[Analysis of Clinical Characteristics and Laboratory Indicators in Patients with Solid Malignant Tumor-Associated Venous Thromboembolism].

OBJECTIVE: To analyze the clinical features and laboratory indicators in patients with solid malignant tumor-associated venous thromboembolism (Ta-VTE), and to study the risk factors for Ta-VTE. METHODS: The hospitalized patients with VTE in Guizhou Provincial People's Hospital from January to December 2020 were enrolled, and they were divided into Ta-VTE group and pure VTE group based on the presence or absence of solid malignant tumor. The differences in clinical data and laboratory indicators between the two groups were analyzed, and the indicators with significant differences were included in logistic regression model to analyze the risk factors of Ta-VTE. RESULTS: A total of 288 patients with VTE were included in this study, including 64 cases in Ta-VTE group and 224 cases in pure VTE group, respectively. There were significant differences in the following indexes between the two groups, including the hospitalization time (14.20±15.29 d vs 10.05±6.90 d, t=3.112, P =0.002), pain (35.94% vs 65.18%, χ2=17.554, P =0.000), recent surgery (75.00% vs 37.50%, χ2=28.196, P =0.000), D-dimer [2.8 (0.92, 7.55) µg/ml vs 5.69 (2.25, 13.91) µg/ml, Z=-2.710, P =0.007], PLR[198.59 (139.54, 312.16) vs 149.76 (114.08, 233.66), Z=-2.924, P =0.003] and TBIL[10.90 (7.63, 15.68) µmol/L vs 12.90 (9.33, 18.28) µmol/L, Z=-2.066, P =0.039]. There was no significant difference in the other indicators (P >0.05). The result of multivariate logistic regression analysis showed that elevated PLR (OR =1.003, 95%CI : 1.000-1.006, P =0.027), recent surgery (OR =4.312, 95%CI : 2.093-8.885, P =0.000) and prolonged hospitalization (OR =1.037, 95%CI : 1.002-1.074, P =0.038）were independent risk factors for Ta-VTE. However, pain (OR =0.274, 95%CI : 0.133-0.564, P =0.000) was a protective factor. CONCLUSION: Elevated PLR level, recent surgery and prolonged hospital stay are independent risk factors for Ta-VTE patients, and rational use of these indicators is helpful for the clinical diagnosis and treatment of Ta-VTE patients.

Feasibility study of use of desflurane combined with dexmedetomidine in inhibiting postoperative neurocognitive disorders in elderly patients under general anesthesia: A perspective study.

This study aimed to explore whether the combined application of desflurane and dexmedetomidine (Dex) reduces the occurrence of postoperative neurocognitive disorders (PND) in patients. We selected patients in our hospital who underwent surgery under general anesthesia, and divided them into two groups: Dex and desflurane (Dex + Des) and desflurane (Des) groups. The data of patients were collected and the Mini-Mental State Examination (MMSE) score was used to assess cognitive status. The blood cell counts were determined preoperatively and on postoperative days 1, 3, and 6, and the percentage of neutrophils and lymphocytes were also recorded. The statistical methods used were the independent-samples t-test and the χ 2 test. Pearson's correlation was used to analyze the correlation between PND and inflammation. The incidence of PND in the Dex + Des group was lower than that in the Des group. The postoperative MMSE scores in the Dex + Des group were higher than those in the Des group (p = 0.032). The percentage of neutrophils in the Dex + Des group was significantly lower than that in the Des group on the first and third days after surgery (p = 0.007; p = 0.028). The MMSE scores on the first day after surgery were negatively correlated with the multiple changes in white blood counts and the percentage of neutrophils (r = -0.3038 and -0.3330). Dex combined with Des reduced the incidence of PND and reduced the postoperative inflammatory cell counts.

NIR-responsive copper nanoliposome composites for cascaded ferrotherapy via ferroptosis actived ICD and IFN-γ released.

