A review of Phyllanthus urinaria L. in the treatment of liver disease: viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma.

Due to the pathological production of liver disease in utility particularly complexity, the morbidity and mortality of liver disease including viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. Considering its insidious onset, rapid progression and drug resistance, finding an effective therapy is particularly worthwhile. Phyllanthus urinaria L. (P. urinaria), an ethnic medicine, can be applied at the stages of viral hepatitis, liver fibrosis/cirrhosis and HCC, which demonstrates great potential in the treatment of liver disease. Currently, there are numerous reports on the application of P. urinaria in treating liver diseases, but a detailed analysis of its metabolites and a complete summary of its pharmacological mechanism are still scarce. In this review, the phytochemical metabolites and ethnopharmacological applications of P. urinaria are summarized. Briefly, P. urinaria mainly contains flavonoids, lignans, tannins, phenolic acids, terpenoids and other metabolites. The mechanisms of P. urinaria are mainly reflected in reducing surface antigen secretion and interfering with DNA polymerase synthesis for anti-viral hepatitis activity, reducing hepatic stellate cells activity, inflammation and oxidative stress for anti-liver fibrosis/cirrhosis activity, as well as preventing tumor proliferation, invasion and angiogenesis for anti-HCC activity via relevant signaling pathways. Accordingly, this review provides insights into the future application of natural products in the trilogy of liver diseases and will provide a scientific basis for further research and rational utilization of P. urinaria.

A Novel Multi-Effect Photosensitizer for Tumor Destruction via Multimodal Imaging Guided Synergistic Cancer Phototherapy.

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.

A SARS-CoV-2 Mpro fluorescent sensor for exploring pharmacodynamic substances from traditional Chinese medicine.

The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL-1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.

A Rapid and Accurate UHPLC Method for Determination of Monosaccharides in Polysaccharides of Different Sources of Radix Astragali and Its Immune Activity Analysis.

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITYTM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R2, 0.9971-0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.

Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy.

The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemotherapy from LST-4 NPs and the synergistic amplification of oxidative damage, through increasing the reactive oxygen species (ROS) by photodynamic therapy (PDT), causing an GSH decrease via LST-4 mediation to effectively kill tumor cells. Therefore, multifunctional LST-4@ZnPc NPs are a promising method for killing cancer cells, which also provides a new paradigm for using natural products to kill tumors.

Significant enhancement of swallowing function and oral hygiene following multidisciplinary team nursing in tongue cancer patients after radical resection.

OBJECTIVE: To determine the effects of multidisciplinary team (MDT) nursing mode on the swallowing function and oral hygiene in patients after radical resection of tongue cancer (TC). METHODS: The data of 88 patients with TC treated in West China School/Hospital of Stomatology, Sichuan University were analyzed retrospectively. Among them, 42 patients who received routine nursing between February 2019 and February 2020 were assigned to a control group, and 46 patients who received MDT nursing between March 2020 and February 2022 were assigned to an observation group. The two groups were compared in the changes of postoperative swallowing function and oral hygiene, postoperative swallowing-related quality of life (QoL), and the survival rate for myocutaneous flap. The risk factors affecting swallowing function were analyzed through Logistic regression. RESULTS: After one month of nursing, the score of swallowing function decreased notably in both groups, with notably lower score in the observation group than that in the control group (P < 0.05). The control group exhibited notably lower oral cleanliness than the observation group after nursing (P < 0.05). Additionally, a notably lower survival rate of myocutaneous flap was found in the control group than that in the observation group (P < 0.05). The QoL scores of the two groups increased notably after nursing, and the observation group had notably higher QoL score than the control group (P < 0.05). The extent of glossectomy and nursing plan were independent risk factors impacting the recovery of swallowing function (P < 0.05). CONCLUSION: MDT nursing have a positive impact on oral hygiene as well as the swallowing function of patients after radical resection of TC, and MDT is a protective factor for swallowing function in the patients after radical resection.

Enhancing labor productivity as a key strategy for fostering green economic growth and resource efficiency.

