Objective:To investigate the efficacy and safety of SIMPLE regimen in the treatment of extranodal NK/T-cell lymphoma (ENKTCL).Methods:The clinical data of 11 patients with ENKTCL who were admitted to the University of Hong Kong-Shenzhen Hospital from January 2012 to January 2022 were retrospectively analyzed. The patients received 4-6 courses of SIMPLE (cisplatin, gemcitabine, ifosfamide, etoposide, dexamethasone, and pegasparaginase) regimen chemotherapy, and stage Ⅰ and Ⅱ patients who also received local radiotherapy after 2 or 3 courses of chemotherapy. Patients were evaluated for mid-treatment and end-of-treatment outcomes, and the adverse effects of patients were evaluated in each treatment cycle. The Kaplan-Meier method was used to analyze the progression-free survival (PFS) and overall survival (OS) of the 11 patients.Results:All 11 patients were nasal type, with the median age of 41 years old (26-67 years old), including 5 males and 6 females, 3 relapsed cases and 8 newly treated cases. Of the 10 patients evaluated for efficacy, 9 achieved complete remission and 1 achieved at least partial remission (efficacy was assessed based on follow-up). All 11 patients were followed up for a median time of 50 months (15-72 months) and 2 relapsed patients died due to disease progression. The expected 5-year PFS rate and OS rate of 11 patients were both 90.0%, and the expected 5-year OS rate was 100.0% and 66.6% in newly treated and relapsed patients, respectively. Common adverse effects were hematologic adverse reactions, infections, gastrointestinal symptoms, elevated transaminases, and hypofibrinogenemia, all of which were curable. There is no treatment-related death.Conclusions:The SIMPLE regimen for the treatment of ENKTCL has a high remission rate, the patients have long survival time, and the regimen is moderately well tolerated.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Objective:To investigate the efficacy of endoscopic stent placement for patients with Bismuth type Ⅳ hilar cholangiocarcinoma.Methods:Data of 229 patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma who successfully underwent endoscopic stent placement at the Department of Endoscopy, the Third Affiliated Hospital of Naval Medical University from January 2002 to January 2019 were retrospectively analyzed. Outcomes included clinical success rate, complication incidence, stent patency period and overall survival time. The patency of stents and overall survival time of patients were estimated by using the Kaplan-Meier method. The independent predictors for stent patency and overall survival of patients were analyzed by a multivariate Cox proportional regression model.Results:The overall clinical success rate was 78.2% (179/229). The incidence of early cholangitis after endoscopic retrograde cholangiopancreatography was 20.5% (47/229). The median stent patency and overall survival time were 5.7 (95% CI: 4.8-6.7) months and 5.1 (95% CI: 4.2-6.0) months, respectively. Further multivariate Cox regression analysis showed that metal stent ( P<0.001, HR=0.452, 95% CI: 0.307-0.666) and bilateral stents with bilateral angiography ( P=0.036, HR=0.644, 95% CI: 0.427-0.971) were independent predictors of stent patency; total bilirubin>200 μmol/L ( P=0.001, HR=1.627, 95% CI: 1.208-2.192), metal stent ( P=0.004, HR=0.636, 95% CI: 0.467-0.866) and antitumor therapy ( P<0.001, HR=0.439, 95% CI:0.308-0.626) were independent predictors of overall survival. Conclusion:There is high incidence of cholangitis in patients with unresectable Bismuth type Ⅳ hilar cholangiocarcinoma treated with endoscopic stenting. Longer stent patency can be achieved with metal stent placement and bilateral drainage. In addition, metal stent for drainage and antitumor therapy can also help increase the survival benefit.

