Research on quality marker based on the processing from Aconiti lateralis radix praeparata to Heishunpian.

INTRODUCTION: Aconiti lateralis radix praeparata (ALRP), the sub root of Aconitum carmichaelii Debx., is a traditional Chinese medicine with good pharmacological effects. Heishunpian (HSP), prepared through the process of brine immersing, boiling, rinsing, dyeing, and steaming ALRP is one of the most widely used forms of decoction pieces in clinical practice. OBJECTIVES: This study aims to investigate the mechanisms of component changes and transformations during the processing from ALRP to HSP, and to screen for their quality markers through UHPLC-QTOF-MS analysis. METHODS: Samples from ALRP to HSP during processing were prepared and analyzed by UHPLC-QTOF-MS. By comparing the differences between before and after each processing step, the purpose of processing and the transformation of components during processing were studied. In addition, multiple batches of ALRP and HSP were determined, and potential quality markers were screened. RESULTS: Through the analysis of ALRP and five key processing samples, 55 components were identified. Immersing in brine, rinsing, and dyeing were the main factors of component loss, and boiling caused a slight loss of components. Some components were enhanced during the steaming process. Combining the screened differences components between multiple ALRP and HSP, 10 components were considered as potential quality biomarkers. CONCLUSION: This study found that the adjacent hydroxyl groups of the ester group may have a positive impact on the hydrolysis of the ester group, and 10 quality markers were preliminarily screened. It provides a reference for quality control and clinical application of ALRP and HSP.

Coinfection with hepatic cystic and alveolar echinococcosis with abdominal wall abscess and sinus tract formation: A case report.

BACKGROUND: Hepatic cystic and alveolar echinococcosis coinfections, particularly with concurrent abscesses and sinus tract formation, are extremely rare. This article presents a case of a patient diagnosed with this unique presentation, discussing the typical imaging manifestations of both echinococcosis types and detailing the diagnosis and surgical treatment experience thereof. CASE SUMMARY: A 39-year-old Tibetan woman presented with concurrent hepatic cystic and alveolar echinococcosis, accompanied by abdominal wall abscesses and sinus tract formation. Initial conventional imaging examinations suggested only hepatic cystic echinococcosis, but intraoperative and postoperative pathological examination revealed the coinfection. Following radical resection of the lesions, the patient's condition improved, and she was discharged soon thereafter. Subsequent outpatient follow-ups confirmed no recurrence of the hydatid lesion and normal surgical wound healing. Though mixed hepatic cystic and alveolar echinococcosis with abdominal wall abscesses and sinus tract formations are rare, the general treatment approach remains consistent with that of simpler infections of alveolar echinococcosis. CONCLUSION: Lesions involving the abdominal wall and sinus tract formation, may require radical resection. Long-term prognosis includes albendazole and follow-up examinations.

A strategy for the preparation of super-hydrophilic molybdenum disulfide composites applied to remove uranium from wastewater.

Due to the radioactivity of uranium, the discharged nuclear wastewater not only causes certain damage to the ecology, but also causes certain harm to human life and health. Adsorption is considered to be one of the most effective ways to remove uranium. In this paper, a kind of MoS2 adsorbent was prepared by the solid phase synthesis method and functionalized with NiCo-LDH. The raw materials of MoS2 are cheap and easy to obtain, and the preparation conditions are simple, and large quantities can be obtained without limitations. MoS2 functionalized with NiCo-LDH provides more adsorption sites for the adsorbent and at the same time improves the hydrophilicity of the adsorbent, so that the active sites can fully combine with uranyl ions. The maximum adsorption capacity of the Langmuir isothermal adsorption model is 492.83 mg g-1. The selective adsorption capacity of uranium can reach 76.12% in the multi-ion coexistence system. By analyzing the adsorption mechanism with FT-IR and XRD, it is believed that on the one hand, UO22+ forms a covalent bond with Mo in MoS2 and coordinates with S on the surface of MoS2. On the other hand, UO22+ enters the NiCo-LDH layer for ion exchange with NO3- and coordinates with -OH on the surface of NiCo-LDH. The successful preparation of the MoS2/NiCo-LDH composite provides a certain application prospect for the uranium adsorption field.

Effect of vinegar steaming on the composition and structure of Schisandra chinensis polysaccharide and its anti-colitis activity.

