Volume 95  ·   Issue 04  ·  2015

In patients with advanced breast cancer, the incidence of bone metastasis is 65% to 75%, while the first-episode bone metastasis accounts for 27% to 50%. Bone-related events (SREs) such as bone pain and bone injury are common complications of bone metastasis of breast cancer, which seriously affect the quality of life of patients. At the time of clinical study, SREs was defined as: aggravation of bone pain or new bone pain, pathological fracture (vertebral fracture, non-vertebral fracture), vertebral compression or deformation, spinal cord compression, symptoms after bone radiotherapy (due to bone pain or prevention of pathological fracture or spinal cord compression), and hypercalcemia. These are the main factors that affect patients' autonomous activity and quality of life^[1,2,3]。

To explore the clinicopathological characteristics, diagnosis, multi-disciplinary therapy and prognosis of accessory breast cancer.

The clinical data were retrospectively analyzed for 22 patients with accessory breast cancer from December 2000 and September 2013.

Three patients underwent breast-conserving local wide excision of tumor plus axillary lymph node dissection while the remainder had Auchincloss or Halsted mastectomy. The most common histological type was infiltrating ductal carcinoma (n=16, 72%) and one of them was associated with mucous adenocarcinoma. There were carcinoma simplex (n=1), papillary adenocarcinoma (n=1) and adenocarcinoma (n=4). The most common pathological stages (according to AJCC Staging of Breast Cancer, 2002, 6th edition) were Ⅱ (n=15, 68%), Ⅰ(n=3), Ⅲ (n=4) and Ⅳ (n=0). The median follow-up period was 3 (1-14) years. And the follow-up rate was 100%. Until October 2014, 2 patients died from metastasis and the remainder survived.

Accessory breast cancer is rare and has a worse prognosis. Now the clinical diagnostic criteria to it remains controversial and the diagnosis is often late. A definite diagnosis is made on the basis of clinical characteristics, postoperative pathology and imaging examinations. And surgery remains a major option.

To explore the relationship between response of primary tumor and positive axillary lymph node to neoadjuvant chemotherapy and examine its correlation with breast cancer distant disease-free survival (DDFS).

The clinical data of 678 needle biopsy proved node positive breast cancer patients on neoadjuvant chemotherapy were analyzed retrospectively.

The median follow-up period was 45 (6-143) months. The 4-year DDFS in group A (ypT0/is ypN0), B (ypT0/is ypN+), C (ypT≥1mi ypN0) and D (ypT≥1mi ypN+) were 96.4%, 85.7%, 86.7% and 80.2% respectively. As compared with group A, the relative risk ratios of groups B, C and D were 2.32, 2.09 and 4.07 (P=0.006). Significant difference existed in DDFS between groups A and B (96.4% vs 85.7%, P=0.045) and groups A and C (96.4% vs 86.7%, P=0.040).

Pathological response of both primary tumor and positive axillary node are prognostic and crucial for evaluating the efficacy of neoadjuvant chemotherapy.

To explore the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in tissue of breast cancer complicated with diabetes and examine the correlation with vascular endothelial growth factor (VEGF) and microvascular density (MVD).

The clinical data were collected by reviewing the relevant medical records. The difference of clinicopathologic features between breast cancer patients with diabetes (diabetic group) and that of those without diabetes (control group) was analyzed retrospectively. Immunohistochemical Streptavidin-Perosidase (SP) method was used to detect the expressions of HIF-1α and VEGF in breast cancer tissue of two groups. Vascular endothelial cells were tagged with CD31 to calculate MVD.

The patients of tumor diameter > 2 cm were 68.4%(67/98) and lymphatic metastasis rate was 59.2%(58/98) in diabetes group. And those in control group were 54.2% (58/107) and lymphatic metastasis rate was 43.9%(47/107). The inter-group difference was significant ( P<0.05). HIP-1α was expressed in both groups. The positive rate of HIF-1α was 80.6%(79/98) in diabetes group versus 64.5%(69/107) in control group (P=0.010). The positive rate of VEGF was 86.7%(85/98) in diabetes group versus 68.2%(73/107) in control group (P=0.002). MVD value was 113.7±32.0 in diabetes group versus 104.7±29.4 in control group (P=0.003). The positive rate of VEGF in HIF-1α positive patients of diabetes group was significantly higher than that in negative counterparts (91.1% vs 68.4%,P=0.009). The values of MVD were 117.1±30.3 and 99.5±35.1 respectively in both groups. And the MVD value of HIF-1α positive group was significantly higher than that of negative group (P=0.03).

