Ecosystem service tradeoff and synergistic relationship in the Yellow River Delta High-Efficiency Eco-Economic Zone.

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.

Research progress of Paris polyphylla in the treatment of digestive tract cancers.

Cancer has become one of the most important causes of human death. In particular, the 5 year survival rate of patients with digestive tract cancer is low. Although chemotherapy drugs have a certain efficacy, they are highly toxic and prone to chemotherapy resistance. With the advancement of antitumor research, many natural drugs have gradually entered basic clinical research. They have low toxicity, few adverse reactions, and play an important synergistic role in the combined targeted therapy of radiotherapy and chemotherapy. A large number of studies have shown that the active components of Paris polyphylla (PPA), a common natural medicinal plant, can play an antitumor role in a variety of digestive tract cancers. In this paper, the main components of PPA such as polyphyllin, C21 steroids, sterols, and flavonoids, amongst others, are introduced, and the mechanisms of action and research progress of PPA and its active components in the treatment of various digestive tract cancers are reviewed and summarized. The main components of PPA have been thoroughly explored to provide more detailed references and innovative ideas for the further development and utilization of similar natural antitumor drugs.

Antihypertensive effect and mechanism of the traditional recipe of medicine food homology (Buyang Huanwu Decoction) in China: Meta analysis and network pharmacological exploration.

Background: Hypertension has become a part of the lives of many people worldwide. With the development, an increasing number of people have begun to control their hypertension through products of medicine food homology, such as Buyang Huanwu Decoction (BYHWD). However, there has been no objective review of the regulation of hypertension by BYHWD. Methods: As of 9 October 2023, this review made a detailed search of nine databases to look for random controlled trials (RCTs) focused on the use of BYHWD for treating hypertension. This was followed by network pharmacological analysis, and molecular docking assessment using AutoDockTools to explore the mode of action. Results: BYHWD was effective in reducing SBP (MD: 0.767; 95 % CI: 0.629, 0.905; p = 0.000), DBP (MD: 0.427; 95 % CI: 0.292, 0.561; p = 0.000), 24h SBP (MD: 0.665; 95 % CI: 0.368, 0.962; p = 0.000), 24h DBP (MD: 0.547; 95 % CI: 0.318, 0.777; p = 0.000), dSBP (MD: 0.625; 95 % CI: 0.395, 0.855; p = 0.000), dDBP (MD: 0.632; 95 % CI: 0.401, 0.862; p = 0.000), nSBP (MD: 0.859; 95 % CI: 0.340, 1.377; p = 0.001), nDBP (MD: 0.704; 95 % CI: 0.297, 1.112; p = 0.001), pv (MD: 1.311; 95 % CI: 0.363, 2.259; p = 0.007) and NIHSS (MD: 1.149; 95 % CI: 0.100, 2.199; p = 0.032), and elevating CER (OR = 2.848; 95 % CI: 1.388, 5.843; p = 0.004). However, BYHWD did not significantly reduce HCY, and there was no significant difference in the incidence of AE. In terms of the mechanism of action, the main active ingredient of BYHWD is quercetin, and the core targets are AKT1, MMP9, and others. Molecular docking also showed that quercetin mainly interacts with the amino acid residue CYS-28 of MMP2. Second, the KEGG analysis showed that BYHWD mainly act on HIF-1, Apelin, and cGMP-PKG signalling pathways, and GO analysis showed that it related to the apical part of the cell, circulatory system processes, and nuclear receptor activity. Conclusion: BYHWD can lowered blood pressure, reduced plasma viscosity, and restored neurological function with good tolerability, and had no significant effect on HCY levels. This study further demonstrated that quercetin is the main active ingredient of BYHWD that acts via the AKT1 and HIF-1 signalling pathways. These results provide new guidance for people's dietary choices by the general public.

Cnidium officinale Makino: Phytology, Phytochemistry, Toxicology, Pharmacology and Prescriptions (1967-2023).

