[Prediction of global potential growth areas for Panax ginseng based on GMPGIS system and MaxEnt model].

The suitable habitat for the endangered and valuable medicinal herb Panax ginseng is gradually decreasing. It is crucial to investigate its suitable growing areas in China for global protection and sustainable utilization of P. ginseng. In this study, 371 distribution points of P. ginseng were collected, and 21 environmental factors were used as ecological indicators. The geographic information system for global medicinal plants(GMPGIS) system, MaxEnt model, and Thiessen polygon method were used to analyze the potential suitable areas for P. ginseng globally. The results showed that the key environmental variables affecting P. ginseng were precipitation in the hottest quarter(Bio18) and the coefficient of temperature seasonality(Bio4). The suitable habitats for P. ginseng were mostly located in the "One Belt, One Road" countries such as China, Japan, South Korea, North Korea, and Russia. The highly suitable habitats were mainly distributed along mountain ranges in southeastern Shandong, southern Shanxi and Shaanxi, northern Jiangsu, and northwestern Henan of China. Data analysis indicated that the current P. ginseng planting sites were all in high suitability zones, and the Thiessen polygon results showed that the geographic locations of P. ginseng production companies were unbalanced and urgently needed optimization. This study provides data support for P. ginseng planting site selection, scientific introduction, production layout, and long-term development planning.

Effect of standardized fluid management on cardiac function after CRS + HIPEC in patients with PMP: a single-center case-control study.

OBJECTIVE: To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis. RESULT: Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p < 0.05). The median daily fluid volume of the control group was higher than that of the study group 3 days after CRS (p < 0.05). Postoperative CTNI > 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors. CONCLUSIONS: SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.

Survival prediction by Bayesian network modeling for pseudomyxoma peritonei after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

OBJECTIVES: To establish a survival prognostic model for pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) based on Bayesian network (BN). METHODS: 453 PMP patients were included from the database at our center. The dataset was divided into a training set to establish BN model and a testing set to perform internal validation at a ratio of 8:2. From the training set, univariate and multivariate analyses were performed to identify independent prognostic factors for BN model construction. The confusion matrix, receiver operating characteristic (ROC) curve and the area under curve (AUC) were used to evaluate the performance of the BN model. RESULTS: The univariate and multivariate analyses identified 7 independent prognostic factors: gender, previous operation history, histological grading, lymphatic metastasis, peritoneal cancer index, completeness of cytoreduction and splenectomy (all p < 0.05). Based on independent factors, the BN model of training set was established. After internal validation, the accuracy and AUC of the BN model were 70.3% and 73.5%, respectively. CONCLUSION: The BN model provides a reasonable level of predictive performance for PMP patients undergoing CRS + HIPEC.

Phylogenomic analyses based on the plastid genome and concatenated nrDNA sequence data reveal cytonuclear discordance in genus Atractylodes (Asteraceae: Carduoideae).

Atractylodes species are widely distributed across East Asia and are cultivated as medicinal herbs in China, Japan, and Korea. Their unclear morphological characteristics and low levels of genetic divergence obscure the taxonomic relationships among these species. In this study, 24 plant samples were collected representing five species of Atractylodes located in China; of these, 23 belonged to members of the A. lancea complex. High-throughput sequencing was used to obtain the concatenated nrDNA sequences (18S-ITS1-5.8S-ITS2-28S) and plastid genomes. The concatenated nrDNA sequence lengths for all the Atractylodes species were 5,849 bp, and the GC content was 55%. The lengths of the whole plastid genome sequences ranged from 152,138 bp (A. chinensis) to 153,268 bp (A. lancea), while their insertion/deletion sites were mainly distributed in the intergenic regions. Furthermore, 33, 34, 36, 31, and 32 tandem repeat sequences, as well as 30, 30, 29, 30, and 30 SSR loci, were detected in A. chinensis, A. koreana, A. lancea, A. japonica, and A. macrocephala, respectively. In addition to these findings, a considerable number of heteroplasmic variations were detected in the plastid genomes, implying a complicated phylogenetic history for Atractylodes. The results of the phylogenetic analysis involving concatenated nrDNA sequences showed that A. lancea and A. japonica formed two separate clades, with A. chinensis and A. koreana constituting their sister clade, while A. lancea, A. koreana, A. chinensis, and A. japonica were found based on plastid datasets to represent a mixed clade on the phylogenetic tree. Phylogenetic network analysis suggested that A. lancea may have hybridized with the common ancestor of A. chinensis and A. japonica, while ABBA-BABA tests of SNPs in the plastid genomes showed that A. chinensis was more closely related to A. japonica than to A. lancea. This study reveals the extensive discordance and complexity of the relationships across the members of the A. lancea complex (A. lancea, A. chinensis, A. koreana, and A. japonica) according to cytonuclear genomic data; this may be caused by interspecific hybridization or gene introgression.

