 84.2% respectively (P=0.24). In the total population, PFS was 12.1 months in treatment group and 9.1 months in control group [hazard ratio (HR) 0.46; 95%CI 0.23-0.9; P=0.025]. Among patients with exon 19 deletion (19-del), PFS between treatment group and control group was 10.5 months and 9.5 months respectively (P=0.17). For patients with exon Leu858Arg point mutation (L858R), PFS was significantly longer with treatment group than withcontrol group (median 13.2 months vs. 7.8 months; HR 0.32, 95%CI 0.10-0.97; P=0.046). Grade 3-4 treatment-related adverse events were less common withtreatment-group (8.33 %) than control group (15.00%) (P=0.65). CONCLUSION: For NSCLC patients with EGFR mutation, EGFR-TKIs combined with TCM has a certain effect to prolong PFS, especially for the patients with L858R.

[Effects of ShenFu Injection on Peripheral Neurotoxicity of Paclitaxel].

OBJECTIVE: To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. METHODS: Twenty-eight adult male Wister rats were randomized into 4 groups (n=7) : control group, paclitaxel group, paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection),low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively,while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL) of rats' hind paw were measured before (0 d) and after the first injection (6 d,14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia,and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. RESULTS: The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group ( P<0.05). The combination of paclitaxel with ShenFu Injection,especially the high dose ( P<0.05),significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group,there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection (P>0.05) . Compared with control group,the serum NGF level significantly decreased ( P<0.05) in paclitaxel group,while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group,particularly in the high dose group ( P<0.05). When compared to control group,the sciatic nerve fiber structure in the paclitaxel group was generally damaged,including myelin sheath swelling,fragmentation and vacuolization,endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups,especially the latter one,when compared to the paclitaxel group. CONCLUSION: Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.

Expression of prolyl 4-hydroxylase beta-polypeptide in non-small cell lung cancer treated with Chinese medicines.

OBJECTIVES: To investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) expressed in lung carcinoma and the intervention effect of Yiqi Chutan Formula (, YQCTF). METHODS: Lung carcinoma model was established by subcutaneously inoculating LEWIS lung carcinoma cells in C57BL/6J mice. The differential expression of P4HB protein between the YQCTF (3.0 g/kg, gavage, once daily, 21 days) group and the control group was acquired by a 2 fluorescence difference gel electrophoresis (2D-DIGE), verified by Western blotting and identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS). The expression of P4HB and P4HB mRNA in cultured A549 cells from cisplatin (DDP) 1.5 µg/mL group and 15% serum combined with DDP 1.5 µg/mL group were detected by cellular immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. RESULTS: The proteomics research discovered that one-third of differential proteins including P4HB were decreased in the YQCTF group (P<0.01). Clinical pathology and tissue microarray studies showed that P4HB expression in lung cancer tissue was stronger than adjacent tissues and normal lung epithelial (P<0.01). In the YQCTF and DDP combined groups, the expression of P4HB and P4HB mRNA in A549 cell were decreased significantly (P<0.01). CONCLUSION: YQCTF could inhibit the LEWIS lung carcinoma's growth, decrease the expression of P4HB in LEWIS lung carcinoma and A549 cells. YQCTF might take effect through regulating P4HB in endoplasmic reticulum to inhibit the incidence and growth process of lung carcinoma.

Use of chinese herb medicine in cancer patients: a survey in southwestern china.

Chinese herb medicine (CHM) is the most commonly reported traditional Chinese medicine (TCM) modality. This study aimed to assess the prevalence and associated factors of CHM use in cancer patients in southwestern China. Cancer patients from eleven comprehensive cancer centers were asked to complete a structured questionnaire. Of 587 available replies, 53.0% used CHM. Multiple logistic regression analysis showed that educational level, stage of disease, duration of cancer since diagnosis, marital status, and previous use of CHM were strongly associated with CHM use after cancer diagnosis. The source of information about CHM was mainly from media and friends/family. CHM products were used without any consultation with a TCM practitioner by 67.5% of users. The majority used CHM to improve their physical and emotional well-beings and to reduce cancer therapy-induced toxicities. About 4.5% patients reported side effects of CHM. This survey revealed a high prevalence of CHM use among cancer patients. However, these patients did not get sufficient consultation about the indications and contradictions of these drugs. It is imperative for oncologists to communicate with their cancer patients about the usage of CHM so as to avoid the potential side effects.

[Apoptosis inducing effect of Hechanpian on human lung adenocarcinoma A549 cells].

OBJECTIVE: To study the apoptosis inducing effects of Hechanpian (HCP) on human lung adenocarcinoma A549 cells. METHODS: HCP containing rat serum was prepared and applied on A549 cells. The cell growth inhibition rate was tested by MTT assay; the effect of HCP on cell apoptosis was observed with Propidium iodide (PI) staining and flow cytometry analysis; the mRNA expression of epidermal growth factor receptor (EGFR) was detected through RT-PCR. RESULTS: The growth of A549 cells was obviously inhibited after being treated by HCP containing serum, and the cells presented an apoptotic change. The cell apoptosis rate after treated by serum containing 10% and 20% HCP was 20.5% and 33.2%, respectively, significantly higher than that in the control (6.1% in cells didn't treated with HCP, P < 0.05). Compared with control, EGFR mRNA expression in HCP treated cells was significantly lower (P < 0.05). CONCLUSION: HCP has apoptosis inducing effect on A549 cell, and its molecular mechanism is probably correlated with the inhibition of EGFR gene transcription.

