A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Comparison of ultrasonic manifestations among triple-negative breast cancer and BI-RADS 4A atypical fibroadenoma or adenosis / 中国医学影像技术

Objective To compare ultrasonic manifestations of triple-negative breast cancer (TNBC),BI-RADS category 4A atypical fibroadenoma and adenosis.Methods Ultrasonic findings of TNBC group (n=42),BI-RADS 4A atypical fibroadenoma group (n=34) and adenosis group (n =36) were analyzed retrospectively,and statistical analysis was performed.Results There were statistically significant differences of age,tumor size,shape,echo,margin and BI-RADS category between TNBC group and fibroadenoma group (all P＜0.016 7).There were statistically significant differences (all P＜0.016 7) of age,size,margin,peripheral duct changes,and BI-RADS category between TNBC group and adenosis group.There were statistically significant differences of shape between fibroadenoma group and adenosis group (P＜0.016 7).There was no statistically significant difference of boundary,halo,posterior acoustic features,orientation,nor calcification among three groups (all P＞0.05).Conclusion TNBC often occurs in women older than 50 years old,and the lesions usually demonstrate larger than 2 cm,very lower echo,and irregular shape with distinct margin.TNBC is usually associated with harder elastography feature,and is classified as more than BI-RADS 4B.Fibroadenoma classified as BI-RADS 4A is most likely to be a mass with lobulated or irregular shape with distinct margin.Adenosis classified as BI-RADS 4A often appears irregular and vertical orientation,which may be confused with breast cancer.

Meta-analysis of the correlation between the rs17401966 polymorphism in kinesin family member 1B and susceptibility to hepatitis B virus related hepatocellular carcinoma

BACKGROUND/AIMS: The association between the kinesin family member 1B (KIF1B) gene polymorphism and the risk of hepatitis B virus-related hepatocellular carcinoma (HCC) has been investigated in many peer-reviewed studies. However, scholars have failed to replicate these results in validation tests. The purpose of the present study was to explore whether the KIF1B rs17401966 polymorphism was associated with susceptibility to HCC. METHODS: The results of case-controlled studies on the correlation between the KIF1B rs17401966 polymorphism and HCC susceptibility were collected using Google Scholar and the EMBASE, PubMed and CNKI databases. Based on inclusion and exclusion criteria, 5 papers with a total of 12 cohorts were included in this study. RESULTS: The 12 cohorts were integrated, and the results showed that the rs17401966 polymorphism reduced the risk for HCC under the allele, heterozygous, homozygous, and dominant models but not under the additive or recessive models. Moreover, the merged results showed strong heterogeneity, and the cumulative meta-analysis results were unreliable. A genetic differentiation analysis of the 12 cohorts found different degrees of genetic differentiation between the 5 cohorts in Zhang et al.’s study and the cohorts in the other studies. We further divided the 12 study cohorts into 2 subgroups based on fixation index value; however, the results of that analysis were inconsistent. CONCLUSIONS: The results of this meta-analysis were not able to verify the association between the KIF1B rs1740199 polymorphism and HCC risk. Therefore, a well-designed, large-scale, multicenter validation study is needed to confirm the relationship.

Clinical and radiographic evaluation of oblique lumbar interbody fusion combined with percutaneous pedicle screw fixation on computer navigation for lumbar spondylolisthesis / 中华骨科杂志