Cnidium officinale Makino (COM), a perennial herbaceous plant in the Apiaceous family, widely distribute in Eastern Asia and Asia-Temperate. It has a long history application as a traditional medicine for invigorating the blood and removing blood stasis, and also has been employed to diet, pesticide, herbal bathing materials, the cosmetic and skin care industry. However, there has been no associated review of literature in the past half a century (1967-2023). By searching the international authoritative databases and collecting 229 literatures closely related to COM, herewith a comprehensive and systematic review was conducted. The phytology includes plant distribution and botanical characteristics. The phytochemistry covers 8 major categories, 208 compounds in total, and the quantitative determination of 14 monomer compounds, total polyphenols and total flavonoids. The clinical trial in pregnant women and toxic experiments in mice, the pharmacology of 7 aspects and 82 frequently used prescriptions are summarized. It is expected that this paper will provide forward-looking scientific thinking and literature support for the further modern research, development and utilization of COM.

Simultaneous removal of nitrate nitrogen and orthophosphate by electroreduction and electrochemical precipitation.

Electrochemical methods can effectively remove nitrate nitrogen (NO3-N) and orthophosphate phosphorus (PO4-P) from wastewater. This work proposed a process for the simultaneous removal of NO3-N and PO4-P by combining electroreduction with electrochemically-induced calcium phosphate precipitation, and its performance and mechanisms were studied. For the treatment of 100 mg L-1 NO3-N and 5 mg L-1 PO4-P, NO3-N removal of 60-90% (per cathode area: 0.25-0.38 mg h-1 cm-2) and 80-90% (per cathode area: 0.33-0.38 mg h-1 cm-2) could be acquired within 3 h in single-chamber cell (SCC) and dual-chamber cell (DCC), while P removal was 80-98% (per cathode area: 0.10-0.12 mg h-1 cm-2) in SCC after 30 min and 98% (per cathode area: 0.37 mg h-1 cm-2) in DCC within 10 min. The faster P removal in DCC was due to the higher pH and more abundant Ca2+ in the cathode chamber of DCC, which was caused by the cation exchange membrane (CEM). Interestingly, NO3-N reduction enhanced P removal because more OH- can be produced by nitrate reduction than hydrogen evolution for an equal-charge reaction. For 10 mg L-1 PO4-P in SCC, when the initial NO3-N was 0, 20, 100, and 500 mg L-1, the P removal efficiencies after 1 h treatment were < 10%, 45-55%, 86-99%, and above 98% respectively. An increase in Ca2+ concentration also promoted P removal. However, Ca and P inhibited nitrate reduction in SCC at the relatively low initial Ca/P, as CaP on the cathode limited the charge or mass transfer process. The removal efficiency of NO3-N in SCC after 3 h reaction can reduce by about 17%, 40%, and 34% for Co3O4/Ti, Co/Ti, and TiO2/Ti. The degree of inhibition of P on NO3-N removal was related to the content and composition of CaP deposited on the cathode. On the cathode, the lower the deposited Ca and P, and the higher the deposited Ca/P molar ratio, the weaker the inhibition of P on NO3-N removal. Especially, P had little or even no inhibition on nitrate reduction when treated in DCC instead of SCC or under high initial Ca/P. It is speculated that under these conditions, a high local pH and local high concentration Ca2+ layer near the cathode led to a decrease in CaP deposition and an increase in Ca/P molar ratio on the cathode. High initial concentrations of NO3-N might also be beneficial in reducing the inhibition of P on nitrate reduction, as few CaP with high Ca/P molar ratios were deposited on the cathode. The evaluation of the real wastewater treatment was also conducted.

[Separation, characterization, and antiviral activity of colloidal phase state of Maxing Shigan Decoction].

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC. METHODS: This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT. RESULTS: Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival. DISCUSSION/CONCLUSIONS: This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry.

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.

[Effect of electroacupuncture at different time points on postoperative urination function in patients with mixed hemorrhoids surgery].

