Cost-Effectiveness Analysis of Camrelizumab Plus Rivoceranib Versus Sorafenib as a First-Line Therapy for Unresectable Hepatocellular Carcinoma in the Chinese Health Care System.

BACKGROUND AND OBJECTIVES: Camrelizumab plus rivoceranib showed significant clinical benefits in progression-free survival and overall survival compared to sorafenib in patients with unresectable hepatocellular carcinoma (HCC). This study aimed to assess its cost effectiveness from the perspective of Chinese health care system. METHODS: A Markov state-transition model was developed based on the Phase 3 randomized CARES-310 clinical trial data. Health state utility values were obtained from the CARES-310 clinical trial, and direct medical costs were derived from the relevant literature and local charges. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to assess the uncertainty of the model. RESULTS: In the base-case analysis, the incremental effectiveness and cost of camrelizumab plus rivoceranib versus sorafenib were 0.41 QALYs and $13,684.84, respectively, resulting in an ICER of $33,619.98/QALY, lower than the willingness-to-pay threshold of China ($35,864.61/QALY). Subgroup analyses revealed that the ICERs of camrelizumab plus rivoceranib versus sorafenib were $35,920.01 and $29,717.98 in patients with ALBI grade 1 and grade 2, respectively. One-way sensitivity analyses indicated that the cost of camrelizumab, the proportion of patients receiving subsequent treatment in the camrelizumab plus rivoceranib group, and the cost of rivoceranib were the most significant factors in the base-case analysis. Probabilistic sensitivity analysis suggested that the probabilities of cost effectiveness of camrelizumab plus rivoceranib were 61.27%, 51.46%, and 82.78% for any grade, and ALBI grade 1 and grade 2, respectively. CONCLUSIONS: Camrelizumab plus rivoceranib was more cost effective than sorafenib as first-line therapy for unresectable HCC in the Chinese setting.

The scaling of elemental stoichiometry and growth rate over the course of bamboo ontogeny.

Stoichiometric rules may explain the allometric scaling among biological traits and body size, a fundamental law of nature. However, testing the scaling of elemental stoichiometry and growth to size over the course of plant ontogeny is challenging. Here, we used a fast-growing bamboo species to examine how the concentrations and contents of carbon (C), nitrogen (N) and phosphorus (P), relative growth rate (G), and nutrient productivity scale with whole-plant mass (M) at the culm elongation and maturation stages. The whole-plant C content vs M and N content vs P content scaled isometrically, and the N or P content vs M scaled as a general 3/4 power function across both growth stages. The scaling exponents of G vs M and N (and P) productivity in newly grown mass vs M relationships across the whole growth stages decreased as a -1 power function. These findings reveal the previously undocumented generality of stoichiometric allometries over the course of plant ontogeny and provide new insights for understanding the origin of ubiquitous quarter-power scaling laws in the biosphere.

New Alkaloid and Aromatic Glucoside from the Flowers of Cymbidium Lunagrad Eternal Green.

In this paper, we investigated the chemical components of the flowers of Cymbidium Lunagrad Eternal Green for the first time. In the whole post-fertilization, a new alkaloid, named Lunagrad A (1), and a new aromatic glucoside, named Lunagrad B (2), were isolated from the MeOH extract of the flowers of Cymbidium Lunagrad Eternal Green, along with other six known aromatic compounds (3-8) and three flavone glucosides (9-11). These structures were determined on the basis of NMR experiments, as well as chemical evidence.

Effects of the polysaccharides extracted from Ganoderma lucidum on chemotherapy-related fatigue in mice.

The weight-loaded swimming capability, tumor growth, survival time and biochemical markers of Ganoderma lucidum polysaccharides (GLPs) in a chemotherapy-related fatigue mouse model were tested in the present study. The results showed that the middle-dose GLPs (GLP-M) and the high-dose GLPs (GLP-H) could increase the exhausting swimming time, which was observed to decrease in the cisplatin control group(PCG) and the tumor control group (TCG).The GLP-M and the GLP-H had reduced serum levels of tumor necrosis factor-αand interleukin-6, which were up-regulated by cisplatin. Cisplatin and the presence of tumor significantly enhanced the malondialdehyde (MDA) content and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of GLPs at a high dose decreased the levels of MDA and up-regulated the SOD activity. The high-dose GLPs+cisplatin group presented a decreased tendency of tumor volume and a lower tumor weight compared with PCG. Moreover, the mice in the GLP-M and GLP-H groups had longer survival times compared with the mice in the TCG and PCG.The levels of creatinine and serum blood urea nitrogen, which are up-regulated by cisplatin, were significantly reduced by GLP-M and GLP-H. Therefore, these results suggest that GLPs might improve chemotherapy-related fatigue via regulation of inflammatory responses, oxidative stress and reduction of nephrotoxicity.

