Volume 95  ·   Issue 02  ·  2015

Cancer is a major disease that endangers human health. In 2010, the incidence rate of cancer in China was 235.23/100,000, and the mortality rate was 148.81/100,000, ranking first as the cause of death^[1]。 Drug therapy is an important means of tumor treatment, and the development of new anti-tumor drugs is an urgent clinical need. Clinical trials are the fastest, safest and most effective way to find new anti-tumor drugs, and at the same time, they provide the best treatment for cancer patients. Because new drugs do not have any data and experience on the human body before entering clinical trials, clinical evaluation is full of unknowns, and the risks and challenges are extremely high. Due to the lack of unified scientific standards in ethical review, efficacy and safety evaluation, painful lessons have taken place in the history of drug research and development in the world.

World Health Organization (WHO) Global Cancer Annual Report 2014^[1]: The total incidence, total death and incidence growth rate of malignant tumors in China ranked first in three items, but the 5-year survival rate is far lower than that of developed countries in Europe and America (30% and 60%). Compared with other malignant tumors, the incidence and mortality of pancreatic cancer are increasing faster, and it has ranked 7th and 6th among malignant tumors in China respectively^[2]； By 2030, the mortality rate of pancreatic cancer patients is expected to reach the second place among malignant tumors^[3]。 Extremely poor treatment effect and 5-year survival rate for pancreatic cancer<5%, one of the reasons is the irregularity of treatment. The problems related to the diagnosis and treatment of pancreatic cancer are described below.

To explore the risk factors for postoperative complications and in-hospital death of distal pancreatectomy (DP).

Retrospective reviews were conducted for 223 patients undergoing distal pancreatectomy. Their perioperative data and postoperative rates of morbidity and mortality were collected. And the risk factors for postoperative complications and in-hospital death were analyzed.

The overall morbidity rate of distal pancreatectomy was 26.9% (60/223). And mortality occurred in 3 patients (1.35%). Pancreatic fistula was the most common complication with an incidence rate of 19.3%. Univariate analysis identified location of tumor, operative duration, estimated intraoperative blood loss, use of stapler, splenectomy and multivisceral resection were risk factors for post-DP complications. And operative duration and estimated intraoperative blood loss contributed to in-hospital death after DP. Multivariate analysis revealed that operative duration was an independent factor for increased postoperative complication rate. No independent factor was found for overall in-hospital morbidity.

Operative duration is an independent risk factor for postoperative complications. Other parameters have no significant effects on postoperative complications or overall in-hospital morbidity.

To evaluate the preoperative necessity of reducing moderate icterus index (preoperative serum total bilirubin of 171 to 342 mmol/L) in obstructive jaundice patients.

A prospective non- randomized control method was used to divide 105 patients into jaundice-reducing (n=58) and non-reducing (n=47) group. And the intraoperative and postoperative parameters were compared between two groups.

In jaundice-reducing group, the level of total bilirubin decreased from (264±76) mmol/L to (183±44) mmol/L after biliary drainage (P<0.001). There were no significant inter-group differences in operative duration, blood loss, inpatient days or postoperative inpatient days (P>0.05). There was no perioperative mortality in jaundice-reducing group while two perioperative mortalities occurred in another group. There was no significant inter-group difference in perioperative mortality rate (P=0.423). The postoperative complication rate of jaundice-reducing group (n=16, 27.59%) was slightly lower than that of non-reducing group (n=14, 29.79%). However, the difference was insignificant (P=0.471). Stratified analysis showed that there was no significant inter-group difference in single complication (wound infection, postoperative hemorrhage, pancreatic fistula, biliary fistula, delayed gastric emptying, abdominal infection, lung infection or cardiovascular complications, etc.) (all P>0.05).

The preoperative necessity is limited for reducing moderate icterus index in obstructive jaundice patients. They should be operated as soon as possible once there is a definite diagnosis.

To explore the clinical efficacies of different surgical strategies for patients with advanced pancreatic carinoma.

Retrospective analyses were conducted for the clinical data of 223 advanced pancreatic carinoma patients between January 2009 and December 2013 according to the inclusion criteria. And, according to different surgical strategies, they were divided into seed group (n=49), radio frequency ablation group (n=51), radiotherapy group (n=17) and control group (n=106). The general data, postoperative complications and follow-up profiles between 4 groups were statistically analyzed.