In this study, infrared spectroscopy, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) technology were applied to systematically explain the Schisandra chinensis's polysaccharide transformation in configuration, molecular weight, monosaccharide composition, and anti-ulcerative colitis (UC) activity after vinegar processing. Scanning electron microscopic results showed that the appearance of S. chinensis polysaccharide changed significantly after steaming with vinegar. The MALDI-TOF-MS results showed that the mass spectra of raw S. chinensis polysaccharides (RSCP) were slightly lower than those of vinegar-processed S. chinensis polysaccharides (VSCP). The RSCP showed higher peaks at m/z 1350.790, 2016.796, and 2665.985, all with left-skewed distribution, and the molecular weights were concentrated in the range of 1300-3100, with no higher peak above m/z 5000. The VSCPs showed a whole band below m/z 3000, with m/z 1021.096 being the highest peak, and the intensity decreased with the increase of m/z. In addition, compared to RSCPs, VSCPs can significantly increase the content of intestinal short-chain fatty acids (SCFAs). This study showed that the apparent morphology and molecular weight of S. chinensis's polysaccharides significantly changed after steaming with vinegar. These changes directly affect its anti-UC effect significantly, and its mechanism is closely related to improving the structure and diversity of gut microbiota and SCFA metabolism.

Research on the effects of processing Heishunpian from Aconiti lateralis radix praeparata on components and efficacy using the "step knockout" strategy.

Heishunpian is obtained through complex processing of Aconiti lateralis radix praeparata. However, the impact of each processing step on chemical compositions and pharmacological activities is still unclear. The mechanism of the processing needs to be further studied. The samples were all prepared using the "step knockout" strategy for UPLC-QTOF-MS analysis, and analgesic and anti-inflammatory efficacy evaluation. Each sample was analyzed by UPLC-QTOF-MS to determine the component differences. The hot plate test and acetic acid writhing test were used to evaluate the analgesic effect. Anti-inflammatory efficacy was evaluated by xylene-induced ear edema test. The correlation between components and efficacies was studied to screen the effective components for further investigating the processing of Heishunpian. Mass spectrum analysis results showed that 49 components were identified, and it appeared that brine immersion and rinsing had a great influence on the components. In the hot plate test, ibuprofen and Heishunpian had the most significant effect, while ibuprofen and the sample without rinsing showed the best efficacy for the acetic acid writhing test. The sample without dyeing had the best effect on ear edema. The correlation analysis indicated that mesaconine, aconine, 3-deoxyaconine, delbruine, and asperglaucide were potentially considered effective analgesic components. It is not recommended to remove brine immersion and rinsing. Boiling and steaming are necessary processes that improve efficacy. Dyeing, which does not have a significant impact on components and efficacy, may be an unnecessary process. This research has been of great significance in identifying anti-inflammatory and analgesic components and optimizing processing for Heishunpian.

[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Rapid evaluation of Ziziphi Spinosae Semen and its adulterants based on the combination of FT-NIR and multivariate algorithms.

Ziziphi Spinosae Semen (ZSS) is a valued seed renowned for its sedative and sleep-enhancing properties. However, the price increase has been accompanied by adulteration. In this study, chromaticity analysis and Fourier transform near-infrared (FT-NIR) combined with multivariate algorithms were employed to identify the adulteration and quantitatively predict the adulteration ratio. The findings suggested that the utilization of chromaticity extractor was insufficient for identification of adulteration ratio. The raw spectrum of ZMS and HAS adulterants extracted by FT-NIR was processed by SNV + CARS and 1d + SG + ICO respectively, the average accuracy of machine learning classification model was improved from 77.06 % to 97.58 %. Furthermore, the R2 values of the calibration and prediction set of the two quantitative prediction regression models of adulteration ratio are greater than 0.99, demonstrating excellent linearity and predictive accuracy. Overall, this study demonstrated that FT-NIR combined with multivariate algorithms provided a significant approach to addressing the growing issue of ZSS adulteration.

Development and Validation of Nomograms Based on Nutritional Risk Index for Predicting Extracapsular Extension and Seminal Vesicle Invasion in Patients Undergoing Radical Prostatectomy.

