The novel HLA-B*40:550 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*40:550 differs from HLA-B*40:01:02:01 by one nucleotide in exon 1.

Characteristics and literature review of ETV6::ABL1 fusion gene-positive acute myeloid leukemia.

OBJECTIVE: To describe the features of ETV6::ABL1 AML as well as the clinical treatment and outcomes. METHODS: Clinical data were collected from three patients diagnosed with ETV6::ABL1 AML at Hebei Yanda Lu Daopei Hospital and Beijing Lu Daopei Hospital. Their clinical and laboratory features were analyzed, and the treatment process and outcomes were described. Ten reported cases of ETV6::ABL1 AML from the literature were also included for analysis. RESULTS: The median age of the patients was 34 years, and 2 patients were male. No patient had a history of blood disorders before diagnosis. After relapse, they were referred to our hospital, where the ETV6::ABL1 gene was detected. Unfortunately, Patient 1 died rapidly after leukemia relapse due to severe infection. Patients 2 and 3 received salvage therapy with a dasatinib-containing regimen, followed by allo-HSCT, and are currently alive and disease-free. CONCLUSION: ETV6::ABL1 is a rare but recurrent genetic aberration in AML, and the combined use of fluorescence in situ hybridization and PCR can better identify this fusion gene. Patients carrying ETV6::ABL1 have a high relapse rate and a poor prognosis. TKIs are a reasonable treatment option for this group, and allo-HSCT may be curative.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Comparison of Efficacy and Safety Between Laparoscopic and Open Radical Resection for Hilar Cholangiocarcinoma-A Propensity Score-Matching Analysis.

Background: Radical resection remains the most effective treatment for hilar cholangiocarcinoma (HCCA). However, due to the complex anatomy of the hilar region, the tumor is prone to invade portal vein and hepatic arteries, making the surgical treatment of HCCA particularly difficult. Successful laparoscopic radical resection of HCCA(IIIA, IIIB) requires excellent surgical skills and rich experience. Furthermore, the safety and effectiveness of this operation are still controversial. Aim: To retrospectively analyze and compare the efficacy and safety of laparoscopic and open surgery for patients with HCCA. Methods: Clinical imaging and postoperative pathological data of 89 patients diagnosed with HCCA (IIIA, IIIB) and undergoing radical resection in our center from January 2018 to March 2022 were retrospectively analyzed. Among them, 6 patients (4 were lost to follow-up and 2 were pathologically confirmed to have other diseases after surgery) were ruled out, and clinical data was collected from the remaining 83 patients for statistical analysis. These patients were divided into an open surgery group (n=62) and a laparoscopic surgery group (n=21) according to the surgical methods used, and after 1:2 propensity score matching (PSM), 32 and 16 patients respectively in the open surgery group and laparoscopic surgery group were remained. The demographic data, Bismuth type, perioperative data, intraoperative data, postoperative complications, pathological findings, and long-term survivals were compared between these two groups. Results: After 1:2 PSM, 32 patients in the open surgery group and 16 patients in the laparoscopic surgery group were included for further analysis. Baseline characteristics and pathological outcomes were comparable between the two groups. Statistically significant differences between the two groups were observed in intraoperative blood loss and operative time, as it were 400-800 mL vs 200-400 mL (P=0.012) and (407.97 ± 76.06) min vs (489.69 ± 79.17) min (P=0.001) in the open surgery group and laparoscopic surgery group, respectively. The R0 resection rate of the open group was 28 cases (87.5%), and the R0 resection rate of the laparoscopic group was 15 cases (93.75%). The two groups showed no significant difference in terms of surgical approach, intraoperative blood transfusion, incidence of postoperative complications, and short- and long-term efficacy (P>0.05). Conclusions: Laparoscopic radical resection of HCCA has comparable perioperative safety compared to open surgery group, as it has less bleeding and shorter operation time. Although it is a promising procedure with the improvement of surgical skills and further accumulation of experience, further investigations are warranted before its wider application.

Efficacy and safety of laparoscopic radical resection following neoadjuvant therapy for pancreatic ductal adenocarcinoma: A retrospective study.