Application of DNA barcoding to the entire traditional Chinese medicine industrial chain: A case study of Rhei Radix et Rhizoma.

BACKGROUND: Safety concerns, caused by complex and unpredictable adulterants, run through the entire industrial chain of traditional Chinese medicines (TCMs). However, the conventional circulation traceability system only focuses on a certain end or link at the back end of the TCM industrial chain, ignoring the integrity of the links cross the entire industrial chain and lacking traceability. In consequence, a strict and rational supervision system is urgently required for the entire industrial chain. HYPOTHESIS/PURPOSE: We hypothesize that DNA barcoding would be a suitable measure for the traceability of adulterants in the entire TCM industrial chain. METHODS: In this study, Rhei Radix et Rhizoma was selected as a model to establish a traceability system for the entire TCM industrial chain. A total of 110 samples, including leaves, seeds, roots, decoction pieces, and traditional Chinese patent medicines (TCPMs), were collected upstream, midstream, and downstream of the entire industrial chain of Rhei Radix et Rhizoma. The ndhF-rpl32 fragment rather than the universal DNA barcodes, which could not distinguish the three original species of Rhei Radix et Rhizoma, was selected as a specific DNA barcode to evaluate the practical application of DNA barcoding in the chain. RESULTS: The results showed that the ndhF-rpl32 fragment in all samples could be amplified and bi-directionally sequenced. Based on the standard operating procedures of DNA barcoding, the ndhF-rpl32 fragment clearly distinguished the seven Rheum species collected upstream of the entire industrial chain. For the samples collected midstream and downstream of the entire industrial chain, 25% of the 36 commercial decoction pieces samples were identified as adulterants, whereas the eight TCPM samples were all derived from genuine Rhei Radix et Rhizoma. CONCLUSIONS: This study shows that DNA barcoding is a powerful and suitable technology that can be applied to trace TCMs in the entire industrial chain, thereby assuring clinical medication safety.

Identification and phylogenetic analysis of five Crataegus species (Rosaceae) based on complete chloroplast genomes.

MAIN CONCLUSION: The chloroplast genomes of the five Crataegus species were shown to have a conserved genome structure. Complete chloroplast genome sequences were more suitable than highly variable regions for the identification and phylogenetic analysis of Crataegus species. Hawthorn, which is commonly used as a traditional Chinese medicine, is one of the most popular sour fruits and has high economic value. Crataegus pinnatifida var. pinnatifida and C. pinnatifida var. major are frequently adulterated with other Crataegus species on the herbal medicine market. However, most Crataegus plants are difficult to identify using traditional morphological methods. Here, we compared five Crataegus chloroplast (CP) genomes comprising two newly sequenced (i.e., C. pinnatifida var. pinnatifida and C. pinnatifida var. major) and three previously published CP genomes. The CP genomes of the five Crataegus species had a conserved genome structure, gene content and codon usage. The total length of the CP genomes was 159,654-159,865 bp. A total of 129-130 genes, including 84-85 protein-coding genes, 37 tRNA genes and 8 rRNA genes, were annotated. Bioinformatics analysis revealed 96-103 simple sequence repeats (SSRs) and 48-70 long repeats in the five CP genomes. Combining the results of mVISTA and nucleotide diversity, five highly variable regions were screened for species identification and relationship studies. Maximum likelihood trees were constructed on the basis of complete CP genome sequences and highly variable regions. The results showed that the former had higher discriminatory power for Crataegus species, indicating that the complete CP genome could be used as a super-barcode to accurately authenticate the five Crataegus species.

