Enhancing Efficacy and Quality of Life in Patients with Herpes Zoster Infection in Hairy Cell Leukemia.

Hairy cell leukemia (HCL) is an infrequent and persistent B-cell inert lymphoid leukemia. In this study, we present the case of a 71-year-old female patient with a previous diagnosis of variant HCL who experienced a severe herpes zoster infection leading to an extensive skin eruption. The patient's initial diagnosis of HCL occurred 7 years ago, and she underwent treatment with cladribine, interferon, COP (cyclophosphamide, vincristine, and prednisone), benztropine tablets + clarithromycin dispersible, and ibrutinib. Immune disorders resulting from repeated prior chemotherapy and targeted therapy may potentially precipitate herpes zoster infection. Despite an initial two-week period of unresponsiveness to antivirals and nerve nutrition treatments, the introduction of topical Coptis liquid to the treatment regimen yielded significant efficacy. This case report underscores the potential of Chinese medicine as an adjunct to conventional antiviral therapy in the management of herpes zoster infection in immunocompromised patients. This treatment protocol has the potential to enhance efficacy, enhance quality of life, and serve as a more robust foundation for clinical diagnosis and improved treatments.

Molecular Determinants of Neurocognitive Deficits in Glioma: Based on 2021 WHO Classification.

Cognitive impairment is a common feature among patients with diffuse glioma. The objective of the study is to investigate the relationship between preoperative cognitive function and clinical as well as molecular factors, firstly based on the new 2021 World Health Organization's updated classification of central nervous system tumors. A total of 110 diffuse glioma patients enrolled underwent preoperative cognitive assessments using the Mini-Mental State Examination and Montreal Cognitive Assessment. Clinical information was collected from medical records, and gene sequencing was performed to analyze the 18 most influenced genes. The differences in cognitive function between patients with and without glioblastoma were compared under both the 2016 and 2021 WHO classification of tumors of the central nervous system to assess their effect of differentiation on cognition. The study found that age, tumor location, and glioblastoma had significant differences in cognitive function. Several genetic alterations were significantly correlated with cognition. Especially, IDH, CIC, and ATRX are positively correlated with several cognitive domains, while most other genes are negatively correlated. For most focused genes, patients with a low number of genetic alterations tended to have better cognitive function. Our study suggested that, in addition to clinical characteristics such as age, histological type, and tumor location, molecular characteristics play a crucial role in cognitive function. Further research into the mechanisms by which tumors affect brain function is expected to enhance the quality of life for glioma patients. This study highlights the importance of considering both clinical and molecular factors in the management of glioma patients to improve cognitive outcomes.

Value of 18F-FDG PET/CT in breast cancer with second primary malignancies.

PURPOSE: To investigate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer (BC) with second primary malignancies (SPMs). MATERIALS AND METHODS: 149 BC patients (149/1419, 10.5 %) ultimately diagnosed with SPMs were included in the study. The following data were evaluated: age, location, the treatment of the first BC, the interval between the first BC and SPMs, the maximum diameter of SPMs, the maximum standardized uptake value (SUVmax) of SPMs, and SPMs metastases. The overall survival (OS) and progression-free survival (PFS) of follow-up patients were analyzed. The diagnostic efficiency of 18F-FDG PET/CT for SPMs and consistency with the pathological findings were calculated. RESULTS: The most common SPMs of BC was lung cancer (81/149, 54.4 %), particularly early-stage lung adenocarcinoma. There were the shorter maximum diameter of SPMs, the lower SUVmax of SPMs, and the fewer SPMs metastases in the lung cancer group than non-lung cancer group (P<0.001). The OS and PFS of the follow-up patients in the lung cancer group were longer than non-lung cancer group (P<0.001). The SPMs metastases was independent prognostic indicator of OS. The pathological grouping and the SPMs metastases were independent prognostic indicators of PFS. 18F-FDG PET/CT efficacy in diagnosing SPMs in BC patients was high. Compared with the pathological findings, the consistency was good (P = 0.010). CONCLUSION: Applying 18F-FDG PET/CT in BC patients might be helpful in detecting SPMs and partially predicting patient prognosis, in addition to its primary function in the diagnosis and staging of BC.