BACKGROUND: Multiple studies have demonstrated that neoadjuvant chemotherapy (NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. However, most studies have focused on open surgery following NACT. AIM: To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC. METHODS: We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography (CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis. RESULTS: All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen (gemcitabine 1000 mg/m2 plus nab-paclitaxel 125 mg/m2 on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen (intravenous oxaliplatin 68 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 on day 1 and fluorouracil 400 mg/m2 on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m2). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy (LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 mL vs 343.75 ± 145.01 mL and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula (POPF) after L-RAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period. CONCLUSION: Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery.

Association of a Modified Blumgart Anastomosis With the Incidence of Pancreatic Fistula and Operation Time After Laparoscopic Pancreatoduodenectomy: A Cohort Study.

Objective: To explore the association between a modified Blumgart anastomosis technique and the operative time and surgical complications. Methods: This is a retrospective cohort study that analyzed the data of patients who underwent laparoscopic pancreaticoduodenectomy from January 2015 to March 2021. The primary outcome was to explore the association between the modified Blumgart anastomosis technique and operative time. Results: A total of 282 patients were enrolled. There were 177 cases of pancreatic duct-to-mucosa anastomosis in the traditional surgery group, and 105 cases of the modified three-step Blumgart anastomosis in the modified group. There were no statistically significant differences in the general and intraoperative characteristics found between the two groups (P > 0.05). The surgical method was an independent predictor of operative time. Overall complications postsurgery were less common in the modified group than in the traditional group. The incidence of postoperative pancreatic fistula was higher in the traditional group than in the modified group (45 cases (25.4%) and 11 cases (10.5%), respectively). Fourteen cases (7.9%) in the traditional group and four case (3.8%) in the modified group had postoperative pancreatic fistula of grades B + C. The two groups had statistically significant differences (P < 0.05). The results of the linear regression showed that the type of surgical method was associated with operation time (95% CI, -73.074 to -23.941, ß: -0.438, P < 0.001). Conclusion: This modified three-step Blumgart pancreaticojejunostomy was associated with the operation time.

Camrelizumab Combined With Gemcitabine and Albumin-Bound Paclitaxel for Neoadjuvant Therapy in the Treatment of Progressive Gallbladder Cancer: A Case Report.

Background: The roles of immune checkpoint inhibitors in the treatment of gallbladder cancer are still unclear and challenged by controversial findings. Recent research has shown that immune checkpoint inhibitors in combination with chemotherapy may alleviate disease progression. Case Summary: A 45-year-old female patient with gallbladder cancer accompanied by multiple abdominal lymph node metastasis was treated with camrelizumab combined with paclitaxel for injection (albumin-bound) and gemcitabine (AG) to downstage the tumor before a radical surgery could be performed. The postoperative quality of life was superior to the preoperative level. Conclusion: Camrelizumab + AG offers a new therapeutic option for gallbladder cancer with multiple abdominal lymph node metastasis, which, however, warrants further validation in clinical trials.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Sequential therapy with combined trans-papillary endoscopic naso-pancreatic and endoscopic retrograde pancreatic drainage for pancreatic pseudocysts.

BACKGROUND: Endoscopic retrograde pancreatic drainage (ERPD) and stent implantation has become the major treatment method for pancreatic pseudocysts. However, it is associated with a high recurrence rate and infection. AIM: To manage pancreatic pseudocysts by sequential therapy with endoscopic naso-pancreatic drainage (ENPD) combined with ERPD and evaluate the treatment outcome. METHODS: One hundred and sixty-two cases of pancreatic pseudocyst confirmed by endoscopic examination at our hospital between January 2014 and January 2020 were retrospectively analyzed. There were 152 cases of intubation via the duodenal papilla, of which 92 involved pancreatic duct stent implantation and 60 involved sequential therapy with combined ENPD and ERPD (two-step procedure). The success rate of the procedure, incidence of complications (infection, bleeding, etc.), recurrence, and length and cost of hospitalization were compared between the two groups. RESULTS: The incidence of infection was significantly higher in the ERPD group (12 cases) than in the two-step procedure group (2 cases). Twelve patients developed infection in the ERPD group, and anti-infection therapy was effective in five cases but not in the remaining seven cases. Infection presented as fever and chills in the two-step procedure group. The reoperation rate was significantly higher in the ERPD group with seven cases compared with zero cases in the two-step procedure group (P < 0.05). Similarly, the recurrence rate was significantly higher in the ERPD group (19 cases) than in the two-step procedure group (0 cases). CONCLUSION: Sequential therapy with combined ENPD and ERPD is safe and effective in patients with pancreatic pseudocysts.