Consensuses and controversies on pseudomyxoma peritonei: a review of the published consensus statements and guidelines.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a clinical malignant syndrome mainly originating from the appendix, with an incidence of 2-4 per million people. As a rare disease, an early and accurate diagnosis of PMP is difficult. It was not until the 1980s that the systematic study of this disease was started. MAIN BODY: As a result of clinical and basic research progress over the last 4 decades, a comprehensive strategy based on cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been established and proved to be an effective treatment for PMP. Currently, CRS + HIPEC was recommended as the standard treatment for PMP worldwide. There are several consensuses on PMP management, playing an important role in the standardization of CRS + HIPEC. However, controversies exist among consensuses published worldwide. A systematic evaluation of PMP consensuses helps not only to standardize PMP treatment but also to identify existing controversies and point to possible solutions in the future. The controversy underlying the consensus and vice versa promotes the continuous refinement and updating of consensuses and continue to improve PMP management through a gradual and continuous process. In this traditional narrative review, we systemically evaluated the consensuses published by major national and international academic organizations, aiming to get a timely update on the treatment strategies of CRS + HIPEC on PMP. CONCLUSION: Currently, consensuses have been reached on the following aspects: pathological classification, terminology, preoperative evaluation, eligibility for surgical treatment, maximal tumor debulking, CRS technical details, and severe adverse event classification system. However, controversies still exist regarding the HIPEC regimen, systemic chemotherapy, and early postoperative intraperitoneal chemotherapy.

Molecular structure and phylogenetic analyses of the complete chloroplast genomes of three original species of Pyrrosiae Folium.

Pyrrosia petiolosa, Pyrrosia lingua and Pyrrosia sheareri are recorded as original plants of Pyrrosiae Folium (PF) and commonly used as Chinese herbal medicines. Due to the similar morphological features of PF and its adulterants, common DNA barcodes cannot accurately distinguish PF species. Knowledge of the chloroplast (cp) genome is widely used in species identification, molecular marker and phylogenetic analyses. Herein, we determined the complete cp genomes of three original species of PF via high-throughput sequencing technologies. The three cp genomes exhibited a typical quadripartite structure with sizes ranging from 158 165 to 163 026 bp. The cp genomes of P. petiolosa and P. lingua encoded 130 genes, whilst that of P. sheareri encoded 131 genes. The complete cp genomes were compared, and five highly divergent regions of petA-psbJ, matK-rps16, ndhC-trnM, psbM-petN and psaC-ndhE were screened as potential DNA barcodes for identification of Pyrrosia genus species. The phylogenetic tree we obtained indicated that P. petiolosa and P. lingua are clustered in a single clade and, thus, share a close relationship. This study provides invaluable information for further studies on the species identification, taxonomy and phylogeny of Pyrrosia genus species.

Perioperative safety after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal origin: Experience on 254 patients from a single center.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a standard treatment for pseudomyxoma peritonei (PMP) recommended by Peritoneal Surface Oncology Group International (PSOGI). The study is to analyze the incidence of perioperative serious adverse events (SAEs) of CRS + HIPEC to treat PMP patients, and identify the risk factors, for guiding the prevention of SAEs. METHODS: This is a retrospective study on the PMP database established at our center. The clinicopathological features, treatment details and SAEs information on the PMP patients are systematically established in this database. The incidence, organ system distribution and severity of perioperative SAEs are analyzed. Univariate and multivariate analyses are performed to identify the independent risk factors. RESULTS: Among the 272 CRS + HIPEC procedures for 254 PMP patients, there are 93 (34.2%) SAEs. Six systems are involved in the SAEs, including infections (9.6%), digestive system (8.1%), respiratory system (6.3%), cardiovascular system (5.5%), hematological system (2.9%), and urinary system (1.5%), in terms of frequency. In terms of severity, the majority is grade III SAEs (27.9%), followed by grade IV SAEs (4.8%) and grade V SAEs (1.5%). Univariate analysis reveals 4 risk factors for perioperative SAEs: HIPEC regimens (P = 0.020), PCI (P = 0.025), intraoperative red blood cell transfusion volume (P = 0.004), and intraoperative blood loss volume (P = 0.002). Multivariate and logistic regression model analysis identifies only one independent risk factor for perioperative SAEs: intraoperative blood loss volume (P = 0.001, OR = 0.344, 95%CI: 0.182-0.649). CONCLUSIONS: PMP patients treated by CRS + HIPEC at experienced centers could have acceptable safety. Improving the surgical techniques and developing the integrated hemostasis techniques are essential to reduce intraoperative blood loss and decrease SAEs rate.