Diabetic complications may play critical roles in the development and metastasis of breast cancer through enhanced angiogenesis of tumor tissue.

To explored the clinicopathological features of Luminal B-like breast cancer and analyze the value of St. Gallen consensus in its treatment.

The patients with invasive breast cancer treated at our hospital between January 2010 and December 2012 were recruited and divided into five subtypes according to the criteria of St. Gallen International Expert Consensus report 2013. And their TNM stages, pathological characteristics and Ki-67 status were analyzed for Luminal B-like subtype.

The Luminal B-like subtype was found in 390 patients (52.8%), human epidermalgrowth factor receptor 2 (HER-2) positive in 89 patients (22.8%) and negative in 301 patients (77.2%). Only 7.3% required chemotherapy based upon the result of gene detection.

Only those patients for whom the need of chemotherapy is to be determined shall really benefit from gene detection.

To test the effectiveness and safety of low-dose vecuronium (0.01 mg/kg) for correcting eccentric eye position during ocular surgery.

A total of 80 ASA Ⅰ-Ⅱ children undergoing cataract or squint surgery were randomized into 2 groups (n=40 each). Fentanyl and propofol were used for induction and then laryngeal mask (LMA) was inserted. 0.01 mg/kg vecuronium was administered to the low-dose group (L group) and 0.08 mg/kg vecuronium for high-dose group (H group). The ToF-Watch was fixed to monitor the train of four ratio (TOFR) of adductor pollicis. Eyeball eccentricity ratio before and after dosing, TOFR, duration of eyeball in central position, duration of surgery, the time from the end of surgery to removal of LMA and oculist satisfaction were recorded.

The incidence of eccentric eyeball position was nearly 100% in both groups. The eyeball eccentricity ratio was 0.30±0.11 in L group and 0.29±0.12 in H group (P=0.852) after/before vecuronium injection. The eyeballs were fixed well in the central position in both groups after vecuronium injection. The duration was shorter in L group than that in H group (23.43±2.45 vs 37.63±7.75 min, P<0.001). The time from the end of surgery to removal of LMA was (8.57±3.49) min in L group and (12.28±4.26) min in H group (P=0.014). TOFR had merely mild reduction in L group and returned to normal in 10 minutes. At the end of surgery, TOFR was 102.43%±4.70% in L group and 80.47±5.53 in H group (P<0.001). Oculists were satisfied with eyeball position in both groups (P=0.958).

Low-dose vecuronium can correct eccentric eyeball position effectively and safely during ocular surgery while it has little effect on respiratory muscles.

To explore the clinicoelectrophysiological characteristics of paraproteinemic neuropathy (PPN).

Retrospective analyses were performed for the clinical data, including clinical characteristics, laboratory and neural electrophysiological examinations, of hospitalized patients with definitively diagnosed PPN from 2008 to 2012. Their objective parameters were compared between different sub-groups.

There were 12 males and 8 females with an average age of 52 years. The average clinical course was 14 (2-36) months. The types were IgM monoclonal gammopathy (MG) (n=2, 10%), IgG MG (n=10, 50%), IgA MG (n=7, 35%) and λ light chain MG ( n=1, 5%). This cohort had predominant sensory and axonal polyneuropathy with distal involvement. And the subtype of IgA and IgG manifested predominant sensory and axonal polyneuropathy.

The PPN patients have predominant sensory, axonal and distal symmetric polyneuropathy with clinical heterogeneities. PPN must be suspected even if sensory impairment and demyelination are not the dominant features. For patients with peripheral neuropathy, typing of monoclonal immunoglobulins should be routinely performed.

To analyze the mutations of COL7A1 gene in two dystrophic epidermolysis bullosa (DEB) pedigrees and make prenatal diagnosis for high-risk 11-week-old fetuses.

COL7A1 gene was first analyzed by next-generation sequencing for detecting suspicious gene mutations of two probands. And then the mutations were confirmed by polymerase chain reaction and Sanger sequencing in probands, parents and unrelated healthy individuals. Prenatal genetic diagnosis for high-risk fetus was performed by chorionic villus sampling after genotyping.

