[Non-targeted metabolomics of spleen and liver metabolism in mice treated with Pruni Semen processed with different methods].

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.

Machine learning model based on RCA-PDCA nursing methods and differentiating factors to predict hypotension during cesarean section surgery.

BACKGROUND: Intraoperative hypotension during cesarean section has become a serious complication for maternal and fetal healthy. It is commonly encountered by subarachnoid anesthesia. However, currently used control methods have varying degrees of side effects, such as drugs. The Root Cause Analysis (RCA) - Plan, Do, Check, Act (PDCA) is a new model of care that identifies the root causes of problems. The study aimed to demonstrate the usefulness of RCA-PDCA nursing methods in preventing intraoperative hypotension during cesarean section and to predict the occurrence of intraoperative hypotension through a machine learning model. METHODS: Patients who underwent cesarean section at Traditional Chinese Medicine of Southwest Medical University from January 2023 to December 2023 were retrospectively screened, and the data of their gestational times, age, height, weight, history of allergies, intraoperative vital signs, fetal condition, operative time, fluid out and in, adverse effects, use of vasopressor drugs, anxiety-depression-pain scores, and satisfaction were collected and analyzed. The statistically different features were screened and five machine learning models were used as predictive models to assess the usefulness of the RCA-PDCA model of care. RESULTS: (1) Compared with the general nursing model, the RCA-PDCA nursing model significantly reduces the incidence of intraoperative hypotension and postoperative complications in cesarean delivery, and the patient experience is comfortable and satisfactory. (2) Among the five machine learning models, the RF model has the best predictive performance, and the accuracy of the random forest model in preventing intraoperative hypotension is as high as 90%. CONCLUSION: Through computer machine learning model analysis, we prove the importance of the RCA-PDCA nursing method in the prevention of intraoperative hypotension during cesarean section, especially the Random Forest model which performed well and promoted the application of artificial intelligence computer learning methods in the field of medical analysis.

Sophoridine exerts anti-arthritic effects on fibroblast-like synoviocytes and collagen-induced arthritis in rats.

The discovery of alternative medicines with fewer adverse effects is urgently needed for rheumatoid arthritis (RA). Sophoridine (SR), the naturally occurring quinolizidine alkaloid isolated from the leguminous sophora species, has been demonstrated to possess a wide range of pharmacological activities. However, the effect of SR on RA remains unknown. In this study, the collagen-induced arthritis (CIA) rat model and tumor necrosis factor alpha (TNFα)-induced fibroblast-like synoviocytes (FLSs) were utilized to investigate the inhibitory effect of SR on RA. The anti-arthritic effect of SR was evaluated using the CIA rat model in vivo and TNFα-stimulated FLSs in vitro. Mechanistically, potential therapeutic targets and pathways of SR in RA were analyzed through drug target databases and disease databases, and validation was carried out through immunofluorescence, immunohistochemistry, and Western blot. The in vivo results revealed that SR treatment effectively ameliorated synovial inflammation and bone erosion in rats with CIA. The in vitro studies showed that SR could significantly suppress the proliferation and migration in TNFα-induced arthritic FLSs. Mechanistically, SR treatment efficiently inhibited the activation of MAPKs (JNK and p38) and NF-κB pathways in TNFα-induced arthritic FLSs. These findings were further substantiated by Immunohistochemistry results in the CIA rat. SR exerts an anti-arthritic effect in CIA rats through inhibition of the pathogenic characteristic of arthritic FLSs via suppressing NF-κB and MAPKs (JNK and p38) signaling pathways. SR may have a great potential for development as a novel therapeutic agent for RA treatment.

Phytochemicals targeting Alzheimer's disease via the AMP-activated protein kinase pathway, effects, and mechanisms of action.