OBJECTIVE: To observe the effect of preoperative, intraoperative and postoperative electroacupuncture (EA) intervention on postoperative urination function in patients with mixed hemorrhoid surgery. METHODS: A total of 240 patients with mixed hemorrhoid surgery under lumbar anesthesia were randomly divided into an EA preconditioning group (group A, 60 cases, 9 cases dropped off), an intraoperative EA group (group B, 60 cases, 4 cases dropped off), a postoperative EA group (group C, 60 cases, 6 cases dropped off), and a non-acupuncture group (group D, 60 cases, 3 cases dropped off). In the groups A, B and C, EA was exerted at Zhongliao (BL 33) and Huiyang (BL 35) , with disperse-dense wave, 4 Hz/20 Hz in frequency, and lasting 30 min, at 30 min before lumbar anesthesia, immediately after lumbar anesthesia and 6 h after surgery, respectively. No EA intervention was performed in the group D. The postoperative urination smoothness score in each group was observed 24 h after surgery. The first urination time, first urination volume, urine residual volume after first urination were recorded, and incidence of indwelling catheterization, postoperative visual analogue scale (VAS) score, number of remedial analgesia, and the incidence of postoperative nausea and vomiting were observed in each group. RESULTS: In the groups A, B and C, the postoperative urination smoothness scores were superior to the group D (P<0.05), and the time of first urination was earlier than the group D (P<0.05). In the group C, the time of first urination was earlier than the group A and the group B (P<0.05), the first urination volume was higher than the group D (P<0.05), and the urine residual volume after first urination was lower than the group D (P<0.05). There was no significant difference in the incidence of indwelling catheterization and postoperative nausea and vomiting among the 4 groups (P>0.05). The VAS scores of the group A, B and C were lower than that in the group D (P<0.05), and the number of remedial analgesia cases was lower than that in the group D (P<0.05). CONCLUSION: EA intervention could promote the recovery of urination function and relieve postoperative pain in patients with mixed hemorrhoids surgery. Early postoperative EA intervention is more conducive to the recovery of urination function.

The Wu-Shi-Cha formula protects against ulcerative colitis by orchestrating immunity and microbiota homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) has become a healthy burden worldwide due to its insidious onset and repetitive relapse, with a rather complex etiology, including inappropriate immune response, dysbiosis, genetic susceptibility, and unhealthy diets. The Wu-Shi-Cha (WSC) formula is a widely utilized drug to protect against gastrointestinal disorders. AIM OF THE STUDY: The study aspired to dissect the pertinent mechanisms of the WSC to treat UC. MATERIALS AND METHODS: Network pharmacology and weighted gene co-expression network analysis (WGCNA) were performed to predict the targets of WSC in the context of UC and colorectal cancer. Dextran sodium sulfate (DSS) was used to construct murine models of experimental colitis, and the WSC was given to colitis mice for 14 days. Feces and colon samples were subjected to 16S rRNA gene sequencing combined with liquid chromatography-mass spectrometry (LC-MS) and biochemical experiments, respectively. RESULTS: Network pharmacology analysis predicted that the WSC formula could orchestrate inflammation, infection, and tumorigenesis, and WGCNA based on The Cancer Genome Atlas (TCGA) database showed a potent anti-neoplastic effect of the WSC therapy for colorectal cancer. The WSC therapy rescued bursts of pro-inflammatory cytokines and colonic epithelial collapse in DSS-induced colitis mice. Moreover, the high dose of WSC treatment facilitated the alternative activation of peritoneal macrophages (Mφs) and these Mφs were conducive to the survival of intestinal stem cells (ISCs), and the disturbed homeostasis of gut microbiota was re-established after WSC treatment, as evidenced by the decreased colonization of pathological taxa in the fecal samples. CONCLUSION: The WSC formula suppresses inflammation and re-establishes the homeostasis of gut microbiota, thereby ameliorating colitis progression.

Pharmacological Mechanism of Pingxiao Formula against Colorectal Cancer.

