Doped nanomaterial facilitates 3D printing target plate for rapid detection of alkaloids in laser desorption/ionization mass spectrometry.

This work aims to rapidly detect toxic alkaloids in traditional Chinese medicines (TCM) using laser desorption ionization mass spectrometry (LDI-MS). We systematically investigated twelve nanomaterials (NMs) as matrices and found that MoS2 and defect-rich-WO3 (D-WO3) were the best NMs for alkaloid detection. MoS2 and D-WO3 can be used directly as matrices dipped onto conventional ground steel target plates. Additionally, they can be conveniently fabricated as three-dimensional (3D) NM plates, where the MoS2 or D-WO3 NM is doped into resin and formed using a 3D printing process. We obtained good quantification of alkaloids using a chemothermal compound as an internal standard and detected related alkaloids in TCM extracts, Fuzi (Aconiti Lateralis Radix Praeparata), Caowu (Aconiti Kusnezoffii Radix), Chuanwu (Aconiti Radix), and Houpo (Magnoliae Officinalis Cortex). The work enabled the advantageous "dip and measure" method, demonstrating a simple and fast LDI-MS approach that achieves clean backgrounds for alkaloid detection. The 3D NM plates also facilitated mass spectrometry imaging of alkaloids in TCMs. This method has potential practical applications in medicine and food safety. Doped nanomaterial facilitates 3D printing target plate for rapid detection of alkaloids in laser desorption/ionization mass spectrometry.

Optimal postoperative surveillance strategies for cancer survivors with gastric neuroendocrine carcinoma based on individual risk: a multicenter real-world cohort study.

BACKGROUND: The best follow-up strategy for cancer survivors after treatment should balance the effectiveness and cost of disease detection while detecting recurrence as early as possible. Due to the low incidence of gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma [G-(MA)NEC], high-level evidence-based follow-up strategies is limited. Currently, there is a lack of consensus among clinical practice guidelines regarding the appropriate follow-up strategies for patients with resectable G-(MA)NEC. MATERIALS AND METHODS: The study included patients diagnosed with G-(MA)NEC from 21 centers in China. The random forest survival model simulated the monthly probability of recurrence to establish an optimal surveillance schedule maximizing the power of detecting recurrence at each follow-up. The power and cost-effectiveness were compared with the National Comprehensive Cancer Network, European Neuroendocrine Tumor Society, and European Society for Medical Oncology Guidelines. RESULTS: A total of 801 patients with G-(MA)NEC were included. The patients were stratified into four distinct risk groups utilizing the modified TNM staging system. The study cohort comprised 106 (13.2%), 120 (15.0%), 379 (47.3%), and 196 cases (24.5%) for modified groups IIA, IIB, IIIA, and IIIB, respectively. Based on the monthly probability of disease recurrence, the authors established four distinct follow-up strategies for each risk group. The total number of follow-ups 5 years after surgery in the four groups was 12, 12, 13, and 13 times, respectively. The risk-based follow-up strategies demonstrated improved detection efficiency compared to existing clinical guidelines. Further Markov decision-analytic models verified that the risk-based follow-up strategies were better and more cost-effective than the control strategy recommended by the guidelines. CONCLUSIONS: This study developed four different monitoring strategies based on individualized risks for patients with G-(MA)NEC, which may improve the detection power at each visit and were more economical, effective. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending follow-up strategies for G-(MA)NEC.

Are the indications for postoperative radiotherapy in the NCCN guidelines for patients with gastric adenocarcinoma too broad? A study based on the SEER database.

BACKGROUND: The types of patients with gastric adenocarcinoma (GA) for whom postoperative radiotherapy can improve the disease-specific survival rate (DSS) remain controversial. This study aims to explore the ideal indications. METHODS: Patients in the Surveillance, Epidemiology, and End Results (SEER) database with T3-4Nx or TxN+ GA from January 1988 to December 2012 were included and divided into a postoperative chemoradiotherapy group (Group R) and a postoperative chemotherapy group (Group C). We established a nomogram to predict DSS and then divided entire patient cohort into low-risk and high-risk groups based on the DSS predicted by the nomogram. RESULTS: The Cox multiple regression analysis demonstrated that various risk factors affected DSS for Group R. Based on these risk factors, a nomogram for predicting DSS was established. The decision curve indicated that the best clinical effect could be obtained when the threshold probability was 0-58%. The patients were then divided into low-risk (< 69 points) and high-risk (≥ 69 points) groups according to the five-year DSS predicted. DSS was significantly better for Group R than for Group C for high-risk patients (P < 0.001) but was similar for low-risk patients (P = 0.732). CONCLUSION: At present, the National Comprehensive Cancer Network (NCCN) guidelines may include an overly broad range of indications for postoperative radiotherapy for patients with GA. For intestinal GA patients with a postoperative pathologic stage of T1 N1 who are younger than 65 years, have had more than 15 lymph nodes dissected, and have received postoperative chemotherapy, postoperative radiotherapy should not be recommended.

Can laparoscopic surgery be applied in gastric gastrointestinal stromal tumors located in unfavorable sites?: A study based on the NCCN guidelines.

