Objective To study the role of mutation of p300/CBP gene in the development of human gastric carcinoma (GC) . Methods Mutations analysis of the p300/CBP gene were carried out in 30 fresh GC samples using a combination of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing,and compared with gastric mucosa distance from the GC. Results p300/CBP genes mutations were detected in 4 of 30 fresh GCs. All the mutation were point mutations, including T to G in nucleotide 4741, 4773,4847 and 4881 in genomic DNA of p300. The mutation site was in the non-coding area in nucleotid 4741;whereas in the others were in the coding area, leading to the change of the amino acids, induding Ser to Arg in nucleotide 4773, Val to Ala in nucleotide 4847 and 4881, respectively. Of the 30 patients, 4 cases with the single site mutation were discovered, 2 cases had the first two sites mutation, while the others had all the four sites mutation. Conclusions Two to four poiuts mutation of p300/CBP gene are presented in GC.

BACKGROUND: The active component in recombinant human bone morphogenetic protein-2/poly(lactide-co-glycolide) (rhBMP-2/PLGA) microsphere prone to be absorbed or lost during solution with physiological saline, and the setting time is uncontrollable using blood solution, so it is necessary to explore an sustained-release carrier that can control the setting time.OBJECTIVE: To construct an injectable BMP release system by combing rhBMP-2/PLGA microsphere with fibrin glue. DESIGN, TIME AND SETTING: An experimental comparative study was performed at the Department of Othopaedics, General Hospital of Chinese PLA from January 2005 to April 2008.MATERIALS: PLGA (polylactic acid/polyglycolic acid 75/25, M_r=3 000, with 0.025 L/g viscosity) was supplied by Shandong Institute of Medical Instruments; rhBMP-2 was offered by The Academy of Military Medical Sciences; and fibrin glue was supplied by Hangzhou Puji Medicine Technology Development Co., Ltd.METHODS:The rhBMP-2/PLGA microsphere was prepared using W/O/W solvent evaporation methods. rhBMP-2 loaded PLGA microsphere were incorporated in fibrin glue to establish injectable BMP release system.MAIN OUTCOME MEASURES: The setting time,release behaviors, electron spectroscopy for chemical analysis (ESCA) as well as pH values of composites were measured.RESULTS:①Compared with fibrin glue, the setting time of composites were slightly increased.②Initial burst release of the composites occurred, the drug release exceeded 16.76% within 2 days, and 76.75% of the drug was release within 42 days. ③ESCA showed that composites prolonged release times.④The PH value of composites was between microsphere and fibrin glue.CONCLUSION: RhBMP-2/PLGA microsphere/fibrin glue composite has satisfactory slow-release effect and syringeability, which not only degrade partial acid environment but also maintain the biological effect of higher density. Therefore, it forms a promising synthetic bone graft.

Objective To explore the effects of L-carnitine on the plasma lipid profile and liver function in elderly patients receiving total parenteral nutrition after abdominal operations.Methods In this prospective blinded randomized controlled trial,24 eligible elderly patients were given 6-day total parenteral nutrition.They were further equally divided into L-carnitine group(administered with L-carnitine 50 mg/kg)and control group(without L-carnitine).The changes of lipid profile and liver function and the clinical outcomes were recorded and compared.Results The plasma triglyeride levels were lower in L-carnitine group than in control group on the 4th and 7th post-operative day,but there were not significant difference(P>0.05);There was a significant difference between the two groups in the change of the 4th post-operative day and pre-operative day(P<0.05).However,the liver function indicators were not significantly different between these two groups.Conclusion Administration of L-carnitine during total parenteral nutrition can improve the triglyeride metabolism in elderly patients after abdominal operations and may benefit the recovery of liver function.

Experimental teaching plays an important role in pathological teaching.We have taken effective measures to renovate the methods for experimental teaching,establishing open teaching mode.As a result,teaching quality increases and students become more active in pathological learning.

