Chinese Medicine Prolongs Overall Survival of Chinese Patients with Advanced Gastric Cancer: Treatment Pattern and Survival Analysis of a 20-Year Real-World Study.

OBJECTIVE: To describe the treatment patterns and survival status of advanced gastric cancer (AGC) in China in the past two decades, and objectively evaluate the impact of standardized Chinese medicine (CM) treatment on the survival of AGC patients. METHODS: This multicenter registry designed and propensity score analysis study described the diagnosis characteristics, treatment-pattern development and survival status of AGC from 10 hospitals in China between January 1, 2000 and July 31, 2021. Overall survival (OS) was evaluated between non-CM cohort (standard medical treatment) and CM cohort (integrated standard CM treatment ≥3 months). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to adjust any difference in average outcomes for bias. RESULTS: A total of 2,001 patients histologically confirmed locally advanced and/or metastasis stomach and gastroesophageal junction adenocarcinoma were enrolled. Among them, 1,607 received systemic chemotherapy, 215 (10.74%) accepted molecular targeted therapy, 44 (2.2%) received checkpoint inhibitor therapy, and 769 (38.43%) received CM. Two-drug regimen was the main choice for first-line treatment, with fluoropyrimidine plus platinum as the most common regimen (530 cases, 60.09%). While 45.71% (16 cases) of patients with HER2 amplification received trastuzumab in first-line. The application of apatinib increased (33.33%) in third-line. The application of checkpoint inhibitors has increased since 2020. COX analysis showed that Lauren mixed type (P=0.017), cycles of first-line treatment >6 (P=0.000), CM (P=0.000), palliative gastrectomy (P=0.000), trastuzumab (P=0.011), and apatinib (P=0.008) were independent prognostic factors for the OS of AGC. After PSM and IPTW, the median OS of CM cohort and non-CM cohort was 18.17 and 12.45 months, respectively (P<0.001). CONCLUSIONS: In real-world practice for AGC in China, therapy choices consisted with guidelines. Two-drug regimen was the main first-line choice. Standardized CM treatment was an independent prognostic factor and could prolong the OS of Chinese patients with AGC. (Registration No. NCT02781285).

Natural products and dietary interventions on liver enzymes: an umbrella review and evidence map.

Background: The association between natural products and dietary interventions on liver enzymes is unclear; therefore, this study aimed to examine their effects on liver enzymes in adults. Methods: PubMed, Embase, and Cochrane Library of Systematic Reviews databases were searched from inception until March 2023. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological and evidence quality, and the therapeutic effects were summarized in a narrative form. Results: A total of 40 meta-analyses on natural products (n = 25), dietary supplements (n = 10), and dietary patterns (n = 5) were evaluated, and results were presented in a narrative form. The overall methodological quality of the included studies was relatively poor. The results indicated that positive effects were observed for nigella sativa, garlic, artichoke, curcumin, silymarin, vitamin E, vitamin D, L-carnitine, propolis, and polyunsaturated fatty acids on certain liver enzymes. The dietary patterns, including high-protein, Mediterranean, and calorie-restriction diets and evening snacks, may reduce liver enzymes; however, other supplements and herbs did not reduce liver enzyme levels or have minimal effects. The evidence quality was generally weak given the risk of bias, heterogeneity, and imprecision. Conclusion: This umbrella review suggests that natural products and dietary interventions have beneficial therapeutic effects on liver enzymes levels. Further clinical trials are necessary to establish the effectiveness of supplements that reduce liver enzymes.

Ginger for treating nausea and vomiting: an overview of systematic reviews and meta-analyses.

Ginger may be a potential remedy for nausea and vomiting. This review aimed to assess the reporting and methodological quality, and integrate the evidence in this field. A total of fifteen meta-analyses were analysed and met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines, providing a relatively complete statement. However, methodological quality, assessed using the Assessment of Multiple Systematic Reviews-2 checklist, was deemed critically low to low. Our review's findings support ginger's effectiveness in managing chemotherapy-induced nausea and vomiting in cancer patients. It also reduces postoperative nausea and vomiting severity, decreasing the need for rescue antiemetics. Furthermore, ginger shows promise in alleviating pregnancy-related nausea and vomiting symptoms. The pooled evidence suggests ginger as a safe botanical option for managing nausea and vomiting, but it is important to improve the scientific quality of published meta-analyses in the future.