Amidst a time when uncontrolled economic growth has frequently harmed the environment, it is crucial to reassess our strategy toward economic progress. The necessity to tackle climate change, resource depletion, and environmental deterioration demands a profound transition towards ecologically sound and sustainable economic development. This study examines the crucial significance of labor productivity in promoting sustainable economic growth and the effective utilization of resources in Asia, Europe, and South America from 1990 to 2020. To accomplish this, we utilized the Data Envelopment Analysis (DEA) methodology to examine a range of input and output characteristics thoroughly. These parameters included labor productivity, renewable energy usage, material efficiency, Green GDP, carbon footprint, and water footprint. The results of our study demonstrate significant regional variations in the efficient utilization of labor and resources to promote sustainable economic development. The findings of the DEA model emphasize that countries with higher labor productivity are more capable of pursuing an environmentally benign and sustainable financial path. Moreover, our research demonstrates a substantial association between enhanced labor productivity and diminished carbon and water footprints. This highlights the importance of labor productivity as a fundamental element for maximizing resource efficiency. In addition, we propose policy suggestions that motivate and improve worker efficiency as a practical strategy to accomplish both economic growth and environmental sustainability.

Yang-Lee Zeros, Semicircle Theorem, and Nonunitary Criticality in Bardeen-Cooper-Schrieffer Superconductivity.

Yang and Lee investigated phase transitions in terms of zeros of partition functions, namely, Yang-Lee zeros [Phys. Rev. 87, 404 (1952)PHRVAO0031-899X10.1103/PhysRev.87.404; Phys. Rev. 87, 410 (1952)PHRVAO0031-899X10.1103/PhysRev.87.410]. We show that the essential singularity in the superconducting gap is directly related to the number of roots of the partition function of a BCS superconductor. Those zeros are found to be distributed on a semicircle in the complex plane of the interaction strength due to the Fermi-surface instability. A renormalization-group analysis shows that the semicircle theorem holds for a generic quantum many-body system with a marginal coupling, in sharp contrast with the Lee-Yang circle theorem for the Ising spin system. This indicates that the geometry of Yang-Lee zeros is directly connected to the Fermi-surface instability. Furthermore, we unveil the nonunitary criticality in BCS superconductivity that emerges at each individual Yang-Lee zero due to exceptional points and presents a universality class distinct from that of the conventional Yang-Lee edge singularity.

An aggregation-induced emission sensor combined with UHPLC-Q-TOF/MS for fast identification of anticoagulant active ingredients from traditional Chinese medicine.

Xuebijing injection (XBJ) has a good therapeutic effect on the patients with severe coronavirus disease, but the material basis of XBJ with the anticoagulant effect to improve the coagulopathy and thromboembolism is still unclear. Herein, we developed a new strategy based on aggregation-induced emission (AIE) for monitoring thrombin activity and screening thrombin inhibitors from XBJ. The molecule AIE603 and the thrombin substrate peptide S-2238 were formed into AIE nanoparticle (AIENP) which emitted notable fluorescence due to the restriction of intramolecular motions. In the presence of thrombin, AIENP was specifically hydrolyzed and AIE603 was released from AIENP, leading to the decrease of fluorescence intensity. Furthermore, AIENP was combined with ultra-high performance liquid chromatography-fraction collector (UHPLC-FC) and ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) for separation, preparation, screening and identification of the thrombin inhibitors from XBJ, a total of 58 chemical constituents were identified, among which 6 compounds possessed higher anticoagulant activity. Notably, the overall inhibition rate of the 6 mixed standards was equivalent to about 60% of the inhibition rate of XBJ. Therefore, this work provides a novel, cheap and simple method for monitoring thrombin activity and is promising to screen active substances from traditional Chinese medicines.

Discrimination of Radix Astragali from Different Growth Patterns, Origins, Species, and Growth Years by an H1-NMR Spectrogram of Polysaccharide Analysis Combined with Chemical Pattern Recognition and Determination of Its Polysaccharide Content and Immunological Activity.

The fraud phenomenon is currently widespread in the traditional Chinese medicine Radix Astragali (RA) market, especially where high-quality RA is substituted with low-quality RA. In this case, focused on polysaccharides from RA, the classification models were established for discrimination of RA from different growth patterns, origins, species, and growth years. 1H Nuclear Magnetic Resonance (H1-NMR) was used to establish the spectroscopy of polysaccharides from RA, which were used to distinguish RA via chemical pattern recognition methods. Specifically, orthogonal partial least squares discriminant analysis (OPLS-DA) and linear discriminant analysis (LDA) were used to successfully establish the classification models for RA from different growth patterns, origins, species, and growth years. The satisfactory parameters and high accuracy of internal and external verification of each model exhibited the reliable and good prediction ability of the developed models. In addition, the polysaccharide content and immunological activity were also tested, which was evaluated by the phagocytic activity of RAW 264.7. And the result showed that growth patterns and origins significantly affected the quality of RA. However, there was no significant difference in the aspects of origins and growth years. Accordingly, the developed strategy combined with chemical information, biological activity, and multivariate statistical method can provide new insight for the quality evaluation of traditional Chinese medicine.