Background: The aim of the study was to investigate the predictive value of the nutritional risk index (NRI) for extracapsular extension (ECE) and seminal vesicle invasion (SVI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), and further develop and validate predictive nomograms for ECE and SVI based on the NRI. Methods: We retrospectively analyzed 734 PCa patients who underwent RP between 2010 and 2020 in the Department of Urology at Peking University Third Hospital. The enrolled patients were randomly divided into a primary cohort (n = 489) and a validation cohort (n = 245) in a 2:1 manner. The baseline NRI of patients was calculated using serum albumin level and body mass index, and a malnutrition status was defined as NRI ≤ 98. Univariate and multivariate logistic regression analyses were conducted to identify predictors for ECE and SVI. Nomograms for predicting ECE and SVI were established based on the results of the multivariate logistic regression analysis. The performance of the nomograms was estimated using Harrell's concordance index (C-index), the area under curve (AUC) of receiver operating characteristic (ROC) curves and the calibration curves. Results: In the primary cohort, 70 (14.3%) patients with NRI ≤ 98 were classified as malnutrition, while the remaining 419 (85.7%) patients with NRI > 98 were considered to have normal nutrition. The nomograms for predicting ECE and SVI shared common factors including NRI, percentage of positive biopsy cores (PPC) and biopsy Gleason score, while prostate-specific antigen (PSA) levels and PSA density (PSAD) were only incorporated in ECE nomogram. The C-indexes of the nomograms for predicting ECE and SVI were 0.785 (95% confidence interval (CI): 0.745 - 0.826) and 0.852 (95% CI: 0.806 - 0.898), respectively. The calibration curves demonstrated excellent agreement between the predictions by the nomograms and the actual observations. The results remained reproducible when the nomograms were applied to the validation cohort. Conclusions: The NRI is significantly associated with ECE and SVI in PCa patients. The nomogram established based on the NRI in our study can provide individualized risk estimation for ECE and SVI in PCa patients, and may be valuable for clinicians in making well-informed decisions regarding treatment strategies and patient management.

[Discrimination of different processing degrees and quantitative study of processing end point of vinegar-processing Cyperi Rhizoma pieces based on electronic sensory technology].

In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.

[Research progress of acupuncture mediated analgesia via regulating the function of endocannabinoid system].

Endocannabinoid system (ECS), which composed of its ligands and receptors, widely distributes in peripheral tissues and nerve system. Through complex regulating mechanisms, ECS exerts a variety of biological functions including analgesia. Its utility in analgesic regulation has attracted extensive attention, and the related achievements have also been transformed into clinical practice. With the deepened understanding of the essence of pain, as well as the advances in research techniques, quantity of research evidences showed that ECS could be regulated by acupuncture treatment and exerted analgesic effect in inflammatory pain, neuropathic pain and other related diseases, and the mechanism had also been revealed gradually. By reviewing literatures related to acupuncture analgesia and ECS, we summarized the effect and mechanism of acupuncture analgesia involved with regulation of ECS, pointed out cannabinoid (CB) 1 receptor and CB2 receptor exerted analgesic effect in central and peripheral neural system through mechanisms of inhibiting neural activation and anti-inflammation, respectively. Therefore, we hope to provide reference and inspiration for relevant research and clinical practice in the future.

Historical changes in surgical strategy and complication management for hepatic cystic echinococcosis.

Echinococcosis is a zoonotic parasitic disease caused by Escherichia larvae. It frequently involves the liver (70%-75%), followed by the lungs (15%-20%), and occasionally the brain, heart, spleen, bone, and other organs. The main pathogenic forms of human echinococcosis currently include cystic echinococcosis (CE) and alveolar echinococcosis (AE). CE is globally distributed, while the distribution of AE is generally restricted to the northern hemisphere. In China, CE accounts for 75% of all echinococcosis cases. With rapid advances in surgical techniques in recent decades, the surgical strategy for CE has changed, especially with the continuous improvement of surgical methods and the expansion of surgical contraindications. To further understand the changes in surgical treatment strategies for hepatic CE, we interpreted and analyzed the existing literature addressing the surgical treatment of hepatic CE both domestically and abroad and briefly summarized them in chronological order. This review aims to provide a deeper understanding of the progress in the surgical treatment of hepatic CE to provide clearer avenues for its clinical diagnosis and treatment.