The increasing variability of tropical cyclone lifetime maximum intensity.

This study investigates long-term changes in the variability of TC intensity of global tropical cyclones, a topic which has been relatively infrequently studied to date. Our study finds that the variability of global TC lifetime maximum intensity (LMI), as measured by the LMI standard deviation, increases during 1981-2016. The increasing trend in LMI variability is statistically significant for both the Northern and Southern Hemispheres, with three individual TC basins: the western North Pacific, the South Indian and the South Pacific also having statistically significant increases. This increasing trend primarily results from distinct changes in the relative percentages of TCs with different intensities. When comparing two periods: 1981-1998 and 1999-2016, the proportions of weak and strong TCs increase, whereas moderate TCs occur relatively less frequently. This bimodal pattern of observed LMI distribution change is further linked to opposite trends in the average intensities of TCs that undergo rapid intensification (RI) during their lifetime (RI TCs) and those that do not (non-RI TCs). The LMI distributions of RI and non-RI TCs migrate to higher and lower intensities, respectively. Our results demonstrate from an observational perspective that strong TCs have strengthened while weak TCs have weakened as the global climate has warmed since 1981.

A Hiatus of the Greenhouse Effect.

The rate at which the global average surface temperature is increasing has slowed down since the end of the last century. This study investigates whether this warming hiatus results from a change in the well-known greenhouse effect. Using long-term, reliable, and consistent observational data from the Earth's surface and the top of the atmosphere (TOA), two monthly gridded atmospheric and surface greenhouse effect parameters (Ga and Gs) are estimated to represent the radiative warming effects of the atmosphere and the surface in the infrared range from 1979 to 2014. The atmospheric and surface greenhouse effect over the tropical monsoon-prone regions is found to contribute substantially to the global total. Furthermore, the downward tendency of cloud activity leads to a greenhouse effect hiatus after the early 1990 s, prior to the warming pause. Additionally, this pause in the greenhouse effect is mostly caused by the high number of La Niña events between 1991 and 2014. A strong La Niña indicates suppressed convection in the tropical central Pacific that reduces atmospheric water vapor content and cloud volume. This significantly weakened regional greenhouse effect offsets the enhanced warming influence in other places and decelerates the rising global greenhouse effect. This work suggests that the greenhouse effect hiatus can be served as an additional factor to cause the recent global warming slowdown.

Purification, characterization, and unfolding studies of arginine kinase from Antarctic krill.

The regulation of enzymatic activity and unfolding studies of arginine kinase (AK) from various invertebrates have been the focus of investigation. To gain insight into the structural and folding mechanisms of AK from Euphausia superba (ESAK), we purified ESAK from muscle properly. The enzyme behaved as a monomeric protein with a molecular mass of about 40kDa and had pH and temperature optima of 8.0 and 30°C, respectively. The Km(Arg) and Km(ATP) for the synthesis of phosphoarginine were 0.30 and 0.47mM, respectively, and kcat/Km(Arg) was 282.7s(-1)/mM. A study of the inhibition kinetics of structural unfolding in the denaturant sodium dodecyl sulfate (SDS) was conducted. The results showed that ESAK was almost completely inactivated by 1.0mM SDS. The kinetics analyzed via time-interval measurements revealed that the inactivation was a first-order reaction, with the kinetic processes shifting from a monophase to biphase as SDS concentrations increased. Measurements of intrinsic and 1-anilinonaphthalene-8-sulfonate-binding fluorescence showed that SDS concentrations lower than 5mM did not induce conspicuous changes in tertiary structures, while higher concentrations of SDS exposed hydrophobic surfaces and induced conformational changes. These results confirmed that the active region of AK is more flexible than the overall enzyme molecule.