Brachytherapy ; Carcinoma, Hepatocellular/drug therapy* ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Humans ; Iodine Radioisotopes ; Liver Neoplasms/drug therapy* ; Portal Vein ; Retrospective Studies ; Sorafenib/therapeutic use* ; Thrombosis ; Treatment Outcome

Objective:To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on the prognosis of critically ill patients with acute gastrointestinal injury (AGI) grade Ⅱ.Methods:A retrospective study was performed to analyze the clinical data of critically ill adult patients with AGI grade Ⅱ, who were enrolled in three randomized controlled trials conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 and May 2019. Data including demographic characteristics, serological indicators of nutrition, the tube tip position confirmed by abdominal X-ray 24 h after tube insertion, and intensive care unit (ICU), 28-day and hospital mortality were collected. Patients were divided into the post-pyloric feeding group and gastric feeding group according to the tube tip position. Propensity score matching method was used to perform 1:1 matching, and the differences of each index between the two groups were compared after matching. Then the influencing factors of P<0.1 were included in multivariate logistic regression analysis to investigate the potential ICU mortality risk factors of critically ill patients with AGI gradeⅡ. Factors with 0.1 level of significance from the univariate analysis were considered in the multivariate analysis. Results:There were 90 patients in post-pyloric feeding group and 90 patients in the gastric feeding group. Demographics and clinical characteristics of study population were well balanced between the two groups after matching. ICU, 28-day and hospital mortality in the post-pyloric feeding group were significantly lower than those in the gastric feeding group (4.4% vs 15.6%, 14.4% vs 27.8%, 6.7% vs 17.8%, all P < 0.05). Multivariate logistic regression analysis indicated that post-pyloric feeding was an independent protective factor [odds ratio ( OR)=0.295, 95% confidence internal (95% CI): 0.091-0.959, P=0.042] and APACHEⅡ score was an independent risk factor ( OR=1.111, 95% CI: 1.025-1.203, P=0.010) for ICU mortality of critically ill patients with AGI gradeⅡ. Conclusions:Post-pyloric feeding for critically ill patients with AGI grade Ⅱ could decrease ICU mortality and is an independent protective factor against mortality.

To explore the effect of post-pyloric feeding by spiral nasoenteric tubes on ventilator-associated pneumonia (VAP) in neurocritical care patients. Methods A retrospective study was performed to analyze the clinical data of 175 neurocritical care adult patients with mechanical ventilation (MV) more than 48 hours, who were enrolled in three randomized controlled trials (RCT) conducted by Guangdong Provincial People's Hospital for post-pyloric tube placement between April 2012 to March 2019. The following patient clinical data were collected when patients were enrolled: gender, age, neurologic diagnosis, comorbidities, medication, endotracheal reintubation, bronchoscope treatment, the distal site of nasoenteric tubes, and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score, sequential organ failure assessment (SOFA) score, Glasgow coma scale (GCS) score, and acute gastrointestinal injury (AGI) grade assessed. Patients were divided into VAP group and non-VAP group according to the occurrence of VAP, and the differences of each index between the two groups were compared. Then the influencing factors of P < 0.1 were included in multivariate Logistic regression analysis to identify the potential risk factors affecting the incidence of VAP. Furthermore, patients were divided into gastric feeding group and post-pyloric feeding group according to the distal site of nasoenteric tubes, and subgroup analysis was performed to evaluate the variety of VAP in patients with different tube sites and status. Results ① Forty-two patients occurred VAP in 175 MV patients, and the incidence of VAP was 24.0%. ② Univariate analysis showed the P value of post-pyloric feeding, APACHE Ⅱscore, GCS score and bronchoscope treatment were less than 0.1, and post-pyloric feeding and GCS score in VAP group were significantly lower than those in non-VAP group [post-pyloric feeding: 19.0% (8/42) vs. 36.8% (49/133), GCS:5 (3, 7) vs. 6 (4, 9), both P < 0.05]. Multivariate Logistic regression analysis indicated that post-pyloric feeding was independent protective factor [odds ratio (OR) = 0.360, 95% confidence internal (95%CI) = 0.151-0.857, P = 0.021] and bronchoscope treatment was the independent risk factor (OR = 2.210, 95%CI = 1.051-4.647, P = 0.036) for VAP. ③ The incidence of VAP was 28.8% (34/118), 0% (0/4), 8.3% (1/12), 26.7% (4/15), 22.2% (2/9) and 5.9% (1/17) respectively when tube tip in stomach, D1, D2, D3, D4 and jejunum confirmed by abdominal radiography. Post-pyloric feeding in each proportion seemed to present lower VAP rate compared with gastric feeding, however, no significant difference was found (all P > 0.05). ④ The incidence of VAP in post-pyloric feeding group was significantly lower than that in gastric feeding group [14.0% (8/57) vs. 28.8% (34/118), OR = 0.403, 95%CI = 0.173-0.941, P = 0.032]. Lower VAP rate appeared on patients with SOFA < 12 (OR = 0.392, 95%CI = 0.154-0.995, P = 0.044) and AGI grade ≥Ⅱ (OR =0.086, 95%CI = 0.011-0.705, P = 0.006) fed by post-pyloric route according to the result of subgroup analysis stratified by age, gender, APACHEⅡ score, SOFA score and AGI grade. Conclusion Post-pyloric feeding would decrease the incidence of VAP in neurocritical care patients on MV.