Hot Spot Engineering in Hierarchical Plasmonic Nanostructures.

The controllable nanogap structures offer an effective way to obtain strong and tunable localized surface plasmon resonance (LSPR). A novel hierarchical plasmonic nanostructure (HPN) is created by incorporating a rotating coordinate system into colloidal lithography. In this nanostructure, the hot spot density is increased drastically by the long-range ordered morphology with discrete metal islands filled in the structural units. Based on the Volmer-Weber growth theory, the precise HPN growth model is established, which guides the hot spot engineering for improved LSPR tunability and strong field enhancement. The hot spot engineering strategy is examined by the application of HPNs as the surface-enhanced Raman spectroscopy (SERS) substrate. It is universally suitable for various SERS characterization excited at different wavelengths. Based on the HPN and hot spot engineering strategy, single-molecule level detection and long-range mapping can be realized simultaneously. In that sense, it offers a great platform and guides the future design for various LSPR applications like surface-enhanced spectra, biosensing, and photocatalysis.

A Non-Immunized and BSA-Template Aggregation-Induced Emission Sensor for Noninvasive Detection of Cystatin C in the Clinical Diagnosis of Diabetes Nephropathy.

Diabetes nephropathy (DN) is one of the main causes of death in patients with diabetes. Cystatin C (Cys C) is a reliable indicator of glomerular filtration function. Therefore, it is urgent and meaningful to obtain early warning of DN by noninvasive measurement of Cys C. In this investigation, a novel fluorescence sensor (BSA-AIEgen sensor) was synthesized by cross-linking the aggregation-induced emission (AIE) characteristics of 2-(4-bromophenyl)-3-(4-(4-(diphenylamino) styryl) phenyl) fumaronitrile (TPABDFN) and bovine serum albumin (BSA), which exhibited the "On" state owing to the restriction of the intramolecular motions (RIM) phenomenon of TPABDFN. Intriguingly, a decrease in fluorescence of BSA-AIEgen sensors could be found owing to BSA on the surface of BSA-AIEgen sensor hydrolyzed by papain, but a reverse phenomenon emerged with the increase of Cys C content as the inhibitor of papain. Hence, Cys C was successfully detected by employing the fluorescent differential display and the linear range was from 12.5 ng/mL to 800 ng/mL (R2 = 0.994) with the limit of detection (LOD) of 7.10 ng/mL (S/N = 3). Further, the developed BSA-AIEgen sensor successfully differentiates patients with diabetes nephropathy from volunteers with the advantages of high specificity, low cost, and simple operation. Accordingly, it is expected to become a non-immunized method to monitor Cys C for the early warning, noninvasive diagnosis, and drug efficacy evaluation of diabetes nephropathy.

Arg-liposome-amplified colorimetric immunoassay for selective and sensitive detection of cystatin C to predict acute kidney injury.

Cystatin C (Cys C) has been considered as a novel biomarker of kidney disease, which is thought to be a better indicator of glomerular filtration rate than creatinine (Scr) in the prediction of acute kidney injury (AKI). Hence, there is strong need to develop a precise, rapid and simple detection method for Cys C. Here we reported a Arg-liposome-amplified colorimetric immunoassay for the detection of Cys C to predict AKI. Cys C antibodies are conjugated on the surface of magnetic beads (MBs) and arginine (Arg)-loaded liposomes to form Ab1-MBs and Ab2-Arg-liposomes, respectively. When Ab1-MBs captured Cys C, Ab2-Arg-liposomes are added and incubated to form the immuno-sandwich complex. After magnetic separation, the surfactant Triton ×100 is added to damage the liposomes, leading to the release of Arg which can induce the gold nanoparticles aggregation. Therefore, the discoloration can be used for visual and quantitative detection of Cys C. Notably, the method has a linear relation in the range of 10-100 µg/L for Cys C with a limit of detection 4.32 µg/L, which is lower than some of the previous reports. In addition, the AKI mice serum samples were tested by the developed method, which were in good agreement with ELISA results. More intriguingly, the results of cisplatin induced acute kidney injury in mice showed that the method could be used to evaluate the protective effect of astragalus membranaceus (AM) on AKI by detecting Cys C in serum, providing a new strategy for screening renal protective drugs. Accordingly, a rapid and highly sensitive Cys C detection system was established with great potential for clinical diagnostics.

A nano-preparation approach to enable the delivery of daphnoretin to potentiate the therapeutical efficacy in hepatocellular cancer.