The general profiles between four groups were not statistically significant (P>0.05). There was no mortality. The postoperative complication rate was the highest at 43%(21/49) in seed group. However all complications were of Clavien grade Ⅱ. The follow-up endpoint was until March 2014. The median follow-up period was 7 (1-52) months. The overall follow-up rate was 88.3%(197/223). And their survival rates of one month, half a year, one year and two years were 95.9%, 53.7%, 19.1% and 7.3% respectively. The average survival time was (9.6±0.3) months. In seed group, the rates were 97.7%, 61.9%, 27.7% and 13.2% respectively. The average survival time was (12.9±1.1) months. In radio frequency ablation group, the rates 88.9%, 54.9%, 22.9% and 7.6% respectively. The average survival time was (9.6±0.9) months. In radiotherapy group, the rates were 93.7%, 56.2%, 18.7% and 6.2% respectively. The average survival time was (8.6±1.4) months. In control group, the rates were 97.8%, 48.9%, 13.8% and 5.4% respectively. The average survival time was (8.5±0.5) months. The survival curves of seed, radio frequency ablation and radiotherapy groups were compared separately with that of control group. The Log-rank test results suggested that the survival rate and mean survival time of seed group were higher than those of control group (P<0.05). However the radio frequency ablation and radiotherapy groups had no significant difference with control group.

The advanced pancreatic carinoma patients have poor outcomes with a short survival time. The intraoperative implantation of seeds is effective for advanced pancreatic cancer patients, but it also has a high incidence of postoperative complications. Radio frequency ablation and intraoperative radiotherapy fail to effectively prolong the patient survival time.

To explore the correlation of food intolerance and hyperlipidemia.

A cross-sectional survey was conducted from August 2008 to June 2009. It recruited a total of 11 434 adults from Health Sciences Center at our hospital. Non-conditional Logistic regression model was utilized for determining odd ratio (OR) and 95% confidencer interval (CI). And statistic analysis was performed with SPSS 13.0.

Among them 6 897 participants were food intolerance positive and 4 537 food intolerance negative. The prevalence of food intolerance was 60.32%. Age, gender, smoking, body mass index, total cholesterol, triglycerides and high density lipoprotein (HDL) cholesterol were significantly different between positive and negative ones (all P<0.05). Multiple regression analysis showed that food intolerance was significantly correlated with age, gender, body mass index, but negatively with hyperlipidemia. Compared with age group ≤40 years, theOR(95%CI) of age groups 41-50, 51-60 and >60 years were 1.125 (1.021-1.238), 1.350 (1.207-1.510) and 1.564 (1.279-1.912) respectively. Compared with males, the OR (95%CI) of females was 1.528 (1.382-1.689). Compared with normal weighters, the OR(95%CI) of low weighters was 1.720 (1.147-2.580). Compared with normal blood lipids, the OR(95%CI) of hyperlipidemia was 0.879 (0.810-0.955).

Food intolerance may be negatively correlated with hyperlipidemia in healthcare population.

To explore the relationship between cytomegalovirus (CMV) infection and risk factors for relapsing patients with acute myeloid leukemia (AML) (non- acute promyelocytic leukemia) after hematopoietic stem cell transplantation (HSCT).

A total of 62 allo-HSCT patients from January 2005 to January 2014 were enrolled and analyzed retrospectively. And the clinical characteristics of donors and recipients and post-transplantation relapse were recorded.

Single factor analysis indicated that there were 5 risk factors correlated with disease relapse (P<0.05). Leucocytosis (>100×10⁹/L), high-risk AML and cyclosporine A concentration under 200 μg/L were correlated with high relapsing rates while CMV reaction and chronic graft versus host disease had a low relapsing rate. Cox regression analysis revealed that high-risk AML ( RR=3.296, 95%CI: 1.274-8.530, P=0.014), CMV negativity (RR=0.285, 95%CI: 0.084-0.973, P=0.045) and non-chronic GVHD (RR=0.167, 95%CI: 0.042-0.668, P=0.011) were major risk factors of relapse.

Human CMV viremia after allo-HSCT has a decreased relapsing risk in patients with AML.

To evaluate the clinical features and reasons of misdiagnosis of connective tissue disease plus pulmonary embolism (PE).

The clinical data were reviewed retrospectively for 22 hospitalized patients with connective tissue disease and PE from February 2006 to March 2014. And the features of onset, clinical and laboratory characteristics, imaging tests and causes of misdiagnosis were analyzed.