Bioinformatics analysis of GPS1 expression and biological function in breast cancer.

G protein pathway suppressor 1 (GPS1) is involved in the development of many diseases including tumors, but its specific regulatory mechanism in breast cancer is not clear. The goal of the present study was to explore the biological effects and underlying mechanism of GPS1 in breast cancer. Public databases were used to analyze GPS1 expression and the relationship with clinicopathological characteristics and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of GPS1 in breast cancer. Data analysis showed that the expression of GPS1 in breast cancer tissues was significantly higher than that in paracancerous tissues (p < 0.001), and the receiver operating curve (ROC) revealed a higher diagnostic efficiency (AUC = 0.832). Survival analyses indicated that patients with high GPS1 expression made the prognosis worse in Luminal B, low to intermediate-grade breast cancers. Enrichment analysis showed that GPS1 was involved in the formation of ribonucleoprotein complexes, which dynamically altered the fate of RNA; it could also enhance the responsiveness of the Wnt pathway by interacting with WBP2. In addition, GPS1 expression was closely related to the immune microenvironment. GPS1 knockdown inhibits the proliferation, invasion and migration of MCF7 and MDA-MB-231 cells in vitro. This study suggests that the upregulation of GPS1 is associated with the malignant biological behavior and prognosis of breast cancer and may promote cancer progression. The correlation between GPS1 and the immune microenvironment suggests that it may be a potential target for immunotherapy.

Jeduxiaoliu Formula can Induce Apoptosis of Lymphoma Cells In Vitro and In Vivo.

OBJECTIVE: Lymphoma is the most common malignancy of the haematological system. Jeduxiaoliu formula (JDXLF) exerts good therapeutic effects against lymphoma, however, the mechanisms underlying these effects remain unclear. Therefore, this study aimed to investigate the mechanism of action of JDXLF. METHOD: RNA-Seq was performed to examine the molecular mechanisms underlying the therapeutic effects of JDXLF against lymphoma. CCK-8 assay was performed to examine the effects of JDXLF on the proliferation of lymphoma cells. Electron microscopy was performed to examine the morphology of lymphoma cells. Flow cytometry was performed to examine the apoptosis and cell cycle of lymphoma cells. qPCR and Western blotting were performed to detect the expression of apoptotic genes and proteins. In vivo, the tumour-suppressive effect of JDXLF on lymphoma transplanted tumours was examined by establishing a subcutaneous transplantation tumour model in nude mice, and the expression of apoptotic proteins in tumour tissues was analysed via immunohistochemical staining. RESULTS: RNA-Seq revealed 71, 350 and 620 differentially expressed genes (DEGs) in the 1mg/mL, 4mg/mL and 8mg/mL JDXLF treatment groups, respectively. KEGG pathway analysis showed that the DEGs were significantly associated with apoptosis, TNF signalling and NF-κB signalling. In vitro experiments revealed that JDXLF inhibited the proliferation of lymphoma (Raji and Jeko-1) cells in a dose-dependent manner, induced apoptosis and upregulated the expression of Bax/Bcl-2 and caspase3. In vivo experiments revealed that JDXLF had a significant tumourshrinking effect on mice and increased the expression of the apoptosis-related proteins caspase3 and Bax/Bcl-2. CONCLUSIONS: This study indicates that JDXLF can induce apoptosis in lymphoma cells in vitro and in vivo. We suggest this may provide a direction for further research into lymphoma therapy.

An electrochemiluminescence resonance energy transfer biosensor based on Luminol-LDH and CuS@Pt for detection of alpha-fetoprotein.

