Three different routes of EHEC O157:H7 infection were used to establish EHEC broiler model.

In order to study the prevention and control EHEC disease measures in poultry, the infection process and development of this disease and the pathological changes of various organs were to be observed. In this study, chickens were infected with different doses of enterohemorrhagic Escherichia coli (EHEC) O157:H7 using different routes of administration to establish EHEC broiler model. A total of 195 14-day-old broilers were randomly divided into 13 groups: including control group, Enema-drip groups (1010, 1011, 1012, 1013 CFUs E. coli O157:H7), gavage groups (P.O) (1011, 1012, 1013, 1014 CFUs E. coli O157:H7), and intraperitoneal injection group (I.P.) (108, 109, 1010, 1011 CFUs E. coli O157:H7). Escherichia coli (E. coli) was given using enema-drip, gavage or intraperitoneal infection. Then the feed intake, weight changes, stool and clinical symptoms of the chicks were recorded during the experiment. 7 d after E. coli infection, blood was collected from the jugular vein and serological tests were carried out. The liver, spleen, and colon of the chicks were extracted to get the organ index, bacteria load, and their histopathological changes. After infection with E. coli, some chicks feces were green or red watery stool, sometimes accompanied by foam, and the material to weight ratio of broilers in I.P. group increased significantly (P < 0.05), the 108 CFUs group were 1.3 times as large as control group. Three modeling methods can result in abnormal serum lipid metabolism and liver function indexes (increase of AST, TBA, T-Bil and TC level; decrease of ALB, TG, and TP level). Infection of chicks with O157:H7 by all 3 methods resulted in its detection in the liver, spleen, and colon. Three modeling methods significantly decreased liver index, and inflammatory cell infiltration and hyperemia were observed in liver. The spleen index in E. coli broilers by gavage and enema-drip was significantly decreased, splenic hyperemia and periarteriolar hyalinosis were observed. The spleen was enlarged with purplish-black spheroids in I.P. group broilers, and the spleen histological changes was more serious. The colon villi of broilers in gavage and enema-drip groups were thinner, more prone to rupture, intestinal lamina propria hyperemia, and inflammatory cell infiltration. Moreover, the number of goblet cells in the mucosal epithelium increased. E. coli O157:H7 can induce liver, spleen and intestinal damage and reduce growth performance of chicks. By comparing these 3 methods, we found that chicks infected with O157:H7 by gavage had more severe liver and intestinal damage, the enema-drip method caused most serious intestinal damage, and I.P. method significantly damaged the liver and spleen of chickens.

Perspectives and Practice in Eastern and Western Medicine for Pain Management in Rehabilitation Training after Orthopedic Trauma Surgery: A Qualitative Study.

BACKGROUND: Despite the increasing emphasis on rehabilitation training after orthopedic surgery, little is known about the pain caused by the procedure itself. Clinical practice is driven by beliefs in pain management. AIMS: This study aimed to explore the perspective of pain management during rehabilitation training after orthopedic trauma in China and its influencing factors from different perspectives in traditional Chinese medicine and Western medicine, respectively. DESIGN: A phenomenological qualitative study involving semi-structured interviews. SETTINGS:   METHODS: A qualitative study was conducted with 16 medical workers working in the Rehabilitation Medicine Department in eastern China from July 2022-February 2023. A directed method to thematic analysis was used to code the transcribed data and identify themes. RESULTS: Four main themes emerged. (1) Inconsistent perspectives and practice: Chinese doctors majoring in Western medicine felt sympathy, helpless, and had a lack of knowledge and misconception about pain. Traditional Chinese medicine deemed that pain is a protective mechanism and attached importance to holism and unique means. (2) Consistent outcome: Insufficient pain management will have a series of negative consequences for patients' recovery, forming a vicious cycle. (3) Expectations: Though they are not optimistic about traditional analgesics, enhancement, cooperation and ideal analgesic methods still be expressed, and (4) Concept transformation: Conducting nitrous oxide is a process not only to promote analgesic technology but also to promote the awareness and concept of pain management. CONCLUSIONS: Our study emphasized that medical workers should be aware of the importance of pain management at the same time while treating the disability. The study provides insight into pain management experiences within different educational backgrounds. The findings enable professionals to recognize the importance of pain management and its influencing factors to provide feasible and effective pain management strategies.