Cystic duct dilation through endoscopic retrograde cholangiopancreatography for treatment of gallstones and choledocholithiasis: Six case reports and review of literature.

BACKGROUND: Choledocholithiasis removal via endoscopic retrograde cholangiopancreatography (ERCP) then followed by laparoscopic cholecystectomy (LC) has gradually become the principal method in the treatment of gallstones and choledocholithiasis. We use ERCP through the cystic duct to treat gallstones combined with choledocholithiasis, with the aim to preserve the normal function of the gallbladder while simultaneously decreasing risk of biliary tract injury. CASE SUMMARY: A total of six cases of patients diagnosed with gallstones and choledocholithiasis were treated with ERCP. The efficacy was evaluated via operation success rate, calculus removal rate, postoperative hospital stay and average hospitalization costs; the safety was evaluated through perioperative complication probability, gallbladder function detection and gallstones recrudesce. The calculus removal rate reached 100%, and patients had mild adverse events, including 1 case of postoperative acute cholecystitis and another of increased blood urinary amylase; both were relieved after corresponding treatment, the remaining cases had no complications. The average hospital stay and hospitalization costs were 6.16 ± 1.47 d and 5194 ± 696 dollars. The 3-11 mo follow-up revealed that gallbladder contracted well, without recurrence of gallstones. CONCLUSION: This is the first batch of case reports for the treatment of gallstones and choledocholithiasis through ERCP approached by natural cavity. The results and effects of six reported cases proved that the new strategy is safe and feasible and is worthy of further exploration and application.

Laparoscopic pancreaticoduodenectomy: a retrospective study of 200 cases and the optimization of the single-center learning curve.

BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is widely used in several centers. This study analyzed the postoperative complications rate curve, possible cause, and solution of LPD and open pancreaticoduodenectomy (OPD). METHODS: Between January 2015 and December 2019, the study included 213 and 204 patients undergoing OPD and LPD, respectively. Postoperative outcomes, complications, and complication risk, along with operation time were analyzed, and the learning curve was determined. RESULTS: The OPD group (378.7±8.98 min) had shorter operation time than the LPD group (402.5±7.12 min) (P=0.037). Blood loss was significantly lower in the LPD group (389.9±19.05 mL) than in the OPD group (530.1±33.55 mL) (P<0.001). The incidence of biliary-enteric anastomosis leakage was higher in the LPD group (2.9%) than in the OPD group (0.5%) (P=0.0495). The LPD group showed lower lung infection (7.4% vs. 17.4%, P=0.037), incision infection (1% vs. 8.5%, P<0.001), and anal exhaust time (3.35±0.07 vs. 4.05±0.07 days, P<0.001) than the OPD group. The biliary-enteric anastomosis leakage was strongly correlated with the pancreatic fistula (B/C) (R=0.6410), intraperitoneal infection (R=0.6126) and Clavien-Dindo Classification ≥3 (R=0.7403). According to the cumulative sum (CUSUM) curve, pancreatic fistula had a negative K value in 44 cases, biliary-enteric anastomosis leakage had a negative K value in 46 cases, and Clavien-Dindo Classification ≥3 had a negative K value in 40 cases. The learning curve for LPD has an inflection point in 86 cases. CONCLUSIONS: LPD is safe and effective for patients with pancreatic cancer, and has a long learning curve and improved postoperative complications in 50 cases. This study's results will help in reducing the complication rates of the first 50 consecutive cases of LPD.

A preliminary study of the clinical significance of folate receptor-positive circulating tumor cell in the management of hepatobiliary-pancreatic cancers.