Alzheimer's disease (AD), characterized by cognitive dysfunction and other behavioral abnormalities, is a progressive neurodegenerative disease that occurs due to aging. Currently, effective drugs to mitigate or treat AD remain unavailable. AD is associated with several abnormalities in neuronal energy metabolism, such as decreased glucose uptake, mitochondrial dysfunction, and defects in cholesterol metabolism. Amp-activated protein kinase (AMPK) is an important serine/threonine protein kinase that regulates the energy status of cells. AMPK is widely present in eukaryotic cells and can sense and regulate energy metabolism to maintain energy supply and demand balance, making it a promising target for energy metabolism-based AD therapy. Therefore, this review aimed to discuss the molecular mechanism of AMPK in the pathogenesis of AD to provide a theoretical basis for the development of new anti-AD drugs. To review the mechanisms of phytochemicals in the treatment of AD via AMPK pathway regulation, we searched PubMed, Google Scholar, Web of Science, and Embase databases using specific keywords related to AD and phytochemicals in September 2023. Phytochemicals can activate AMPK or regulate the AMPK pathway to exert therapeutic effects in AD. The anti-AD mechanisms of these phytochemicals include inhibiting Aß aggregation, preventing Tau hyperphosphorylation, inhibiting inflammatory response and glial activation, promoting autophagy, and suppressing anti-oxidative stress. Additionally, several AMPK-related pathways are involved in the anti-AD mechanism, including the AMPK/CaMKKß/mTOR, AMPK/SIRT1/PGC-1α, AMPK/NF-κB/NLRP3, AMPK/mTOR, and PERK/eIF2α pathways. Notably, urolithin A, artemisinin, justicidin A, berberine, stigmasterol, arctigenin, and rutaecarpine are promising AMPK agonists with anti-AD effects. Several phytochemicals are effective AMPK agonists and may have potential applications in AD treatment. Overall, phytochemical-based drugs may overcome the barriers to the effective treatment of neurodegenerative diseases.

KCNK5 Regulating Potassium Efflux and Inducing Pyroptosis in Corneal Epithelial Cells Through TNFSF10-Mediated Autophagy in Dry Eye.

Purpose: The purpose of this study was to elucidate the involvement of potassium two pore domain channel subfamily K member 5 (KCNK5)-mediated potassium efflux in the pathogenesis of dry eye and to unravel the underlying molecular mechanisms. Methods: To induce experimental dry eye in adult wild-type C57BL/6 mice, scopolamine was administered via subcutaneous injection, and the mice were subjected to desiccating stress. To create an in vitro model of dry eye, desiccation stress was applied to the human corneal epithelial cell line (HCE-T). Intracellular potassium concentration was quantified using inductively coupled plasma mass spectrometry. Cellular death was assessed through lactate dehydrogenase assays. Gene expression profiling was conducted through both RNA sequencing and quantitative real-time PCR. Protein analysis was carried out through Western blotting and immunofluorescence staining. Assessment of the corneal epithelial defect area was conducted through fluorescein sodium staining. Tear secretion was quantified using the phenol red cotton thread method. Results: Potassium efflux was observed to further facilitate corneal epithelial pyroptosis. KCNK5 exhibited upregulation in both in vivo and in vitro models of dry eye. The overexpression of KCNK5 was observed to induce potassium efflux and activate the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in vitro. Silencing KCNK5 effectively mitigated pyroptosis in dry eye. Additionally, the overexpression of KCNK5 results in the downregulation of TNF superfamily member 10 (TNFSF10) and subsequent impairment of autophagy. TNFSF10 supplementation could promote autophagy and mitigate pyroptosis in dry eye. Conclusions: The upregulation of KCNK5 mediates TNFSF10 to impair autophagy and induce pyroptosis in dry eye. Consequently, targeting KCNK5 may represent a novel and promising approach to therapeutic intervention in the management of dry eye.

Pseudo-targeted lipidomics insights into lipid discrepancies between yak colostrum and mature milk based on UHPLC-Qtrap-MS.

Yak milk is essential to maintain the normal physiological functions of herders in Tibetan areas of China. However, the lipid components of yak colostrum (YC) and mature milk (YM) have not been systematically studied. We employed a quantitative lipidomics to comprehensively describe the alterations in the milk lipid profile of lactating yaks. Herein, totally 851 lipids from 28 lipid subclasses in YC and YM were identified and screened for 43 significantly different lipids (SDLs; variable importance in projection > 1, fold change < 0.5 or > 2 with P < 0.05), with cholesterol ester (CE, 16:0) and triacylglycerol (TAG, 54:6 (20:5), 50:1 (16:0), 56:6 (20:5)) were the potential lipid biomarkers. Fourteen SDLs were modulated downwards, and 29 SDLs were modulated upwards in YM. Moreover, by analyzing lipid metabolic pathways in these SDLs, glycerophospholipid metabolism was the most critical. Our results furnish integral lipid details for evaluating yak milk's nutritional quality.