Systematic characterization of the chemical constituents in vitro and in vivo of Qianghuo by UPLC-Q-TOF-MS/MS.

The Chinese herb Qianghuo is an antiphlogistic herb with many effects and complex components. In this study, the chemical composition of Qianghuo and its components in rat plasma after oral administration were investigated using ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). The extracts, blank plasma, and plasma containing the drug were analyzed by mass spectrometry, and data collected in both positive and negative ion modes were analyzed using Masslynx software, and the structures were confirmed by combining the compound fragment ions and mass spectrometry cleavage pathways. A total of 62 in vitro chemical components were identified, including 27 coumarins, 18 organic acids, 5 amino acids, 5 glycosides, 2 flavonoids, 4 nucleotides, and 1 ester, which were summarized from the obtained compounds in terms of their possible cleavage patterns. Among the identified 31 compounds in rat plasma, 21 were prototypes, mostly coumarins, organic acids, and flavonoids, and 10 were metabolites, which were mainly generated via hydroxylation and methylation pathways. Based on these, this study provides a theoretical foundation for quality control and basic research on Qianghuo medicinal substances.

Analgesic effect of nitrous oxide during manual therapy after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial.

BACKGROUND: Many patients during manual therapy after anterior ligament reconstruction will experience severe pain, which has a negative impact on their rehabilitation. However, there is rarely an analgesic method for these patients during rehabilitation. Nitrous oxide with rapid analgesic and sedative effects is often used to relieve pain in minor procedures. The purpose of this study is to determine whether or not nitrous oxide analgesia decreases pain compared to oxygen during manual therapy after anterior ligament reconstruction. METHODS/DESIGN: This single-center, randomized, double-blind and controlled trial will recruit 120 patients. Patients ≥ 18 years old undergoing manual therapy after anterior ligament reconstruction (1 month post-operative) with acute pain (VAS ≥ 4) are included. The main exclusion criteria included the following: pulmonary embolism, intestinal obstruction, pneumothorax. Patients will be randomly allocated to the intervention group (A) and the control group (B) in a ratio of 1:1. Doctors, therapists, patients, and data collectors are all blind to the study. The manual therapy will be performed by therapists. Nurses who implemented the intervention handed the doctors envelopes containing the patients' codes and allocation of A or B. Group A will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesic) given as 30-min treatment sessions, once daily, and group B will receive oxygen plus conventional treatment (no analgesic) under the same conditions. Assessments will be taken 2 min before the intervention (T0), 5 min after the beginning of the intervention (T1), and 5 min after the intervention finished (T2). The primary outcome is pain score. Secondary outcomes include vital signs, side effects, joint range of motion, adjuvant analgesia need, therapist and patient satisfaction, and whether willing to receive the same gas again. EXPECTED OUTCOMES: We expect nitrous oxide inhalation to have a beneficial effect on the pain of patients who receive manual therapy after anterior ligament reconstruction. DISCUSSION: If this treatment appears beneficial, it could improve patients' satisfaction and quality of life potentially and even be implemented widely in hospital and rehabilitation settings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2200061175 (Version 2.0 June 15, 2022), https://www.chictr.org.cn .

Essential nutrients and cerebral small vessel diseases: a two-sample Mendelian randomization study.

Background: Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed. Object: We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis. Method: We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR-Egger method were adopted for sensitivity analyses. Results: For ICH or SVS, increased levels of phenylalanine (OR = 1.188, p < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, p = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, p < 0.001), zinc (OR = 0.919, p < 0.001), and arachidonic acid (OR = 0.966, p = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, p < 0.001), zinc (OR = 0.918, p < 0.001), and retinol (OR = 0.753, p < 0.001) showed risk effects; DPA (OR = 0.682, p = 0.022), gamma-linolenic acid (OR = 0.120, p = 0.033) and 25(OH)D (OR = 0.874, p = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, p < 0.001) and phenylalanine (OR = 1.175, p = 0.001) showed risk effects. Conclusion: Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.

Integrated Dose-Effect Relationship of Near-Infrared Light-Emitting Diode Light on Bone Regeneration in Disuse Osteoporosis Rats.