Objective To evaluate the postoperative pain induced by various therapeutic catheters after abdominal surgery.Methods A prospective study was conducted in patients selected based on the inclusion criteria.The general condition of the patients was recorded,and nutritional risk screening was performed.The indwelling of therapeutic catheters after abdominal surgery were recorded,including urinary catheter,nasogastric tube,peritoneal drainage tube,common bile duct drainage tube,wound drainage tube,central venous catheter and peripherally inserted central catheter.The pain caused by each type of catheters was evaluated using visual analog scale at 24,48 and 72 hours after tube/catheter insertion.Results A total of 157 patients were selected,including 70 males and 87 females,aged (60.5 ± 12.5) years,with a body mass index of (23.8 ± 3.2) kg/m2,and a total nutritional risk rate of 42％.According to visual analog scale scores,the degrees of pain due to the therapeutic catheters,in descending order,were as follows:4.9 ± 1.7 for nasogastric tube,3.6 ± 0.9 for wound drainage tube,3.0 ±0.9 for urinary catheter,2.6 ±0.9 for central venous catheter,2.4 ± 1.0 for peritoneal drainage tube,1.9 ± 0.7 for common bile duct drainage tube,and 1.8 ± 0.8 for peripherally inserted central catheter.The catheter-induced pain accounted for (44.9 ± 14.1)％ of the total pain during the hospital stay.Conclusions Nasogastric tube,wound drainage tube and urinary catheter can increase the pain of patients.It is therefore recommended to remove the indwelling tubes as early as possible if only the removal does not harm the outcome of the patient.

With the new-style thoracentesis needles with spring-loaded valve designed by ourselves, thoracentesis were carried out in 60 patients with ages ranging from 2 to 74 years. The successful rate for the operation was 100% (198/198), without any major complications such as pneumothorax, hemothorax, pleural shock or infection. The results show that this kind of puncture needle is multi-purpose and easy to operate, with high safety and reliability.
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Equipment Design ; Female ; Humans ; Male ; Middle Aged ; Needles ; Paracentesis ; instrumentation ; methods ; Pleural Effusion ; diagnosis ; therapy ; Young Adult

OBJECTIVETo examine the correlation between serum human epithelial growth factor receptor 2 extracellular domain (HER2 ECD) and circulating tumor cells (CTC), as well as the dynamic variation of HER2 ECD and its correlation to the therapeutic efficacy.

METHODSFifty-three advanced gastric cancer (AGC) patients who treated in Peking University Cancer Hospital and ever enrolled into CTC study (ClinicalTrial gov. ID: NCT01625702) were retrospectively included in this study.

INCLUSION CRITERIAthe patients were histologically confirmed as locally advanced or recurrent and/or metastatic adencarcinoma; they received two or more cycles of fluorouracil-based chemotherapy or combination targeted therapy; serum CTC was counted before and after therapy; the clinical response was evaluated every 2 cycles of treatment by the presence of at least one measurable lesion according to RECIST version 1.1 criteria. This study was approved by Ethics Committee of Peking University Cancer Hospital, and informed consents were signed by patients. The sera before and after two cycles of treatment were collected for CTC enumeration and HER2 ECD detection, in which the levels of HER2 ECD were measured by chemiluminescence immunoassays method. The positive threshold value of HER2 ECD and CTC number were ≥15 μg/L and ≥3 CTCs/7.5 ml respectively. The progression-free survival (PFS) and overall survival (OS) were compared among different groups using Log-rank tests.

