Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise.@*METHODS@#A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated.@*RESULTS@#After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01).@*CONCLUSION@#Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Risk factors and the prognosis of sexual dysfunction in male patients with pituitary adenomas: a multivariate analysis / 亚洲男科学杂志(英文版)

The impact of sexual dysfunction (SD) is distressing to many male patients with pituitary adenomas which affect both physical and psychological health. The research explored to identify risk factors affecting sexual function and the prognosis of male patients with pituitary adenomas. Two hundred and fifty-four male patients, who aged between 18 and 60 (mean ± s.d.: 44.16 ± 10.14) years and diagnosed with pituitary adenomas, were retrospectively analyzed. One hundred and fifty-nine patients (62.6%) complained of SD prior to surgery. The mean International Index of Erectile Function (IIEF-5) in patients with giant adenomas was 16.13 ± 2.51, much smaller than those with microadenomas or macroadenomas (P < 0.05). All the patients showed significant improvement in terms of erectile dysfunction (ED) following surgery (P < 0.05). In addition, complete resection achieved a higher degree of SD relief than partial resection. The incidence of SD in functioning pituitary adenomas (FPAs) was much higher than that in nonfunctioning pituitary adenomas (NFPAs) (P < 0.05). In addition, compared with NFPAs, males with prolactinomas (82.8%) had the higher prevalence of SD and significantly improvement following surgical intervention (P < 0.05). An inverse relationship was identified between decreasing testosterone levels and increasing incidence of SD before surgery (P < 0.05). There was no significant difference between 6 months and 12 months after surgery in serum testosterone level (P > 0.05). Our results indicated that surgical therapy could be optimized for improvements in SD and that testosterone levels can be used as a sensitive indicator to predict the recovery rate of sexual function in patients with pituitary adenomas following surgery and the serum testosterone level will stay stable in 6 months after surgery.

Clinical Features and Prognostic Risk Factors of Choroid Plexus Tumors in Children / 中华医学杂志(英文版)

Background@#Decision-making concerning the treatment of choroid plexus tumor (CPT) in pediatric patients remains a topic of considerable debate. The aim of this work was to describe clinical features and prognostic risk factors of CPT in the pediatric population and to provide theoretical opinions regarding clinical decisions for CPT.@*Methods@#The data of 96 patients with CPT and younger than 14 years were retrospectively analyzed. Clinical characteristics such as pathological type of CPTs, rate and severity of hydrocephalus, treatment and outcome, and recurrence were investigated. For categorical variables, the Pearson's Chi-square test was performed. The Mann-Whitney U-test was used for comparisons between nonnormally distributed parameters. Log-rank test was used for progression-free survival (PFS).@*Results@#The study included 70 choroid plexus papilloma (CPP) cases, 17 atypical choroid plexus papilloma (aCPP) cases, and 9 choroid plexus carcinoma (CPC) cases. Compared with patients with CPP or aCPP, patients with CPC had a shorter disease course (median: CPP, 4 months; aCPP, 2 months; CPC, 1 month; H: 23.5, P 0.05). Patients with CPC experienced shorter time for recurrence than those with CPP or aCPP (χ = 40.1, P < 0.0001).@*Conclusions@#Our results indicated that CPP in the fourth ventricle could trigger serious clinical symptoms at an early stage, requiring early intervention. Adjuvant treatment might be necessary for patients with partially resected CPP, aCPP, and CPC to achieve a favorable outcome.

Effect of miR-21 on migration and invasion ability in human laryngeal squamous carcinoma cell Hep 2 / 重庆医学

Objective To explore the effect of microRNA‐21(miR‐21) on the migration and invasion ability in human laryn‐geal squamous carcinoma cell Hep2 .Methods The MTT method was used to detect the viability of Hep2 cells at 48 h after miR‐21 inhibitor and miR‐21 NC transferring into Hep2 cells by LipofectamineTM 2000 .The cell migration ability was detected by using the scratch test .The cell invasion ability was detected by using the Transwell method .The activation of phosphatase and tensin homo‐logue deleted on chromosome 10 (PTEN)/phosphatidylinositol 3 kinase (PI3K) /protein kinase B(Akt) signal pathway and the expression of matrix metalloproteinase 2 (MMP2) ,MMP9 ,reversion inducing cysteine rich protein with kazal motif (RECK) was detected by using the Western blotting .Results Compared with miR‐21 NC ,miR‐21 inhibitor could significantly reduce the Hep2 cellviability[(0.688±0.043)vs.(0.375±0.012)],inhibitedthemigrationability[(6.57±0.02)μm vs.(20.49±2.18)μm]and invasion ability[(100 .7 ± 10 .2) vs .(46 .8 ± 4 .3)] ,and the differences were statistically significant (P<0 .01) ,meanwhile miR‐21 inhibitor could down‐regulate the expression of PI3K ,MMP2 and MMP9(P<0 .01) ,and reduced the phosphorylation level of Akt (P<0 .01) ,up‐regulated the expression of PTEN and RECK (P<0 .01) .Conclusion miR‐21 inhibitor can significantly suppress the migration and invasion ability of Hep2 ,which may be related with the PTEN/PI3K/Akt signal pathway .