[Efficacy and Safety of Flumatinib in Treatment of Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To analyze the efficacy and safety of flumatinib in the treatment of patients with chronic myeloid leukemia (CML). METHODS: The clinical data of 56 CML patients treated with flumatinib from January 2020 to December 2021 in the First Affiliated Hospital of Nanchang University were retrospectively analyzed. Patients were divided into three groups: 35 new diagnosed CML patients treated with flumatinib (group A), 10 patients with imatinib/dasatinib intolerance (group B) and 11 patients with imatinib/dasatinib resistance (group C) switched to flumatinib treatment, respectively. The molecular response and adverse effects of flumatinib treatment were evaluated. RESULTS: In group A, the early molecular response (EMR) at 3 months was 40.0%, and the major molecular response (MMR) at 6 and 12 months was 43.7% and 46.2%, respectively. In group B, the EMR was 50.0% at 3 months, and the MMR was 70.0% and 66.2% at 6 and 12 months, respectively. Among evaluable patients, 6 cases in group B achieved molecular response of 4.5 (MR4.5) at 12 months after switching to flumatinib treatment. In group C, 3 cases who switched from imatinib resistance to flumatinib achieved MR4.5 at 12 months, but 2 cases who switched from dasatinib resistance to flumatinib failed. Subgroup analysis showed significant differences in EUTOS long-term survival (ELTS) scores for patients in the medium-risk/high-risk group compared with those in the low-risk group for 3-month EMR (18.8% vs 57.9%), 6-month MMR (15.4% vs 63.2%) and 12-month MR4.5 (15.4% vs 69.2%) (P =0.036, P =0.012,P =0.015). The most common adverse effect in group A was thrombocytopenia, accounting for 54.5%, and 22.8% (8/35) patients discontinued the drug due to haematological adverse effects. Compared with patients who did not discontinue the drug or whose recovery time from discontinuation due to haematological toxicity was <1 month, patients whose recovery time from discontinuation was ≥1 month had a significantly worse 3-month EMR, 6-month MMR and 12-month MR4.5 (P =0.028, P =0.021, P =0.002). CONCLUSIONS: Flumatinib has better molecular response and tolerance in patients with primary, imatinib/dasatinib-intolerant or resistant CML. Medium-risk/high-risk in ELTS score and time to recovery from discontinuation due to haematological toxicity ≥1 month are important factors influencing achievement of better molecular response in flumatinib treatment.

Outcome comparison of radical prostatectomy versus seed brachytherapy for clinically localized prostate cancer using two biochemical recurrence definitions.

OBJECTIVE: We compared the outcome of radical prostatectomy (RP) with seed brachytherapy (BT) in clinically localized prostate cancer (LPCa) using two different biochemical recurrence (BCR) definitions. METHODS: Clinical data of 1117 patients with non-metastatic prostate cancer (PCa) treated with either RP or BT as the basis of the multimodal therapy from a single tertiary hospital between 2007 and 2021 were retrospectively analyzed. 843 LPCa patients (RP = 737, BT = 106) with at least one prostate-specific antigen (PSA) test after treatment were finally included. The BCR survival was evaluated by direct comparison and one-to-one propensity score matching (PSM) analysis using surgical definition (PSA ≥ 0.2ng/ml) for RP and surgical/Phoenix definition (PSA nadir + 2ng/ml ) for BT. The propensity score (PS) was calculated by multivariable logistic regression based on the clinicopathological parameters. RESULTS: Median follow-up was 43 months for RP patients and 45 months for BT patients. Kaplan-Meier analysis did not show any statistically significant differences in terms of BCR-free survival (BFS) between the two groups when using Phoenix definition for BT (P > 0.05). Similar results were obtained in all D'Amico risk groups when stratified analyses were conducted. However, RP achieved improved BFS compared to BT in the whole cohort and all risk groups with the surgical definition for BT(P < 0.05). After adjusting PS, 192 patients were divided into RP and BT groups (96 each). RP presented a better BFS than BT when using the surgical definition (P < 0.001), but no significant difference was found when using the Phoenix definition (P = 0.609). CONCLUSION: Inconsistent BCR-free survival outcomes were acquired using two different BCR definitions for BT patients. RP provided comparable BFS with BT using the Phoenix definition but better BFS using the surgical definition, regardless of whether the PSM was performed. Our findings indicated that an exact BCR definition was critical for prognostic assessment. The corresponding results will assist physicians in pretreatment consultation and treatment selection.

Recombinant Neorudin for the Prevention of Deep-Vein Thrombosis After Spinal-Cord Injury.