Four mutations were detected in 2 pedigrees: c. 5230G>T (p. E1744X), c. 5932C>T (p. R1978X), c. 5605-10 T>G (IVS66-10 T>G), c. 8305-1G>A (IVS110-1G>A) among which p. E1744X, IVS66-10 T>G and IVS110-1G>A mutations were first reported. The proband in No.1 family carried p. E1744X and p. R1978X nonsense mutations and her parents were carriers. The proband in No.2 family carried IVS66-10 T>G and IVS110-1G>A splicing mutations and her parents were carriers. All four mutations were not found in 100 healthy individuals. Prenatal diagnosis in No.1 family indicated that the fetus also carried p. E1744X and p. R1978X nonsense mutations as the proband. The fetal parents decided to terminate pregnancy and the result of gene analysis for aborted tissue was consistent with that of prenatal diagnosis.

COL7A1 gene mutation is etiological for two DEB families. Next-generation sequencing plus Sanger sequencing is effective and accurate for making gene diagnosis and prenatal diagnosis.

To evaluate the risk factors for patients with an acute exacerbation of bronchiectasis.

Retrospective analyses were conducted for 228 patients diagnosed with acute exacerbation of bronchiectasis at Affiliated Beijing Anzhen Hospital, Capital Medical University from January 2008 to December 2012. Depending on whether there were recurrences with exacerbation within one year after discharge, they were divided into two groups. Their basic profiles, clinical symptoms and signs, blood tests, sputum culture, dyspnea score (mMRC) and imaging data were analyzed.

There were 110 males and 118 females with an average age of (64.5+ 14.5) years. The incidence of the recurrence of acute exacerbation was 55.7% (127/228) within one year after discharge. Multivariate Logistic regression analysis showed that age ≥60 years (OR=2.583, 95%CI: 1.188-5.613), body mass index (BMI)<18.5 kg/m² (OR=2.991, 95%CI: 1.112-8.042), high dyspnea score (OR=7.905, 95%CI: 2.288-27.309), Pseudomonas aeruginosa in sputum culture (OR=3.227, 95%CI: 1.041-10.004), chest high-resolution computed tomography (CT) displayed bronchiectasis involving ≥3 lobes (OR=3.179, 95%CI: 1.449-6.976) and staying in intensive care unit (ICU) (OR=2.499, 95%CI: 1.301-4.801) were associated with the acute exacerbation of bronchiectasis (all P<0.05).

There are multiple risk factors of acute exacerbation in patients with bronchiectasis. And their proper identification and management shall improve the prognosis of bronchiectasis patients.

To evaluate the external quality survey results of newborn hereditary deafness gene mutations to improve and enhance the testing quality of hereditary deafness gene mutations.

Each of 30 voluntarily participating laboratories testing newborn hereditary deafness gene mutations received 15 lots of quality control blood spots in this survey at May 2013, including mitochondria DNA 12SrRNA 1555A>G (201311-201315), SLC26A4 IVS7-2A>G (201321-201325) and GJB2 235delC (201331-201335). The testing results, methods, equipments and reagent information were submitted for analyses of Clinet EQA, Microsoft Excel 2007 and SPSS 13.0. The rates of correction (number of correct results/total number of submitted results) were used for evaluating the performance of laboratories.

Among them, 24 laboratories submitted the testing results of mitochondria DNA 12SrRNA 1555A>G and the rate of submission was 80.0% (24/30). The rates of correction for each lot were 95.8% (23/24), 95.8% (23/24), 100% (24/24), 95.8% (23/24) and 95.8% (23/24) respectively and the overall rate was 96.7% (116/120). And 23 laboratories submitted the other two kinds of genetic test results, the rate of submission was 76.7% (23/30); the rates of correction for each lot of SLC26A4 IVS7-2A>G genetic test were 95.7% (22/23), 95.7% (22/23), 100% (23/23), 95.7% (22/23) and 95.7% (22/23) respectively and the overall rate was 96.5% (111/115); the genetic test results of GJB2 235delC were all correct (23/23). In this survey, 2/3 laboratories employed fluorescent polymerase chain reaction (PCR) and the remainder microarray chips.