Three new ring-A modified ursane triterpenes from Davidia involucrata.

Three new ursane triterpenes, 3α,19α-dihydroxy-2-nor-urs-12-en-23,28-dioic acid-23-methyl ester (1), 19α,23-dihydroxy-3-oxo-2-nor-urs-12-en-28-oic acid (2), and 2,3-seco-3-methoxy-3,19α,23-trihydroxy-urs-12-en-2-al-28-oic acid (3), were isolated from the MeOH extract of the branch barks of Davidia involucrata, together with six known compounds. Their structures were elucidated by means of various spectroscopic analyses. The isolated triterpenes provide important evolutionary and chemotaxonomic knowledge about the monotypic genus Davidia. Five of the identified compounds showed moderate cytotoxicities against the cell proliferation of SGC-7901, MCF-7, and BEL-7404 with IC50 range from 7.26 to 47.41 µM.

The slow afterhyperpolarization: a target of ß1-adrenergic signaling in hippocampus-dependent memory retrieval.

In rodents, adrenergic signaling by norepinephrine (NE) in the hippocampus is required for the retrieval of intermediate-term memory. NE promotes retrieval via the stimulation of ß1-adrenergic receptors, the production of cAMP, and the activation of both protein kinase A (PKA) and the exchange protein activated by cAMP. However, a final effector for this signaling pathway has not been identified. Among the many targets of adrenergic signaling in the hippocampus, the slow afterhyperpolarization (sAHP) is an appealing candidate because its reduction by ß1 signaling enhances excitatory neurotransmission. Here we report that reducing the sAHP is critical for the facilitation of retrieval by NE. Direct blockers of the sAHP, as well as blockers of the L-type voltage-dependent calcium influx that activates the sAHP, rescue retrieval in mutant mice lacking either NE or the ß1 receptor. Complementary to this, a facilitator of L-type calcium influx impairs retrieval in wild-type mice. In addition, we examined the role of NE in the learning-related reduction of the sAHP observed ex vivo in hippocampal slices. We find that this reduction in the sAHP depends on the induction of persistent PKA activity specifically in conditioned slices. Interestingly, this persistent PKA activity is induced by NE/ß1 signaling during slice preparation rather than during learning. These observations suggest that the reduction in the sAHP may not be present autonomously in vivo, but is likely induced by neuromodulatory input, which is consistent with the idea that NE is required in vivo for reduction of the sAHP during memory retrieval.

Combined treatment of Pseudomonas aeruginosa PA01 biofilm formation with the water-soluble extract of Ligustrum sinense and gentamicin sulphate.

Ligustrum sinense are commonly used for their anti-inflammatory, anti-rheumatic, diuretic, and hypotensive activities in traditional Chinese medicine. To observe the effects of the combined treatment of a water-soluble extract of Ligustrum sinense (WEL) and gentamicin sulphate (GS) on Pseudomonas aeruginosa PA01, the micro-dilution method was used to determine the minimal inhibitory concentration (MIC) of GS. Formation of a PA01 biofilm was observed under an optical microscope after treatment with different dosages of WEL and combined treatment with GS. The MIC of WEL was 8g l(-1), and permanent activity was also observed. The effect of WEL with GS was synergistic. The motility, biomass of biofilms, and production of pyocyanin of P. aeruginosa were strongly suppressed in the presence of WEL. The conclusion can be drawn that combined antibiotics can be used to treat the contamination due to the biofilm formation caused by P. aeruginosa.

Chinese herbal medicine liu jun zi tang and xiang sha liu jun zi tang for functional dyspepsia: meta-analysis of randomized controlled trials.

Objectives. To assess the efficacy and safety of Liu Jun Zi Tang (LJZT) and Xiang Sha Liu Jun Zi Tang (XSLJZT) for treating functional dyspepsia. Methods. Literature searches were carried out on Medline database, Cochrane Library, CNKI database, Chinese Biomedical Literature database, Wanfang database, and VIP database up to July 2012. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results. Fifteen publications in total were suitable for inclusion. There was evidence that LJZT compared with prokinetic drugs increased symptom improvement (odds ratio 1.96, 95% CI 1.15 to 3.36). There was also evidence that XSLJZT compared with prokinetic drugs increased symptom improvement (odds ratio 2.63, 95% CI 1.72 to 4.03). No adverse events were reported in LJZT or XSLJZT group in any of these randomized controlled trials. Conclusion. LJZT and XSLJZT might be more effective compared with prokinetic drugs in the treatment of functional dyspepsia, and no side effects are identified in the included trials. However, due to poor methodological quality in the majority of included studies, the potential benefit from LJZT and XSLJZT need to be confirmed in rigorously designed, multicentre, and large-scale trials.