Daphnoretin (DAP), isolated from a traditional Chinese medicine Wikstroemia indica (Linn. C. A. Meyer), could induce apoptosis of hepatocellular cancer (HCC) and inhibit tumor growth. However, the application of DAP in cancer therapies was hampered because to its poor solubility. Herein, this study aimed to design an approach of double-targeted nano-preparation to enable the delivery of DAP to potentiate the therapeutical efficacy in liver cancer via glycyrrhetinic acid-polyethylene glycol-block-poly (D,L-lactic acid)/polyethylene glycol-block-poly (D,L-lactic acid)-DAP (GPP/PP-DAP). In particular, the purity of separated DAP was up to 98.12% for preparation research. GPP/PP-DAP was successfully prepared by the thin-film hydration method. Subsequently, the GPP/PP-DAP was optimized by univariate analysis and the response surface methodology, producing a stable and systemically injectable nano-preparation. Impressively, on the one hand, cytotoxicity studies showed that the IC50 of the GPP/PP-DAP was lower than that of free DAP. On the other hand, the GPP/PP-DAP was more likely to be endocytosed by HepG2 cells and targeted to the liver with orthotopic tumors, potentiating the therapeutical efficacy in HCC. Collectively, both in vitro and in vivo results indicated the excellent tumor inhibition and liver targeting of GPP/PP-DAP, suggesting the nano-preparation could serve as a potential drug delivery system for natural ingredients with anti-hepatoma activity to lay the theoretical foundation for clinical application.

Rapid Fluorescence Sensor Guided Detection of Urinary Tract Bacterial Infections.

Introduction: Urinary tract infections (UTI) are one of the most serious human bacterial infections affecting millions of people every year. Therefore, simple and reliable identification of the urinary tract pathogenic bacteria within a few minutes would be of great significance for diagnosis and treatment of clinical patients with UTIs. In this study, the fluorescence sensor was reported to guide the detection of urinary tract bacterial infections rapidly. Methods: The Ami-AuNPs-DNAs sensor was fabricated by the amino-modified Au nanoparticles (Ami-AuNPs) and six DNAs signal molecules, which bound to the urinary tract pathogenic bacteria and generated corresponding response signals. Further, based on the collected response signals, identification was performed by principal component analysis (PCA) and linear discriminant analysis (LDA). The Ami-AuNPs and Ami-AuNPs-DNAs were characterized by transmission electron microscopy, UV-vis absorption spectrum, Fourier transform infrared spectrum, dynamic light scattering and zeta potentials. Thereafter, the Ami-AuNPs-DNAs sensor was used to discriminate and identify five kinds of urinary tract pathogenic bacteria. Moreover, the quantitative analysis performance towards individual bacteria at different concentrations were also evaluated. Results: The Ami-AuNPs-DNAs sensor were synthesized successfully in terms of spherical, well-dispersed and uniform in size, which could well discriminate five main urinary tract pathogenic bacteria with unique fingerprint-like patterns and was sufficiently sensitive to determine individual bacteria with a detection limit to 1×107 cfu/mL. Furthermore, the sensor had also been successfully applied to identify bacteria in urine samples collected from clinical UTIs. Conclusion: The developed fluorescence sensor could be applied to rapid and accurate discrimination of urinary tract pathogenic bacteria and holds great promise for the diagnosis of the disease caused by bacterial infection.

Accurate identification of kidney injury progression via a fluorescent biosensor array.

Identifying the progress of kidney injury may aid the effective treatment and intervention. Herein, we developed a fluorescent biosensor array for instantaneous and accurate identification of the kidney injury progression via "doubled" signals. The multichannel biosensor array consisted of polydopamine-polyethyleneimine (PDA-PEI) and multicolor-labelled different length of DNAs including AAAAA-Cyanine7 (5A-Cy7), AAAAAAAAAA-Texas Red (10A-Texas Red), and AAAAAAAAAAAAAAAAAAAA-VIC (20A-VIC). Facing to the variety of protein in urine with alterable charge accompanied with different progress of kidney injury, the composition of urine replaces the DNA signal molecules, forming their special fluorescence patterns. Taking the size of protein into consideration, the original three variables induced by the protein charge were extended to six variables induced by the two factors of protein particle size and charge difference, which could provide a more accurate strategy to identify the progress of kidney injury. Notably, this strategy not only opened up new perspective for identification the progress of kidney injury via the size and charge of urine protein, but also improved the resolving power of sensor array by increasing the number of sensor elements for extending their potential application to various diseases.