Alpha-fetoprotein (AFP) is the best diagnostic marker for hepatocellular carcinoma (HCC) and plays an important role in the general surveillance of the population. Therefore, the establishment of an ultra-sensitive AFP assay is essential for the early screening and clinical diagnosis of HCC. In this work, we designed a signal-off biosensor for ultra-sensitive detection of AFP based on an electrochemiluminescent resonance energy transfer (ECL-RET) strategy using luminol intercalated layered bimetallic hydroxide (Luminol-LDH) as an ECL donor and Pt nanoparticles-grown on copper sulfide nanospheres (CuS@Pt) as ECL acceptor. The (Au NPs/Luminol-LDH)n multilayer nanomembrane synthesized by our intercalation and layer-by-layer electrostatic assembly process not only effectively immobilizes luminol but also significantly enhances the ECL signal. The CuS@Pt composite has well visible light absorption ability and can burst the light emitted from luminol by ECL-RET. The biosensor showed good linearity in the range from 10-5 ng mL-1 to 100 ng mL-1 and a minimum detection limit of 2.6 fg mL-1. Therefore, the biosensor provides a novel and efficient strategy for the detection of AFP, which is important for the early screening and clinical diagnosis of HCC.

GOLPH3 modulates expression and alternative splicing of transcription factors associated with endometrial decidualization in human endometrial stromal cells.

Endometrial decidualization is a decidual tissue formed by the proliferation and re-differentiation of endometrial stroma stimulated by decidualization inducing factors. It is very important for the proper maintenance of pregnancy. Previous studies speculated that Golgi phosphoprotein 3 (GOLPH3) may have a regulatory role in the process of endometrial decidualization, while the specific molecular mechanisms of GOLPH3 is unclear. In this part, GOLPH3 was silenced in human endometrial stromal cells (hESCs), and the transcriptome data (RNA-seq) by GOLPH3 knockdown (siGOLPH3) was obtained by high-throughput sequencing technology so as to analyze the potential targets of GOLPH3 at expression and alternative splicing levels in hESCs. Through bioinformatics analysis, we found that siGOLPH3 can significantly affect the overall transcriptional level of hESCs. A total of 6,025 differentially expressed genes (DEGs) and 4,131 differentially alternative splicing events (DASEs) were identified. Through functional cluster analysis of these DEGs and genes where differential alternative splicing events are located, it is found that they are enriched in the PI3K/Akt signaling pathway, RNA splicing and processing, transcription factors and other pathways related to endometrial decidualization and important biological processes, indicating the important biological function of GOLPH3. At the same time, we focused on the analysis of the transcription factors regulated by GOLPH3, including gene expression regulation and the regulation of variable splicing. We found that GOLPH3can regulate the expression of transcription factors such as LD1, FOSL2, GATA2, CSDC2 and CREB3L1. At the same time, it affects the variable splicing mode of FOXM1 and TCF3. The function of these transcription factors is directly related to decidualization of endometrium. Therefore, we infer that GOLPH3 may participate in endometrial de membrane by regulating expression and alternative splicing levels of transcription factors. We further identified the role of GOLPH3 in the transcriptional mechanism. At the same time, it also expands the function mode of GOLPH3 protein molecule, and provides a theoretical basis for downstream targeted drug research and development and clinical application.

α-Synuclein induces prodromal symptoms of Parkinson's disease via activating TLR2/MyD88/NF-κB pathway in Schwann cells of vagus nerve in a rat model.