Metallic biomaterials activate tumor ferroptosis by increasing oxidative stress, but their efficacy is severely limited in tumor microenvironment. Although interferon gamma (IFN-γ) can promote tumor ferroptosis sensitivity by inhibiting the antioxidant system and promoting lipid accumulation, this effect limited by the lack of IFN-γ accumulation in tumors. Herein, we report a near-infrared (NIR)-responsive HCuS nanocomposite (HCuS-PE@TSL-tlyp-1) that can stimulate immunogenic cell death (ICD)-mediated IFN-γ secretion through exogenous oxidative stress, thereby achieving cascaded ferrotherapy by mutually reinforcing ferroptosis and systemic immunity. Upon laser irradiation, the dissolution of the thermal coating, and the introduction of Cu ions and piperazine-erastin (PE) simultaneously induce oxidative stress by reactive oxygen species (ROS)/lipid peroxide (LPO) accumulation and deplete cystine-glutamate transporter (xCT)/GSH. The onset of oxidative stress-mediated ferroptosis is thus achieved, and ICD is triggered, significantly promoting cytotoxic T-cell (CTL) infiltration for IFN-γ secretion. Furthermore, IFN-γ induces immunogenic tumor ferroptosis by inhibiting xCT-antioxidant pathways and enhancing the ACSL4-fatty acid recruitment pathway, which further promotes sensitivity to ferroptosis in cells. These HCuS nanocomposites combined with aPD-L1 effectively in inhibiting tumor metastasis and recurrence. Importantly, these cascade ferrotherapy results broadens the application of HCuS biomaterials.

Correction: Chen et al. Identification of the Causal Agent of Brown Leaf Spot on Kiwifruit and Its Sensitivity to Different Active Ingredients of Biological Fungicides. Pathogens 2022, 11, 673.

In the original publication [...].

Effects of mind-body exercise on cognitive performance in middle-aged and older adults with mild cognitive impairment: A meta-analysis study.

BACKGROUND: To systematically evaluate the clinical efficacy of physical and mental exercise on cognitive performance in middle-aged people with mild cognitive impairment (MCI). METHODS: Computer searches of PubMed, Web of science, Embase, Cochrane Library, China Biomedical Literature Service, Wanfang database, China Knowledge Network, and VIP full-text database of Veep journals were conducted to obtain clinical randomized controlled trials on physical and mental exercise interventions in middle-aged and elderly people with MCI. The literature was screened according to inclusion and exclusion criteria, and the final included literature was subjected to data extraction and risk of bias assessment. Meta-analysis was performed using Review Manager 5.4.1 software, and publication bias test was performed using stata17.0 software. RESULTS: A total of 27 publications with a total of 2565 cases of elderly people with MCI were included. The control group was conventional care, health education, or blank control, and the physical and mental exercise group was exercises including Tai Chi, dance, orthopraxia, and qigong for 30 to 90 minutes each time, 3 to 6 times per week, for a total duration of 8 to 36 weeks. Meta-analysis results showed that Montreal cognitive assessment scores (mean difference [MD] = 2.33, 95% CI [1.55, 3.10], P < .00001), the mini-mental state examination score (MD = 1.73, 95% CI [0.60, 2.86], P = .003), trail making test-A score (MD = -4.00, 95% CI [-6.75, -1.25], P = .004), trail making test-B score (MD = -18.46, 95% CI [-23.87, -13.06], P < .00001), global deterioration scale score (MD = -0.72, 95% CI [-1.09, -0.34], P = .0002), Wechsler Logical Memory Scale score (MD = 2.07, 95% CI [0.03, 4.10], P = .05), berg score (MD = -0.70, 95% CI [0.32, 1.07], P < .0003), cerebrospinal fluid Tau protein level (MD = -166.69, 95% CI [-196.93, -136.45], P < .00001), and cerebrospinal fluid levels of αß1-42 protein (MD = 180.39, 95% CI [134.24, 226.55], P < .00001). CONCLUSION: Mind-body exercise can improve cognitive performance, depressive status, and balance as well as increase αß1-42 protein levels and decrease Tau protein levels in middle-aged and older adults with mild cognitive impairment.

Genetic and Clinical Characteristics of Patients with Philadelphia-Negative Myeloproliferative Neoplasm Carrying Concurrent Mutations in JAK2V617F, CALR, and MPL.