Sequence Analysis of the UGT1A1 Gene Untranslated Region in Chinese Han Population / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the 5' and 3'-untranslated region sequences of the UGT1A1 gene in Chinese Han population and to find polymorphic variants within the untranslated region.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral leukocytes in 220 healthy Han individuals. The 5' and 3'-untranslated region sequences of the UGT1A1 gene were amplified by polymerase chain reaction, and followed by DNA sequencing.</p><p><b>RESULTS</b>Two polymorphic loci were identified in the 5'-untranslated region of the UGT1A1 gene with -64(G/C) and A(TA)6TAA/A(TA)7TAA in TATAA box region among Chinese Han population. Genotype frequencies were 98.4% (G) and 1.6% (C) in -64 locus of the UGT1A1 gene among the 220 individuals. The allele frequency of A(TA)6TAA and A(TA)7TAA within the promoter region was found to be 93.4% and 6.6%, respectively. Two polymorphic loci of 1813(C/T) and 1941(C/G) were detected in the 3'-untranslated region of the UGT1A1 gene, they showed a homozygous state at two loci with cosegregation pattern at 1813 and 1941 locus. The haplotype frequencies were 73.6% (CC/1813+CC/1941) and 26.4% (TT/1813+GG/1941) for 1813 and 1941 loci in the UGT1A1 gene.</p><p><b>CONCLUTION</b>Cosegregation pattern, at 1813 and 1941 locus with homozygous state in the 3'-untranslated region of the UGT1A1 gene may be selected from the human genome among Chinese Han population. More studies should be focused on the mechanism of homozygous cosegregation.</p>

Roles of Tumor-infiltrating Lymphocytes in Non-small Cell Lung Cancer Recurrence and Metastasis:A Meta Analysis / 中国医学科学院学报

<p><b>OBJECTIVE</b>To determine the prognostic value of tumor-infiltrating lymphocytes in the recurrence and metastasis of non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A PubMed, EMBASE, Cochrane Library databases, NIH databases, and China Biology Medicine disc, China National Knowledge Infrastructure, Chinese Science and Technology Periodical literature search strategy was designed. Studies on the prognostic values of intratumoural CD3⁺,CD4⁺,CD8⁺, and FoxP3+lymphocytes for NSLCL were retrieved. RevMan 5.1 was applied for Meta analysis.</p><p><b>RESULTS</b>Totally 8 studies entered the final analysis. In pooled analysis of 1197 patients,the high expressions of CD3⁺ and CD8⁺ cells were correlated with the increase of overall survival (OS) (OR=0.52,95% CI=0.40- 0.68, P<0.0001; OR=0.52,95% CI=0.34-0.79,P=0.002), and the high expression of CD8⁺ was significantly correlated with the increase of disease-free survival (DFS) (OR=0.68,95% CI=0.51-0.91,P=0.01). The CD4⁺ cell expression level was not significantly correlated with OS or DFS (P=0.14, P=0.73). The high expression of FoxP3⁺ cells did not favor the DFS(OR=1.78,95% CI=1.36-2.31; P<0.0001).</p><p><b>CONCLUSION</b>The expression levels of CD3⁺, CD8⁺ and FoxP3⁺ in NSCLC microenviroment are related with the prognosis of NSCLC, while the role of CD4⁺ in the development of NSCLC warrants further investigations.</p>

Effect of FCGR3A Polymorphisms on Antibody-dependent Cetuximab-mediated Cytotoxicity in A549 Cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of FCGR3A polymorphisms on the antibody-dependent cell-mediated cytotoxicity (ADCC) activity induced by cetuximab against A549 cells.</p><p><b>METHODS</b>A549 cell line was used as target cells and NKTm cells as effector cells. FCGR3A polymorphisms were detected by direct sequencing. The ADCC activity mediated by cetuximab was assessed by CCK-8 assay.</p><p><b>RESULTS</b>Three genotypes of FCGR3A were detected:V/V,V/F,and F/F. The ADCC activity of NKTm cells with these three different genotypes mediated by cetuximab were significantly different (P=0.0015). NKTm cells with FCGR3A-158V/V genotypes had significantly higher ADCC activity than FCGR3A-V/F or F/F genotypes (P<0.01),whereas the ADCC activity between V/F and F/F genotype showed no statistical significance(P>0.05).</p><p><b>CONCLUSION</b>FCGR3A polymorphisms have an impact on ADCC activity mediated by cetuximab in NKTm cells.</p>