There were 12 males and 10 females with an average age of (36.2±14.2) years. And 12 (54.5%) PE patients had concurrent deep venous thrombosis. Antiphospholipid syndrome and Behcet's disease were the major causes of connective tissue disease. Chest distress, palpitation and extremity swelling were initial symptoms. There were elevated erythrocyte sedimentation rate (n=11, 50.0%), elevated C-reactive protein (n=8, 36.4%) and abnormal autoantibody (n=15, 68.2%) respectively. Computed tomography showed pulmonary arteries stenosis, occlusion and aneurismal dilation. Eighteen (81.8%) patients had pulmonary hypertension with a systolic pulmonary pressure of (72±20) mmHg (1 mmHg=0.133 kPa). And 3 of them presented severity of pulmonary pressure non-matched to the degree of pulmonary vascular involvement. And 18 (81.8%) patients with connective tissue disease were missed due to a lack of typical symptoms and physician understanding of disease before admission. Three (13.6%) patients had a misdiagnosis of idiopathic pulmonary arterial hypertension. The median time of diagnosis was 12 months.

Connective tissue disease may develop PE as the initial symptom. And some patients lack typical clinical manifestations of connective tissue disease. It should raise an alert with the physicians.

To identify the genetic mutation of TGFBI gene in four Chinese families with corneal dystrophy. The pedigrees were Reis-Bücklers corneal dystrophy (RBCD), Avellino corneal dystrophy (ACD), lattice corneal dystrophy type Ⅰ(LCDⅠ) and lattice corneal dystrophy typeⅠ/ⅢA (LCDⅠ/ⅢA) (n=1 each).

Genomic DNA was extracted from leukocytes from 22 patients, 22 phenotypic normal family members and 100 normal controls from February 2010 to October 2012. And 17 exons of TGFBI gene were amplified by polymerase chain reaction and sequenced directly. The corneas were examined with slit-lamp biomicroscope and photographed.

Mutations of TGFBI gene occurred in all 22 patients, including R124L (c.371G>T) in 14 patients with RBCD, R124H (c.371G>A) mutation in 1 patient with ACD, R124C (c.370C>T) mutation in 3 patients with LCDⅠand H626R (c.1877A>G) mutation in 4 patients with LCDⅠ/ⅢA. The mutations were absent in all participating unaffected family members and normal controls.

TGFBI gene-linked corneal dystrophy has close genotype-phenotype relationship. And R124 is a mutant hotspot of TGFBI gene of corneal dystrophy.

To assess the diagnostic values of novel biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys c), in the diagnosis of delayed graft function (DGF).

A total of 114 patients undergoing kidney transplantation from deceased donors from October 2012 to October 2013 were enrolled. Recipients on dialysis during the first postoperative week were included into DGF group while those without DGF into early graft function (EGF) group. sNGAL, sCys c and serum creatinine (sCr) were measured pre-operation, as well as at 4, 12, 24, 72 and 168 h post-operation. Furthermore, uNGAL leveks were measured at 4, 12 and 24 h post-transplantation. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of DGF.

Among 114 recipients enrolled, 23 presented DGF and 91 EGF. In EGF group, within 4 h post-transplantation sNGAL and sCys c decreased more significantly than sCr (51.31%(40.30%, 62.31%), 56.39%(50.02%, 68.40%) vs 21.40%(6.77%, 27.44%), P=0.009 and 0.029 respectively). Between two groups, differences of sequential decrease were observed earlier in sNGAL and sCys c than uNGAL and sCr. It demonstrated better performance in predicting DGF. The AUC of sCr was between uNGAL and sNGAL, sCys c. Combination of both sNGAL and sCys c yielded a ROC-AUC of 1.000.

sNGAL and sCys are ideal for predicting the recovery of graft function during early period after kidney transplantation. And a combination of both biomarkers may dramatically improve the specificity and sensitivity of diagnosing DGF.

To compare two different methods in detecting epidermal growth factor receptor (EGFR) mutation status of non-small cell lung cancer (NSCLC), and investing the influences of different conserving methods in DNA quantity, quality and detecting results of formalin-fixed paraffin embedded (FFPE) tissue samples.