Precise species detection of traditional Chinese patent medicine by shotgun metagenomic sequencing.

BACKGROUND: Current quality control methods for traditional Chinese patent medicines (TCPMs), e.g., microscopy, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC), cannot detect herbal species composition with adequate precision. To address this issue, more effective detection methods should be explored. HYPOTHESIS/PURPOSE: We hypothesized that shotgun metagenomic sequencing can fulfill the requirements for the species detection of multi-ingredient TCPMs. METHODS: Longdan Xiegan Wan (LDXGW), once thought to be the chief culprit in aristolochic acid nephropathy (AAN), was selected to establish the method. It was used for both reference and commercial LDXGW samples. The precision authentication of herbal species contained in multi-ingredient TCPM is based on the shotgun metagenomic sequencing of genomic DNA without PCR amplification. Chemical analyses were also conducted as a contrast test. RESULTS: Over 100 G of raw data was obtained, and this value represented more than 0.75 billion reads. After assembling and filtering all the reads, a total of 261 contigs were obtained, which belonged to the ITS2, psbA-trnH, and matK regions of the reference and commercial samples. Because the homology of the rbcL region was high, it was not analyzed in the HTS data. Bioinformatics analysis indicated that the ITS2 region, as a DNA barcode, showed the highest identification efficiency. It could successfully detect all prescribed species, including four processed herbal ingredients, in the lab-made reference samples. The commercial samples all met the requirements of the Chinese Pharmacopoeia according to the TLC and HPLC tests. However, the shotgun metagenomic sequencing detected the substitution of Akebiae Caulis (Mutong) in the commercial samples, while the chemical analyses could not distinguish. CONCLUSION: The results highlight that shotgun metagenomic sequencing is a complementary method for the precise species detection of TCPMs.

Biomonitoring for traditional herbal medicinal products using DNA metabarcoding and single molecule, real-time sequencing.

Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and psbA-trnH regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.

Ling-Yang-Gou-Teng-decoction prevents vascular dementia through inhibiting oxidative stress induced neurovascular coupling dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke (LS). The oxidative stress induced neurovascular coupling (NVC) dysfunction involves in the pathogenesis of VaD. Currently, there is no specific drug for VaD. Ling-Yang-Gou-Teng -Decoction (LG), a well-known traditional Chinese formula, has been used for preventing VaD in clinic. AIM OF THE STUDY: In this study, we aimed to investigate the underlying mechanism of LG on VaD in rats. MATERIALS AND METHOD: VaD was replicated with autologous micro-thrombi against the background of hypercholesterolemia induced with high fatty diet. PTX (68.90 mg/kg/day), LG with three dosages (2.58, 8.14, 25.80 g/kg/day) was orally administrated to VaD rats, respectively. The NVC sensitivity was defined as the ratio of the microcirculative cerebral blood velocity (CBV) to the electroencephalograph (EEG) before and after penicillin stimulation. Behavioral performance, pathological changes of brain and oxidation related molecules were detected to assess the effects of LG on VaD. RESULTS: LG exhibited beneficial effects on the VaD, which was demonstrated as improved exploratory, learning and memory abilities, relieved vascular or neural pathological changes in cerebral cortex or hippocampus. LG maintained NVC sensitivity, which was confirmed as significantly increased ΔCBV and the elevated ratio of ΔCBV/ΔqEEG. The underlying mechanisms of LG was associated with antioxidant effects, which was confirmed as significantly decreased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression, and increased superoxide dismutase 3 (SOD3) expression. LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability. CONCLUSIONS: The results suggested that LG prevented VaD may associate with inhibiting oxidative stress, protecting NO bioavailability, and then maintaining NVC sensitivity.