Background: Whether anticoagulant therapy should be used after spinal-cord injury (SCI) surgery was controversial. The anticoagulation characteristics of a newly developed anticoagulant, recombinant neorudin (EPR-hirudin (EH)), were explored using a rat model of SCI to provide a basis for clinical anticoagulation therapy of SCI. Methods: A rat model of SCI was developed by Allen's method. Then, thrombosis in the inferior vena cava was induced by ligation. The low-bleeding characteristics of EH were explored by investigating dose-response and time-effect relationships, as well as multiple administration of EH, on thrombus formation complicated with SCI. Results: EH inhibited thrombosis in a dose-dependent manner by reducing the wet weight and dry weight of the thrombus. An inhibiting action of EH on thrombosis was most evident in the group given EH 2 h after SCI. After multiple intravenous doses of EH, thrombosis inhibition was improved to that observed with low molecular weight heparin (LMWH) (87% vs 90%). EH administration after SCI neither increased bleeding in the injured spine nor damaged to nerve function. Bleeding duration and activated partial thromboplastin time were increased in the high-dose EH group compared with that in the normal-saline group, but were lower than those in the LMWH group. Conclusion: EH can reduce thrombus formation in a rat model of SCI, and bleeding is decreased significantly compared with that using LMWH. EH may prevent thrombosis after SCI or spinal surgery.

Characterization and intrinsic quality correlation of raw and vinegar-processed Curcumae Radix.

Among the existing criteria, the traits of Curcumae Radix (CW) rely on traditional empirical identification, and the correlation between extrinsic traits and intrinsic components hasn't been systematically studied. In this study, a spectrophotometer, HS-GC-MS, and fast GC e-nose, combined with chemometrics were used to correlate the trait characteristics and intrinsic qualities of CW and vinegar-processed CW (VCW). The overall color of VCW was dark, red, and yellow, but the powder color was similar and difficult to distinguish with the naked eye. The exclusive discriminatory functional equations were established for the characterization between the two. 31 odor components were identified by fast GC e-nose. After vinegar preparation, 3 odor components disappeared and 8 odor components were generated. In addition, there were significant differences between the common components. 27 volatile components were identified by HS-GC-MS, 21 of which were terpenoids. Meanwhile, the difference discrimination models could be used for the rapid and accurate identification of CW and VCW. Through the comprehensive analysis of the color-odor-component, it was speculated that curzerene, germacrene D, and germacrone were potential chemical markers. The quality evaluation model based on the color-odor-composition of trait characteristics combined with internal components provided a basis for rapid identification and quality control of CW and VCW.

Gut Microbiota and Acylcarnitine Metabolites Connect the Beneficial Association between Estrogen and Lipid Metabolism Disorders in Ovariectomized Mice.

Decreased estrogen level is one of the main causes of lipid metabolism disorders and coronary heart disease in women after menopause. Exogenous estradiol benzoate is effective to some extent in alleviating lipid metabolism disorders caused by estrogen deficiency. However, the role of gut microbes in the regulation process is not yet appreciated. The objective of this study was to investigate the effects of estradiol benzoate supplementation on lipid metabolism, gut microbiota, and metabolites in ovariectomized (OVX) mice and to reveal the importance of gut microbes and metabolites in the regulation of lipid metabolism disorders. This study found that high doses of estradiol benzoate supplementation effectively attenuated fat accumulation in OVX mice. There was a significant increase in the expression of genes enriched in hepatic cholesterol metabolism and a concomitant decrease in the expression of genes enriched in unsaturated fatty acid metabolism pathways. Further screening of the gut for characteristic metabolites associated with improved lipid metabolism revealed that estradiol benzoate supplementation influenced major subsets of acylcarnitine metabolites. Ovariectomy significantly increased the abundance of characteristic microbes that are significantly negatively associated with acylcarnitine synthesis, such as Lactobacillus and Eubacterium ruminantium group bacteria, while estradiol benzoate supplementation significantly increased the abundance of characteristic microbes that are significantly positively associated with acylcarnitine synthesis, such as Ileibacterium and Bifidobacterium spp. The use of pseudosterile mice with gut microbial deficiency greatly facilitated the synthesis of acylcarnitine due to estradiol benzoate supplementation and also alleviated lipid metabolism disorders to a greater extent in OVX mice. IMPORTANCE Our findings establish a role for gut microbes in the progression of estrogen deficiency-induced lipid metabolism disorders and reveal key target bacteria that may have the potential to regulate acylcarnitine synthesis. These findings suggest a possible route for the use of microbes or acylcarnitine to regulate disorders of lipid metabolism induced by estrogen deficiency.