BACKGROUND: Increasing evidence suggests that patients with Parkinson's disease (PD) present with peripheral autonomic dysfunction (AutD) that even precedes motor deficits, through which α-synuclein can spread to the central nervous system. However, the pathological mechanisms underlying AutD in prodromal PD remain unclear. Here, we investigated the role of α-synuclein and its interplay with the activation of Schwann cells (SCs) of the vagus nerve in AutD. METHODS: Rats were subjected to injection with adeno-associated viruses containing the human mutated A53T gene (AAV-A53T) or an empty vector into the left cervical vagus nerve and evaluated for gastrointestinal symptoms, locomotor functions, intestinal blood flow, and nerve electrophysiology. Further, we examined the impact of α-synucleinopathy on vagus nerves, SCs, and central nervous system neurons using electron microscopy, immunofluorescence, immunohistochemistry, and western blot. Finally, the role of Toll-like receptor 2 (TLR2) in regulating the neuroinflammation in the vagus nerve via MyD88 and NF-κB pathway was determined using genetic knockdown. RESULTS: We found that rats injected with AAV-A53T in the vagus nerve exhibited prominent signs of AutD, preceding the onset of motor deficits and central dopaminergic abnormalities by at least 3 months, which could serve as a model for prodromal PD. In addition, reduced intestinal blood flow and decreased nerve conduction velocity were identified in AAV-A53T-injected rats, accompanied by disrupted myelin sheaths and swollen SCs in the vagus nerve. Furthermore, our data demonstrated that p-α-synuclein was deposited in SCs but not in axons, activating the TLR2/MyD88/NF-κB signaling pathway and leading to neuroinflammatory responses. In contrast, silencing the TLR2 gene not only reduced inflammatory cytokine expression but also ameliorated vagal demyelination and secondary axonal loss, consequently improving autonomic function in rats. CONCLUSIONS: These observations suggest that overexpression of α-synuclein in the vagus nerve can induce symptoms of AutD in prodromal PD, and provide support for a deeper understanding of the pathological mechanisms underlying AutD and the emergence of effective therapeutic strategies for PD.

l-Cysteine Treatment Delayed the Quality Deterioration of Fresh-Cut Button Mushrooms by Regulating Oxygen Metabolism, Inhibiting Water Loss, and Stimulating Endogenous H2S Production.

Although fresh-cut button mushrooms are popular with consumers, quality deterioration presents a significant shelf-life challenge. In this study, fresh-cut button mushrooms were treated with 0.25 g/L l-cysteine (l-Cys) and evaluated in terms of quality, physiology, and transcriptome sequencing. The results indicated that l-Cys application significantly delayed the browning degree of fresh-cut button mushrooms and reduced weight loss. l-Cys treatment reduced the malondialdehyde content, lipoxygenase activity, and reducing sugar levels while enhancing the soluble protein and total phenolic content. Furthermore, l-Cys treatment reduced the O2- generation rate and H2O2 accumulation while enhancing the catalase activity. Moreover, l-Cys improved the superoxide dismutase, glutathione reductase, and phenylalanine ammonia-lyase activities while reducing those of polyphenol oxidase and peroxidase. Additionally, l-Cys treatment increased endogenous H2S production and AbCBS enzyme activity while decreasing AbCSE enzyme activity. Notably, additional treatment with 1 mM propargylglycine significantly reduced the effect of l-Cys. Moreover, transcriptome sequencing analysis indicated that the differentially expressed genes in the l-Cys group were primarily related to the reactive oxygen species metabolism, oxidoreductase process, membrane integrality, and sulfur metabolism. These findings suggested that l-Cys treatment delayed the aging and extended the shelf life of fresh-cut button mushrooms by regulating the active oxygen species metabolism and water loss and stimulating endogenous H2S production.

How climate, landscape, and economic changes increase the exposure of Echinococcus Spp.