One hundred and fifty FFPE samples of advanced NSCLC were collected in Cancer Institute/Hospital, Chinese Academy of Medical Sciences from November 2010 to August 2011. Both scorpions amplification refractory mutation system (scorpions ARMS) and direct sequencing were used to detect EGFR mutation in exon 18, 19, 20 and 21, together analyzed the differences between these two methods. Samples with inconsistent results were collected clinical treatment and survival information for further analysis. Extracted DNA from 30 FFPE samples and conserved at -20 ℃ for 3 years, meanwhile the same 30 FFPE samples DNA were extracted after conserving for 3 years. The DNA quantity、quality and testing results of the two conserving methods were compared.

The detection success rate of Scorpions ARMS (100%) was higher than direct sequencing (87.3%), with statistical significance (χ²=20.28, P<0.05). The consistent rate of the two methods was 84.7%, and there were no significant differences between these two methods, with a high consistence (Kappa=0.738, P<0.001). The clinical treatment and survival status of 5 patients with different testing results were analysed, which were consistent with ARMS testing results. The quality of DNA extracted from FFPE tissues which were conserved for 3 years according to the conventional way was worse and with more fragments compared with DNA conserved at -20 ℃ for 3 years, but the EGFR mutation detecting results of the DNA acquired from the two conserved ways were consistent.

Combination of Scorpions ARMS and direct sequencing could make the detecting result more comprehensive and reliable. Clinical treatment and survival data may provide diagnosis support for cases with different mutation testing results. DNA extracted from FFPE samples and stored at low temperature is better for conserving the integrity.

To evaluate the correlation between three variables of neck circumference, body mass index (BMI) and Epworth sleepiness scale (ESS) and obstructive sleep apnea-hypopnea syndrome (OSAHS) and the value of three-variable screening tool among snorers in Guangxi region.

From May 2009 to June 2014, 2 955 middle-aged consecutive patients with snoring were recruited from four hospitals of Guangxi Province. All subjects underwent polysomnography (PSG) and physical examinations including neck circumference, BMI and ESS. The diffrences of neck circumference, BMI and ESS were compared between OSAHS and non-OSAHS groups; the correlation between apnea-hypopnea index (AHI) and neck circumference, BMI and ESS were analyzed. The optimal cutoff point of three variables was selected by SPSS's Optimal Binning methods and screening score was assigned according to the Logistic regression coefficient. The recommended cutoff points were neck circumference ≥38.5 cm (3 points), BMI ≥25.7 kg/m² (5 points), ESS ≥9 points (1 point) for males and neck circumference ≥34.5 cm (5 points), BMI ≥24.5 kg/m² (2 points), ESS ≥7 points (1 points) for females. The best integral value was obtained through the receiver operating characteristic (ROC) curve.

A total of 2 803 subjects fulfilled the study criteria. There were 2 366 males and 437 females. The average values of neck circumference, BMI and ESS were (38.7±3.5) cm, (27.3±3.6) kg/m² and (8.6±5.4) score respectively. Both males and females had a positive association between AHI and neck circumference, BMI and ESS (r=0.389, 0.485, 0.293, 0.386, 0.439 and 0.291 respectively, all P<0.001). For males, at an integral value ≥6, the sensitivity was 71.4% in the diagnosis of OSAHS, specificity 65.5% and positive predictive value 91.1%. For females, at an integral value ≥3, the sensitivity was 73.3% in the diagnosis of OSAHS, specificity 63.6% and positive predictive value 66.3%.

In middle-aged snorers in Guangxi, neck circumference, BMI and ESS are correlated with OSAHS. And a positive association exists between AHI and neck circumference, BMI and ESS. Simple three-variable screening tool is highly valuable for diagnosing OSAHS, especially among male snorers.

To observe the therapeutic effects of exogenous pulmonary surfactant (PS) on acute lung injury induced by severe burn-blast combined injury in a rat model.

A total of 180 adult male SD rats were randomly divided into 3 groups of sham, treatment and control (n=60 each). Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury and a full-thickness burn injury of 25% total body surface area. The treatment and control groups received exogenous PS (2 ml/kg) and saline (2 ml/kg) by trachea respectively. At the time points of 0, 6, 24, 48 and 72 h, 12 rats per timepoint in each group underwent PaO₂, PaCO₂ and pulmonary function tests respectively. And they were then sacrificed for other analyses. Lung tissues were harvested for histological studies. Their arterial blood samples were collected for blood gas analysis. All data were expressed as mean ± standard deviation and analyzed with SPSS 20.0 (SPSS Inc., Chicago, IL, USA). The differences were considered to be statistically significant at P<0.05.