Small-Molecule Photoacoustic Imaging Probe with Aggregation-Enhanced Amplitude for Real-Time Visualization of Acute Kidney Injury.

Acute kidney injury (AKI) has become a growing issue for patients with the extensive use of all kinds of drugs in clinic. Photoacoustic (PA) imaging provides a noninvasive and real-time imaging method for studying kidney injury, but it has inherent shortages in terms of high background signal and low detection sensitivity for exogenous imaging agents. Intriguingly, J-aggregation offers to tune the optical properties of the dyes, thus providing a platform for developing new PA probes with desired performance. In this study, a small-molecule PA probe (BDP-3) was designed and synthesized. We serendipitously discovered that BDP-3 can transform into renal clearable nanoaggregates under physiological conditions. The hydrodynamic diameter of the BDP-3 increased from 0.64 ± 0.11 to 3.74 ± 0.39 nm when the content of H2O increased from 40 to 90%. In addition, it was surprising that such a transforming process can significantly enhance its PA amplitude (2.06-fold). On this basis, PA imaging with BDP-3 was applied as a new method for the noninvasive detection of AKI induced by anticancer drugs, traditional Chinese medicine, and clinical contrast agents in animal models and exhibited higher sensitivity than the conventional serum index test, demonstrating great potential for further clinical diagnostic applications.

Clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Chemical characteristics of Rhodiola Crenulata and its mechanism in acute mountain sickness using UHPLC-Q-TOF-MS/MS combined with network pharmacology analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata (Hook.f. & Thomson) H.Ohba has a long history of clinical application for the prevention and treatment of acute mountain sickness (AMS) in traditional Chinese medicine. However, gaps in knowledge still exist in understanding the underlying mechanisms of Rhodiola crenulata against AMS. AIMS: To address this problem, a comprehensive method was established by combining UHPLC-Q-TOF-MS/MS analysis and network pharmacology. MATERIALS AND METHODS: The ingredients of Rhodiola crenulata were comprehensively analyzed using UHPLC-Q-TOF-MS/MS method. On this basis, a network pharmacology method incorporated target prediction, protein-protein interaction network, gene enrichment analysis and components-targets-pathways network was performed. Finally, the possible mechanisms were verified through molecular docking, in vitro and in vivo experiments. RESULTS: A total of 106 constituents of Rhodiola crenulata were charactered via UHPLC-Q-TOF-MS/MS. The 98 potentially active compounds out of 106 were screened and corresponded to 53 anti-AMS targets. Gene enrichment analysis revealed that hypoxia and inflammation related genes may be the central factors for Rhodiola crenulata to modulate AMS. Molecular docking revealed that TNF, VEGFA and HIF-1α had high affinities to Rhodiola crenulata compounds. Subsequently, Rhodiola crenulata extract was indicated to inhibit the protein expression level of TNF in hypoxia induced H9c2 cells. Lastly, Rhodiola crenulata extract was further verified to ameliorate heart injury and decreased the heart levels of TNF, VEGFA and HIF-1α in acute hypoxia-induced rats. CONCLUSIONS: This study used UHPLC-Q-TOF-MS/MS analysis and a network pharmacology to provide an important reference for revealing the potential mechanism of Rhodiola crenulata in the prevention and treatment of AMS.

Based on Multi-Activity Integrated Strategy to Screening, Characterization and Quantification of Bioactive Compounds from Red Wine.

According to French Paradox, red wine was famous for the potential effects on coronary heart disease (CHD), but the specific compounds against CHD were unclear. Therefore, screening and characterization of bioactive compounds from red wine was extremely necessary. In this paper, the multi-activity integrated strategy was developed and validated to screen, identify and quantify active compounds from red wine by using ultra high performance liquid chromatography-fraction collector (UHPLC-FC), ultra fast liquid chromatography-quadrupole-time-of-flight/mass spectrometry (UFLC-Q-TOF/MS) and bioactive analysis. UHPLC-FC was employed to separate and collect the components from red wine, which was further identified by UFLC-Q-TOF/MS to acquire their structural information. Furthermore, the active fractions were tested for antioxidant activity, inhibitory activity against thrombin and lipase activities in vitro by the activity screening kit. As the results, there were 37 fractions had antioxidant activity, 22 fractions had thrombin inhibitory activity and 28 fractions had lipase inhibitory activity. Finally, 77 active components from red wine were screened and 12 ingredients out of them were selected for quantification based on the integration of multi-activity. Collectively, the multi-activity integrated strategy was helpful for the rapid and effective discovery of bioactive components, which provided reference for exploring the health care function of food.