Objective To assess the clinical effect of oblique lumbar interbody fusion (OLIF) combined with percutaneous pedicle screw fixation on computer navigation for lumbar spondylolisthesis.Methods Total 20 patients (8 males and 12 females with average age of 54.1± 12.3 years) with lumbar spondylolisthesis were enrolled in our study during Oct.2014 and May.2016.All patients were treated with OLIF combined with percutaneous pedicle screw fixation on computer navigation.Operation time,blood loss and complications were all recorded.Clinical and Radiographic evaluation were investigated on 1 week,3 months,6 months,12 months postoperatively and final follow-up.Visual analogue scale (VAS) for low back pain and leg pain,Oswestry disability index (ODI) for low back pain and the MOS item short form health survey (SF-36) were used to evaluate the clinical efficacy of surgery.Disc height,disc angle,lumbar lordosis and degree of upper vertebral slip of patients were investigated with X-ray.Cross-sectional area of intervertebral foramina was measured with three-dimensional CT and MRI.The cross-sectional area and sagittal diameter of the thecal sac were measured on T2-weighted axial and sagittal magnetic resonance images.Accuracy of pedicle screw placement was investigated with three-dimensional CT.Fusion rate was investigated with three-dimensional CT and Xray.Results All patients were followed for 12-30 months (22.9±4.8 months).The mean operation time was (119.0±23.8) min,the mean blood loss was (57.8±20.6) ml.VAS for low back pain,VAS for leg pain,and ODI were significantly improved from (6.7± 2.6),(6.3±2.7) and 50.5％±18.2％ preoperatively to (1.3±1.0),(0.8±1.0) and 14.0％±9.6％ at the latest follow-up.The SF-36 PCS and MCS scores were improved from (27.1 ± 13.9) and (51.0±22.7) preoperatively to (67.3± 18.9) and (81.2±14.1) at the latest follow-up.Disc height,disc angle,lumbar lordosis were significantly increased from (6.0±3.6) mm,1.8°±6.2° and 39.2°±8.4° preoperatively to (10.8± 1.7) mm,6.2°±3.5° and 45.0°±7.8° at the latest follow-up.Degree of upper vertebral slip of patients was reduced from 23.5％±7.4％ preoperatively to 4.2％±3.1％ at the latest follow-up.Cross-sectional area of intervertebral foramina in CT and MRI were significantly increased from (140.6±36.0) mm2 and (78.1±31.2) mm2 before surgery to (179.8±35.6) mm2 and (141.7±29.5) mm2 at 6 months after surgery.Cross-sectional area and sagittal diameter of thecal sac were significantly increased from (73.4±29.3) mm2 and (5.2±3.2) mm before surgery to (124.5±26.6) mm2 and (9.5±2.0) mm at 6 months after surgery.Accuracy of pedicle screw placement was 95％,and fusion rate was 100％ at 6 months after surgery.There were no severe vascular and nerve injuries.Conclusion OLIF combined with percutaneous pedicle screw fixation on computer navigation has good indirect decompression effect on lumbar spondylolisthesis,and was associated with high fusion rate.It can also effectively decrease the surgical trauma,improve the accuracy of pedicle screw placement,and increase disc height,disc angle and lumbar lordosis.

Fst statistical method for evaluating KIF1B gene rs17401966 polymorphism and heterogeneity source of hepatocellular carcinoma risk meta-analysis / 国际检验医学杂志

Objective To adopt Fst statistical method to assess the heterogeneity sources of meta‐analysis by dichotomous varia‐ble .Methods The case‐control studies on the relationship between KIF1B gene rs17401966 polymorphism and hepatocellular carci‐noma(HCC) risk were collected by retrieving the databases including Google Scholar ,EMBASE ,PubMed ,ISI Web of Knowledge and CNKI .The meta analysis was performed by using the Stata12 .0 software .The genetic differentiation degree among populations was analyzed and researched by using the Arlequin 3 .5 software .Results A total of 5 case‐control studies were finally included ,in‐volving 12 research populations .The meta analysis on 12 populations showed that KIF1B gene rs17401966G allele was negatively correlated with HCC risk (OR=0 .77 ,95% CI:0 .65-0 .93 ;P=0 .005) .However ,the strong heterogeneity existed in this pooled re‐sults .The genetic differentiation test in the included 12 populations found that Zhang′s five research populations had varying de‐grees of genetic differentiation compared to other populations .Then the proper subgroup analysis was further conducted based on Fst value ,and then the I2 value of the heterogeneity test in the group 8 and 9 was descended to less than 25% .However ,the meta analysis results of the group 8 and 9 were inconsistent .Conclusion This study showed that conducting the meta‐analysis of KIF1B gene rs17401966 polymorphism and the HCC risk can find the heterogeneity sources of meta‐analysis by conducting the genetic dif‐ferentiation test in the included population .