Objective: To examine the integrated dose-effect relationship of near-infrared (NIR) light-emitting diode (LED) light therapy in promoting bone defect repair in the rat model for osteoporosis (OP). Background: Low-intensity laser therapy has been shown to promote bone regeneration in OP rats. However, its integrated dose-effect relationship is not clear. Methods: Twenty-week-old male Sprague-Dawley rats were randomly assigned to 11 groups: (1) no-treatment control group (C group), (2) tail suspension (TS)-induced disuse OP experimental group (TS-OP group), and (3) OP rats with LED light treatment at nine dosages (L1-L9 groups). The tail of the rat was tied and suspended on the beam of the cage to suspend their hind limbs to induce bone loss for 4 or 7 weeks. The rats were then released and returned to their regular positions. An NIR LED at 810 nm was used on the bilateral hind limbs daily for 4 weeks. The C group rats were not given any treatment. The TS-OP group rats were subjected to identical procedures with L groups, with the exception that the light power was not turned on. After the experiment, the dual-energy X-rays or the microcomputed tomography scan analysis was performed to evaluate bone tissue status. Data analysis was done using SPSS and the health scale. Results: The trabecular thickness, trabecular number, bone volume/total volume, and connectivity density of cancellous bone and the biomechanical properties of femur in light groups were significantly increased compared with the TS-OP group, while the trabecular separation and structure model index were significantly decreased. Conclusions: NIR LED light therapy may promote trabecular bone repair of TS-OP rats. Light intensity influences photobiomodulation. In our dose levels, the greater the light intensity, usually the more effective.

Parental Phubbing and Adolescent Depressive Symptoms during COVID-19: A Serial Meditating Model.

BACKGROUND: During the COVID-19 pandemic, depressive symptoms, a common emotional problem among adolescents, have become more prominent. Regarding the influencing factors of adolescent depressive symptoms, it is widely accepted that parents' problematic cellphone use around the family (specifically parental phubbing) is a strong predictive factor for the development of depressive symptoms among adolescents. Notably, the COVID-19 pandemic caused a sharp increase in the number of individuals with depressive symptoms, and the negative consequences of parental phubbing and depressive symptoms might have been exacerbated. Accordingly, this study aimed to examine the association between parental phubbing and adolescent depressive symptoms as well as their underlying mechanism. METHOD: To test our hypotheses, we conducted an offline/online survey with 614 adolescents in Central China from May to June 2022, which corresponded to a period of strict lockdowns in some areas due to the outbreak of the Omicron variant. The participants completed a set of measures, including a technology interference questionnaire, a parent-child relationship scale, a self-concept clarity scale, and the depressive symptoms scale. RESULTS: Parental phubbing was positively associated with adolescent depressive symptoms; the parent-child relationship and self-concept clarity could independently mediate this relationship; and the parent-child relationship and self-concept clarity were also serial mediators in this association. These findings extend previous research by highlighting the impact of parental technology use on their children and the underlying mechanism explaining adolescent depressive symptoms. They provide practical recommendations for parents to prioritize fostering a positive family environment and minimizing phubbing behaviors to enhance adolescent development, particularly in the context of the COVID-19 pandemic.

Resveratrol inhibits oxidative damage in lungs of heat-stressed broilers by activating Nrf2 signaling pathway and autophagy.

The purpose of this study was to investigate the effects of resveratrol on heat stress-induced lung injury in broilers and the mechanism underlying this process. Sixty two-week-old SPF BWEL broilers were randomly divided into the heat stress group (HS), resveratrol group (heat stress + 400 mg/kg resveratrol), and the control group after one week of feeding, with 20 chickens in each group. Broilers in the control group were reared at 23 ± 2 â„ƒ. Those in the HS and resveratrol group were reared under heat stress (35 â„ƒ ± 2 â„ƒ) for 8 h/day for seven days. Broilers in the resveratrol group were fed a diet supplemented with 400 mg/kg resveratrol two days before the start of the experiment. The feeding was continued for nine days. The results showed that HS decreased body weight (BW), average daily feed intake (ADFI), average daily gain (ADG), and lung weight. It, however, increased the lung index, induced lung congestion, and promoted infiltration of inflammatory cells to the lung. Resveratrol improved growth performance and inhibited heat stress-induced lung damage. Compared with broilers in the control group, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), Beclin-1, LC3 Ⅰ, and LC3 Ⅱ genes in the lung of heat-stressed broilers was significantly lower. The levels of kelch-like ECH-associated protein 1 (Keap1), NQO1, and HO-1 showed a similar trend with gene expressions. Immunofluorescence indicated that HS inhibited the expression of Nrf2 and LC3B proteins. Finally, the ratio of LC3 Ⅱ/LC3 Ⅰ was also significantly lower in the HS group. Further analyses revealed that resveratrol supplements in feeds enhanced antioxidation in the lung by activating the Nrf2 signaling pathway and autophagy. In conclusion, HS causes oxidative damage and inhibits autophagy in broilers. However, resveratrol protects against lung injury by alleviating oxidative stress and enhancing autophagy.