[Proteomics in Chinese medicine researches: current status, problems and strategies].

Proteomics plays important roles in Chinese medicine research at post-genomics era. Its research idea and methods are beneficial for elucidating some elemental features of Chinese medicine. At present, Chinese medicine proteomic studies are mainly focusing on the syndromatology and medical herbal pharmacology. However, there are still some problems, the most important matter was that most of the results were merely the superficial delineations. Further research should put emphasize on the unremitting and penetrating study of proteomics, molecular biology and bioinformatics integrally for illuminating Chinese medicine theory deeply to promote the modernization of Chinese medicine research.

[Bioinformatics analysis and function prediction of the novel gene AY358935].

OBJECTIVE: To obtain the functional information of AY358935 gene. METHODS: The properties, subcellular location, and structure of AY358935 protein, and the expression profile of AY358935 gene were analyzed by bioinformatics software and the biological functions of the gene were predicted. AY358935 expression was detected by Western blot analysis in early virus infection. RESULTS: AY358935 was evolutionally conserved. The human AY358935 protein had an amino acid similarity of 74%, 60%, 38% and 33% with its counterpart in horses, mice, zebrafish and Xenopus laevis, respectively. Bioinformatics analysis indicated that AY358935 protein was located likely in the mitochondria. There was a N-terminal signal peptide and single transmembrane structure in AY358935 protein, which contained several phosphorylation sites. The secondary structure mainly comprised of alpha helices and random coils. AY358935 was ubiquitously expressed in normal tissues and carcinomas and regulated by the expression of double-stranded RNA-dependent protein kinase. AY358935 protein expression was obviously upregulated in cells 2 h after infection by vesicular stomatitis virus. CONCLUSION: As a predicted secretary protein with a small molecular weight, AY358935 might have important functions in cellular proliferation and anti-viral innate immune regulation.

Vascular endothelial cell antigen (VECA), a novel secreted protein: overexpression in Escherichia coli of the hexahistidine- tagged protein and production of polyclonal antibodies.

A novel VECA (vascular endothelial cell antigen) was previously identified by using an antibody pool against antigens in HUVECs (human umbilical-vein endothelial cells). VECA has been evolutionarily conserved in vertebrate species ranging from frog and fish to mouse and human. Bioinformatics analysis indicated that VECA was 10.1 kDa in size, with a predicted signal sequence and transmembrane domain, indicating that VECA may have important biological functions. The present paper describes a procedure for obtaining and purifying human recombinant VECA expressed in Escherichia coli as a fusion protein, via a human VECA cDNA linked pQE30 expression vector to DNA coding for hexahistidine. The purified protein was used to raise anti-(human VECA) polyclonal antibodies, which were suitable for detecting the presence of VECA in cells, cell-culture supernatant and tissues by immunoblotting and immunohistochemistry. To our knowledge, this is the first study on the protein expression and polyclonal-antibody production for human VECA. In addition, we report for the first time the positive identification of VECA in humans at the protein and subcellular level and provide the first experimental verification that VECA was indeed a secreted protein. The anti-(human VECA) polyclonal antibodies prepared may serve as a useful tool for future biological function studies on VECA.

Soluble expression of human DRR1 (down-regulated in renal cell carcinoma 1) in Escherichia coli and preparation of its polyclonal antibodies.

Human DRR1 (down-regulated in renal cell carcinoma 1) is widely expressed in normal tissues but dramatically reduced or even undetectable in a number of different cancer cell lines and primary tumour types. DRR1 from Homo sapiens was cloned into the pQE30 vector for fusion-protein expression with six histidine residues in Escherichia coli BL21(DE3). A soluble protein with a molecular mass of approx. 19 kDa on SDS/PAGE that matches the expected rDRR1 (recombinant DRR1) molecular mass (18.7 kDa) was obtained. The soluble and insoluble expression of recombinant protein DRR1 (rDRR1) was temperature-dependent. The expression rDRR1 was in soluble and insoluble forms at 37 degrees C, and approx. 80% of total rDRR1 was soluble at 37 degrees C, while rDRR1 was almost exclusively expressing in soluble form at 20 degrees C. The expressed rDRR1 at 20 degrees C was affinity-purified on Ni(2+)-charged resin under native conditions. The purified protein was further identified by ESI-MS (electrospray ionization MS). The purified recombinant protein rDRR1 was further used to raise anti-(human DRR1) polyclonal antibodies, which were suitable for detecting both the recombinant exogenous DRR1 and the endogenous DRR1 from tissues and cells by immunoblotting and immunohistochemistry. The purified rDRR1 and our prepared anti-(human DRR1) polyclonal antibodies may provide useful tools for future biological function studies on DRR1.