The survey of newborn deafness gene mutation testing results is generally satisfactory. Only mitochondria DNA 12SrRNA and SLC26A4 have some errors. The laboratories of gene testing should improve their quality control system, correct mistakes during the test period without any delay and boost the rate of correction for newborn hereditary deafness gene testing.

To evaluate the clinical value of viral detection of liquid chip method in community-acquired pneumonia (CAP).

A total of 342 swabs were collected from 171 patients of community-acquired pneumonia from October 2013 to September 2014. The methods of xTAG^® RVP and Seeplex RV15 ACE were employed to detect respiratory viruses. And traditional methods of indirect immunofluorescence and specific antigen were used for comparison. All results were validated by realtime-PCR and statistically analyzed.

Of 171 CAP patients with an average age of 49.17 years, 35.7% (61/171) were virus positive. Influenza A (FluA), influenza B (FluB), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (hMPV) accounted for 90.5% of all detected viruses. The detection rates of mouth swabs and nasopharyngeal swabs were 31.6% and 33.9% respectively. Two specimen types showed no significant differences (Kappa=0.714, P<0.001;McNemar χ ²=0, P=1.000). The positive rates of viral detection by xTAG^® RVP and Seeplex RV15 were 32.5% and 29.5% respectively. And the consistence rate of results was up to 85.4% (292/342) (Kappa=0.66). The positive rate of traditional methods was 14.0%. However, xTAG^® RVP had a higher sensitivity (93.3%), higher consistence rate (92.4%) and negative predictive value (96.9%) compared with Seeplex RV15 and traditional methods. Also xTAG^® RVP had a high consistent rate of realtime-PCR (Kappa =0.83).

Liquid chip is superior to other detection methods. And it may be used routinely for viral detection of CAP.

To explore the effects of itraconazole (ITC) plus adriamycin (ADM) on proliferation and apoptosis of acute myeloid leukemia cells in vitro.

The growth inhibition effects of different concentrations of ITC, ADM or ITC (2, 6, 15 μmol/L) plus ADM (0.30, 0.75 μmol/L) were detected by CCK8 assay in KG1α and primary adult acute leukemia cells. Different concentrations of ITC for 7, 14 and 21 days were applied for observing the effect on colony formation. After 48 h treatments with 6 μmol/L ITC, 0.75 μmol/L ADM or ITC (6 μmol/L) plus ADM (0.75 μmol/L), the morphological changes of cells were observed by Wright staining. Flow cytometry was used to detect cell apoptotic rate, mitochondrial membrane potential and cell cycle arrest. And the expression levels of Sonic Hedgehog (Shh) signal pathway-related proteins Shh and glima-associated oncogene homdog1 (Gli1) were determined by Western blot.

ITC and ADM inhibited the proliferation of KG1α and primary adult acute leukemia cells and ITC reduced the colony-formation ability of KG1α cells both in dose-dependent manners. Compared with control or single drug group, the changes of cell morphology were more apparent in combined group. Weeb coefficient test revealed a synergistic effect (D≤70%C) of 0.75 μmol/L ADM plus 6 μmol/L ITC. When KG1α cells were treated with 6 μmol/L ITC plus 0.75 μmol/L ADM, the apoptotic rate was 31.72%±1.58%. And it was significantly higher than that in control, ITC and ADM groups (4.17%±0.74%, 4.33%±1.12%, 9.53%±1.15%,P<0.01). Detection of mitochondrial membrane potential showed that low red-fluorescent cells (P3) of combined group were obviously higher than that in control, ADM and ITC single drug groups (18.80%±0.96% vs 5.00%±0.38%, 9.70% ±0.43%, 7.10%±0.77%,P<0.01). KG1α cells were obviously arrested in G2 phase in combined group and it showed no statistical significance compared with control or single drug group. Western blot showed that the expression levels of Shh and Gli1 decreased with rising concentration of ITC.

ITC plus ADM can obviously inhibit cell proliferation and increase KG1α cell apoptotic rate, mitochondrial damage and G2 phase retardation. And ITC inhibits the Shh signal pathways.

To explore the role of cyclic stretch with different amplitudes on the transformation of normal skin fibroblasts (NSFB) into hypertrophic scar fibroblasts (HSFB).