After removing death drain during the experiment, 8 rats were put equally into five phase points of the last three groups, the results were analyzed statistically. PaO_2: At each timepoint of 6, 24, 48, 72 h, the control group PaO₂ were obviously lower than the sham group ((69.55±5.11), (62.05±6.54), (53.24±7.65), (50.00±7.45) vs (93.75±3.41), (94.25±2.19), (93.63±2.33), (93.25±1.83) mmHg (1 mmHg=0.133 kPa), all P<0.01); at 6 h treatment group was close to sham group ((92.63±3.74) vs (93.75±3.41) mmHg,P=0.594); at 6 h control group PaO₂ decreased to 70 mmHg and then gradually declined. And at each timepoint the treatment group PaO₂ was significantly higher than the control group ((92.63±3.74), (87.50±3.34), (78.75±3.11), (71.38±3.74) vs (69.55±5.11), (62.05±6.54), (53.24±7.65), (50.00±7.45) mmHg, all P<0.01); PaCO_2: treatment group PaCO₂ was lower than that of control group at 6, 24, 48 h ((45.50±6.79), (49.38±7.52), (54.13±4.82) vs (53.25±2.76), (59.50±6.61), (63.60±7.33) mmHg, all P<0.01), both treatment and control groups were significantly higher than those in the sham group ((59.63±6.87), (68.88±6.85) vs (36.38±1.85) mmHg, allP<0.01). No difference existed between the control and treatment groups (P=0.051). Deep inspiratory capacity, central airway resistance, lung compliance and tissue elasticity, treatment group was significantly better than control group at 24 h (P<0.05). And it was close to sham group (P>0.05). The treatment group alveolar structural damage and pulmonary hemorrhage and edema were better than those in the control group.

Exogenous pulmonary surfactant (PS) can improve oxygenation and alleviate pulmonary edema and pulmonary capillary membrane permeability of rats with severe burn blast combined injury.

To explore the apoptosis-inducing effect of Ad-p53 plus fulvestrant in MCF-7 breast cancer cells.

ER-positive MCF-7 breast cancer cells were used. MCF-7 cells were established with control, fulvestrant alone, Ad-p53 alone and Ad-p53 plus fulvestrant. The morphological changes of MCF-7 after drug combination were observed by inverted microscopy. Methyltetrazolium salt (MTS) assay was used to determine the proliferation of MCF-7 cells. The protein expressions of p53 and ER were examined by Western blot. Flow cytometry was used to detect apoptosis.

Significant inhibition of cell growth was observed by inverted microscopy. Flow cytometry revealed that the apoptosis rate of using fulvestrant alone or Ad-p53 alone was (13.3±1.2)% and (14.5±2.9)%. The apoptosis rate of combined group was (38.1±5.9)% and it was higher than Ad-p53 or fulvestrant alone (P=0.001, P=0.001). MTS assay indicated that, after treating for 24, 48, 72, 96 h by Ad-p53 alone or fulvestrant alone, the inhibition of cell proliferation rate was (8.21±0.54)%, (28.50±1.42)%, (50.14±0.78)%, (58.25±2.92)% and (9.73±1.68)%, (25.26±0.82)%, (35.25±3.94)% and (46.37±2.56)% respectively. Simultaneously, the inhibition of cell proliferation rate of combined group was (12.42±1.76)%, (35.20±0.58)%, (62.08±2.56)% and (75.43±3.56)%. It further confirmed the increase of cell proliferation inhibition rate after drug combination (P<0.05). Western blot showed that the p53 protein expression level increased obviously with Ad-p53 in MCF-7cells. Ad-p53 increased the level of ER expression while drug combination reduced the level of ER expression.

Ad-p53 plus fulvestrant can significantly inhibit cell growth and induce cell apoptosis. And there is probably some synergistic effects between both.

To explore the Helicobacter pylori(Hp) infection rate among army and navy recruits, examine its associated risk factors and provide theoretic rationales for Hp control.

A cross-sectionalstudy was performed for 1 732 subjects (aged 17-24 years) selected from 18 new recruit populations in Inner Mongolia and Zhoushan area from September 2013 to November 2013. Hp infection was detected by ¹³C-urea breath test. Meanwhile, a questionnaire containing 62 potential factors related to Hp infection was surveyed. In addition, ¹³C-urea breath test was performed in 513 navy veterans (aged 19-51 years) in Zhoushan area from April 2013 to October 2013. The data of risk factors were analyzed by χ ² test and multivariate Logistic regression.