BACKGROUND: Echinococcosis is a global enzootic disease influenced by different biological and environmental factors and causes a heavy financial burden on sick families and governments. Currently, government subsidies for the treatment of patients with echinococcosis are only a fixed number despite patients' finical income or cost of treatment, and health authorities are demanded to supply an annual summary of only endemic data. The risk to people in urban areas or non-endemic is increasing with climate, landscape, and lifestyle changes. METHODS: We conducted retrospective descriptive research on inpatients with human echinococcosis (HE) in Lanzhou hospitals and analyzed the healthcare expenditure on inpatient treatment and examined the financial inequalities relating to different levels of gross domestic product. The livestock losses were also estimated by infection ratio. The occurrence records of Echinococcus spp. composed of hospitalized patients and dogs infected in the Gansu province were collected for Ecological niche modeling (ENM) to estimate the current suitable spatial distribution for the parasite in Gansu province. Then, we imported the resulting current niche model into future global Shared Socioeconomic Pathways scenarios for estimation of future suitable habitat areas. RESULTS: Between 2000 to 2020, 625 hospitalized HE patients (51% men and 49% women) were identified, and 48.32 ± 15.62 years old. The average cost of hospitalization expenses per case of HE in Gansu Province was ï¿¥24,370.2 with an increasing trend during the study period and was negative with different counties' corresponding gross domestic product (GDP). The trend of livestock losses was similar to the average cost of hospitalization expenses from 2015 to 2017. The three factors with the strongest correlation to echinococcosis infection probability were (1) global land cover (GLC, 56.6%), (2) annual precipitation (Bio12, 21.2%), and (3) mean temperature of the Wettest Quarter (Bio12, 8.5% of variations). We obtained a robust model that provides detail on the distribution of suitable areas for Echinococcus spp. including areas that have not been reported for the parasite. An increasing tendency was observed in the highly suitable areas of Echinococcus spp. indicating that environmental changes would affect the distributions. CONCLUSION: This study may help in the development of policies for at-risk populations in geographically defined areas and monitor improvements in HE control strategies by allowing targeted allocation of resources, including spatial analyses of expenditure and the identification of non-endemic areas or risk for these parasites, and a better comprehension of the role of the environment in clarifying the transmission dynamics of Echinococcus spp. Raising healthcare workers' and travelers' disease awareness and preventive health habits is an urgent agenda. Due to unpredictable future land cover types, prediction of the future with only climatic variables involved needs to be treated cautiously.

Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol.

Objective: To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with the gonadotropin-releasing hormone antagonist protocol and to establish a nomogram prediction model of ovarian response. Methods: A retrospective cohort analysis of the clinical data of 1,944 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from April 1, 2018, to June 30, 2020. According to the number of oocytes obtained, there were 659 cases in the low ovarian response group (no more than five oocytes were retrieved), 920 cases in the normal ovarian response group (the number of retrieved oocytes was >5 but ≤18), and 365 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian responsiveness were screened by logistic regression, which were the model entry variables, and a nomogram prediction model was established based on the regression coefficients. Results: There were statistically significant differences in age, anti-Mullerian hormone, antral follicle count, the diagnosis of endometriosis, decreased ovarian reserve, polycystic ovary syndrome, basal follicle-stimulating hormone and basal luteinizing hormone among the three groups (P < 0.001). Multifactorial stepwise regression analysis showed that female age (0.95 [0.92-0.97], P = 0.000), decreased ovarian reserve (0.27 [0.19-0.38]), P = 0.000), endometriosis (0.81 [0.56-0.86], P = 0.000), antral follicle count (1.09 [1.06-1.12], P = 0.000), basal follicle-stimulating hormone (0.90 [0.85-0.96], P = 0.001), Anti-Mullerian hormone (1.19 [1.13-1.26], P= 0.000) and luteinizing hormone on trigger day (0.73 [0.66-0.80], P= 0.000), were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The predictive model of ovarian responsiveness was constructed based on the above factors, and the model was verified with 589 patients' data from July 1, 2020, to December 31, 2020, at this center. The predicted ovarian response (number of eggs obtained) of a total of 450 patients was consistent with the actual results, with a coincidence degree of 76.4%, and the consistency index of the model is 0.77. Conclusion: The nomogram model was successfully developed to effectively, intuitively, and visually predict the ovary reactivity in the gonadotropin-releasing hormone antagonist protocol and provide guidance for clinical practice.

TREM2 ameliorates anesthesia and surgery-induced cognitive impairment by regulating mitophagy and NLRP3 inflammasome in aged C57/BL6 mice.