NSFB and HSFB were cultured in vitro. Cyclic stretch with 10%, 15% and 20% amplitude was applied for 24 h on NSFB of experimental groups (Group N10%, Group N15% and Group N20%). And control groups (groups N0 and H0), NSFB and HSFB were cultured without stretch. Cell Counting Kit-8 method was used to detect the proliferation of fibroblasts. The gene expressions of integrin β ₁, P130Cas, TGF-β₁, COL1A1 and COL3 A1 were detected by real-time polymerase chain reaction (PCR). And the protein expressions of TGF-β₁, collagen typesⅠand Ⅲ were detected by enzyme-linked immunosorbent assay.

Cyclic stretch had stimulatory effect on cell proliferation. The proliferation capacity of group N10% was higher than that of group N20% (0.91±0.09 vs 0.8±0.07, P<0.05). Cyclic stretch could induce increased levels of gene expression. Gene expression levels of integrin β₁, P130Cas, TGF-β₁, COL1A1 and COL3 A1 in group N10% was higher than those in group N20% (3.14±0.24, 5.01±0.49, 1.55±0.08, 2.38±0.08, 1.37±0.11 vs 1.78±0.32, 3.07±0.41, 1.18±0.05, 1.97±0.05, 1.26±0.19; all P<0.05). Cyclic stretch could stimulate NSFB to secrete TGF-β₁. The protein level of TGF-β₁ in group N10% was higher than that in group N20% ((459±12.96) vs (372±10.49) pg/ml, P<0.05). The protein levels of collagen typesⅠand Ⅲ in experiment groups were higher than those in group N0 and lower than those in group H0 (allP<0.05). The protein level of collagen typeⅠin group N10% was higher than that in group N20% ((12.66±1.16) vs (11.23±0.75) ng/ml,P<0.05).

NSFB loaded cyclic stretch with 10% amplitude could exhibit some biological characteristics of HSFB. And cyclic stretch with optimal amplitude might transform NSFB into HSFB.

To explore whether renal tubulointerstitial lesions are early renal pathological changes and its interventions in diabetic rats.

The type 2 diabetic rat model was induced by a high-sugar and high-fat diet with a low-dose intraperitoneal injection of streptozotocin. And Shenkang Injection (SKI) was used as an intervention drug. A total of 30 Sprague-Dawley rats were divided randomly into diabetic (DM), DM+ SKI (DMSK) and normal control (NC) groups. The general status, blood biochemical parameters, microalbuminuria and urinary N-acetyl-D-glueosaminidas (NAG) were recorded. The insulin resistance of diabetic rats was detected with hyperinsulinemic-euglycemic clamp test. Renal pathological changes were evaluated with periodic acid-Schiff (PAS) staining. The expression of Toll-like receptor 4 (TLR4) in kidney tissue and renal interstitial CD68⁺ cells was detected with immunohistochemistry.

The levels of microalbuminuria, urinary NAG, glomerular volume, renal tubular score, TLR4 expression and renal interstitial CD68⁺ cells significantly increased in DM rats with body weight loss and insulin resistance (IOD value of TLR4: 6 289.86±272.45 vs 207.14±22.37; CD68⁺ cells: 8.79±0.79 vs.1.23±0.52). All changes in DM rats improved after SKI intervention (P<0.05).

Renal tubulointerstitial lesions are early renal damages in type 2 diabetic rats. SKI can attenuate diabetic tubulointerstitial damage and delay the progression of diabetic nephropathy associated with the inhibition of TLR4 expression and inflammation-mediated macrophage infiltration.

In recent years, with the development of free donation of remains in various places, this noble cause is gradually on the right track, and countless patients have benefited from it. However, due to the huge clinical demand, more patients are still waiting. According to the statistics of the World Health Organization (WHO), there are more than 10 million burn patients in the world every year. Due to many factors such as population and society, there are many burn patients in China. Many local and systemic problems that occur after burns are closely related to the loss of the skin barrier, and restoration or reconstruction of the skin barrier is the ultimate goal of burn treatment^[1]。 Skin transplantation is one of the main methods for surgical repair of skin loss. The autologous skin source available for transplantation in patients with large area deep burn is limited, and various wound covering materials are often used. Compared with all kinds of skin substitutes such as xenogenic skin, biofilm and synthetic dressings that lack corresponding functional cells and skin accessories, full-thickness xenogenic skin is recognized as the best covering material^[2]。 Allogeneic skin has an irreplaceable position, but the lack of its source has seriously affected the treatment of burn patients.