The toxicity assessment of neorudin in cynomolgus monkeys.

In this study, the toxicity effects on circulatory system and respiratory system, and the acute toxicity test of recombinant neorudin (EPR-hirudin, EH) in cynomolgus monkeys were evaluated to provide reference information for clinical studies. Eighteen cynomolgus monkeys were randomly divided into three groups for single intravenous administration of 3, 30 mg/kg EH and normal saline, respectively. The changes of respiratory frequency, respiratory intensity, blood pressure and electrocardiogram before and after administration were recorded. In acute toxicity test, six cynomolgus monkeys were intravenously received EH at a single dose of 171, 257, 385, 578, 867 and 1300 mg/kg respectively. The vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of the animals were determined before administration and on the 7th and 14th day after administration. As the results showed that there were no significant abnormal changes in respiratory frequency, respiratory intensity, blood pressure or electrocardiogram in cynomolgus monkeys after receiving EH at 3 mg/kg and 30 mg/kg, and there was no statistical difference between the treated groups and normal saline group. In the acute toxicity test, no significant abnormalities were observed in vital signs, hematology, serum biochemistry, coagulation indexes and electrocardiogram indexes of six cynomolgus monkeys at day 7 and 14 after EH administration. Furthermore, autopsies of all cynomolgus monkeys showed no abnormalities. The results of toxicokinetics showed that AUClast of the drug increased in proportion to the EH dose in the range of 171-578 mg/kg, and increased in over proportion to the EH dose in the range of 578-1300 mg/kg. The variation of Cmax was basically consistent with AUClast. In a sum, A single intravenous injection of 3 and 30 mg/kg of EH did not affect the circulatory system and respiratory system in cynomolgus monkeys and the maximum tolerated dose of EH in cynomolgus monkey is over 1300 mg/kg (equivalent to 619-1300 times of the proposed clinical equivalent dose).

[Rapid identification and differential markers of Curcumae Radix decoction pieces of different sources based on Heracles Neo ultra-fast gas phase electronic nose].

Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as ß-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.

The therapeutic mechanism of Curcumae Radix against primary dysmenorrea based on 5-HTR/Ca2+/MAPK and fatty acids metabolomics.

Background: Curcumae Radix (CW) is traditionally used to treat primary dysmenorrea (PD). However, the mechanisms of action of CW in the treatment of PD have not yet been comprehensively resolved. Objective: To investigate the therapeutic effects of CW on PD and its possible mechanisms of action. Methods: An isolated uterine spastic contraction model induced by oxytocin was constructed in an in vitro pharmacodynamic assay. An animal model of PD induced by combined estradiol benzoate and adrenaline hydrochloride-assisted stimulation was established. After oral administration of CW, a histopathological examination was performed and biochemical factor levels were measured to evaluate the therapeutic effect of CW on PD. The chemical compositions of the drug-containing serum and its metabolites were analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Network pharmacology and serum untargeted metabolomics were used to predict the mechanism of CW treatment for PD, and the predicted results were validated by RT-qPCR, WB, and targeted fatty acid (FA) metabolism. Results: In vitro, CW can relax an isolated uterus by reducing uterine motility. In vivo, the results showed that CW attenuated histopathological damage in the uterus and regulated PGF2α, PGE2, ß-EP, 5-HT, and Ca2+ levels in PD rats. A total of 66 compounds and their metabolites were identified in the drug-containing serum, and the metabolic pathways of these components mainly included hydrogenation and oxidation. Mechanistic studies showed that CW downregulated the expression of key genes in the 5-HTR/Ca2+/MAPK pathway, such as 5-HTR2A, IP3R, PKC, cALM, and ERK. Similarly, CW downregulated the expression of key proteins in the 5-HTR/Ca2+/MAPK pathway, such as p-ERK/ERK. Indirectly, it ameliorates the abnormal FA metabolism downstream of this signaling pathway in PD rats, especially the metabolism of arachidonic acid (AA). Conclusion: The development of PD may be associated with the inhibition of the 5-HTR/Ca2+/MAPK signaling pathway and FA metabolic pathways, providing a basis for the subsequent exploitation of CW.

Effects of different steaming times on the composition, structure and immune activity of Polygonatum Polysaccharide.