Epidermal growth factor receptor mutations in primary tumors, N2 lymph nodes, and plasma samples in Chinese patients with stageⅢA-N2 non-small cell lung cancer / 中国肿瘤临床

Objective:Mutations in epidermal growth factor receptor (EGFR) can predict tumor response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, not all cases of NSCLC with EGFR mutations can respond well;thus, discovering the heterogeneity of NSCLC at the molecular level is necessary. This study aimed to determine the discrepancy in EGFR mutations in primary tumors, N2 lymph nodes, and plasma samples. Methods:Primary tumors, N2 lymph nodes, and plasma samples obtained from 49 patients with stageⅢA-N2 NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using mutant-enriched liquidchip technology. Results:In 49 patients, we detected 18 (36.7%) EGFR mutations in primary tumors, 11 (22.4%) mutations in N2 lymph nodes, and 2 (4.1%) mutations in plasma samples. Eleven (22.4%) cases showed discordance in EGFR mutations between primary tu-mors and N2 lymph nodes. In nine cases, EGFR mutations were detected only in primary tumors, whereas EGFR mutations were de-tected only in N2 lymph nodes in two cases. In addition, EGFR mutations were detected in the plasma samples of two patients, who al-so carry mutations in their primary tumors. Conclusion:A considerable proportion of NSCLC cases showed discrepancy in EGFR muta-tions between primary tumors and N2 lymph nodes. In addition, the detection rate of EGFR mutations was lower in plasma samples obtained from patients with stage IIIA-N2 NSCLC. All of the results indicated tumor heterogeneity at the molecular level during metas-tasis, and this heterogeneity may have implications during treatment with TKIs.

Research on the Treatment of Depression with Sleep Disorders by Paroxetine Combined with Olanzapine / 中国药师

Objective:To observe the clinical efficacy and adverse reactions of paroxetine combined with olanzapine in the treat-ment of depression complicated with sleep disorders. Methods: Totally 150 cases of sleep disorder patients were selected, and then randomly divided into the control group and the observation group with 75 ones in each. The control group was given paroxetine treat-ment, the observation group was given paroxetine combined with olanzapine treatment, and the treatment course was four weeks. The sleep latency, total sleep time, wake-up time and the number of awakening in the two groups were recorded, and the HAMD scale score and treatment efficacy were compared. Results:Compared with those in the control group, the sleep latency, total sleep time, wake-up time and the number of awakening in the observation group were obviously improved (P<0. 05). The clinical cure rate, the HAMD scale score and the incidence of adverse reactions between the two groups all had significant differences (P<0. 05). Conclu-sion:Paroxetine combined with olanzapine in the treatment of depression with sleep disorders shows fast efficacy, which can improve the sleep disorder symptoms and reduce the incidence of adverse reactions significantly.

The application of virtual patient in gynecology and obstetrics clinical teaching / 中华医学教育探索杂志

Gynecology and obstetrics is a theoretical and practical subject. It is an important goal for the medical students to develop the clinical thinking ability and operating skills and apply them in the diagnosis and treatment of disease. To overcome the limited teaching resources, the rare clinical skills opportunities caused by doctor-patient relationship tension, virtual patient (VP) combined with clinical teaching was applied in clinical teaching, which can reproduce the real, and bring the students to the role of the clinician , enrich the content of the obstetrics and Gynecology clinical teaching. Along with the reform the teaching faculty with high quality was established, their clinical teaching experiences and innovative thinking were improved significantly. The results were evaluated by means of clinical comprehensive ability test. The present study aimed to establish virtual patients of OBGYN (virtual patient, VP) learning to promote learning of basic knowledge, clinic skills, and thinking ability.