CMAUP database update 2024: extended functional and association information of useful plants for biomedical research.

Knowledge of the collective activities of individual plants together with the derived clinical effects and targeted disease associations is useful for plant-based biomedical research. To provide the information in complement to the established databases, we introduced a major update of CMAUP database, previously featured in NAR. This update includes (i) human transcriptomic changes overlapping with 1152 targets of 5765 individual plants, covering 74 diseases from 20 027 patient samples; (ii) clinical information for 185 individual plants in 691 clinical trials; (iii) drug development information for 4694 drug-producing plants with metabolites developed into approved or clinical trial drugs; (iv) plant and human disease associations (428 737 associations by target, 220 935 reversion of transcriptomic changes, 764 and 154121 associations by clinical trials of individual plants and plant ingredients); (v) the location of individual plants in the phylogenetic tree for navigating taxonomic neighbors, (vi) DNA barcodes of 3949 plants, (vii) predicted human oral bioavailability of plant ingredients by the established SwissADME and HobPre algorithm, (viii) 21-107% increase of CMAUP data over the previous version to cover 60 222 chemical ingredients, 7865 plants, 758 targets, 1399 diseases, 238 KEGG human pathways, 3013 gene ontologies and 1203 disease ontologies. CMAUP update version is freely accessible at https://bidd.group/CMAUP/index.html.

Echinacoside exerts neuroprotection via suppressing microglial α-synuclein/TLR2/NF-κB/NLRP3 axis in parkinsonian models.

BACKGROUND: Echinacoside (ECH), a natural active compound, was found to exert neuroprotection in Parkinson's disease (PD). However, the underlying molecular mechanisms remain controversial. PURPOSE: This study aimed to explore the roles of ECH in PD and its engaged mechanisms. CONCLUSION: In vivo, MPTP was adapted to construct subacute PD mouse model to explore the regulation of ECH on NLRP3 inflammasome. In vitro, α-synuclein (α-syn)/MPP+ was used to mediate the activation of NLRP3 inflammasome in BV2 cells, and the mechanism of ECH regulation of it was explored with molecular docking, immunofluorescence, Western blotting, and small molecule inhibitors. CONCLUSION: The activation of microglial NLRP3 inflammasome could be evoked by MPTP in vitro, but its toxic metabolite MPP+ alone cannot trigger the activation of NLRP3 inflammasome in vitro, which requires α-synuclein (α-syn) priming. Exogenous α-syn could evoke microglial TLR2/NF-κB/NLRP3 axis, playing the priming role in MPP+ -mediated NLRP3 inflammasome activation. ECH can suppress the upregulation of α-syn in MPTP-treated mice and BV2 microglia. It can also suppress the activation of the TLR2/NF-κB/NLRP3 axis induced by α-syn. CONCLUSION: ECH exerts neuroprotective effects by downregulating the TLR2/NF-κB/NLRP3 axis via reducing the expression of α-syn in the PD models.

Antifeedant, Antifungal Cryptic Polyketides with Six Structural Frameworks from Tea Endophyte Daldinia eschscholtzii Propelled by the Antagonistic Coculture with Phytopathogen Colletotrichum pseudomajus and Different Culture Methods.