Colorectal cancer (CRC) is the most common cancer worldwide and develops due to a broad range of causative factors. Pingxiao (PX) formula and Xihuang (XH) formula are two commonly used drugs to treat CRC, especially as an alternative therapy for those patients who could not suffer surgery, chemotherapy, or immunotherapy, namely, elder or advanced CRC patients. However, the pertinent pharmacological mechanisms are still elusive. The investigation was designed to explain the pharmacological mechanisms of the PX formula. A murine model of CRC was established by injecting CT26.WT cells into the caecum of 4-week-old male Balb/c mice, following PX or XH treatment for 30 days. Network pharmacology analysis combined with weighted gene coexpression network analysis (WGCNA) predicted the pharmacological mechanisms and therapeutic value. High-throughput 16S rRNA sequencing determined the alterations in the gut microbiota communities. Western blotting, immunofluorescence, and flow cytometry examined the influence of PX on the tumor microenvironment (TME). Injection of CT26.WT-induced CRC in Balb/c mice was markedly attenuated by PX treatment. Compared with XH administration, PX exhibited a stronger antitumor effect, such as smaller tumor volume, lower interleukin 17 (IL-17), IL-6 and tumor necrosis factor-alpha (TNFα) serum levels, and higher interferon-gamma (IFN-γ) concentration. Network pharmacology analysis demonstrated that both PX and XH targets were enriched in cancers and inflammatory responses. RNA sequencing confirmed that PX treatment induced cancer cell apoptosis and inhibited inflammatory reactions within the tumor. Moreover, the PX formula considerably restored homeostasis of the gut microbiota, which was not observed in the XH group. PX targets, those associated with the survival probability of CRC patients, correlated with macrophage (Mφ) infiltration, which presented an independent risk factor for the CRC outcome. PX treatment promoted the transition of alternatively activated Mφs (M2 Mφs) to classically activated Mφs (M1 Mφs). Moreover, the peritoneal Mφs from the PX group inhibited the migration of CW26.WT cells, as evidenced by the wound healing experiment and transwell assay, which was consistent with the decreased expression of the vascular endothelial growth factor (VEGF). Furthermore, the coculturing system confirmed that PX-treated Mφs suppressed colorectal tumor-derived organoid proliferation. PX formula exhibits a potential antitumor effect against CRC by suppressing the colonization of pathological microorganisms, reshaping Mφ effector functions and hence inhibiting cancer cell proliferation.

Comparison of near-infrared and dielectric spectra for quantitative identification of bovine colostrum adulterated with mature milk.

The nonhomogeneity of bovine colostrum leads to strong scattering effects for electromagnetic waves, which affects the application of electromagnetic spectroscopy in detecting colostrum. This work aimed to compare the performance of near-infrared spectroscopy (NIRS) and dielectric spectroscopy (DS) in quantitatively predicting the content of mature milk as an adulterant in colostrum. The near-infrared spectra in the range of 833 to 2,500 nm and the dielectric spectra in the range of 20 to 4,500 MHz of 150 adulterated colostrum samples containing 0 to 50% mature milk were analyzed. The different proportions of mature milk in colostrum significantly changed near-infrared and dielectric spectra. The principal component analysis score plot showed that both NIRS and DS could identify the proportion of mature milk in colostrum, but the 2 methods had different characteristics. Linear partial least squares regression and nonlinear least squares support vector machine (LSSVM) models based on near-infrared and dielectric spectra were established to identify doping proportions. The results showed that DS had better identification performance with a root-mean-square error of prediction of 4.9% and a residual prediction deviation of 3.441 by successive projection algorithm LSSVM, whereas NIRS was relatively weak with a root-mean-square error of prediction of 7.3% and a residual prediction deviation of 2.301 by full-spectra LSSVM. This work provides important insights for the quantitative prediction of nonhomogeneous liquid food by DS.

Qualitative identification of mature milk adulteration in bovine colostrum using noise-reduced dielectric spectra and linear model.

BACKGROUND: The rapid and accurate identification of colostrum, a strong non-homogeneous food, remains a challenge. In the present study, the dielectric spectra including the dielectric constant (ε') and loss factor (ε″) of 154 colostrum samples adulterated with 0-50% mature milk were measured from 20 to 4500 MHz. RESULTS: The results showed that the noise-reducing spectral preprocessing, including Savitzky-Golay (S-G), second derivative (SD), and S-G + SD, was significantly better than scattering-eliminating, including standard normal variate (SNV), multiplicative scatter correction (MSC), and SNV + MSC. The combination of S-G and SD was the best. Principal component analysis results demonstrated that dielectric spectroscopy is less susceptible to the inhomogeneity of colostrum and can be used to identify doped colostrum. The identification performance of linear models was better than that of non-linear models. The established linear discriminant analysis model based on full spectra had the best accuracy rates of 99.14% and 97.37% in the calibration and validation sets, respectively. Confirmatory tests on samples from different sources confirmed the satisfactory robustness of the proposed model. CONCLUSION: We found that the main unfavorable effect on the identification based on dielectric spectroscopy was noise interference, rather than scattering effect caused by inhomogeneity of colostrum. The satisfactory results undoubtedly cast light on rapid detection of strongly non-homogeneous foods based on dielectric spectroscopy. © 2022 Society of Chemical Industry.