Simultaneous mutations in Janus kinase 2 (JAK2), calreticulin, and myeloproliferative leukemia (MPL) genes are generally not considered for characterizing Philadelphia-negative myeloproliferative neoplasms (MPNs), leading to misdiagnosis. Sanger sequencing and quantitative polymerase chain reaction were used to detect gene mutations in patients with MPN. We retrospectively screened the data of patients with double mutations in our center and from the PubMed database. Two patients tested positive for both JAK2V617F and CALR mutations (2/352 0.57%) in our center, while data of 35 patients from the PubMed database, including 26 patients with essential thrombocythemia (ET), 6 with primary myelofibrosis (PMF), 2 with unexplained thrombosis, and 1 with polycythemia vera were screened for double mutations. Among these mutations, co-mutation of JAKV617F-CALR constituted the majority (80.0%), when compared with JAKV617F-MPL (17.1%) and CALR-MPL (2.9%) mutations. Moreover, patients with concurrent mutational myeloproliferative neoplasm (MPN) were relatively older (P = .010) with significantly higher platelet counts than their counterparts with single gene mutations (P < .001). The occurrence of palpable splenomegaly (P < .001) and leukocyte count (P = .041) were also significantly different between patients with single and simultaneous gene mutations. These 4 risk factors also showed significant test effectiveness in the ET and PMF cohorts (P < .05). In terms of clinical characteristics of patients with ET, those with JAK2V617F-CALR mutation had higher but normal hemoglobin levels (P = .0151) than those carrying JAK2V617F-MPL mutation. From a clinical perspective, patients with multiple mutational MPN are different from those with single gene mutations. The poor treatment response by patients in our center and unfavorable indicators for patients with co-mutations in published literature indicate that customized treatment may be the best choice for patients with MPN carrying co-mutations.

A review of hemostatic chemical components and their mechanisms in traditional Chinese medicine and ethnic medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine and ethnic medicine together play an important value in the modern medicine system that is different from that of chemical drugs. Chinese medicine and ethnic medicine with hemostatic effect have unique advantages and development potential in the prevention and treatment of clinical hemorrhagic diseases, reflecting multi-component, multi-target and multi-pathway effects. AIM OF THE STUDY: In this paper, the active ingredients related to the hemostatic effect of traditional Chinese medicine and ethnic medicine are taken as the starting point, and the traditional Chinese medicine and ethnic medicine with traditional hemostatic purposes are reviewed, and the existing research progress on the active ingredients and their mechanism of action of these drugs is systematically expounded, aiming to provide theoretical reference for the development of traditional hemostatic drugs, the discovery of hemostatic active ingredients and the research of new hemostatic methods. MATERIALS AND METHODS: Hemostatic chinese medicine and ethnic medicine were collected and summarized from the classic books of Materia Medica, public literature database and doctoral or master's thesis repositories. At the same time, we discussed the classification of various types of hemostatic active ingredients of traditional Chinese medicine and ethnic medicine according to the different mechanisms of hemostasis. RESULTS: A total of 436 traditional Chinese medicine and ethnic medicine with hemostatic effects have been collected, and their hemostatic active ingredients include alkaloids, quinones, flavonoids, phenylpropanoids, organic acids, amino acids, terpenoids, steroids, phenols, tannins, esters, polysaccharides and herbal extracts, etc. These active ingredients accelerate the formation of hemostasis by improving endogenous and exogenous hemostatic pathways mainly through enhancing vascular wall contraction, increasing platelet aggregation, promoting coagulation system activation and inhibiting fibrinolysis. CONCLUSIONS: This article reviews the previous data on various aspects of the hemostatic effect of traditional Chinese medicine and ethnomedicine. Many traditional hemostatic drugs have been discovered and many active ingredients and mechanisms have been reported. However, although there are a large number of drugs with traditional hemostatic effects, there are still few developed and applied. At the same time, the hemostatic components of many drugs still remain in the study of the activity of their total extracts, and the potential link between some drug components achieving hemostatic effects through different mechanisms remains to be elucidated.