The antagonistic coculture with tea phytopathogen Colletotrichum pseudomajus induces antifungal cryptic metabolites from isogenesis endophyte Daldinia eschscholtzii against tea phytopathogens. Sixteen new polyketides with six structural frameworks including ten cryptic ones, named coldaldols A-C (1-3), collediol (5), and daldinrins A-L (10-20 and 23), were found from the coculture of C. pseudomajus and D. eschscholtzii by different culture methods. The unique framework of compounds 11 and 12 featured a benzopyran-C7 polyketone hybrid, and compounds 13-16 were characterized by the novel benzopyran dimer. The structures were determined mainly by spectroscopic methods, including extensive one-dimensional (1D), two-dimensional (2D) NMR, high resolution electrospray ionisation mass spectroscopy (HRESIMS), ECD calculation, and single-crystal X-ray diffraction. The configuration of acyclic compounds 5 and 18 were determined by application of the universal NMR database. Most compounds showed significant antifungal activities against the tea pathogens C. pseudomajus and Alternaria sp. with MICs of 1-8 µg/mL. Compound 12 had stronger antifungal activity than that of positive drug nystatin. The ether bond at C-4 of the benzopyran derivative increased the antifungal activity. Compounds 4-9 and 11-23 showed antifeedant activities against silkworms with feeding deterrence indices of 15-100% at the concentration of 50 µg/cm2.

The antifungal metabolites isolated from maize endophytic fungus Fusarium sp. induced by OSMAC strategy.

Six new sesquiterpenes, fusarchlamols A-F (1, 2, 4-7); one new natural product of sesquiterpenoid, methyltricinonoate (3); and ten known compounds were found from Fusarium sp. cultured in two different media by the one strain many compounds strategy. The compounds (1, 2, and 4-11) were isolated from Fusarium sp. in PDB medium, and compounds (3-5, 8, and 10-17) were discovered from Fusarium sp. in coffee medium. Additionally, the configuration of 8 was first reported in the research by Mosher's method. The structures were established by 1D, 2D NMR, mass spectrometry, calculated ECD spectra, and Mosher's method. Compounds 1, 2, 6/7, 12, and 16 indicated significant antifungal activities against the phytopathogen Alternaria alternata isolated from Coffea arabica with MICs of 1 µg/mL. The investigation on the anti-phytopathogen activity of metabolites can provide lead compounds for agrochemicals.

[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Efficacy and safety of transurethral thulium laser enucleation versus robot-assisted prostatectomy for large-volume benign prostatic hyperplasia: a systematic review and meta-analysis.

To compare perioperative outcomes between Holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple pasta-ectomy (RASP)for large-volume benign prostatic hyperplasia(> 80 ml). In August 2023, we undertook a comprehensive search of major global databases including PubMed, Embase, and Google Scholar, focusing solely on articles written in English. Studies that were merely reviews or protocols without any specific published data were omitted. Furthermore, articles that comprised conference abstracts or content not pertinent to our subject of study were also disregarded. To calculate the inverse variances and 95% confidence intervals (CIs) for categorical variables' mean differences, we employed the Cochran-Mantel-Haenszel approach along with random-effects models. The findings were denoted in the form of odds ratios (ORs) and 95% CIs. A p-value less than 0.05 was deemed to indicate statistical significance. Our finalized meta-analysis incorporated six articles, including one randomized controlled trial (RCT) and five cohort studies. These studies accounted for a total of 1218 patients, 944 of whom underwent Holmium Laser Enucleation of the Prostate (HoLEP) and 274 who underwent Robotic-Assisted Simple Prostatectomy (RASP). The pooled analysis from these six papers demonstrated that compared to RASP, HoLEP had a shorter hospital stay, shorter catheterization duration, and a lower blood transfusion rate. Moreover, HoLEP patients exhibited a smaller reduction in postoperative hemoglobin levels. Statistically, there were no significant differences between the two procedures regarding operative time, postoperative PSA, the weight of prostate specimens, IPSS, Qmax, PVR, QoL, and postoperative complications. (HoLEP) and (RASP) are both effective and safe procedures for treating large-volume benign prostatic hyperplasia. HoLEP, with its benefits of shorter catheterization and hospitalization duration, lesser decline in postoperative hemoglobin, and reduced blood transfusion needs, stands as a preferred choice for treating extensive prostate enlargement. However, further validation through more high-quality clinical randomized trials is required.

[Effects of acupuncture on pulmonary function and airway smooth muscle spasm in asthma rats].