Objective: To synthesize a folic acid (FA)-modified pH-sensitive nanomicelle containing sorafenib (SF) and superparamagnetic iron oxide (SPIO), and to access its visibility in MRI and anti-cancer efficacy on hepatocellular carcinoma (HCC) in vitro. Methods: The copolymer FA-PEG-Pasp (DBA/DIP) of FA, poly(ethylene glycol), N,N-dibutylethylenediamine and N,N-diisopropylethylenediamine grafted poly (L-aspartic acid) were prepared. SF and SPIO were encapsulated inside the copolymer to synthesize the targeting micelle FA-PEG-PAsp (DBA/DIP)-SPIO/SF (FPASS). The folate-free micelle[PEG-PAsp (DBA/DIP)-SPIO/SF (PASS)] was used as nontargeting micelle. The physicochemical properties and drug release behavior of the micelles were analyzed. MRI of HepG2 cells incubated with FPASS and PASS with different Fe concentrations and Prussian blue staining of cells treated with the micelles (Fe concentration of 20 μg/ml) was performed to assess the drug delivery capability and imaging function of the micelles. For the FA competitive inhibition assay in these experiments, HepG2 cells were pre-treated with an excess amount of free FA prior to the incubation with FPASS. Cell viability, cell apoptosis, cell cycle and tube formation assays were conducted for evaluating the anti-HCC effects of the micelles. Comparison between groups was analyzed by one-way ANOVA, and multiple comparisons correction was performed by LSD test. Results: The diameters of FPASS and PASS were (102.3±5.2) nm and (107.1±5.7) nm, respectively; the δ potentials of them were (29.7±1.6) mV and (31.5±1.4) mV, respectively. The T₂ relaxivity of both the micelles was (5.2±0.4) ml·μg^-1·s^-1, which was much higher than that of water soluble Fe₃O₄ nanoparticles [(2.3±0.1) ml·μg^-1·s^-1; F=76.45, P<0.01]. SF released from the micelles was much faster at pH5.0 than at pH7.4, which indicated that the micelles had a pH-triggered drug release behavior. MRI of HepG2 cell samples revealed the signal intensity on T₂WI images and the T₂ value on T₂-map images decreased with the increasing Fe concentrations in the micelles. At the same Fe concentration (5, 10, 20 and 40 μg/ml), the cells of FPASS group exhibited a more significant decrease in T₂ signal intensity and T₂ value compared with those of PASS group or FA competitive inhibition group (F=8.69, 14.03, 27.27, 32.25 and 19.80, 45.76, 113.20, 66.80; P<0.01). Prussian blue staining verified the existing of SPIO in the cytoplasm of cells. Compared with PASS, FPASS presented significantly higher anticancer effects on inducing apoptosis, causing G0/G1 phase arrest on HepG2 cells and inhibiting tube formation on human umbilical vein endothelial cells (t=7.905, 4.399 and 3.454, respectively; P<0.01). Conclusions The pH-sensitive nanomicelle FPASS was successfully constructed. This micelle possessed a hypersensitive MRI-visible function and a targeting SF delivery capability which may contribute to a significant anti-HCC effect.