Diet quality of primary and secondary school students in Yunnan Province / 中国学校卫生

Objective@#To evaluate diet quality and related problems among children and adolescents in Yunnan Province, in order to provide a theoretical basis for the formulation of targeted dietary interventions for children and adolescents in this region.@*Methods@#Using a stratified random sampling method, 1 078 primary and secondary school students from six prefecture level cities in Yunnan Province were selected from August to November 2022. Dietary quality was evaluated by applying the China Children s Dietary Index (CCDI-2016) on the basis of a 3 d 24 h dietary survey.@*Results@#The total dietary index score of children and adolescents in Yunnan Province was 62.63(54.57,71.19). The overall recommended intakes were largely achieved by consumption of cereals, eggs and sugary drinks, with dietary index scores of 9.91(8.24,10.00), 5.58(0,8.58) and 9.20(7.38,10.00), respectively; there were inadequate intakes of vegetables, legumes, water, vitamin A and dietary fiber, with scores of 5.63(4.09,7.59), 3.48 (0,9.70), 4.23(2.67,5.50), 2.33(1.56,3.53), 3.19(1.63,5.67), respectively; intake of fruits, dairy and aquatic products were severely deficient, with scores of 0(0,1.74), 0(0,2.37), 0(0,9.85), respectively; excessive intake of meat was found, with a dietary index score of 0(0,2.46). The stratified analysis showed that children and adolescents aged 11-13 years had the highest total dietary scores[65.35(54.29,72.03)], followed by those aged 7-10 years[63.46(56.19,72.63)], while the 14-17 year old age group had the lowest scores[59.07(51.15,68.30), H=32.23, P <0.01]. Girls had higher total dietary scores than that of boys[64.20(56.12,72.56), 59.32(52.60,69.72), Z=-5.16, P <0.01], while urban children and adolescents had higher total dietary scores than rural children and adolescents[65.30(54.84,73.62), 62.17(54.31,70.70), Z=-2.11, P <0.05]. Furthermore, higher total dietary index scores were observed among children and adolescents whose parents had a higher educational level( H=27.68, 22.58, P <0.01). The comparison of ethnic groups revealed that the Wa children and adolescents had the highest total dietary index scores, while the Hani children had the lowest( H=27.51, P <0.01).@*Conclusion@#The overall dietary quality of children and adolescents in Yunnan Province is not high, the imbalance of dietary nutrition is prominent, and the dietary structure needs to be adjusted and optimized. Intervention programs should focus on the problem of insufficient intake of fruits and vegetables, milk and legumes, aquatic products and excessive intake of poultry meat among children and adolescents.

Identification of the Causal Agent of Brown Leaf Spot on Kiwifruit and Its Sensitivity to Different Active Ingredients of Biological Fungicides.

Kiwifruit (Actinidia chinensis) is an important commercial crop in China, and the occurrence of diseases may cause significant economic loss in its production. In the present study, a new pathogen that causes brown leaf spot disease on kiwifruit was reported. The fungus was isolated from an infected sample and identified as Fusarium graminearum based on morphological and molecular evaluation. Koch's postulates were confirmed when the pathogen was re-isolated from plants with artificially induced symptoms and identified as F. graminearum. Based on the biological characteristics of the pathogen, it was determined that: its optimal growth temperature was 25 °C; optimal pH was 7; most suitable carbon source was soluble starch; most suitable nitrogen source was yeast powder; and best photoperiod was 12 h light/12 h dark. Further investigations were conducted by determining 50% effective concentrations (EC50) of several active ingredients of biological fungicides against F. graminearum. The results showed that among the studied fungicides, tetramycin and honokiol had the highest antifungal activity against this pathogen. Our findings provide a scientific basis for the prevention and treatment of brown leaf spot disease on kiwifruit.

Intralayer Phonons in Multilayer Graphene Moiré Superlattices.