[Phosphorus Adsorption Characteristics and Loss Risk in Sediments of Lake Bay During the Overwinter Period of Cyanobacteria].

The overwinter period is the pre-stage of the algal bloom, and the endogenous phosphorus (P) in sediments is one of the main P sources of algal blooms during this period. Based on the investigation of the water quality and sediment pollutants during the overwinter period of cyanobacteria (recruitment period and dormancy period), this study analyzed the P release characteristics of sediments in the horizontal and vertical directions and clarified the P release risk of sediments and the change in microbial community structures. The results showed that the lake bay was moderately eutrophic in the two periods of the study area, and the water quality and sediment nitrogen and P pollution were more serious, and the chlorophyll a content (Chl-a) was still at a high level in the overwinter period. The pseudo-second order model and the modified Langmuir model could respectively describe the P kinetics and sorption isotherm behavior in the sediment. The theoretical maximum P sorption capacities (Qmax) of sediments were bottom layer>middle layer>surface layer, and the highest value was 1.648 mg·g-1 with the highest P sorption rate constant of the pseudo second-order kinetic model of 6.292 g·(mg·min)-1. Additionally, the P adsorption parameters (Qmax, NAP, and EPC0) were mainly affected by the physical and chemical properties of the sediment itself and the nutritional level of the lake bay. The surface sediments from the dormancy period mainly played the role of P sinks, and the part of sediments from the recruitment period played the role of P sources, in which existed the risk of endogenous P release. The analysis of the microbial community structure in sediments indicated that the microbial diversity in the sediments during the dormancy period was higher than that during the recruitment period, and some microbial categories with phosphate-solubilizing function of relative abundance was high.

Pharmacological mechanism of Shenlingbaizhu formula against experimental colitis.

BACKGROUND: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by an overactive immune response and destruction of the colorectal epithelium with intricate pathological factors. Shenlingbaizhu (SLBZ) formula, included in the Chinese Pharmacopoeia 2020, has been widely utilized to treat UC. PURPOSE: The present study was designed to uncover the underlying molecular mechanisms of SLBZ formula against UC. METHODS: A murine model of experimental colitis was established by orally feeding 2% dextran sodium sulfate (DSS) to mice for 7 days, followed by SLBA treatment for the next 15 days. Network pharmacology analysis was performed to predict the pharmacological mechanisms. High-throughput 16S rRNA sequencing integrated with liquid chromatography-mass spectrometry (LC-MS) was conducted on mouse stool in order to determine alterations in the composition of the intestinal microbiota and metabolites. Western blotting, immunofluorescence, and flow cytometry were performed to examine the anti-inflammatory role of SLBZ. RESULTS: DSS treatment induced experimental colitis, and this induction was alleviated by SLBZ treatment, as evidenced by rescued pathological symptoms in the experimental colitis mouse groups. Network pharmacology analysis showed that SLBZ-target genes were enriched in pathogen-induced infectious and inflammatory pathways, as well as neoplastic processes. SLBZ administration also modulated the gut microbiota composition and metabolic profiles of experimental colitis mice and alleviated the progression of experimental colitis. We further showed via in-vitro experiments that SLBZ suppressed macrophage (Mφ) transition to pro-inflammatory phenotype (M1), rescued tumor necrosis factor-α (TNFα)-induced pyroptosis of intestinal organoids (IOs), and decreased the recruitment of Mφs by epithelial cells. CONCLUSION: SLBZ formula is an effective treatment for murine colitis and showed a stronger therapeutic capacity than melasazine. The pharmacological mechanisms of SLBZ involve the re-establishment of an anti-inflammatory milieu and healthy microbiome, which favors mucosal healing.

High ORAI3 expression correlates with good prognosis in human muscle-invasive bladder cancer.