A model for anticancer surveillance was pharmacologically developed to evaluate vitality principle in breast cancer rats.

OBJECTIVE: To evaluate vitality principle in breast cancer rats by pharmacologically developing a model for anticancer surveillance. METHODS: The breast cancer in rats was replicated with 7,12-Dimethylbenz[a]anthracene (DMBA, i.g., 100 mg/kg) at d001. The anticancer surveillance was defined as the intervals between the primary sensitization and the first challenge stirred with complete Freund's adjuvant (CFA), the various intervals (k = 0.80) were dominated from d025 (600.00 h) to d095 (2288.82 h). The optimal surveillant status was confirmed with the median effective interval (EI50) from tumor volume regressive curve, for developing the pharmacodynamic model. The tumor and tumor infiltrating lymphocyte histopathology was used to confirm the immune surveillance being affected with CFA in breast cancer tumorigenesis. The availability of this model was confirmed with Shugan Liangxue prescription (SLP), from the vitality principle, and assured further from interleukin-12 levels. RESULTS: The regressive curve was set up between the intervals and tumor volumes, the EI50 in SLP-treated rats (1475.00 h, YSLP = 0.1026 + 0.8780/[1 + 10(27.1425-8.565x)]) was postponed, which was 1.87 multiple of the EI50 in CFA rats (791.40 h, y = -0.0525 + 0.9452/[1 + 10(30.4870-10.52x)], so did prepone the curve between the intervals and the immunological biomarker, serum interleukin-12 levels, the EI50 in SLP-treated rats (744.90 h, YSLP = -0.0145 + 0.7455/[1 + 10(52.09636-18.13x)]) be 0.78 multiple of the EI50 in CFA rats (960.10 h, YCFA = 0.2460 + 0.7270/[1 + 10 (-67.1546 + 22.52x)]), this immunological action being mediated the anticancer prognosis. Tumor histology was confirmed the more tumor infiltrating lymphocytes activated in SLP rats with CFA stirred immunity than rats only received CFA. CONCLUSION: The model for anticancer surveillance was pharmacologically established as the optimal interval (791.40 h) between the primary sensitization and the first challenge stirred with complete Freund's adjuvant. This available model was confirmed with SLP, from the vitality principle, for evaluating immunological effects against breast cancer.

Identification of crude drugs in the Japanese pharmacopoeia using a DNA barcoding system.

Kampo is the general designation for traditional Japanese herbal medicines, which are recognized as official medicines and listed in the Japanese pharmacopoeia (JP). In most cases, it is difficult to identify the crude drug materials to species level using only traditional identification methods. We report the first online DNA barcode identification system, which includes standard barcode sequences from approximately 95% of the species recorded in the JP (16th edition). This tool provides users with basic information on each crude drug recorded in the JP, DNA barcoding identification of herbal material, and the standard operating procedure (SOP) from sampling to data analysis. ITS2 sequences (psbA-trnH was an alternative when ITS2 could not be amplified) were generated from a total of 576 samples to establish the database. An additional 100 samples (from different medicinal parts, from both single origin and multiple origins and from both retailers and the planting base) were identified using the system. A total of 78% of the test samples were identified as the species listed on their label. This system establishes a model platform for other pharmacopeias from countries like China, Korea, the US and the European Union, for the safe and effective utilization of traditional herbal medicines.

Survey of commercial Rhodiola products revealed species diversity and potential safety issues.

The adulteration of herbal products is a threat to consumer safety. Here we surveyed the species composition of commercial Rhodiola products using DNA barcoding as a supervisory method. A Rhodiola dietary supplement DNA barcode database was successfully constructed using 82 voucher samples from 10 Rhodiola species. Based on the DNA barcoding standard operating procedure (SOP), we used this database to identify 100 Rhodiolae Crenulatae Radix et Rhizoma decoction piece samples that were purchased from drug stores and hospitals. The results showed that only 36 decoction piece sequences (40%) were authentic R. crenulata, which is recorded in Chinese Pharmacopeia, whereas the other samples were all adulterants and may indicate a potential safety issue. Among the adulterants, 35 sequences (38.9%) were authenticated as R. serrata, nine sequences (10%) were authenticated as R. rosea, which is documented in the United States Pharmacopeia, and the remaining samples were authenticated as other three Rhodiola species. This result indicates decoction pieces that are available in the market have complex origins and DNA barcoding is a convenient tool for market supervision.