ETHNOPHARMACOLOGICAL RELEVANCE: As a commonly used traditional Chinese herbal medicine, Polygonati Rhizoma has high medicinal value, it can enhance the immune capacity of the body, regulate the metabolism of blood glucose and lipids, treat weakness of the stomach and intestines and physical fatigue, and so on. There are three plant varieties of Polygonati Rhizoma recorded in Chinese Pharmacopoeia, including Polygonatum sibiricum Red., Polygonatum kingianum Coll. et Hemsl. and Polygonatum cyrtonema Hua, compared with the first two, Polygonatum cyrtonema Hua is less studied. Polygonatum cyrtonema Hua is one of the basal plants of the Chinese herb Polygonati Rhizoma, that strengthens the spleen, moistens the lungs, and benefits the kidneys. Polygonatum polysaccharide is the main active substance of Polygonatum cyrtonema Hua, which has various biological effects of regulating immune system, anti-inflammatory, anti-antidepressant, antioxidant and other effects. AIM OF THE STUDY: In order to analyze the necessity and scientificity of multiple cycles of steaming during the traditional nine-steaming and nine-drying process of the concoction of Polygonatum, we investigated the changes in the composition and structure of polysaccharides, and explored its immunomodulatory activity and molecular biological mechanism. METHODS: The structural characterization and molecular weight of polysaccharides were studied by scanning electron microscope (SEM), high-performance size exclusion chromatography-evaporative light scattering detector (HPSEC-ELSD) and Matrix.assisted laser resolutionu ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The composition and proportion of monosaccharides were determined by PMP-HPLC method. A mouse immunosuppression model was established by intraperitoneal injection of cyclophosphamide to compare the immunomodulatory effects and mechanisms of different steaming times of Polygonatum, The changes of body mass and immune organ indices of mice were measured; the secretion levels of interleukin-2 (IL-2), interferon γ (IFN-γ) and the expression levels of immunoglobulin M (IgM) and immunoglobulin A (IgA) in serum were determined by enzyme-linked immunosorbent assay; and then flow cytometry was used to detect T-lymphocyte subpopulations to evaluate the differences of immunomodulatory effects of polysaccharides during the processing and preparation of Polygonatum. Finally, the Illumina MiSeq high-throughput sequencing platform was used to analyze short-chain fatty acids and to investigate the effects of different steaming times of Polygonatum polysaccharides on immune function and intestinal flora in immunosuppressed mice. RESULTS: The structure of the Polygonatum polysaccharide with different steaming times changed significantly, the relative molecular weight of Polygonatum polysaccharide decreased significantly, and the monosaccharide composition of Polygonatum cyrtonema Hua with different steaming times was the same but the content was different. The immunomodulatory activity of the Polygonatum polysaccharide was enhanced after concoction, which significantly increased the spleen index and thymus index, and increased the expression of IL-2, IFN-γ, IgA and IgM. The CD4+/CD8+ ratio of Polygonatum polysaccharide also increased gradually with different steaming times, indicating enhanced immune function and significant immunomodulatory effect. The content of short-chain fatty acids in the feces of mice in both six steaming six sun-drying of Polygonatum polysaccharides (SYWPP) and nine steaming nine sun-drying of Polygonatum polysaccharides (NYWPP) groups increased significantly, including the content of propionic acid, isobutyric acid, valeric acid, and isovaleric acid, and also had a good effect on the regulation and improvement of microbial community abundance and diversity, SYWPP and NYWPP increased the relative abundance of Bacteroides and the ratio of Bacteroides and Firmicutes (B:F), while SYWPP significantly increased the abundance of Bacteroides, Alistipes and norank_f__Lachnospiraceae, but the effect of raw Polygonatum polysaccharides (RPP) and NYWPP was not significant than SYWPP. CONCLUSION: Overall, both SYWPP and NYWPP could significantly enhance the immune activity of the organism, improve the imbalance of intestinal flora in immunosuppressed mice, and increase the content of intestinal short chain fatty acids (SCFAs), it is noteworthy that SYWPP has a better effect on the improvement of the immune activity of the organism. These findings can explore the stage of the concoction process of Polygonatum cyrtonema Hua to achieve the best effect, provide a reference basis for the development of quality standards, and at the same time promote the application of new therapeutic agents and health foods in raw and different steaming times of Polygonatum polysaccharide.