Toxic effects of mixture of volatile organic compounds on mice testis related enzymes and hormones / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the toxic effects of mixture of volatile organic compounds (VOCs) on Mice Testis related enzymes and hormones.</p><p><b>METHODS</b>After determining the median lethal dose (LD₅₀) of VOCs using the acute toxicity test, 40 male clean inbred Kunming mice were assigned to 1/8 LD₅₀ VOCs exposure group, 1/4 LD₅₀ VOCs exposure group, and 1/2 LD₅₀ VOCs exposure group, as well as positive control group with cyclophosphamide (60 mg/kg) and negative control group with tea oil, with 8 mice in each group. The mice were intraperitoneally injected with respective agents for 5 days. The levels of testis testosterone, estradiol, follicle stimulating hormone, and luteinizing hormone were determined by ELISA. Meanwhile, the activity of testicular marked enzymes such as lactate dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase, and glucose-6-phosphate dehydrogenase were examined.</p><p><b>RESULTS</b>Compared with the negative control group, the 1/8 LD₅₀ exposure group had a significantly increased testis coefficient (P<0.05). Both the activity of testicular marked enzymes and the levels of testicular sex hormones in all exposure groups showed significant downward trends with increasing VOC doses compared with those in the negative control group (P<0.05).</p><p><b>CONCLUSION</b>VOCs have obvious toxicity to mouse testis by changing the levels of testicular sex hormones and the activity of testicular marked enzymes.</p>

Expression of EGFL7 in human glioma and its relationship with FAKpY397 and MVD / 国际肿瘤学杂志

ObjectiveTo test the expression of epidermal growth factor-like domain 7 (EGFL7),microvessel density (MVD) and foeal adhesion kinase pY397 (FAKpY397) in human glioma tissues,and to evaluate their relationship.MethodsThe expression of EGFL7 and FAKpY397 in 56 cases of human glioma and 8 cases of normal brain tissues were detected by immunohistochemistry test,and MVD was detected by CD34 staining.ResultsThere was a significant difference of the positive rates of EGFL7 between normal brain tissue (0) and gliomas (75％),χ2 =17.45,P ＜0.01.With the increased pathological grade,the expression level of EGFL7 increased (χ2 =26.24,P ＜ 0.01 ).There was a significant difference of the positive rates of FAKpY397 between normal brain tissue ( 12.5％ ) and gliomas (73.2％),χ2 =6.23,P ＜ 0.05.With the increased pathological grade,the expression level of FAKpY397 increased (χ2 =6.71,P ＜ 0.01 ). MVD on normal brain was( 15 ± 4 )/HP,on Ⅰ - Ⅱ grade and Ⅲ -Ⅳ grade gliomas was ( 27 ± 3 )/HPand ( 60 ± 4 )/HP respectively,there was a significant difference on MVD between normal brain tissue and gliomas (P ＜ 0.01 ).Higher level of MVD was found in gliomas with higher grade ( P ＜ 0.01 ).There was a positive correlation between EGFL7 and FAKpY397 expressions in gliomas (r =0.314,P ＜0.01 ).There was a significant difference on MVD between positive and negative expression of EGFL7 ( t =26.55,P ＜ 0.01 ). MVD was (56 ± 4 )/HP and (25 ± 3 )/HP respectively.ConclusionThe expression of EGFL7 of human gliomas has a favorable positive correlation with the degree of malignancy,MVD and FAKpY397.It is indicated that EGFL7not only palys an important regulative role in glioma neovascularization,but also it may participate directly in glioma occurrence and invasion.

Ultrasound-guided percutaneous centesis in the treatment of pericardial effusion / 中国介入影像与治疗学

Objective To assess the practical value of ultrasound-guided percutaneous pericardium centesis in patients with pericardial effusion.Methods Twenty-eight patients with pericardial effusion were treated with ultrasound-guided percutaneous pericardium centesis from May 2004 to May 2009.Results Operations were successfully done in all 28 patients.The puncture needle,guide wire and drainage catheter could be clearly visualized under ultrasound.Complications included ache,bleeding and drainage catheter obstruction or prolapsus.Conclusion Able to be used bedside,ultrasoundguided percutaneous pericardium centesis is a real time,exact,safe and convenient method for the diagnosis and treatment of pericardial effusion.