Anti-fatigue activity of polysaccharides extract from Radix Rehmanniae Preparata.

The anti-fatigue effects of the Radix Rehmanniae Preparata polysaccharides (RRPP) were studied in mice. The RRPP were orally administered at doses of 50, 100 and 200 mg/kg for 4 weeks and the anti-fatigue activity was evaluated using a weight-loaded swimming test, along with the determination of serum urea nitrogen (SUN), hepatic glycogen and blood lactic acid (BLA) contents. The results showed that there was no significant difference in the body weight of mice in the three RRPP groups compared with the negative control group during initial, intermediate and terminal stages in the experiment (p>0.05). The ratio of exhausting swimming time was obviously increased 31.48% (p<0.05) and 61.51% (p<0.01) in the middle-dose group and the high-dose RRPP group, respectively. The BLA and SUN levels were decreased in middle-dose and high-dose RRPP groups (p<0.01). Hepatic glycogen level was increased in three RRPP treated groups (p<0.01). Therefore, RRPP may be responsible for the pharmacological effect of anti-fatigue of Radix Rehmanniae Preparata. The mechanism was related to the increase of the storage of hepatic glycogen and the decrease of the accumulation of SUN and BLA.

A new phenolic glycoside and cytotoxic constituents from Celosia argentea.

A new phenolic glycoside, 4-O-ß-D-apifuranosyl-(1→2)-ß-D-glucopyranosyl-2-hydroxy-6-methoxyacetophenone (2) and 11 known compounds were isolated from the MeOH extract of the plant Celosia argentea. The structures of the compounds were elucidated on the basis of spectroscopic analysis and chemical methods. Among the isolated compounds, stigmasterol (10) showed moderate inhibitory activities against SGC-7901 and BEL-7404 cells.

Water-soluble constituents from the bark of Elaeagnus pungens and their cytotoxic activities.

Three new water-soluble compounds, pungens A-C, along with four known compounds including two phenol glycosides, one secoiso-flavanol and one phenol ether, have been isolated from the bark of Elaeagnus pungens. Among them, pungen C (7) (200 microg/ml) was tested in SGC-7901 and BEL-7404 tumor cell lines, and showed moderate cytotoxic activity. The structures of the new compounds were elucidated on the basis of spectroscopic data and chemical evidence.

[Prophylactic effect of acupuncture on nausea and vomiting after laparoscopic operation].

OBJECTIVE: To explore the prophylactic effect of acupuncture Neiguan (PC 6) on nausea and vomiting after laparoscopic operation. METHODS: One hundred patients with laparoscopic gastrointestinal operation were randomly divided into an acupuncture group and a control group, 50 patients in each group. The operation was carried out with the combined infusion and inhalation anesthesia. The patients in the acupuncture group were being punctured at bilateral Neiguan (PC 6) before anesthesia and during the operation. The needles were extracted after operation, and the acupoints were covered with opaque tape. In contrast, the patients in the control group only accepted tape covering without acupuncture. After operation, all patients were given the self-controlled intravenous analgesia, and followed up at 6 h, 12 h, 24 h, 48 h for recording the incidence rate of the nausea, retching and vomiting, then scoring with VAS. RESULTS: At 6 h, 12 h, 24 h, 48 h after operation, in the acupuncture group, the incidence rates of the nausea were 12.0%, 6.0%, 6.0% and 2.0%, and the incidence rates of the retching were 0, 0, 2.0% and 2.0%, respectively; in the control group, the incidence rates of the nausea were 28.0%, 20.0%, 12.0% and 2.0%, and the incidence rates of the retching were 2.0%, 6.0%, 2.0% and 0, respectively. At 6 h, 12 h after operation, the incidence rates of the nausea and retching in the acupuncture group were lower than those of the control group (P < 0.05, P < 0.001). The vomiting was not happened in both groups. There was no difference between the two groups according to the scoring with VAS. CONCLUSION: Acupuncturing at Neiguan (PC 6) can reduce the incidence rates of the patients' nausea and retching after laparoscopic operation, especially in 24 h.

Constituents from the seeds of Brucea javanica with inhibitory activity of Tobacco mosaic virus.