Moiré pattern in twisted multilayers (tMLs) induces many emergent phenomena by subtle variation of atomic registry to modulate quasiparticles and their interactions, such as superconductivity, moiré excitons, and moiré phonons. The periodic superlattice potential introduced by moiré pattern also underlies patterned interlayer coupling at the interface of tMLs. Although this arising patterned interfacial coupling is much weaker than in-plane atomic interactions, it is crucial in moiré systems, as captured by the renormalized interlayer phonons in twisted bilayer transitional metal dichalcogenides. Here, we determine the quantitative relationship between the lattice dynamics of intralayer out-of-plane optical (ZO) phonons and patterned interfacial coupling in multilayer graphene moiré superlattices (MLG-MS) by the proposed perturbation model, which is previously challenging for MLGs due to their out-of-phase displacements of adjacent atoms in one atomic plane. We unveil that patterned interfacial coupling introduces profound modulations on Davydov components of nonfolded ZO phonon that are localized within the AB-stacked constituents, while the coupling results in layer-extended vibrations with symmetry of moiré pattern for moiré ZO phonons. Our work brings further degrees of freedom to engineer moiré physics according to the modulations imprinted on the phonon frequency and wavefunction.

Capsaicin Prevents Contrast-Associated Acute Kidney Injury through Activation of Nrf2 in Mice.

Capsaicin, a transient receptor potential vanilloid 1 channel agonist, possesses antioxidative properties through activating nuclear factor-erythroid 2-related factor 2 (Nrf2). As oxidative stress is a major contributor to the development of contrast-associated acute kidney injury (CA-AKI), we investigated the protective effect of capsaicin against CA-AKI via Nrf2. C57BL/6J mice were treated with dehydration and iodixanol to establish the model of CA-AKI. For pretreatment, capsaicin (0.3 mg/kg) was given via intraperitoneal injection one hour before iodixanol injection. Nrf2-specific siRNA was given through the tail vein to knock down Nrf2. The CA-AKI mouse model had remarkable mitochondrial fragmentation and dysfunction and apoptosis of tubular cells, overproduction of superoxide in renal tubules, increased renal malondialdehyde, tubular epithelial cell injury, and renal dysfunction. Importantly, pretreatment with capsaicin significantly ameliorated tubular cell injury and renal dysfunction with decreased superoxide, renal malondialdehyde, and apoptotic tubular cells and improved mitochondrial morphology and function in the CA-AKI mouse model. The expression of Nrf2 was increased in the kidney from the CA-AKI mouse model and was further enhanced by capsaicin. Administration of siRNA through the tail vein successfully decreased Nrf2 expression in the kidney, and knockdown of Nrf2 by siRNA abolished the beneficial effects of capsaicin on CA-AKI. The present study demonstrated a protective effect of capsaicin pretreatment against CA-AKI via Nrf2.

The role of transient receptor potential ankyrin 1 in age-related endothelial dysfunction.

Oxidative stress plays a key role in age-related vascular disease. The present study aimed to investigate the role of an antioxidant channel, transient receptor potential ankyrin 1 (TRPA1), in age-related endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) were grown to induce replicative senescence, and 6-month-old young, 12-month-old middle-aged, and 24-month-old aged mice were used. TRPA1 was downregulated in senescent HUVECs, so were endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), and uncoupling protein 2 (UCP2). Activating TRPA1 with cinnamaldehyde prevented downregulation of eNOS, Nrf2, and UCP2, inhibited superoxide production and apoptosis, and preserved nitric oxide bioavailability in senescent HUVECs. TRPA1, phosphorylated eNOS, Nrf2 and UCP2 were significantly downregulated in aged aortas compared with young aortas after a compensatory upregulation in middle-aged aortas. Dietary administration of cinnamaldehyde for 12 months prevented mitochondrial dysfunction, improved endothelium-dependent relaxation, and increased expression of eNOS, Nrf2, and UCP2 in aged aortas. Importantly, the effects of cinnamaldehyde can be blocked by a TRPA1 antagonist HC-030031. These findings suggest that TRPA1 may play a critical role in age-related endothelial dysfunction and may become a therapeutic target for the treatment and prevention of age-related vascular disease.

Renal denervation in a patient with a highly tortuous renal artery using a guide extension catheter: a case report.