Postoperative cognitive dysfunction (POCD) is a major postoperative complication. Triggering receptor expressed on myeloid cells 2 (TREM2) exerts a neuroprotective function against neuro-inflammatory responses. The present study investigated the role of TREM2 in anesthesia and surgery-induced cognitive impairment and the potential related mechanism. Our results revealed that TREM2 was downregulated, coupled with activation of the NLRP3 inflammasome and subsequent IL-1ß expression on postoperative day 3. A corresponding decline in PSD-95 and BDNF was found at the same time point. The key regulator of mitophagy PINK1 and Parkin protein levels were significantly decreased following surgery and anesthesia. TREM2 overexpression partially reversed postoperative cognitive impairment and enhanced PSD-95 and BDNF expression. TREM2 overexpression also improved mitophagy function and inhibited activation of the NLRP3 inflammasome and associated production of IL-1ß. Our findings demonstrate that TREM2 rescues anesthesia and surgery-induced spatial learning and memory impairment and neuro-inflammation in aged C57/BL6 mice, which may be at least partially mediated through the activation of mitophagy and subsequent inhibition of the NLRP3 inflammasome.

A comparison of the analgesic efficacy of serratus anterior plane block vs. paravertebral nerve block for video-assisted thoracic surgery: a randomized controlled trial.

INTRODUCTION: Patients who undergo video-assisted thoracic surgery (VATS) frequently experience moderate to severe postoperative pain. Serratus anterior plane block (SAPB) is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. AIM: To evaluate the analgesic efficiency of deep serratus plane block (DSPB) and superficial serratus anterior plane block (SSPB) as well as paravertebral nerve block (PVB) in patients undergoing VATS. MATERIAL AND METHODS: A total of 74 patients aged 16-80 undergoing VATS were randomized to receive either DSPB or SSPB as well as PVB. Ultrasound (US) guided DSPB or SSPB as well as PVB was performed preoperatively on the patients according to their groups. All patients were provided with patient-controlled intravenous analgesia (PCIA) for postoperative analgesia. The primary outcomes were the levels of postoperative pain at rest and on coughing evaluated by the visual analog scale (VAS), and intraoperative and postoperative opioid consumption. The secondary outcomes included PCIA pressing times, side effects and satisfaction with analgesia, duration of nerve block, intraoperative hemodynamic changes and vasoactive drug dosage. RESULTS: No significant differences of VAS score were found. During the operation, PVB reduced consumption of opioids (27.23 ±5.10 mg) compared to DSPB (31.20 ±3.80 mg) and SSPB (32.61 ±5.28 mg). The effective pressing times of PCIA in the SSPB group (0.18 ±0.65) were significantly lower compared to the PVB group (1.09 ±1.50) at 12 h postoperatively. Accordingly, SSPB also reduced the dosage of PCIA (26.55 ±4.72 ml) compared to PVB (31.45 ±7.60 ml). Time of the PVB procedure was longer (11.14 ±1.66 min) than DSPB (5.68 ±1.10 min) and SSPB (4.77 ±1.04 min). CONCLUSIONS: DSPB and SSPB are easy to perform and can serve as a promising alternative technique to PVB that may offer comparable analgesic effectiveness for patients undergoing VATS.

Anti-inflammatory action of geniposide promotes wound healing in diabetic rats.

CONTEXT: As a major active iridoid glycoside from Gardenia jasminoides J. Ellis (Rubiaceae), geniposide possesses various pharmacological activities, including anti-platelet aggregation and anti-inflammatory action. OBJECTIVES: This study explores the effect of geniposide in diabetic wound model by anti-inflammatory action. MATERIALS AND METHODS: Diabetic rodent model in Wistar rats was induced by streptozotocin combined with high-fat feed. The selected rats were divided into control group, the diabetic model group and geniposide subgroups (200, 400 and 500 mg/kg), and orally administrated once daily with saline or geniposide. Wound area and histochemical indicators were measured on day 7 after continuous administration, to assess lesion retraction, inflammatory cells and fibroblasts. RESULTS: Geniposide notably enhanced lesion retraction by 1.06-1.84 times on day 7 after surgical onset in diabetic rats (p < 0.05). In the pathological experiment by HE staining, geniposide significantly reduced inflammatory cell infiltration and proliferation of fibroblasts in the central lesion regions. In diabetic rats treated with geniposide, the levels of pro-inflammatory factors (tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß)) and IL-6 were significantly reduced (p < 0.05), followed with the increment of IL-10 in a dose-dependent manner. The IC50 of geniposide on TNF-α, IL-1ß and IL-6 could be calculated as 1.36, 1.02 and 1.23 g/kg, respectively. It assumed that geniposide-induced IL-10 expression contributed to inhibiting the expression of pro-inflammatory factors. DISCUSSION AND CONCLUSIONS: Geniposide promoted diabetic wound healing by anti-inflammation and adjusting blood glucose. Further topical studies are required to evaluate effects on antibacterial activity and skin regeneration.