A total of 2 162 soldiers were enrolled and 1 649 new recruits completed two surveys. The overall Hp infection rate was 46.5%(768/1 649), which is lower than the previous studies (52.9%). And it was 47.0%(377/802) in army new recruits and 46.0%(390/847) in navy new recruits. For new recruits, Hp infection was associated with number of family members, washing tableware with detergents, first drinking age and paring fruits before eating (all P<0.05). However, there was no association with age, education level or washing hands before meal (allP>0.05). The Hp infection rate was higher in recruits from the West China and North China. In addition, the infection rate was 60.8%(312/513) in a population of 513 veterans. It was 46.6%(768/1 649) in recruits less than onemonth of service, 59.2%(180/304) in recruits less than two years of service and 63.2%(132/209) in recruits more than two years of service, the difference had statistical significance (P<0.05). Logistic analysis of multiple variables showed that number of family members, washing tableware with detergents, first drinking age and paring fruits before eating were independent risk factors (OR=1.574, 0.538, 0.638, 0.855; 95%CI: 1.077-2.301, 0.362-0.798, 0.486-0.837, 0.457-0.961).

The Hp infection rate is similar between army and navy recruits. It has dropped significantly and its epidemic region changed in new male recruits compared to a decade ago in china. Hp infection clustered within families. The factors including fewer family members, washing tableware without detergents, first drinking at young age and no paring fruits before eating are risk factors of Hpinfection. And a longer service time is associated with higher Hp infection rate in recruits.

A 51-year-old male patient. In February 2012, he went to the Institute of Hematology of Peking University due to low back pain for 2 months and right lower limb pain for 1 month. Blood routine: white blood cells 7.79×10⁹/L, absolute eosinophils (AEC) 1.96×10⁹/L, hemoglobin 122 g/L, platelets 132×10⁹/L. Biochemistry: serum calcium 1.47 mmol/L decreased (↓), creatinine 75 μ mol/L, albumin 33.5 g/L↓. Blood β 2 microglobulin 3.31 mg/L increased (↑), IgG 25.00 g/L↑, κ light chain 4.61 g/L↓, λ light chain 14.30 g/L↑, IgA 0.50 g/L↓, IgM 0.27 g/L↓. Blood M protein identification: IgG lambda type, M protein quantification was 14.69 g/L. No abnormalities were observed by urinary immunofixation electrophoresis. Anterior and lateral X-ray films of the skull showed diffuse perforated bone destruction of different sizes in the skull, which was consistent with multiple myeloma (MM). Pelvic CT: Multiple round low-density foci were seen in lumbar vertebra, sacral vertebra, ilium, pubic bone, ischium and bilateral femur. Morphology of bone marrow cells: hyperplasia grade V, granulocyte 78%, eosinophilic proportion increased, accounting for 18%; Plasma cells accounted for 3%. Immunotyping of bone marrow cells: Abnormal clonal plasma cells expressed CD45dim, CD38, CD138, C λ, CD200, CD56, some cells expressed CD117, CD9, and eosinophils accounted for 22.43%. Bone marrow biopsy: Fibroblasts proliferate extensively, and lymphocyte-like plasma cells are diffused or distributed in patches, with different cell sizes, widened perinuclear bands in some cells, with foamy feeling, and occasionally binuclear. Karyotype analysis G banding: 46, XY [4]. Fluorescence in situ hybridization (FISH): No 1q21 amplification, 13q14.3 deletion, RB1 deletion, IgH rearrangement, P53 deletion were observed. The diagnosis was MM IgG type λ, Durie/Salmon (DS) stage IIIA/International Staging System (ISS) stage II. After that, TAD regimen (thalidomide + epirubicin + dexamethasone) was given to induction chemotherapy for a total of 4 courses. After the end of the first course of treatment, the AEC decreased to normal (AEC<0.50×10⁹/L). The AEC fluctuated slightly in the subsequent 3 courses, and the AEC could rise to 0.96×10 before chemotherapy⁹/L, AEC could be reduced to 0 after chemotherapy, and AEC continued to be at a normal level after the fourth course of treatment. The blood M protein quantification was 4.48 g/L after re-examination, and the efficacy evaluation reached partial remission (PR). Two more courses of TAD regimen were given for consolidation therapy, and then serum β 2 microglobulin 2.39 mg/L, IgG 8.91 g/L, and λ light chain 5.22 g/L were reexamined, all of which decreased significantly. M protein was not observed by serum protein electrophoresis, and monoclonal IgG λ was still observed by immunofixation electrophoresis. No abnormalities were observed in urine immunofixation electrophoresis. Efficacy was assessed as a very good partial response (VGPR).