BACKGROUND: Hepatobiliary-pancreatic cancers (HBPs) are highly lethal, partly because of their usually late diagnosis. This multi-center, observational study aimed to explore the clinical significance of folate receptor-positive circulating tumor cell (FR+CTC) as a liquid biopsy approach in the differential diagnosis and management of HBPs. METHODS: We recruited 119 patients suspicious for HBPs and 60 cancer-free healthy individuals in the present study. Patients without definitive pathological assessment or without pre-operative FR+CTC analysis were excluded. FR+CTC was tested prior to surgery or tissue biopsy using the CytoploRare® Detection Kit. Serum biomarkers, including CA 125, CA 19-9, and CEA, were tested in selected patients. Post-operative FR+CTC analysis was also performed in a subset of the patients receiving surgical resection. RESULTS: With 8.65 FU/3 mL as the cut-off value, the sensitivity and specificity of FR+CTC in differential diagnosis were 98.1% and 79.1%, respectively. The detection rate of FR+CTC was superior to conventional serum biomarkers (CA 19-9 > CA 125 > CEA). For the 16patients with matched post-operative FR+CTC analysis, FR+CTC levels significantly reduced after surgery (P=0.0084). CONCLUSIONS: Our results demonstrated that FR+CTC analysis could be an efficacious non-invasive biomarker in differential diagnosis and surveillance of HBPs, though further investigation with a larger sample size is required.

Two new prenylated C6-C3 compounds from Illicium micranthum Dunn.

Phytochemical investigation of Illicium micranthum led to the isolation of two new prenylated C6-C3 compounds, 12-O-methyl-2,3-dehydroillifunone C (1) and illiciminone A (2), together with three known analogues (3-5) and one known sesquiterpene lactone (6). The structures were established by extensive spectroscopic characterization and the reported data. All the isolates were evaluated for their acetylcholinesterase (AChE) inhibition activity. Compound 5 showed weak inhibitory activity (46.0%) at 50 µM concentration.

Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network.

BACKGROUND: The potential role of chronic inflammation in the development of cancer has been widely recognized. However, there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC). AIM: To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach. METHODS: First, maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes. Second, the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test. In addition, key regulators were detected by pivot analysis. Finally, targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information. RESULTS: The study found that 67 genes continued to increase in the HBV-HCC process. Moreover, 366 overlapping genes in the module network participated in multiple functional blocks. It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer. Correspondingly, significant crosstalk constructed a module level bridge for HBV-HCC molecular processes. On the other hand, a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified. Among them, some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192, microRNA-215, and microRNA-874, and early growth response 2, FOS, and Kruppel-like factor 4. Therefore, the study concluded that these pivots are the key bridge molecules outside the module. Last but not least, a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted, but their mechanisms still need to be further explored. CONCLUSION: The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC, which is supported by molecular evidence.

Palladium-Catalyzed Highly Enantioselective Cycloaddition of Vinyl Cyclopropanes with Imines.

Palladium-catalyzed asymmetric formal [3 + 2] cycloaddition of vinyl cyclopropanes and aldimines or isatin-derived ketimines proceeded smoothly in the presence of chiral phosphoramidite ligands. The corresponding highly functionalized and optically enriched pyrrolidine or spiro[pyrrolidin-3,2'-oxindole] derivatives are obtained in up to 94% yield and with up to 96% ee and 7:1 dr.

Correction: ShRNA-Targeted COMMD7 Suppresses Hepatocellular Carcinoma Growth.

[This corrects the article DOI: 10.1371/journal.pone.0045412.].

[Effects of Tyrosine Kinase Inhibitors on the Th1 and Treg Cells of CML Patients].