Resveratrol relieves chronic heat stress-induced liver oxidative damage in broilers by activating the Nrf2-Keap1 signaling pathway.

Heat stress (HS) affects poultry production and welfare, causing enormous damage to poultry. Resveratrol, an antioxidant and anti-inflammatory natural plant polyphenol, is widely used in agriculture for the prevention of oxidative stress-related diseases. This study aimed to explore the effects and potential mechanism of resveratrol on liver oxidative damage in heat-stressed broilers. Sixty SPF chickens were randomly divided into control, heat stress (HS) and HS+ resveratrol (resveratrol) groups. Broilers were exposed to 35 ± 2 â„ƒ (8 h/d) for 7 consecutive days to induce HS, and the other 16 h/d were kept at 23 ± 2 â„ƒ, similar to the control group. Broilers received 400 mg/kg resveratrol in the basic diet 2 days before exposure to HS and for the following 7 days. The results showed that resveratrol improved growth performance by increasing the average daily gain (ADG) and reducing the feed conversion ratio (FCR), compared with the HS group. Heat stress reduced liver weight and index, increased inflammatory cell infiltration in the liver, enhanced serum AST levels, and decreased TP and ALB II levels, which resulted in liver injury in broilers, and resveratrol effectively alleviated liver injury. Moreover, supplementation with resveratrol enhanced the activities of liver antioxidant enzymes resulting in higher GPX and SOD levels than those in the heat-stressed broilers, and decreased MDA levels. Furthermore, resveratrol alleviated liver oxidative stress by activating the gene and protein levels of Nrf2 and HO-1, enhancing NQO1 and SOD1 gene levels, and decreasing protein levels of HSP70, p62, and Keap1, and thereby alleviated the liver injury of heat-stressed broilers. Compared with the HS group, Nrf2 immunofluorescence was significantly up-regulated in the livers of resveratrol group. These results suggest that resveratrol can enhance the liver antioxidant function by activating the Nrf2-Keap1 signaling pathway to promote growth performance in broilers under HS.

Association of polysubstance use disorder with treatment quality among Medicaid beneficiaries with opioid use disorder.

INTRODUCTION: The opioid crisis is transitioning to a polydrug crisis, and individuals with co-occurring substance use disorder (SUDs) often have unique clinical characteristics and contextual barriers that influence treatment needs, engagement in treatment, complexity of treatment planning, and treatment retention. METHODS: Using Medicaid data for 2017-2018 from four states participating in a distributed research network, this retrospective cohort study documents the prevalence of specific types of co-occurring SUD among Medicaid enrollees with an opioid use disorder (OUD) diagnosis, and assesses the extent to which different SUD presentations are associated with differential patterns of MOUD and psychosocial treatments. RESULTS: We find that more than half of enrollees with OUD had a co-occurring SUD, and the most prevalent co-occurring SUD was for "other psychoactive substances", indicated among about one-quarter of enrollees with OUD in each state. We also find some substantial gaps in MOUD treatment receipt and engagement for individuals with OUD and a co-occurring SUD, a group representing more than half of individuals with OUD. In most states, enrollees with OUD and alcohol, cannabis, or amphetamine use disorder are significantly less likely to receive MOUD compared to enrollees with OUD only. In contrast, enrollees with OUD and other psychoactive SUD were significantly more likely to receive MOUD treatment. Conditional on MOUD receipt, enrollees with co-occurring SUDs had 10 % to 50 % lower odds of having a 180-day period of continuous MOUD treatment, an important predictor of better patient outcomes. Associations with concurrent receipt of MOUD and behavioral counseling were mixed across states and varied depending on co-occurring SUD type. CONCLUSIONS: Overall, ongoing progress toward increasing access to and quality of evidence-based treatment for OUD requires further efforts to ensure that individuals with co-occurring SUDs are engaged and retained in effective treatment. As the opioid crisis evolves, continued changes in drug use patterns and populations experiencing harms may necessitate new policy approaches that more fully address the complex needs of a growing population of individuals with OUD and other types of SUD.