Atherosclerosis is the most common cause of renal artery stenosis. Atherosclerotic renal artery stenosis (ARAS) accounts for 60% ~70% of all the causes of renal artery stenosis in China^[1]Whereas about 90% in European and American countries^[2]。 ARAS often occurs in older adults with a history of hypertension. In the hypertensive population, the literature reports that approximately 1% to 6% of patients have ARAS at the same time^[3]； The prevalence of ARAS in older adults over 65 years can be as high as 7%^[4]； Among patients undergoing cardiac catheterization, the prevalence of ARAS exceeds 30%; Among patients who already have atherosclerosis, the prevalence of ARAS exceeds 50%^[5]。 Recently Cooper et al.^[6]The results of a published large-scale prospective randomized controlled trial suggest that no significant benefit was observed in renal artery stenting on top of drug therapy compared with drug therapy alone. This new evidence raises serious questions about the place of renal artery stents in the treatment of ARAS. Are renal artery stents effective for ARAS? How should we decide whether to perform renal artery stenting in clinical treatment of ARAS patients? Or which subgroups of ARAS patients may benefit from renal artery stents? This paper summarizes this hot issue as follows.

The initiation of youth is influenced by the interaction of genetic, nutritional, environmental, social and psychological factors, etc. The biological manifestation is that the secretion frequency and amplitude of hypothalamic gonadotropin-releasing hormone (GnRH) increases, which stimulates the pituitary gland to synthesize and secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thus activating gonadal function. The development of secondary sexual characteristics before the age of 8 in girls and before the age of 9 in boys is called precocious puberty (PP). Precocious puberty induced by premature initiation of the hypothalamic-pituitary-gonadal axis is called GnRH-dependent precocious puberty (GDPP), also known as central precocious puberty (CPP). Central nervous system diseases, trauma, etc. can lead to CPP, but most patients can't find organic lesions, which are called idiopathic CPP (ICPP), of which the proportion of ICPP in girls can account for 90%. The consistency of adolescent developmental age in the same race or family indicates that genetic factors play an important role in the initiation of adolescence, and many scholars have been devoting themselves to the genetic basic research of ICPP. In this paper, the research progress of ICPP gene in recent years will be reviewed.

Long-chain non-coding RNAs (lncRNAs) are a class of RNAs with transcripts ranging from 200 nt to 100 kb in length, lacking a reading frame of significant length (less than 100 amino acids), regulating gene expression levels at various levels but not encoding proteins in the form of RNAs^[1,2]。 According to the relationship with the nearest encoding protein gene, lncRNA are divided into: (1) sense lncRNA, located in the same strand as the encoding protein gene; (2) an antisense lncRNA located in a strand distinct from that gene encoding the protein; (3) bidirectional lncRNA, which is dispersed or aggregated in the direction closest to the lncRNA of the encoding protein gene during transcription; (4) an intron lncRNA located within an intron of a gene encoding a protein; (5) Intergenic lncRNA, located in the intergenic region of the two encoded proteins^[3]。 Initially, lncRNAs were considered to be the "noise" of genome transcription, a by-product of RNA polymerase II transcription, and did not have any biological function. However, later studies have found that the expression of some lncRNAs is tissue-specific and spatiotemporal specific, and many lncRNAs have conserved secondary structures, suggesting that lncRNAs have important biological functions^[2,3]。 Current studies have shown that lncRNA is involved in the pathophysiological processes of many diseases, especially in many kinds of tumors^[4,5,6]。 In this paper, the research progress of the relationship between lncRNA and the occurrence, development, diagnosis, treatment and prognosis of gastric cancer in recent years is summarized as follows.