OBJECTIVE: To observe the effects of acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) on the latent period of inducing asthma, pulmonary function and the expression of endothelin-1 (ET-1) and metallothionein-2 (MT-2) in asthma rats, and to explore the possible mechanism of acupuncture in alleviating airway smooth muscle spasm and improving the acute attack of asthma. METHODS: A total of 40 male SD rats of SPF-grade were randomly divided into a normal group, a model group, a medication group and an acupuncture group, 10 rats in each group. Except for the normal group, ovalbumin sensitization method was used to establish the asthma model in the other 3 groups. Salbutamol nebulization was adopted in the medication group, while acupuncture was applied at bilateral "Kongzui" (LU 6) and "Yuji" (LU 10) in the acupuncture group. The intervention was given once a day for 14 days in the two groups. The latent period of inducing asthma and pulmonary function were observed, the levels of ET-1 and tumor necrosis factor (TNF)-α in serum and bronchoalveolar lavage fluid (BALF) were detected by ELISA method, the morphology of the airway was observed by Masson staining, the ultrastructure of the airway smooth muscle was observed by transmission electron microscopy, the mRNA and protein expression of ET-1 and MT-2 in lung tissue was detected by real-time PCR and Western blot methods. RESULTS: Compared with the normal group, in the model group, the latent period of inducing asthma was shortened (P<0.01); the airway resistance (RL) was increased while the dynamic compliance (Cdyn) was decreased (P<0.01, P<0.05); the levels of ET-1 and TNF-α in serum and BALF were increased (P<0.01); collagen fibers and collagen depositions were found around the bronchi, airway smooth muscle was thickened, the cell damage was severe and mitochondria were swollen; the mRNA and protein expression of ET-1 was increased while the mRNA and protein expression of MT-2 was decreased (P<0.01). Compared with the model group, in the acupuncture group, the latent period of inducing asthma was prolonged (P<0.05), the RL was decreased while the Cdyn was increased (P<0.01, P<0.05). Compared with the model group, in the medication group and the acupuncture group, the levels of ET-1 and TNF-α in serum and BALF were decreased (P<0.01, P<0.05); collagen fibers and collagen depositions around the bronchi were reduced, the thickened airway smooth muscle was lightened, the cell damage was improved; the mRNA and protein expression of ET-1 was decreased while the mRNA and protein expression of MT-2 was increased (P<0.01). Compared with the medication group, the mRNA expression of MT-2 was increased in the acupuncture group (P<0.05). CONCLUSION: Acupuncture at "Kongzui" (LU 6) and "Yuji" (LU 10) can improve the pulmonary function and alleviate the airway smooth muscle spasm in rats with asthma. Its mechanism may be related to the down-regulation of ET-1 expression and up-regulation of MT-2 expression.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

CONTEXT: Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. OBJECTIVE: To explore the synergistic effect of NJ combined with levodopa against PD. MATERIALS AND METHODS: The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. RESULTS: Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. DISCUSSION AND CONCLUSIONS: NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

The impact of psychological resilience on chronic patients' depression during the dynamic Zero-COVID policy: the mediating role of stigma and the moderating role of sleep quality.

OBJECTIVE: Chronic patients are experiencing depression caused by themselves or the surrounding environment, how to cope with the change of mentality and adjust the psychological stress response, especially under the background of the current dynamic Zero-COVID policy in China, is a problem worth further discussion. The researchers constructed a mediating regulation model to test the influence of psychological resilience on depression of chronic patients during dynamic Zero-COVID, as well as the mediating role of stigma and the moderating role of sleep. METHOD: From October 2021 to February 2022, this study used a multi-stage sampling method and random number table method to collect data in the Shang Cheng District of Hangzhou City, Zhejiang Province. Firstly, the Second Affiliated Hospital of the Zhejiang University School of Medicine, a third-class hospital was randomly selected from the Shang Cheng District. Secondly, three departments were strategically selected from this hospital: endocrinology, dermatology, and traditional Chinese medicine. Thirdly, survey points were set up in each department, and chronic patients were strategically selected for questionnaire surveys. Finally, a face-to-face survey was conducted on 398 chronic patients who met the criteria for inclusion. In addition, chronic medical illness burden was assessed using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G), psychological resilience was measured by the Conner-Davidson Resilience Scale (CD-RISC), stigma was measured by the Stigma Scale for Chronic Illness (SSCI), sleep was measured by the Pittsburgh Sleep Quality Index(PSQI) and depression was estimated by the Patient Health Questionaire-9(PHQ-9). SPSS (version 25.0) and PROCESS (version 4.0) were used for correlation analysis, mediation analysis, and mediated moderation analysis. RESULTS: Psychological resilience was negatively correlated with depression, stigma, and sleep. Depression was positively correlated with stigma and sleep. Stigma and sleep were positively correlated; Stigma played a mediating role in the relationship between psychological resilience and depression; Sleep moderated the first half of the pathway "psychological resilience [Formula: see text] stigma [Formula: see text] depression". CONCLUSION: Psychological resilience affected depression directly and indirectly through stigma. At the same time, sleep played a moderating role between psychological resilience and depression. The correlation between psychological resilience and stigma was stronger when levels of sleep levels were higher.