Chronic effects of different exercise types on brain activity in healthy older adults and those with Parkinson's disease: A systematic review.

Objective: This study aimed to compare the regulation of brain activity by different kinds of long-term exercises (Tai Chi, treadmill training, and dancing) in healthy older adults and those with PD. Methods: From January 2000 to October 2021, the electronic databases PubMed, Web of Science, and Scopus were searched. All articles were screened throughout the inclusion and exclusion criteria, which was followed by PICOS criteria. Finally, all articles were systematically reviewed with analyses. Results: 29 studies were identified for this review, 24 of which were finally included in a group of healthy older adults, and five of which in a group of people with PD. All studies showed that significant changes were showed on people with PD and healthy older adults' brain activity after three terms of the exercises we chose. An inverse change trend on the functional connectivity in people with PD was observed after treadmill training, whereas increased brain activity, cognitive function, memory, and emotion were noticed in healthy older adults. Conclusion: Our findings suggest that different patterns of brain activity were also observed between healthy older adults and people with PD after treadmill training. However, more robust evidence and comprehensive studies are needed to determine if there is a difference between healthy older adults and people with PD.

The complete chloroplast genome of Bauhinia racemosa Lam. (Fabaceae): a versatile tropical medicinal plant.

Bauhinia racemosa Lam. (1783), a versatile medicinal plant, belongs to the family Fabaceae (subfamily Cercidoideae). In this study, we analyzed the complete chloroplast genome to facilitate its use in genetic research. The complete chloroplast genome of B. racemosa was found to be 155,501 bp long, including two inverted repeat (IR) regions of 25,446 bp, which are separated by a small single-copy (SSC) region of 18,295 bp and a large single-copy (LSC) region of 86,314 bp. The overall GC content is 36.4%. The genome of B. racemosa contains 129 genes, including 83 protein-coding genes, 37 tRNAs, 8 rRNAs, and 1 pseudogene (rps19). Phylogenetic analysis suggests that B. racemosa forms a monophyletic clade with the other four Bauhinia species (B. brachycarpa, B. purpurea, B. blakeana and B. variegata var. variegata).

Whole transcriptome and proteome analyses identify potential targets and mechanisms underlying tumor treating fields against glioblastoma.

Glioblastoma (GBM) is one of the most malignant types of brain cancer. Tumor treating fields (TTFields) is the up-to-date treatment for GBM. However, its molecular mechanism requires additional investigation. Herein, a novel TTFields system was developed (CL-301A) and its efficiency in suppressing GBM cell proliferation and inducing cell apoptosis was demonstrated. Through the whole proteomic and transcriptomic analyses, a multitude of differentially expressed proteins (1243), mRNAs (4191), miRtNAs (47), lncRNAs (4286), and circRNAs (13,903) were identified. Bioinformatic analysis indicated that TTFields mainly affected nuclear proteins and interrupt cell mitosis-related events. Moreover, the inhibition of autophagy could significantly enhance the anti-GBM activity of TTFields. And CDK2-AS1 might be a target of TTFields to mediate cell cycle arrest via regulating CDK2 mRNA stability. This study provided valuable resources for understanding the mechanism of TTFields, which might further assist the investigation of TTFields in GBM treatment.

An enzyme-responsive and NIR-triggered lipid-polymer hybrid nanoplatform for synergistic photothermal/chemo cancer therapy.