Pathogenic Genes of A Hereditary Hemorrhagic Telangiectasia Pedigree / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To identify the mutation of ENG and ALK1 genes in a hereditary hemorrhagic telangiectasia pedigree.</p><p><b>METHODS</b>14 exons of ENG gene and 9 exons of ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were screened by direct sequencing.</p><p><b>RESULTS</b>A nonsense mutation c.447G > A was found in exon 4 of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no gene mutation was found in ALK1 gene.</p><p><b>CONCLUSION</b>The hereditary hemorrhagic telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in ENG gene.</p>

Effects of Bu-Shen-An-Tai recipe and its two components on endometrial morphology during peri-implantation in superovulated mice / 华中科技大学学报（医学）（英德文版）

The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe (BSATR) and its two components (Bushen recipe, and Huoxue recipe) on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal (N), model (M), Bushen (BS), Huoxue (HX) and Bu-Shen-An-Tai (BH) groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density (MVD) and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the endometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes (Bushen, Huoxue and BSATR) could improve the endometrial environment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects.

TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without recieiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

TGF-β1 precursor and CD8 are potential prognostic and predictive markers in operated breast cancer / 华中科技大学学报（医学）（英德文版）

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.

Effects of Bu-Shen-An-Tai recipe and its two components on endometrial morphology during peri-implantation in superovulated mice / 华中科技大学学报（医学）（英德文版）

The aim of this study was to investigate the effect of Bu-Shen-An-Tai recipe (BSATR) and its two components (Bushen recipe, and Huoxue recipe) on endometrial morphology during peri-implantation in superovulated mice. Mice were randomly divided into five groups, including the normal (N), model (M), Bushen (BS), Huoxue (HX) and Bu-Shen-An-Tai (BH) groups. The uteri were collected on day 4 of pregnancy, and the endometrium thickness, microvessel density (MVD) and number of pinopodes observed. Compared with the M group, the endometrial thickness in the BS, HX and BH groups was significantly increased and there was a significant difference in endometrial thickness between the BS and the BH groups. The mean MVD was significantly lower in the M group than in the N group, and there was a significant increase in MVD in the BS, HX and BH groups as compared with the M group. Compared with the M group, the pinopode scores in the endometrium were significantly increased in the HX and BH groups; and the BS group had significantly higher pinipode scores than the HX and BH groups. In conclusion, the results of the present study demonstrated that the recipes (Bushen, Huoxue and BSATR) could improve the endometrial environment by regulating the endometrial thickness, MVD and the number of pinopodes at the window of implantation. Moreover, the Huoxue recipe and the BSATR were more efficient than the Bushen recipe, with the BSATR tending to have the most beneficial effects.

Role of epidermal growth factor receptor expression level in cetuximab cytotoxicity and antibody-dependent cell-mediated cytotoxicity effect against A549 lung cancer cell line / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the role of epidermal growth factor receptor (EGFR) expression level in cetuximab cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) effect against A549 lung cancer cell line.</p><p><b>METHODS</b>A549 cell line and NKTm cells were used as the target cell and the effector cell, respectively. pEGFR-EGFP plasmids were transfected into A549 cells by nucleofector method. EGFR expression levels were measured by immunohistochemistry. The ADCC activity induced by cetuximab was assessed by cell counting kit-8 assay.</p><p><b>RESULTS</b>A549 cells transfected with pEGFR-EGFP plasmids expressed higher level of EGFR protein on membrane and were more sensitive to ADCC activity mediated by cetuximab (P<0.05). The inhibition rate of A549 cells showed no significant difference between transfection group and wild-type group when treated with cetuximab alone (P> 0.05).</p><p><b>CONCLUSION</b>EGFR expression level influences the sensitivity of A549 lung cancer cell line to ADCC activity mediated by cetuximab but not to cetuximab alone.</p>

Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer

OBJECTIVE@#To investigate the expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer (NSCLC).@*METHODS@#Fresh non-small lung cancer specimens were transplanted into nude mice. Twenty mice were randomized into two groups: experimental group receiving gemcitabine plus cisplatin and control group receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in tumor tissue were detected by real-time fluorescent quantitative PCR. The volume of tumor, the weight of nude mice and tumor volume were respectively measured and calculated 2-3 times per week. Tissue samples were collected from NSCLC mice treated with gemcitabine plus carboplatin.@*RESULTS@#The histological examination showed that many tumor cells were well preserved in nude mice. The rate of transplanted tumor cells was 86.7%. The concomitant treatment study showed that the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC obviously influenced the body weight. Compared with NS group, DDP group, GEM group, the survival period and the level of hENTl of DDP+GEM group increased obviously, the level of ERCC1 decreased significantly (P<0.05).@*CONCLUSIONS@#The expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with the response to chemotherapy and prognosis of patients with NSCLC treated with gemcitabine plus cisplatin.

Large and giant medial sphenoid wing meningiomas involving vascular structures: clinical features and management experience in 53 patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Large and giant medial sphenoid wing meningiomas that are located deeply in the skull base where they are closely bounded by cavernous sinus, optic nerve, and internal carotid artery make the gross resection hard to achieve. Also, this kind of meningiomas is often accompanied by a series of severe complications. Therefore, it was regarded as a formidable challenge to even the most experienced neurosurgeons. This study aimed to investigate the clinical features and management experience of patients with large and giant medial sphenoid wing meningiomas.</p><p><b>METHODS</b>In this study, 53 patients (33 female and 20 male, mean age of 47.5 years) with large and giant medial sphenoid wing meningiomas were treated surgically between April 2004 to March 2012, with their clinical features analyzed, management experience collected, and treatment results investigated retrospectively.</p><p><b>RESULTS</b>In this study, gross total resection (Simpson I and II) was applied in 44 patients (83%). Fifty-three patients had accepted the routine computed tomography scan and magnetic resonance imaging scan as postoperative neuroradiological evaluation. Their performance showed surgical complications of vascular lesions and helped us evaluate patients' conditions, respectively. Meanwhile, the drugs resisting cerebral angiospasm, such as Nimodipine, were infused in every postoperative patient through vein as routine. As a result, 11 patients (21%) were found to have secondary injury of cranial nerves II, III, and IV, and nine patients got recovered during the long-term observing follow-up period. Temporary surgical complications of vascular lesions occurred after surgery, such as cerebral angiospasm, ischemia, and edema; 24 patients (45%) appeared to have infarction and dyskinesia of limbs. Overall, visual ability was improved in 41 patients (77%). No patient died during the process.</p><p><b>CONCLUSIONS</b>Microsurgical treatment may be the most effective method for the large and giant medial sphenoid wing meningiomas. The surgical strategy should focus on survival and postoperative living quality.</p>

Effect of BCL11A gene on transcription of γ-globin gene / 中国实验血液学杂志

This study was aimed to explore the effect of BCL11A gene on transcription of γ-globin gene in K562 cells. B-cell lymphoma/leukemia 11A (BCL11A) gene was silenced by small interfering RNA (siRNA) expression vectors in K562 cells (human erythroblastic leukemia cell line). Gamma-globin mRNA level in K562 cells was determined by RT-PCR. Association between the BCL11A gene and γ-globin gene transcription was explored by comparison of mRNA levels. The results indicated that the silence rate of the BCL11A gene in K562 cells by 4 siRNA expression vectors was 49.7%, 55.4%, 78.2%, and 84.1%, respectively. The siRNA expression vector with 84.1% silence rate was transfected into K562 cells, transcription level of γ-globin mRNA in K562 cells transfected with siRNA expression vector increased 2.4 times as compared with control K562 cells. It is concluded that level of γ-globin mRNA increases when the BCL11A gene is silenced. It indicates that the BCL11A gene may be a negative regulator for γ-globin gene expression.