Adult growth hormone deficiency (AGHD) is common in structural or functional damage of the hypothalamus and/or pituitary gland, more common in sellar tumors, followed by cranial surgery and radiotherapy, and can also be caused by pituitary ischemic necrosis, infection or leukemia cell infiltration. Idiopathic, autoimmune hypophysitis and decreased growth hormone (GH) secretion caused by organ function deterioration in the elderly are also common causes of AGHD. According to statistics, there are nearly 50,000 adults with growth hormone deficiency in the United States, and about 6,000 new cases are increasing every year^[1]。 Pituitary Group, Department of Endocrinology, Beijing Tiantan Hospital^[2]Twelve patients with craniopharyngioma 6 months after surgery underwent an insulin tolerance test to evaluate their adenopituitary growth hormone reserve function. It was found that all subjects had complete growth hormone deficiency and none received appropriate growth hormone replacement therapy. Domestic and foreign literature^[1,2]It is reported that the proportion of patients with growth hormone deficiency after pituitary tumor surgery is very high. Although most adult patients with hypopituitary function after pituitary tumor surgery receive different degrees of replacement therapy for pituitary and target gland hormones (such as thyroid hormone, glucocorticoid, sex hormone, etc.), the replacement therapy of growth hormone is often neglected. The physical function and psychological well-being index of AGHD patients decreased significantly compared with the control group of the same age^[1]And deserves more attention.

With the development of medical immunology and molecular biology, cancer treatment is no longer limited to traditional drugs and surgical therapies. From the initial tumor vaccine to the world-renowned chimeric antigen receptor (CAR) modified T cells, cancer immunotherapy is gradually moving to the clinical stage and benefiting cancer patients. The concept of CAR originates from people's further understanding of cancer immunotherapy: that is, immune cells can break through the limitations of MHC to directly recognize and kill cancer cells. 1989 Gross et al.^[1]The concept of CAR is proposed for the first time, which integrates the variable region of monoclonal antibody against tumor cell antigen and T cell receptor (TCR) to redirect the immune response of T cells. With the development of translational medicine, the research of CAR is attracting more people's attention, and it has made major breakthroughs in clinical trials to treat malignant hematological tumors such as leukemia and lymphoma^[2,3]。 In this paper, the composition and development of CAR-T cells, research status, challenges and application prospects are reviewed.

Surgical pulmonary volume reduction (LVRS) aims to achieve therapeutic objectives by removing emphysema tissue. National Emphysema Treatment Trial (NETT) results suggest that LVRS benefit only in the upper lobe-dominated, low exercise endurance group population^[1]。 However, even among the most skilled surgeons, the postoperative mortality rate of LVRS patients remains high^[2]。 For this reason, scientists are constantly exploring new technologies that are less invasive and can achieve good volume reduction effects. Against this background, trans-bronchoscopic pulmonary volume reduction (BLVR) has emerged and developed rapidly. Its efficacy is comparable to that of LVR, but the risk of complications and death is significantly reduced^[3]。 In view of this, the 2013 and 2014 editions of the Global Chronic Obstructive Pulmonary Disease (COPD) Prevention and Treatment Initiative (GOLD) officially recommended BLVR as a new option for the treatment of COPD. The application of this technology in China started late, and there are few reports^[4]。 The progress of BLVR in the treatment of COPD in recent years is summarized as follows.

The patient was a 15-year-old male. He was admitted to hospital on June 12, 2014 due to "repeated cough and expectoration for 2 months and intermittent hemoptysis for 4 days". Two months ago, the patient had repeated cough and expectoration without obvious trigger. The sputum was white sticky sputum with moderate amount, occasionally accompanied by shortness of breath after activity, without fever, night sweats and chest pain. Four days ago, the patient had hemoptysis once without obvious trigger, which was bright red and dosed about 20 ml, so he went to the local hospital. Chest CT showed tracheal mass, and it was recommended to be transferred to our hospital for further diagnosis and treatment. Deny history of exposure to chemical, radioactive, toxic substances, deny history of smoking.