OBJECTIVE: To compare the immunomodulatory effects of the 2nd generation of tyrosine kinase inhibitors (TKIs)-dasatinib and nilotinib as well as the 1st generation of TKI-imatinib on chronic myeloid leukemia (CML) patients. METHOD: To evaluate the T cell subtypes by flow cytometry on the CML patients of our center who received the treatment with dasatinib (n=10), nilotinib (n=26) or imatinib (n=44) for more than 3 months, and to analyze and correlate these data with the clinical remission situations and prognosis. RESULTS: 80.0% of the patients in dasatinib group, 16.6% of the patients in nilotinib group and 27.5% of the patients in imatinib group respectively had a Th1 proportion in the peripheral blood (Th1/CD4+ T) above the upper limit of normal. More specifically, the Th1 proportion in dasatinib group (30.86%±9.75%) was significantly higher than that in nilotinib group(17.37%±9.35%) (P<0.001) and that in imatinib group (20.79%±9.01%) (P<0.001). Among the 3 groups, both the CD8+ T cell proportion (CD8+ T/Lymphocyte) and the Th2 proportion (Th2/CD4+ T) in the peripheral blood did not show a statistically significant difference. The Treg proportion (Treg/CD4+ T) in dasatinib group (1.31%±0.10%) was significantly lower than that in nilotinib group (2.65%±0.97%) (P<0.001) and that in imatinib group(2.99%±1.40%) (P<0.001).Among all the CML patients analyzed, for CML patients who had a Th1 proportion above the upper limit of normal(25.8%) (n=28), 84.62% of these patients obtained CCyR (complete cytogenetic response), 71.43% of these patients obtained MMR (major molecular response), 71.43% of these patients obtained MR4.5; for CML patients who had the Th1 proportion in the normal range(11.8%-25.8%) (n=45), 90.7% of these patients obtained CCyR, 75.56% of these patients obtained MMR, and 75.56% of these patients obtained MR4.5; for CML patients who had the Th1 proportion below the lower limit of normal (11.8%) (n=21), 57.14% of these patients obtained CCyR, 47.62% of these patients obtained MMR, and 47.62% of these patients obtained MR4.5. The above-mentioned data shows that the patients in high Th1 group and the normal Th1 group obtained the higher remission rate as well as the deeper remission level. CONCLUSION: This study shows that during the CML treatment with TKIs, the increased or normal Th1 proportion indicates a bigger chance for CCyR, MMR, and MR4.5. Dasatinib may significantly increase the level of Th1 while decrease the level of Treg in the patients, as compared with nilotinib and imatinib.

Aspirin Derivative 5-(Bis(3-methylbut-2-enyl)amino)-2-hydroxybenzoic Acid Improves Thermotolerance via Stress Response Proteins in Caenorhabditis elegans.

Aging is a major risk factor for many prevalent diseases. Pharmacological intervention to improve the health span and extend the lifespan could be a preventive elixir for aging and age-related diseases. The non-steroid anti-inflammation medicine aspirin was reported to delay aging in Caenorhabditis elegans (C. elegans) and mice. We are wondering if the analogues of aspirin could also present antiaging activity. Here, we synthesized several aspirin derivatives and investigated their thermotolerance and antiaging effect in C. elegans. One of the compounds, 5-(bis(3-methylbut-2-en-1-yl)amino)-2-hydroxybenzoic acid, moderately increased the survival of C. elegans under heat stress, but could not extend the lifespan under optimum conditions. This compound could increase the mRNA level of stress response gene gst-4, and the mRNA and protein expression level of heat shock protein hsp-16.2 under heat stress. The failure of activating the transcription factor DAF-16 might explain why this compound could not act as aspirin to extend the lifespan of C. elegans. Our results would help further the investigation of the pharmacological activity of aspirin analogues and the relationship between structures and activity.

Paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in patients with recurrent or metastatic gastric cancer.

PURPOSE: This study evaluated the efficacy and toxicity of combination chemotherapy with paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin (POFL) in patients with recurrent or metastatic gastric cancer. METHODS: One hundred and thirty-eight patients with histologically confirmed recurrent or metastatic gastric adenocarcinoma were treated with the POFL regimen: paclitaxel at a dose of 135 mg/m2 as a 3-hour intravenous infusion on day 1, oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2 as an intravenous infusion over 2 hours on day 1, followed by 5-fluorouracil 2,400 mg/m2 as an infusion over a 46-hour period on 3 consecutive days, in a 2-week cycle. RESULTS: Twelve patients could not be evaluated for response because of the absence of any measurable lesions or early discontinuation of therapy, so responses were assessed in 126 patients. The overall objective response rate was 56.3% (95% CI, 47.5%-64.9%). The median time to progression was 6.7 months (95% CI, 5.8-7.6 months), and the median overall survival was 12.6 months (95% CI, 11.3-13.9 months). The most common grade 3 and 4 toxicities were neutropenia (50.7%), peripheral neurotoxicity (16.7%) and alopecia (27.5%). CONCLUSIONS: Combination chemotherapy with POFL offers a new, active and safe approach to the treatment of recurrent or metastatic gastric cancer.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.

AIM: To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction. METHODS: A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α was examined. RESULTS: FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. CONCLUSION: FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.