Changes of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the change of lymphocyte subsets before and after chemotherapy in colorectal carcinoma patients.</p><p><b>METHODS</b>Twenty-one peripheral blood lymphocyte subsets from 62 colorectal carcinoma patients before and after FOLFOX4(including oxaliplatin, 5-fluorouracil and leucovorin) , FOLFRI(including irinotecan, 5-fluorouracil and leucovorin) , or XELOX(including oxaliplatin and capecitabine) regimen chemotherapy were examined by flow cytometry.The differences of these lymphocyte subsets were analyzed.</p><p><b>RESULTS</b>After chemotherapy, the percentages of CD3(+), CD3(+)CD8(+), CD29(+), CD4(+)CD29(+), and CD4(+)CD25(+) cells in peripheral blood of colorectal carcinoma patients increased significantly, while the percentages of CD19(+) and human leukocyte antigen(locus) DR(HLA-DR) (+) cells decreased significantly(P<0.05) .The results of subgroup analysis showed that the patients' CD3(+)CD8(+) and CD4(+)CD25(+) cells increased significantly, CD19(+) and HLA-DR(+) cells decreased significantly after FOLFOX4 regimen chemotherapy(P<0.05) ;CD3(+)CD8(+) cells increased significantly and CD19(+) cells decreased significantly after XELOX regimen chemotherapy(P<0.05) ;while after FOLFRI regimen chemotherapy, there were no significant changes in all 21 lymphocyte subsets(P>0.05) . CD3(+), CD3(+)CD8(+), memory T lymphoctye(45RO(+)) , and CD4(+)CD45RO(+) cells increased significantly(P<0.05) in patients who received no more than 4 cycles of chemotherapy. However, in patients that received 5 to 8 cycles and more than 9 cycles chemotherapy, we only found significant decrease of HLADR(+) cells and significant increase of CD29(+) cells, respectively(P<0.05) .</p><p><b>CONCLUSIONS</b>The humoral immunity is attenuated after chemotherapy in colorectal carcinoma patients. FOLFOX4 may suppress the cellular immunity.Chemotherapy that is less than 4 cycles will strengthens the cellular immunity by modulating body immunity arrangement;however, along with the increase of chemotherapy cycles, the cellular immunity gradually declines in these patients.</p>

Prognostic value of T lymphocytes infiltration in breast cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.</p><p><b>METHODS</b>Paraffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) .</p><p><b>RESULTS</b>Intraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.</p><p><b>CONCLUSIONS</b>In the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.</p>

Trastuzumab in combination with chemotherapy versus chemotherapy alone for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction cancer: a Phase III, multi-center, randomized controlled trial, Chinese subreport / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab in combination with chemotherapy versus chemotherapy alone in the first-line treatment of HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p><p><b>METHODS</b>Fifteen Chinese research centers are involved in the BO18255 (ToGA) study. Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumor showed overexpression of HER-2 protein by immunohistochemistry +++ or FISH-positive. Patients were randomly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine or 5-FU plus cisplatin or chemotherapy in combination with intravenous trastuzumab. The primary endpoint was overall survival.</p><p><b>RESULTS</b>Eighty-five Chinese patients were enrolled in this study, of whom 84 were included in the primary analysis: trastuzumab plus chemotherapy (FP/H) (n = 36) and chemotherapy alone (FP)(n = 48). The median follow-up was 15.2 months in the FP/H group and 14.2 months in the FP group. The median survival time was 12.6 months in the FP/H group compared with 9.7 months in the FP group [hazard ratio 0.72, 95%CI (0.40; 1.29)]. Grade 3/4 adverse events were higher in the FP/H(63.9%)than FP (47.9%) groups, including neutropenia, vomiting and nausea. Two mild cardiac adverse events occurred in the FP/H group. Severe adverse events occurred in 3 cases of both two groups, respectively.</p><p><b>CONCLUSIONS</b>Addition of trastuzumab to chemotherapy is well tolerated and shows improved survival in Chinese patients with advanced gastric or gastro-oesophageal junction cancer. These results are consistent with the results of ToGA whole population trial. Trastuzumab in combination with chemotherapy can be considered as a new option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer.</p>

Mutation analysis of UGT1A1 gene in patients with unconjugated hyperbilirubinemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze potential mutations of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene in patients with unconjugated hyperbilirubinemia, and to explore the correlation between the mutations and total serum bilirubin levels.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of patients. Coding sequence and promoter region of the UGT1A1 gene were amplified. Mutations were identified through DNA sequencing.</p><p><b>RESULTS</b>Mutations of the UGT1A1 gene were found in 46 out of 61 patients with unconjugated hyperbilirubinemia. Five types of mutations were detected, with a decreasing order of 211G>A, TA insertion in the TATAA promoter element, 686C>A, 1091C>T and 1352C>T. Compared with those carrying a single homozygous mutation or compound heterozygous mutations, total serum bilirubin was higher in those carrying a homozygous mutation in combination with other heterozygous mutations (P< 0.05). Based on the UGT1A1 gene mutations and level of total serum bilirubin, 44 patients were diagnosed with Gilbert syndrome, and 2 were diagnosed with Crigler-Najjar syndrome type 2.</p><p><b>CONCLUSION</b>The level of total serum bilirubin is correlated with the number of UGT1A1 gene mutations as well as their heterozygous or homozygous status.</p>