BACKGROUND: Catheter-based renal denervation (RDN) has been introduced to treat resistant hypertension. Although the technology of RDN has been largely improved, denervation of tortuous renal arteries remains challenging. CASE PRESENTATION: This is a case report of a 49-year-old man with drug resistant hypertension. The patient was selected for RDN after ruling out possible causes of secondary hypertension. Computed tomography angiography showed a highly tortuous left renal artery. An Iberis multielectrode ablation catheter failed to reach the target vessel with a regular guiding catheter. A 5-French extension catheter was introduced into the proximal segment of the main left renal artery to provide extra support force, which enabled successful ablation of the highly tortuous left renal artery. His ambulatory blood pressure was significantly decreased at 1 month follow-up. CONCLUSIONS: It is feasible and effective to use a guide extension catheter for denervation of highly tortuous renal arteries. The present study provides a useful method to ablate tortuous and angled renal arteries and branches.

[Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action].

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.

[Antipyretic activity and potential mechanism of Indigo Naturalis on 2,4-dinitrophenol-induced fever rat model].

As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%. However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated. In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects. The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1ß and IL-6 were determined by ELISA. Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients. The results showed that the rising trend of rectal temperature in rats was suppressed 0. 5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group( P < 0. 05),among which Indigo Naturalis and organic matter had better antipyretic effect. ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP( P<0. 01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α( P<0. 05). A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.

[Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation].

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1ßand TNF-αin serum and IL-1ßand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1ßlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world

BackgroundAlthough effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China. Methods and findingsSerum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University Peoples Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels ({chi}2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference ({chi}2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old ({chi}2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference ({chi}2=0.222, P >0.05). ConclusionsThe positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination. Author summaryO_ST_ABSWhy was this study done?C_ST_ABSO_LIAt present, the inactivated vaccines that have been approved to market in China have passed clinical trials to prove their effectiveness and safety. But the level of neutralizing antibodies induced by vaccination in the real world remains unclear. C_LIO_LISerological testing for neutralizing antibodies against COVID-19 is important for assessing vaccine and treatment responses and comparing multiple drug candidates. We assessed the levels of neutralizing antibodies produced in populations receiving inactivated vaccines and assessed the persistence of these vaccines in producing COVID-19 neutralizing antibodies in healthy adults. C_LI What did the researchers do and find?O_LIWe collected serum samples from 1,335 people aged 18 and above who had received COVID-19 vaccine in Peking University Peoples Hospital, and divided them into two groups according to one dose of inactivated vaccine and two doses of inactivated vaccine. C_LIO_LIOur study found that the positive rate of NAbs was 66.2% in adults who received one or two doses of inactivated vaccine and 77.3% in adults who received two doses of inactivated vaccine in the real world. C_LIO_LIFrom 11 to 70 days after the second dose of vaccine, the positive rate of neutralizing antibodies against COVID-19 was 82-100%; On days 71-332, the positive rate of neutralizing antibodies decreased to 27%. C_LIO_LIThe titer and the positive rate of NAbs in 18-40 years old group were significantly higher than that in 41-60 years old group. C_LI What do these findings mean?O_LIWhat is novel is we observed that in the real world, the positive rate of neutralization antibody was the highest at 10 to 70 days after the second vaccination, and with the extension of the vaccination time, the positive rate of antibody gradually decreased. Therefore, we recommend that the third dose of vaccine be administered at day 61 to day 70 for COVID-19 neutralizing antibodies levels. C_LIO_LIWe observed that there was a high linear correlation between COVID-19 neutralization antibodies and COVID-19 IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, COVID-19 IgM/IgG antibodies can be detected instead. C_LIO_LIIn our manuscript, we found that the titer and positive rate of neutralizing antibodies in 18-40 years old group were higher than those in 41-60 years old group. The level of neutralizing antibodies produced after vaccination was affected by age, but not by gender. C_LIO_LIWe also observed that the highest levels of NAbs were produced between shots 21 to 35 days apart, suggesting that 21 to 35 days between shots is suitable for vaccination. C_LI

Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice.

Background: Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined. Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury. Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting. Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1. Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

OBJECTIVE: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity. METHODS: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. RESULTS: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1ß (P＜0.05), IL-6 (p＜0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract. CONCLUSIONS: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.

Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. AIM OF THE STUDY: To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). MATERIALS AND METHODS: COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200-220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. RESULTS: The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. CONCLUSION: In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.