Atractylenolide III inhibits epithelial­mesenchymal transition in small intestine epithelial cells by activating the AMPK signaling pathway.

Compared with the available drugs for the treatment of fibrosis in other organs, the development of intestinal anti­fibrosis drugs is limited. Therefore, it is of practical significance to examine novel drugs to delay or block the development of intestinal fibrosis. The present study aimed to investigate the effect of atractylenolide III (ATL­III) on intestinal fibrosis. An MTT assay was used to detect the effect of ATL­III on the activity of IEC­6 cells. The migration and invasion of fibrotic cells stimulated with TGF­ß were determined via wound healing and Transwell assays. An immunofluorescence assay and western blotting were conducted to assess the expression levels of protein associated with epithelial­mesenchymal transition (EMT). The role of the AMP­activated protein kinase (AMPK) pathway was verified using compound C (an AMPK inhibitor) treatment. The results of the present study indicated that ATL­III had no effect on the cells at a dose of 1­20 µmol/l. Moreover, ATL­III can inhibit the invasion and migration of cells induced by TGF­ß1, as well as block the EMT process. It was found that ATL­III could also activate the AMPK pathway. Furthermore, compound C reduced the inhibitory effect of ATL­III on stimulated cells, which indicated that the AMPK pathway plays a role in the inhibition process. In conclusion, ATL­III may inhibit the EMT of IEC­6 cells stimulated with TGF­ß1 by activating the AMPK signaling pathway.

A comparison of paravertebral block, erector spinae plane block and the combination of erector spinae plane block and paravertebral block for post-operative analgesia after video-assisted thoracoscopic surgery: A randomised controlled trial.

BACKGROUND: This study was to determine the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) and paravertebral block (PVB) as well as the combination of PVB and ESPB (P + E) after video-assisted thoracoscopic surgery (VATS). PATIENTS AND METHODS: Patients were randomly assigned to receive ESPB, PVB or PVB combined with ESPB with 0.5% ropivacaine (20 ml). The primary outcomes were cumulative hydromorphone consumption and Visual Analogue Scale (VAS) scores at rest and while coughing at 0 h, 12 h, 24 h, 48 h and 72 h postoperatively. The secondary outcomes were effective PCA usage count and rescue analgesia requirement at the same time points. RESULTS: The median (interquartile range) hydromorphone consumption, including converted oxycodone, was significantly different at 48 h postoperatively among the three groups (ESPB, 10.24 [9.53-11.71] mg; PVB, 9.94 [9.19-10.75] mg; P + E, 9.44 [8.96-9.97] mg; P = 0.011). Hydromorphone consumption in P + E group was lower compared with that in ESPB group at 12 h, 24 h and 48 h (P < 0.001, P = 0.004 and P = 0.003, respectively). VAS scores at rest were significantly higher for ESPB group compared to P + E group at 0 h postoperatively (P = 0.009). VAS scores while coughing were significantly higher for ESPB group compared to P + E group at 0 h and 12 h postoperatively (P = 0.015 and P < 0.001) and to the PVB group at 12 h postoperatively (P = 0.002). The effective PCA usage count in P + E group was lower than in ESPB group in 0-12 h (P < 0.001). More patients needed rescue analgesia in ESPB group compared to those in P + E group in 0-12 h, 0-24 h and 0-48 h (P = 0.022, 0.035 and 0.035, respectively). CONCLUSIONS: Ultrasound-guided PVB combined with ESPB provided superior analgesia to ESPB for VATS. The combination of PVB and ESPB had a similar analgesic effect compared with PVB alone.

Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells.

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 µM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.

A two-adjuvant multiantigen candidate vaccine induces superior protective immune responses against SARS-CoV-2 challenge.

An ideal vaccine against SARS-CoV-2 is expected to elicit broad immunity to prevent viral infection and disease, with efficient viral clearance in the upper respiratory tract (URT). Here, the N protein and prefusion-full S protein (SFLmut) are combined with flagellin (KF) and cyclic GMP-AMP (cGAMP) to generate a candidate vaccine, and this vaccine elicits stronger systemic and mucosal humoral immunity than vaccines containing other forms of the S protein. Furthermore, the candidate vaccine administered via intranasal route can enhance local immune responses in the respiratory tract. Importantly, human ACE2 transgenic mice given the candidate vaccine are protected against lethal SARS-CoV-2 challenge, with superior protection in the URT compared with that in mice immunized with an inactivated vaccine. In summary, the developed vaccine can elicit a multifaceted immune response and induce robust viral clearance in the URT, which makes it a potential vaccine for preventing disease and infection of SARS-CoV-2.

Atractylenolide III Ameliorates TNBS-Induced Intestinal Inflammation in Mice by Reducing Oxidative Stress and Regulating Intestinal Flora.

The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mouse colitis model. TNBS-induced colitis was established in mice, which were treated with 8-ß-Hydroxyasterolide (Atractylenolide III) for 14 days. The body weight of the mice in the middle and high dose groups of Atractylenolide III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolide III, as determined by histological analysis. Moreover, Atractylenolide III downregulated the expression levels of the inflammatory factors interleukin-1ß and tumor necrosis factor-α, and greatly suppressed the levels of the pro-oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptor 1 (FPR1) and nuclear respiratory factor 2 (Nrf2) were upregulated in the colonic tissues of TNBS-treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS-induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.

Neuroprotective effect of targeted regulatory Nrf2 gene on rats with acute brain injury induced by carbon monoxide poisoning.

Oxidative stress has been considered as an important cause of neurocyte damage induced by carbon monoxide (CO) poisoning; however, the precise mechanisms are not fully understood. The study aimed to elucidate the molecular mechanism and the neuroprotective effect of targeted regulatory nuclear factor erythroid2-related factor 2 (Nrf2) gene on acute brain injury in CO poisoning rats. An acute CO poisoning rat model was established by CO inhalation in hyperbaric oxygen chamber and followed by the administration of Nrf2 gene-loaded lentivirus. Mitochondrial membrane potential (ΔΨM), the levels of Nrf2, glutamate-cysteine ligase catalytic subunit (GCLC), catalase (CAT) and glutathione peroxidase (GSH-Px), and cell apoptosis were determined in brain tissue in rats. We found that CO poisoning could decrease ΔΨm of cells, slightly increase the expressions of Nrf2 and GCLC at mRNA and protein levels, reduce CAT and GSH-Px, and thus initiate apoptosis process. The Nrf2 gene treatment could obviously enhance the expressions of Nrf2 at mRNA and protein levels, and increase the concentrations of CAT and GSH-Px, maintain the ΔΨm of cells in brain tissue, significantly inhibit cell apoptosis as compared with the CO poisoning group (p < .05). These findings suggest that CO poisoning could induce oxidative stress and impair mitochondrial function of cells in brain tissue. The administration of Nrf2 gene could notably strengthen the antioxidant capacity of cells through regulating the downstream genes of Nrf2/antioxidant responsive element signal pathway, and positively protect cells against brain injury induced by acute severe CO poisoning.