Phase II multicentered study of low-dose everolimus plus cisplatin and weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin as first-line treatment for patients with advanced gastric cancer.

OBJECTIVE: This phase II trial investigates the efficacy and safety of low-dose everolimus in combination with cisplatin-fluorouracil chemotherapy in patients with advanced gastric cancer. METHODS: Eligible patients with chemotherapy-naïve advanced gastric cancer received low-dose everolimus (10 mg p.o. on days 1, 8 and 15) plus cisplatin and a weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin (HDFL) chemotherapy (cisplatin 35 mg/m(2) intravenous infusion for 24 h on days 1 and 8, 5-fluorouracil 2,000 mg/m(2) and leucovorin 300 mg/m(2) intravenous infusion for 24 h on days 1, 8 and 15) every 28 days. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.0. RESULTS: Forty patients (19 men; 21 women; median age, 54.1 years; range, 33.7-73.3 years) received a median of 6 (range, 1-30; 95% CI, 4.9-8.0) cycles of study treatment. The ORR was 52.5% (21 confirmed partial response). The median progression-free survival and overall survival were 6.9 (95% CI, 4.9-8.4) and 10.5 (95% CI, 8.6-12.3) months, respectively. Most adverse events were mild. CONCLUSION: Adding low-dose everolimus to cisplatin-HDFL chemotherapy failed to increase the ORR as in a preplanned statistical assumption but may prolong progression-free survival in treatment-naïve advanced gastric cancer patients.

[Stability and accuracy of the identification of Notopterygii Rhizoma et Radix using the ITS/ITS2 barcodes].

In this study, Notopterygii Rhizoma et Radix was used to verify the stability and accuracy of DNA barcodes in identification of Chinese materia medica for the first time. All genomic DNAs from thirty one samples were extracted. The ITS (internal transcribed spacer) regions were amplified and sequenced bi-directionally. Obtained sequences were assembled using the CodonCode Aligner. And the sequences of the ITS regions were aligned through Clustal-W and the genetic distances were computed using MEGA 5.0 in accordance with the kimura 2-parameter (K2P) model. The neighbor-joining (NJ) phylogenetic trees were constructed. The ITS2 regions were obtained by using the hidden Markov model (HMM)-based annotation methods from the ITS sequences. Results indicated that the lengths of ITS regions of Notopterygii Rhizoma et Radix were 603-604 bp, while the lengths of ITS2 regions were 228 bp. The haplotypes of ITS/ITS2 regions of Notopterygii Rhizoma et Radix were the same as those of the original plant leaves. The intra-specific genetic distances were smaller than inter-specific ones in ITS/ITS2 regions of Notopterygium incisum and N. franchetii. The NJ trees showed that N. incisum, N. franchetii and its adulterants can be easily differentiated according to their monophyly. Therefore, ITS/ITS2 regions as DNA barcodes can stably and accurately distinguish Notopterygii Rhizoma et Radix from its adulterants and could provide a new technique to ensure clinical safety in utilization of traditional Chinese medicines.