Three new constituents were obtained along with 10 known compounds from the seeds of Brucea javanica. The structures of these compounds were determined based on spectral and chemical evidence. These new compounds included a monoterpenoid glycoside and two sesquiterpenes. Bioactivity screening of these constituents showed that compounds 1, 3, 8, 9, and 13 with obvious activities in inhibiting multiplication of the Tobacco mosaic virus.

Two new phenolic water-soluble constituents from branch bark of Davidia involucrata.

Two new phenolic water-soluble constituents, involcranoside A (1) and involcranoside B (2) have been isolated along with five known phenolic compounds: 3,4-dimethoxyphenyl-O-beta-D-gluco-pyranoside (3), picein (4), and 1,4-dihydroxy-3-methoxy-phenyl-4-O-beta-D-glucopyranoside (5), leonuriside A (6) and 4-hydroxy-3-methoxybenzoic acid (7) from the branch bark of Davidia involucrata. Identification of their structures was achieved by 1D and 2D NMR experiments, including (1)H-(1)H COSY, NOESY, HMQC and HMBC methods and FAB mass spectral data.

Antiphytoviral activity of bruceine-D from Brucea javanica seeds.

BACKGROUND: Brucea javanica (L.) Merr. is widely distributed throughout the southern parts of China and has been used in traditional medicine to treat a variety of diseases. The objective of the present study was to identify the active antiphytoviral compound in the seeds of B. javanica and evaluate the inhibitory activity of the compound against plant virus. RESULTS: Bioassay-guided fractionation of the most active extract from the seeds led to the isolation of an antiphytoviral compound which was identified as bruceine-D by conventional spectroscopy methods. The compound exhibited significant inhibitory activity against the infection and replication of tobacco mosaic virus (TMV), with IC(50) values of 13.98 and 7.13 mg L(-1) respectively. The compound also showed a strong inhibitory effect on the infectivity of potato virus Y (PVY) and cucumber mosaic virus (CMV). Furthermore, the compound could effectively inhibit systemic TMV infection in the host tobacco plant under glasshouse conditions. CONCLUSION: The results suggested that bruceine-D from Brucea javanica may have the potential to be used as a natural viricide, or a lead compound for new viricides.

Rhusemialins A-C, new cyclolignan esters from the roots of Rhus javanica var. roxburghiana.

Three new cyclolignan esters and seven known compounds including two cyclolignan isolariciresinol, lynoiresinol, and five aromatic compounds methyl ferulate, vanillin, 4-hydroxy-3,5-dimethoxybenaldehyde, 4-methoxygallic acid, gallic acid were isolated from n-butanol extract of Rhus semialata (Anacardiaceae). The structural elucidations of rhusemialins A (1), B (2), and C (3) were based on FAB-MS, 1D and 2D NMR spectra.

Anti-tobacco mosaic virus (TMV) triterpenoid saponins from the leaves of Ilex oblonga.

Ten triterpene saponins have been isolated from a MeOH extract of the leaves of Ilex oblonga. In their structures, six new triterpenoid saponins were named as oblonganosides H-M (2, 4, 5, and 8-10). All structures were elucidated on the basis of spectroscopic analysis. Among the triterpenoid saponins, three compounds (7, 8, and 10) showed obvious activities in inhibiting multiplication of the tobacco mosaic virus (TMV).

Structure-activity relationship of triterpenes and triterpenoid glycosides against tobacco mosaic virus.

A new activity of triterpenes and triterpenoid glycosides against phytovirus has been found. Based on the anti-TMV replication activity in vivo, 47 triterpenes and triterpenoid glycosides were screened through the leaf-disk method together with indirect ELISA. Structure-activity relationships were analyzed according to the results of bio-activity screening. Besides, the EC(50) values of those compounds having higher activities were measured.

Three new saponins from the leaves of Ilex hylonoma.

Three new triterpenoid saponins, hylonosides III-V (1-3) have been isolated, along with three known oleanolic acid saponins (4-6), from the methanol extract of leaves of Ilex hylonoma. The structures were elucidated using a combination of homo- and hetero-nuclear 2D NMR techniques (COSY, TOCSY, NOESY, HMQC and HMBC) and negative FAB-MS. The new compounds were characterized as 3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucuronopyranosyl siaresinolic acid-28-O-beta-D-glucopyranosyl ester (1), 3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl siaresinolic acid-28-O-beta-D-glucopyranosyl ester (2), 3-O-beta-D-glucopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl oleanolic acid-28-O-beta-D-glucopyranosyl ester (3).