Endostar (rh-endostatin) consolidation therapy after sequential chemoradiotherapy in stage III, unresectable lung adenocarcinoma with novel STK11, TP53 and ATM mutations: a case report.

Concurrent chemoradiotherapy (cCRT) has been predominantly used as the standard therapy for locally advanced or unresectable non-small cell lung cancer (NSCLC) patients with stage III disease. Based on the outstanding results of Phase III Pacific study, Programmed Death-Ligand 1 (PD-L1) inhibitor consolidation therapy after cCRT without progression disease (PD) has been recommended by National Comprehensive Cancer Network (NCCN) guideline as standard therapy for these patients. However, not all patients can tolerate a full course of cCRT due to the poor performance status, concurrent complications, or poor pulmonary function. Therefore, sequential chemoradiotherapy (sCRT) is often conducted for these selected patients who have been assessed as not suitable for cCRT. Moreover, not all patients are suitable for immunotherapy, especially for those with auto-immune disease or certain gene mutations associated with non-response of immunotherapy. Hence, we presented a case with both autoimmune disease and serine/threonine kinase 11 (STK11) mutation, who underwent angiogenesis inhibitor Endostar consolidation therapy after sCRT, and achieved a progression-free survival (PFS) more than 17 months and still in the process of follow-up. This case may offer an effective consolidation treatment for these patients with stage III disease unsuitable for immunotherapy. Further clinical trials are required to confirm this treatment option.

Effects of Soybean Phosphate Transporter Gene GmPHT2 on Pi Transport and Plant Growth under Limited Pi Supply Condition.

Phosphorus is an essential macronutrient for plant growth and development, but phosphate resources are limited and rapidly depleting due to massive global agricultural demand. This study identified two genes in the phosphate transporter 2 (PHT2) family of soybean by bioinformatics. The expression patterns of two genes by qRT-PCR at leaves and all were induced by low-phosphate stress. After low-phosphate stress, GmPHT2;2 expression was significantly higher than GmPHT2;1, and the same trend was observed throughout the reproductive period. The result of heterologous expression of GmPHT2 in Arabidopsis knockout mutants of atpht2;1 shows that chloroplasts and whole-plant phosphorus content were significantly higher in plants complementation of GmPHT2;2 than in plants complementation of GmPHT2;1. This suggests that GmPHT2;2 may play a more important role in plant phosphorus metabolic homeostasis during low-phosphate stress than GmPHT2;1. In the yeast backfill assay, both genes were able to backfill the ability of the defective yeast to utilize phosphorus. GmPHT2 expression was up-regulated by a low-temperature treatment at 4 °C, implying that GmPHT2;1 may play a role in soybean response to low-temperature stress, in addition to being involved in phosphorus transport processes. GmPHT2;1 and GmPHT2;2 exhibit a cyclic pattern of circadian variation in response to light, with the same pattern of gene expression changes under red, blue, and white light conditions. GmPHT2 protein was found in the chloroplast, according to subcellular localization analysis. We conclude that GmPHT2 is a typical phosphate transporter gene that can improve plant acquisition efficiency.

[Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke].

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.