Studies have shown that microRNA plays a role of oncogene or tumor suppressor gene in the carcinogenesis and progression of tumor.However, the role of microRNA-143 (miR-143) in esophageal squamous cell carcinoma (ESCC) needs further study.Aims: To investigate the expression and clinical significance of miR-143 in ESCC.Methods: Sixty-three ESCC tissues and corresponding para-cancerous tissues, 40 esophageal intraepithelial neoplasia (IEN) tissues and corresponding normal tissues from Jan.2013 to Dec.2013 at the First Affiliated Hospital with Nanjing Medical University were enrolled.The expression of miR-143 was examined by real-time quantitative PCR, and its correlations with clinicopathological features were analyzed.Results: Compared with controls, expression of miR-143 was down-regulated in ESCC and IEN (P<0.05).Expression of miR-143 was correlated with pathological type (P<0.001), but not with gender and age (P>0.05).Expression of miR-143 was correlated with pathological staging, lymph node metastasis and TNM staging (P<0.05), but not correlated with tumor infiltration depth in ESCC patients (P>0.05).Conclusions: Expression of miR-143 is down-regulated in ESCC and IEN tissues, which may be closely related to the development and progression of ESCC, and has the potential to be used as a new target for diagnosis of ESCC.

Objective To establish a rat model of nonalcoholic fatty liver disease (NAFLD) using high-fat diet,and to dynamically observe the influence of the changes in gut microbiota on the development and progression of NAFLD in rats during and after modeling.Methods Sprague-Dawley rats were given high-fat diet to establish the model of NAFLD,and these rats were randomly divided into high-fat group,antibiotic pretreatment group,antibiotic treatment group,restricted diet group,and control group.The rats were sacrificed in different feeding periods,and 16sRNA fluorescent quantitative PCR was used to analyze the changes in ileocecal microbiota in rats.The liver pathological scores were determined,and enzymatic colorimetry was used to measure blood lipid level in serum and liver homogenate.The sample mean t-test was used for comparison between groups.Results Compared with the high-fat group,the restricted diet group showed the most significant improvements in quality of life and biochemical parameters.In the restricted diet group,the number of probiotics (Bifidobacterium and Lactobacillus) at the end of the ileum gradually increased and tended to increase over the time of intervention,and the most significant difference between this group and the high-fat group occurred at the 10th week (Bifidobacterium:0.91±0.23 vs 0.28±0.12,P ＜ 0.05;Lactobacillus:0.78±0.04 vs 0.21±0.03,P ＜ 0.05),while the number of enterococci decreased.There were no significant differences in enteric bacilli between groups (all P ＞ 0.05).At the 10th week,the liver pathological scores in the control group,antibiotic treatment group,and restricted diet group were 1.13±1.74,4.86±0.86,and 2.94±1.91,respectively,significantly lower than 7.09±2.03 in the high fat group (all P ＜ 0.05).Conclusion Diet structure change and antibiotic intervention can adjust gut microecology,alleviate the lesions of NAFLD,and thus provide new strategies for the prevention and treatment of NAFLD from the perspective of microecology.

Objective To investigate the effects of functional electrical stimulation (FES) on motor function and on the expression, proliferation, migration and differentiation of endogenous neural stem cells in the subventricular zone (SVZ) after cerebral ischemia.Methods Middle cerebral artery occlusion (MCAO) was used to induce a model of cerebral ischemia in 108 rats using the modified Zea-Longa method of intraluminal filament occlusion.They were then randomly divided into an FES group, a placebo stimulation group and a control group with 36 cases in each.Superficial FES electrodes were pasted on the paralyzed forelimbs of the rats in the first two groups, though FES treatment was administered only to the FES group beginning on the 3rd day after the MCAO operation.The stimulation was designed to produce extension of the wrist and digits of the paralyzed forelimb.Before, and after 1,3, 7 and 14 days of the treatment, the neurological deficit was evaluated using modified neurological severity scoring (mNSS).BrdU +/GFAP+, BrdU+/DCX+ and BrdU+/NeuN + cells in the SVZ were detected using immunofluorescence technique.Results After 7 and 14 days of treatment, the average motor function of the rats in the FES group had improved significantly when compared with the averages of the other two groups.Compared with the other two groups, the average number of BrdU +/GFAP+ positive cells in the ischemic SVZ was also significantly greater in the FES group after 7 and 14 days of treatment.After 14 days, BrdU +/Dcx + positive cells in the FES group had also increased significantly more,but only a few BrdU +/NeuN + cells had appeared in any of the three groups.Conclusion FES can improve motor function after cerebral ischemia, and promote proliferation and differentiation of neural stem cells in the SVZ.