The endoplasmic reticulum, as a major site for secreted protein folding modification and calcium storage, plays a key role in maintaining cellular homeostasis. Endoplasmic reticulum homeostasis is disrupted such as misfolded protein aggregation, Ca^2＋Depletion and lipid synthesis disorders will trigger a series of intracellular responses, called endoplasmic reticulum stress (ERS), through corresponding signaling pathways. Among them, the research on unfolded protein response (UPR) is the most in-depth. In the respiratory system, ERS can play an antioxidant protective effect, and can also affect the expression of some important proteins in the lung, induce inflammation and apoptosis. These effects play an important role in the occurrence and development of various respiratory diseases, including chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma and lung cancer. The biological effects of ERS in respiratory diseases are reviewed below.

A 58-year-old male, farmer, was admitted to the hospital on 28 November 2013 due to "blood in sputum for 1 week and aggravation for 2 days". One week before admission, the patient showed blood in sputum without inducement, bright red color, small amount, 1 to 2 times/d, no chest pain, and no treatment. Hemoptysis began to occur 2 days ago, bright red or dark red in color, mixed with blood clots, 3~10 times a day, no dysphagia, no hot flashes and night sweats, came to our hospital for treatment, lung CT showed "multiple nodular shadows in both lungs, pericardial effusion" (Figure 1), was admitted for further diagnosis and treatment. There was no significant weight gain or loss since the onset of the disease. He had "bronchial asthma" when he was young, but he did not attack in adulthood. Has a history of "hypertension" and is currently treated with oral "indapamide"; He claimed to have "history of metallurgical tours" and "history of contact with raw poultry", and had no history of allergies and tobacco and alcohol habits.

A 43-year-old male went to the Second Affiliated Hospital of Zhejiang University School of Medicine on November 7, 2013 because he found a painless mass behind his left ear for 3 years and increased by half a year. Physical examination: A soft mass was palpable behind the left ear, with clear borders, no tenderness, and movable. Considering a benign tumor of the parotid gland, parotid mass resection was performed under general anesthesia on November 15, 2013.

The proband was a 36-year-old male, tall and thin, 1.95 m tall, with aortic dilatation, having undergone aortic valve replacement surgery, ocular lens subluxation, and the clinical diagnosis was Marfan syndrome (MFS, MIM#154700); The daughter of the proband, 6 and a half years old, was tall and thin, 1.43 m tall, with slender fingers and no abnormalities in the eyes and heart. The family patients were all from Hebei Province, China (Figure 1)。 Because the proband couple was pregnant and wanted to give birth again, they came to the prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University for treatment. High-throughput sequencing of the proband (Ⅰ:1) was performed at BGI using an exon capture chip, and the MFS pathogenic gene fibrillin-1 (FBN1) was selected for detection, and three mutations were found (Table 1)。 The mutation of c. 8569G>T (p. Glu2857Ter) was found to be a suspected pathogenic mutation by comparison analysis of dbSNP137 database, 1 000 genome database and 200 healthy people control local database, and high-throughput sequencing sequence alignment of this mutation site was performed (Figure 2)。 A nonsense mutation c.8569G>T (p.Glu2857Ter) was detected in exon 65 of the FBN1 gene of the proband (I:1) in the Sanger sequencing verification family, which is heterozygous (Figure 3), consistent with the high-throughput sequencing detection results. This mutation causes glutamate at position 2857 to become a stop codon, causing the premature termination of FBN1 encoding, synthesizing a truncated protein, which may affect protein function. Sanger sequencing found that the daughter of the proband in the family (Ⅱ:1) carried the pathogenic mutation c.8569G>T (p.Glu2857Ter) and was genetically diagnosed as a patient with MFS. The wife of the proband in the family (Ⅰ:2) did not have this mutation (Figure 3)。 After identifying the pathogenic mutation c.8569G>T (p.Glu2857Ter) in this family, the proband's wife underwent prenatal diagnosis at 11 weeks of pregnancy, and Sanger sequencing found that there was a nonsense mutation c.8569G>T (p.Glu2857Ter) in exon 65 of FBN1 gene in the fetus (Ⅱ:2) (Figure 3)。 The pregnant women and their families were informed that the fetus carried the pathogenic nonsense mutation c.8569G>T (p.Glu2857Ter), which was more likely to be a patient with MFS after birth. The pregnant women and their families chose to terminate the pregnancy. The results of DNA analysis of abortus showed that the fetus carried the nonsense mutation c.8569G>T (p.Glu2857Ter), which was consistent with the results of prenatal diagnosis.