Detection of Skp2 mRNA gene expression using fluorogenic probe quantitative RT-PCR method in laryngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#The current study was designed to examine the expression of Skp2 gene in laryngeal squamous cell carcinoma (LSCC) and to investigate the role of Skp2 gene in tumorigenesis and progression of LSCC.@*METHOD@#FQ-PCR method was used to examined the expression of Skp2 gene in 40 LSCC and 10 normal laryngeal mucosa tissues, and relationship between its expression and clinical biological factors of patients with LSCC was analyzed.@*RESULT@#The median copy number of Skp2 mRNA expression in LSCC was 6622.54 copy/microg RNA, the median copy number of Skp2 mRNA expression in normal laryngeal mucosa tissues was 0 copy/microg RNA, there was a very significant difference between them (P < 0.01); The positive rate of Skp2 mRNA expression in LSCC and adjacent normal laryngeal tissue were 50%, 0, respectively (P < 0.01). The median copy number of Skp2 RNA expression in LSCC with cervical lymph node metastasis was 617138.4 copy/microg RNA, the median copy number of Skp2 mRNA expression in LSCC without cervical lymph node metastasis was 0 copy/microg RNA, there was a very significant difference between them (P < 0.05); The positive rate of Skp2 mRNA expression in LSCC with and without cervical lymph node metastasis were 100.00%, 35.48%, respectively (P < 0.01).@*CONCLUSION@#Skp2 gene might have relation with the cervical lymph node metastasis of LSCC. FQ-PCR is an accurate assay to detecting expression of Skp2 mRNA in patient with LSCC. The level of Skp2 mRNA expression might be a new and more accurate marker, and it can be used to predict cervical lymph node metastasis of LSCC.

Skp2 and p27 protein expression and their significance in laryngeal squamous cell carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the correlation of S-phase kinase associated protein 2 (Skp2) and p27 expression with the clinical factors and prognosis of patients with laryngeal squamou cell carcinoma (LSCC). METHODS The expressio of Skp2 and p27 in 79 specimens of LSCC and 1 specimens of adjacent normal laryngeal mucos tissues were evaluated by SP immunohistochemist methods. RESULTS The overexpression rate Skp2 was significantly higher in LSCC(53.16 %) tha in adjacent normal laryngeal mucosa tissue (0 % (P

Expression of E-cadherin and ?-catenin proteins and their significance in laryngeal squamous cell carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE The purpose of this studywas to investigate the correlation of E-cadherin(E-cad) and ?-catenin(?-cat) expression with clinical factors and prognosis in laryngeal squamous cell carcinoma (LSCC) patients. METHODS The expression of E-cad and ?-cat in 79 cases of LSCC and 10 cases of adjacent normal laryngeal mucosal tissues were evaluated by SP immunohistochemical methods. RESULTS All 10 normal samples were positive for expression of E-cad and ?-cat , The positive expression of E-cad and ?-cat in LSCC were 34.18 % and 40.51 % respectively. There was a statistically significant difference in the positive expression of E-cad and ?-cat between normal samples and LSCC (P

Expression and significance of TGF-β1 in nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To study the expression and significance of transforming growth factor-β1 (TGF-β1) in nasal polyps.Method:Expression of TGF-β1 in nasal polyps from 34 patients and middle turbinates from 30 patients with deviation of nasal septum were prospectively studied with immunohistochemistry.Each tissue section was observed under optical microscope.Result:①The TGF-β1 positivity in extracellular matrix and in cells in the stroma was significantly higher in nasal polyps than in middle turbinates (P＜0.01).②The distribution and shape of TGF-β1 expressing cells in nasal polyps was similar to that of eosinophil,their positivities were significantly correlative (P＜0.05).③The positivity of TGF-β1 did not correlate with clinical type of nasal polyps (P＞0.05),eosinophil infiltration correlated significantly with clinical type of nasal polyps(P＜0.05).Conclusion:①The TGF-β1 may contribute to some of the pathologic changes observed in nasal polyps,such as thickening of the epithelial basement membrane and stromal fibrosis.②Eosinophils in nasal polyps represent a major source of TGF-β1.③Eosinophils infiltration may play a prominent role in the development and recurrence of nasal polyps.