A combination of photothermal therapy (PTT) and chemotherapy is an emerging therapeutic strategy with promising clinical prospects in cancer treatment. Despite the huge progress achieved in the past years, a number of obstacles still hamper the therapeutic efficacy of this synergistic modality such as uneven heat distribution, lack of targetability of anti-cancer agents and dosage-related side effects. Thus, developing a nanoplatform for targeted drug delivery against cancer is of great necessity. Herein, a lipid-polymer hybrid nanosystem (LP/ID) based on polyethyleneimine (PEI)-lecithin-polyethylene glycol (PEG) was fabricated to co-load indocyanine green (ICG) and dichloroacetate (DCA) for combined photothermal/chemotherapy. DCA and ICG were linked to the PEI backbone to form a dense hydrophobic core through amide bonds and electrostatic interactions, which increased the payload of DCA and ICG as well as achieved enzyme-responsive drug release because of the overexpressed amidase in tumor cells. Lecithin and DSPE-PEG2000 self-assembled around the hydrophobic complexes to obtain prolonged blood circulation and attenuated systemic toxicity of the hybrid nanosystem. The prepared LP/ID exhibited favourable stability in a physiological environment, good tumor imaging properties, and satisfactory photothermal/chemotherapeutic performance. Moreover, LP/ID could also enhance the cellular uptake and tumor retention capacity in comparison with free drug administration. Notably, by co-loading two therapeutic agents with different anti-cancer mechanisms, an obvious inhibitory effect on tumor growth was observed with negligible damage to normal tissues and organs because of the synergistic photothermal/chemotherapy effect, indicating the great potential of LP/ID as a robust nanoplatform for cancer treatment.

Effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis: a multi-center, double-blind, randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness and safety of Ginkgo biloba extract (GBE50) in the treatment of dizziness caused by cerebral arteriosclerosis. METHODS: This was a multi-center, double-blind, double-dummy, positive-controlled, parallel randomized controlled clinical trial with 1? allocation. We recruited 404 patients with dizziness caused by cerebral arteriosclerosis (blood stasis symptom pattern) in 10 hospitals in China. GBE50 group received GBE50 and Naoxinqing tablet (NXQ) of mimetic agent, control group received NXQ and GBE50 of mimetic agent. The main outcome was Traditional Chinese Medicine (TCM) symptom pattern score of blood stasis after 6 weeks. The secondary outcomes were changes in the dizziness handicap inventory (DHI) score, vertigo visual analogue scale (VAS) score, the university of California vertigo questionnaire (UCLA-DQ) score and single-item symptom score of TCM from baseline to 2, 4 and 6 weeks. Safety indicators included the incidence of adverse events, severe adverse events and laboratory examination including blood routine, liver function, renal function, and so forth. RESULTS: The total effective rate of TCM symptom pattern score in the GBE50 group after 6 weeks of treatment was higher than that in the control group, the difference in rate was statistically significant (92.67% vs 83.07%, P = 0.004). Compared with the control group, there was no difference in the incidence of adverse reactions (9.95% vs 14.85%, P = 0.136). CONCLUSION: The treatment of dizziness caused by cerebral arteriosclerosis with GBE50 is effective, safe and reliable.

[Expert consensus on clinical application of GBE50 Dispersible Tablets for ischemic cardiovascular and cerebrovascular diseases].

Ginkgo biloba Extract( GBE50) Dispersible Tablets is a new standardized prescription,which is widely used in the treatment of ischemic cardiovascular and cerebrovascular diseases. However,there are still many problems in its clinical application.Rational and safe use of GBE50 Dispersible Tablets is pivotal to the medication safety and clinical prognosis of patients. This consensus has been jointly formulated by clinical experts of traditional Chinese medicine and western medicine in cardiovascular and cerebrovascular diseases and followed the Manual for the Clinical Experts Consensus of Chinese Patent Medicine published by the China Association of Chinese Medicine. The present study identified clinical problems based on clinical investigation,searched the research papers according to PICO clinical problems,carried out evidence evaluation,classification,and recommendation by GRADE system,and reached the expert consensus with nominal group technique. The consensus combines evidence with expert experience. Sufficient evidence of clinical problems corresponds to " recommendations",while insufficient evidence to " suggestions". Safety issues of GBE50 Dispersible Tablets,such as indications,usage and dosage,and medication for special populations,are defined to improve clinical efficacy,promote rational medication,and reduce drug risks. This consensus needs to be revised based on emerging clinical issues and evidencebased updates in practical applications in the future.

Multifunctional inorganic nanomaterials for cancer photoimmunotherapy.