RESULTSIn 53 enrolled patients, 39 were histologically identified as negative HER2, 9 as positive HER2 and another 5 cases were unknown. All the patients received fluorouracil-based chemotherapy, and 9 positive HER2 patients received combined anti-HER2 targeted therapy. Before therapy, the median HER2 ECD concentration of 53 cases was 10.45 (8.0 to 83.2) μg/L. Seven patients exhibited positive HER2 ECD levels, in whom 4 were histologically HER2 positive, but 3 were histologically HER2 negative. The median CTC number of 53 cases was 2 (0 to 668) CTCs/7.5 ml, and the positive rate of CTC was 47.2%(25/53). Following 2 cycles of therapy, a total of 10 histologically HER2 negative patients exhibited positive HER2 ECD levels, in whom 2 also possessed positive HER2 ECD levels, 83.3 μg/L and 46.9 μg/L before therapy, and 22.4 μg/L and 20.4 μg/L after therapy respectively, whereas another 8 patients (10.3 to 14.5 μg/L before therapy) acquired the elevated expression of HER2 ECD following therapy (15.1 to 19.5 μg/L). It seems that the increased level of HER2 ECD after therapy was, though not statistically significant, correlated to low number of CTCs. In histologically HER2 negative patients, pretherapeutic HER2 ECD level (positive vs. negative) was not significantly correlated to PFS (7.6 months vs. 4.4 months, P=0.328) and OS (13.6 months vs. 10.9 months, P=0.679). However, in histologically HER2 positive patients, patients with positive HER2 ECD level before therapy exhibited longer PFS (10.7 months vs. 4.2 months, P=0.025) and OS (16.5 months vs. 8.9 months, P=0.015) compared to those with negative HER2 ECD level. Additionally, CTC number was significantly correlated to prognosis in histologically HER2 negative patients. Patients with positive pretherapeutic CTC number showed longer PFS (5.3 months vs. 3.3 months, P=0.049) and OS (14.3 months vs. 7.6 months, P=0.001) as well. While in histologically HER2 positive patients, CTC number was not obviously correlated to the PFS and OS. In above 8 negative HER2 patients acquiring elevated expression of HER2 ECD following therapy, the increased HER2 ECD level was not correlated to PFS and OS (all P>0.05). In 9 histologically HER2 positive patients, 4 patients who exhibited decreased HER2 ECD level and reduced or constant CTC number had longer PFS (7.5 to 15.3 months) and OS (11.0 to 26.3 months) compared with those 2 patients who suffered from acquired HER2 ECD level following therapy (PFS 3.0 to 4.8 months and OS 7.3 to 8.6 months).

CONCLUSIONSIn histologically HER2 positive patients, increased pretherapeutic HER2 ECD level predicts better prognosis. The acquired elevated HER2 ECD level following therapy is correlated to inefficient therapeutic response. The acquirement of elevated HER2 ECD level can also be found in histologically HER2 negative patients, which may be correlated to the corresponding variation of CTC number.

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China displayed distinct clinical characteristics compared to patients in endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts of the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of Chinese Medical Association,and the Society of Emergency Medicine,China Association of Chinese Medicine have reached this guideline based on guidelines for diagnosis,treatment,prevention and control of dengue (World Health Organization,2009);guidelines for diagnosis and treatment of dengue (National Health and Family Planning Commission of the People's Republic of China,2014,Edition 2),health industry standard of the People's Republic of China "diagnosis for dengue fever (WS216-2018)" and systemic reports on dengue.The guideline includes 8 aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment and problems to be solved.

Objective: To evaluate the preliminary efficacy and safety of the 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin (FOLF-OXIRI) and capecitabine, irinotecan, and oxaliplatin (CAPIRINOX) regimens as first-line therapy for unresectable advanced colorectal cancer. Methods: Between January 2013 and November 2018, 73 patients with metastatic colorectal cancer (mCRC) were analyzed. All patients received first-line chemotherapy. Of them, 45 patients were administered FOLFOXIRI, and the remaining 28 patients were ad-ministered CAPIRINOX. The clinical outcomes and safety profiles were evaluated according to the objective response rate (ORR), con-version resection rate, and adverse effects. Results: The ORR, median progression-free survival (mPFS), and R0 resection rate in the FOLFOXIRI group were not statistically different from those in the CAPIRINOX group (60% vs. 57.1%, 7.7 months vs. 9.6 months, 24.4% vs . 17.9% , respectively; P>0.05). No treatment-related deaths occurred. The major adverse events were leukopenia, neutropenia, fa-tigue, nausea, vomiting, diarrhea, alopecia, aspartate aminotransferase/alanine aminotransferase elevation, and neurotoxicity. The to-tal rate of grade 3/4 adverse events in the FOLFOXIRI group was 33.3% (15/45), while the total rate of grade 3/4 adverse events in the CAPIRINOX group was 46.4% (13/28). Toxicities between the two groups were not statistically significant (P=0.263). Conclusions: Both the FOLFOXIRI and CAPIRINOX regimens are effective as first-line treatment for metastatic colorectal cancer. The triple-agent chemo-therapy was associated with good efficacy and tolerable toxicity.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.