[Construction and biological function of eukaryotic expression vector for myc-tagged HER2].

OBJECTIVE: To construct eukaryotic expression vector of myc-tagged human HER2 and investigate its role in breast cancer cell proliferation and drug resistance. METHODS: Human HER2 gene was amplified by PCR and cloned into the pXJ-40-myc vector. The recombinant myc-HER2 was identified by enzyme digestion and sequencing, transfected into breast cancer cell line ZR75-1, and then was detected by Western blotting. Next, CCK8 assay was performed to investigate myc-Her2 transfected cell proliferation. Trastuzumab, anti-Her2 antibody, was added to determine the sensitivity of cells transfected with myc-Her2. RESULTS: Enzyme digestion and sequencing confirmed the myc-HER2 vector was constructed successfully. Western blotting showed the expression of myc-HER2 in the ZR75-1 cells. The result of cell growth curve showed that cells transfected with myc-her2 grew significantly faster than the control cells. Moreover, trastuzumab obviously suppressed the growth of ZR75-1 cells transfected with myc-HER2. CONCLUSION: The myc-HER2 vector was successfully constructed which lays an experimental foundation for the study of HER2 drug resistance to trastuzumab.

[Efficacy and prognostic analysis of retreatment with trastuzumab-based therapy after multi-line targeted therapy resistance in HER2-positive metastatic breast cancer].

OBJECTIVE: To evaluate the predictive factors for efficacy and prognosis of retreatment trastuzumab in the patients with HER2 positive metastatic breast cancer (MBC) developing successive resistance to multi-line targeting therapies. METHODS: The data of 29 patients with HER2 positive MBC were collected from July 2008 to July 2010 at our department. All patients were treated with trastuzumab, lapatinib and retreated with trastuzumab sequentially. Twenty-one patients progressed during the initial trastuzumab therapy. All patients were treated with lapatinib to disease progression and retreated with trastuzumab to disease progression or death subsequently. A Log-rank test was used for univariate analysis and a Cox regression model was employed for multivariate analysis. RESULTS: The efficacy showed no significant difference between the patients with progression or those without progression during the initial trastuzumab therapy. The time-to-progression (TTP) of prior lapatinib therapy was an influencing factor of median progression-free survival (PFS) (P < 0.0001) and the duration from discontinuation of lapatinib to trastuzumab retreatment an influencing factor of median overall survival (OS) (P = 0.008) of trastuzumab retreatment in our univariate analysis. The median PFS of trastuzumab retreatment for patients with TTP of lapatinib therapy > 12 weeks (hazard ratio (HR) = 0.02, P = 0.003) or whose duration of double trastuzumab treatment ≤ 1 year (HR = 0.26, P = 0.03) was significantly prolonged in multivariate analysis. Meanwhile, the death risk of patients whose duration from discontinuation of lapatinib to trastuzumab retreatment ≤ 4 weeks decreased 89% as compared with trastuzumab retreatment (HR = 0.11, P = 0.004). CONCLUSION: TTP of prior lapatinib therapy and the duration of double trastuzumab treatment are two predictive factors of PFS of trastuzumab retreatment. And the duration from discontinuation of lapatinib to trastuzumab retreatment is an important independent prognostic factor for trastuzumab retreatment. The patients with HER2 positive MBC should be treated continually with anti-HER2 targeted therapy.

Evaluation of treatment response for breast cancer: are we entering the era of "biological complete remission"?

Breast cancer is one of the most common malignancies in women. The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality. In this study, we tried to explore the role of circulating tumor cell (CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile, we attempted to assess the concept of "biological complete remission" (bCR) in this regard. A 56-year-old patient with breast cancer (T(2)N(1)M(1), stage IV left breast cancer, with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab. Then, she underwent CTC detection and PET/CT for efficacy evaluation. CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer. The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological (pathological) complete remission. The integrated application of the concepts including bCR, imageological CR, and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.