The involvement of store-operated calcium channels (SOCCs) in tumor initiation and metastatic dissemination has been extensively studied, but how its member ORAI3 influences tumor progression is still elusive. The present study aimed to evaluate the prognostic value of ORAI3 expression and examine the correlation between ORAI3 expression and immune cell infiltration within the tumor microenvironment (TME) in human muscle-invasive bladder cancer (MIBC). We examined the expression profile of ORAI3 in MIBC using data from two databases; analyzed the correlation between ORAI3 expression and patient survival; explored cellular pathways related to ORAI3 expression by Gene Set Enrichment Analysis (GSEA); and predicted potential drugs using Connectivity Map (CMap). ORAI3 was significantly lower expressed in tumor mass compared to normal samples in MIBC, with a higher level of methylation at the promoter region in tumor than in normal tissue, indicating that ORAI3 is suppressed during cancer progression. Survival analysis showed that higher expression of ORAI3 correlated with good prognosis in MIBC. GSEA demonstrated that ORAI3 expression inversely correlated with cell differentiation, development and gene silencing, with differential expression of genes involved in epidermal and keratinocyte differentiation pathways and inflammatory responses. RNA sequencing of an ORAI3-silenced human bladder cancer cell line (T24 cells) corroborated enhancement of pro-neoplastic pathways in absence of ORAI3. Western blottingMoreover, ORAI3 facilitated the recruitment of Th17 cells and natural killer cells, whereas hampered Th2 and macrophage infiltration. Our results revealed 4 molecules with potential to be beneficial as adjuvant drugs in MIBC treatment. We concluded that high ORAI3 expression correlates with increased survival in human MIBC.

[Exploration and practice of post-marketing survival benefit evaluation of Chinese patent medicine for cancer].

Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.

A comparison of the MNA-SF, MUST, and NRS-2002 nutritional tools in predicting treatment incompletion of concurrent chemoradiotherapy in patients with head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) treatment incompletion is a known negative prognosticator for patients with head and neck cancer (HNC). Malnutrition is a common phenomenon which leads to treatment interruption in patients with HNC. We aimed to compare the performance of three nutritional tools in predicting treatment incompletion in patients with HNC undergoing definitive CCRT. MATERIAL AND METHODS: Three nutritional assessment tools, Mini Nutritional Assessment-Short Form (MNA-SF), Malnutritional Universal Screening Tool (MUST), and Nutritional Risk Screening 2002 (NRS-2002), were prospectively assessed prior to CCRT for HNC patients. Patients were stratified into either normal nutrition or malnourished groups using different nutrition tools. Treatment incompletion and treatment-related toxicities associated with CCRT were recorded. RESULTS: A total of 461 patients were included in the study; malnourished rates ranged from 31.0 to 51.0%. The CCRT incompletion rates were 4.9-6.3% and 14.5-18.2% for normal nutrition patients and malnourished patients, respectively. The tools had significant correlations with each other (Pearson correlation 0.801-0.837, p<0.001 for all) and accurately predicted the incompletion of CCRT. MNA-SF had the highest performance in predicting treatment-related toxicity, including emergency room visits, need for hospitalization, any grade III or higher hematological adverse events, and critical body weight loss, compared to the other tools. CONCLUSIONS: MNA-SF, MUST, and NRS2002 were all shown to be competent tools for prediction of treatment incompletion and treatment-related toxicity in HNC patients undergoing CCRT. We suggest implementing nutritional assessment prior to treatment to improve the rate of treatment completion and to reduce treatment-related toxicity in HNC patients.

Determination of insulin lispro in rat plasma by LC-MS/MS and its application in a pharmacokinetics study / 药学学报

Compared with human insulin, insulin lispro shows a faster hypoglycemic effect and a higher peak plasma concentration, which can better control postprandial hyperglycemia. In this study, we used a solid phase extraction pretreatment method and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify insulin lispro in rat plasma. Bovine insulin was used as an internal standard. Plasma samples were separated on an ACQUITY UPLC Peptide CSH C18 column (2.1 mm × 50 mm, 1.7 μm) after solid phase extraction. Positive electrospray ionization was performed using multiple reaction monitoring (MRM) with transitions of m/z 1 162.5→217.2 for insulin lispro and m/z 1 157.5→136.0 for insulin bovine (internal standard). The method validation results showed that the linear range was 0.1 ng·mL-1 - 100 ng·mL-1; intra- and inter-day accuracy and precision met the acceptance criteria for biological sample analysis. The recovery of insulin lispro ranged from 63.1% to 68.1%. The method was applied in a pharmacokinetic study of insulin lispro following a single-dose subcutaneous administration to rats. Animal experiments were approved by the Experimental Animal Ethics Committee of Shanghai Institute of Materia Medica, Chinese Academy of Sciences.

Exploration and practice of post-marketing survival benefit evaluation of Chinese patent medicine for cancer / 中国中药杂志

Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.