Pharmacological basis for the medicinal use of muskmelon base (Pedicellus Melo.) for abdominal distention and constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: Muskmelon base (Pedicellus Melo.) has a long history (Ming Dynasty) as a Chinese traditional medicine. According to traditional use, it was prepared as rectal suppositories for treating abdominal distention and constipation. The present study was carried out on the pharmacological basis for the medicinal use of muskmelon base. AIM OF THE STUDY: The objective of this study was to determine the pharmacological basis for the medicinal use of the ethanol extract from muskmelon base (EMB) for abdominal distention and constipation. MATERIALS AND METHODS: In this study, we report the gastrointestinal prokinetic action of EMB following single rectal or large intestinal administration. Laxative activity, gastric emptying and small intestinal transit tests were examined in ICR mice. SD rats were used to determine changes in large intestinal transit and contractile effects of the proximal colon in vivo. Guinea pigs were used to evaluate the contractile effects of the proximal colon and the possible mechanism or mechanisms on proximal colon activity ex vivo. Moreover, the acute toxicity of EMB was evaluated. RESULTS: In the in vivo experiments, the acute toxicity test showed that the maximum tolerated dose (MTD) of EMB was 400 mg/kg. A laxative effect was observed in mice at different dosages (6.5, 13 and 26 mg/kg). EMB showed a dose-dependent acceleration of gastric emptying (13 and 26 mg/kg). It also promoted both small intestinal (6.5, 13 and 26 mg/kg) and large intestinal (4, 8 and 16 mg/kg) transit activity. In the SD rat model, single rectal administration of EMB (8 and 16 mg/kg) showed a significant increase in both the frequency and amplitude of proximal colon smooth muscle contractility. These increases in amplitude and frequency peaked 30-60 min after EMB administration and corresponded with the results of the laxative activity test. The ex vivo experiments showed that varying doses of EMB (11.5, 23 and 46 mg/kg) had a direct prokinetic effect that was sensitive to atropine. CONCLUSIONS: Our results show that EMB is a low dosage, fast acting drug with a large therapeutic window (4-400 mg/kg) and shows significant gastrointestinal prokinetic action after single rectal or large intestinal administration. This gastrointestinal prokinetic effect was stronger in the intestines than in the stomach. This effect was sensitive to atropine, suggesting that EMB acts mainly through cholinergic mechanisms.

FOLFOX4 in the adjuvant treatment of colon cancer in Asian patients.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Surgery is the only way to potentially cure the disease and may be accomplished in 70% to 80% of newly diagnosed cases. However, 40% to 50% of patients who undergo surgery alone ultimately relapse and die of metastatic disease. Adjuvant chemotherapy, which has been developed to reduce the recurrence of CRC, has evolved from the single agent fluorouracil (5FU) to combinations with oxaliplatin, which now have an established role in stage III CRC. FOLFOX4 has been widely used as an adjuvant treatment of CRC, including the Asia-Pacific region. Adjuvant chemotherapy for CRC has been extensively investigated in the West but whether treatment outcomes in Asian individuals vary due to racial differences is uncertain. Racial differences should be considered, and differences in outcomes have been shown in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors. This article critically reviews the evolution of adjuvant chemotherapy in CRC and focuses on the side effects of FOLFOX4 when administered to Asian patients for the adjuvant treatment of CRC. Comparisons of the tolerability of FOLFOX4 in different races from well-designed studies conducted in the West and Asia will be reviewed.

Validation of the ITS2 region as a novel DNA barcode for identifying medicinal plant species.

BACKGROUND: The plant working group of the Consortium for the Barcode of Life recommended the two-locus combination of rbcL+matK as the plant barcode, yet the combination was shown to successfully discriminate among 907 samples from 550 species at the species level with a probability of 72%. The group admits that the two-locus barcode is far from perfect due to the low identification rate, and the search is not over. METHODOLOGY/PRINCIPAL FINDINGS: Here, we compared seven candidate DNA barcodes (psbA-trnH, matK, rbcL, rpoC1, ycf5, ITS2, and ITS) from medicinal plant species. Our ranking criteria included PCR amplification efficiency, differential intra- and inter-specific divergences, and the DNA barcoding gap. Our data suggest that the second internal transcribed spacer (ITS2) of nuclear ribosomal DNA represents the most suitable region for DNA barcoding applications. Furthermore, we tested the discrimination ability of ITS2 in more than 6600 plant samples belonging to 4800 species from 753 distinct genera and found that the rate of successful identification with the ITS2 was 92.7% at the species level. CONCLUSIONS: The ITS2 region can be potentially used as a standard DNA barcode to identify medicinal plants and their closely related species. We also propose that ITS2 can serve as a novel universal barcode for the identification of a broader range of plant taxa.