This article investigated the feasibility of laparoscopic surgery in unfavorable site gastric gastrointestinal stromal tumors (GISTs).We identified 214 patients who underwent primary gastric GIST resection at our institution (January 2006-December 2014) from a prospectively collected database. These patients were divided into a Favorable group (140 cases) and an Unfavorable group (74 cases) according to the 2014 version of the National Comprehensive Cancer Network Clinical Guidelines (NCCN guidelines).The wedge resection rate of the Favorable group was higher than that of the Unfavorable group, and most procedures were performed laparoscopically (P < 0.05). In addition, there were no differences in the other clinicopathological features between these groups (P > 0.05). The postoperative stay of the Unfavorable group was longer than that of the Favorable group (P = 0.02). Laparoscopic surgery in both groups resulted in a shorter operative time, lower blood loss, faster time to first flatus, faster time to first fluid diet, and shorter postoperative stay than open surgery (P < 0.05). Although the difference was not significant (P = 0.09), the postoperative complication incidence of the Favorable group was less than that of the Unfavorable group (10% vs 17.6%). Furthermore, in the Unfavorable group, the incidence of postoperative complications from laparoscopic surgery was significantly lower than that of open surgery (P = 0.001). There were no differences in the 5-year overall survival (OS) and recurrence-free survival (RFS) of these groups (P > 0.05). Furthermore, in the Unfavorable group, the 5-year OS and RFS were similar for both laparoscopic and open procedures. Multivariate Cox regression analysis showed that imatinib (IM) treatment was an independent risk factor for poor prognosis.Laparoscopic operation for gastric GISTs located in unfavorable sites can yield similar long-term outcomes compared with an open operation. However, laparoscopic surgery has the obvious advantage of being minimally invasive, and the incidence of postoperative complications was low. Laparoscopic surgery is thus an option for the treatment of localized gastric GISTs.

Two new cucurbitane-type triterpenoid saponins isolated from ethyl acetate extract of Citrullus colocynthis fruit.

Two new cucurbitacins I (1 and 2), together with eight known compounds (3-10), were isolated from the ethyl acetate extract of the fruit of Citrullus colocynthis. Compounds 3, 5-9 were isolated from C. colocynthis for the first time. The structures of new compounds were determined primarily from IR, HR-MS, 1D-, and 2D-NMR analysis.

In vitro evaluation of 9-(2-phosphonylmethoxyethyl)adenine ester analogues, a series of anti-HBV structures with improved plasma stability and liver release.

Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis and hepatocellular carcinoma, but few drugs are available for its treatment. Acyclic nucleoside phosphonates (ANPs) have remarkable antivirus activities but are not easily absorbed from the gastrointestinal tract and accumulate in the kidneys, resulting in nephrotoxicity. Therefore, there is a need to find effective liver site-specific prodrugs. The dipivaloyloxymethyl ester of 9-(2-phosphonylmethoxyethyl)adenine (PMEA)-adefovir dipivoxil (ADV)-is a first-line therapy drug for chronic hepatitis B with a low therapeutic index because of renal toxicity and low hepatic uptake. In this study, a series of PMEA derivatives were synthesized to enhance plasma stability and liver release. The metabolic stability of ADV (Chemical I) and its two analogues (Chemicals II and III) was evaluated in rat plasma and liver homogenate in vitro. An ion-pair reverse-phase HPLC-UV method and a hybrid ion trap and high-resolution time-of-flight mass spectrometry (LC-IT-TOF-MS) were used to evaluate the degradation rate of the analogues and to identify their intermediate metabolites, respectively. Chemicals I and II were hydrolyzed by cleavage of the C-O bond to give monoesters. Sufficient enzymatic activation in the liver homogenate through a relatively simple metabolic pathway, in addition to a favorable stability profile in rat plasma, made Chemical II an optimal candidate. Next, six analogues based on the structure of Chemical II were synthesized and evaluated in plasma and liver homogenate. Compared to Chemical II, these compounds generated less active PMEA levels in rat liver homogenate. Therefore, chemical modification of Chemical II may lead to new promising PMEA derivatives with enhanced plasma stability and liver activation.

Treatment of locally advanced gastric cancer with the XELOX program of neoadjuvantchemotherapy combined with laparoscopic surgery: the experience in China.

BACKGROUND/AIMS: Although the XELOX regimen has been recommended as first-line adjuvant chemotherapy for advanced gastric cancer (AGC), its role in a neoadjuvant setting is not well established. Therefore, we aimed to assess the clinical effect of XELOX neoadjuvant chemotherapy on AGC when combined with laparoscopic surgery. METHODOLOGY: We compared the effects of perioperative XELOX (neoadjuvant chemotherapy group, NCG) with the effects of adjuvant XELOX (direct surgical group, DSG) in patients with locally AGC. The response to chemotherapy was assessed according to Recist criteria and pathological changes. The Kaplan-Meier log-rank test was used to calculate and compare survival differences. RESULTS: Seventy patients were included (neoadjuvant=35). The rate of effective neoadjuvant chemotherapy was 62.9%, and the disease control rate was 91.5%. In the NCG, 32 (94.7%) of the patients underwent laparoscopic-assisted D2 radical gastrectomy. The R0 resection rate was 100%. However, rates were 26 (74.3%) and 85.7% in the DSG, respectively (P<0.05). The 3-year overall survival (OS) in the NCG was 77.1% vs. 62.3% in the DSG (P=0.119). The 3-year disease-free survival (DFS) was 74.3% in the NCG, and the DFS was 59.3% in the DSG (P=0.033). CONCLUSIONS: XELOX can enhance the R0 resection rate, increase potential for laparoscopic surgery with rather good safety and improve the 3-year DFS of patients with AGC.