Phototherapy and immunotherapy in combination is regarded as the ideal therapeutic modality to treat both primary and metastatic tumors. Immunotherapy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted elimination. Phototherapy destroys the primary tumors by light irradiation, which induces a series of immune responses through triggering immunogenic cancer cell death. Therefore, when integrating immunotherapy with phototherapy, a novel anti-cancer strategy called photoimmunotherapy (PIT) is emerging. This synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations, opening a new era for the current anti-cancer therapy. Recently, the advancement of nanomaterials affords a platform for PIT. From all these nanomaterials, inorganic nanomaterials stand out as ideal mediators in PIT due to their unique physiochemical properties. Inorganic nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug-loading capacity but also function as photothermal agents or photosensitizers in phototherapy because of their great optical characteristics. In this review, the recent advances of multifunctional inorganic nanomaterial-mediated drug delivery and their contributions to cancer PIT will be highlighted.

Study on the Multitarget Mechanism and Active Compounds of Essential Oil from Artemisia argyi Treating Pressure Injuries Based on Network Pharmacology.

In order to comprehensively explore multitarget mechanism and key active compounds of Artemisia argyi essential oil (AAEO) in the treatment of pressure injuries (PIs), we analyzed the biological functions and pathways involved in the intersection targets of AAEO and PIs based on network pharmacology, and the affinity of AAEO active compounds and core targets was verified by molecular docking finally. In our study, we first screened 54 effective components according to the relative content and biological activity. In total, 103 targets related to active compounds of AAEO and 2760 targets associated with PIs were obtained, respectively, and 50 key targets were overlapped by Venny 2.1.0. The construction of key targets-compounds network was achieved by the STRING database and Cytoscape 3.7.2 software. GO analysis from Matespace shows that GO results are mainly enriched in biological processes, including adrenergic receptor activity, neurotransmitter clearance, and neurotransmitter metabolic process. KEGG analysis by the David and Kobas website shows that the key targets can achieve the treatment on PIs through a pathway in cancer, PI3K-Akt signaling pathway, human immunodeficiency virus 1 infection, MAPK signaling pathway, Wnt signaling pathway, etc. In addition, molecular docking results from the CB-Dock server indicated that active compounds of AAEO had good activity docking with the first 10 key targets. In conclusion, the potential targets and regulatory molecular mechanisms of AAEO in the treatment of PIs were analyzed by network pharmacology and molecular docking. AAEO can cure PIs through the synergistic effect of multicomponent, multitarget, and multipathway, providing a theoretical basis and new direction for further study.

Identification of epigenetic modifications mediating the antagonistic effect of selenium against cadmium-induced breast carcinogenesis.

The antagonistic effect of selenium (Se) against cadmium (Cd)-induced breast carcinogenesis was reported, but underlying mechanisms were unclear. The aim of this study was to identify the epigenetically regulated genes and biological pathways mediating the antagonistic effect. We exposed MCF-7 cells to Cd and Se alone or simultaneously. Cell proliferation was assessed by MTT assay, and differential epigenome (DNA methylation, microRNA, and long non-coding RNA) was obtained by microarrays. We cross-verified the epigenetic markers with differential transcriptome, and the ones modulated by Cd and Se in opposite directions were regarded to mediate the antagonistic effect. The epigenetically regulated genes were validated by using gene expression data in human breast tissues. We further assessed the biological functions of these validated genes. Our results showed that Se alleviated the proliferative effect of Cd on MCF-7 cell. A total of 10 epigenetically regulated genes were regarded to mediate the antagonistic effect, including APBA2, KIAA0895, DHX35, CPEB3, SVIL, MYLK, ZFYVE28, ABLIM2, GRB10, and PCDH9. Biological function analyses suggested that these epigenetically regulated genes were involved in multiple cancer-related pathways, such as focal adhesion and PI3K/Akt pathway. In conclusion, we provided evidence that Se antagonized the Cd-induced breast carcinogenesis via epigenetic modification and revealed the critical pathways.

NIR Light-Triggered Chemo-Phototherapy by ICG Functionalized MWNTs for Synergistic Tumor-Targeted Delivery.

The combinational application of photothermal therapy (PTT), chemotherapy, and nanotechnology is a booming therapeutic strategy for cancer treatment. Multi-walled carbon nanotube (MWNT) is often utilized as drug carrier in biomedical fields with excellent photothermal properties, and indocyanine green (ICG) is a near-infrared (NIR) dye approved by FDA. In addition, ICG is also a photothermal agent that can strongly absorb light energy for tumor ablation. Herein, we explored a synergistic strategy by connecting MWNT and a kind of ICG derivate ICG-NH2 through hyaluronic acid (HA) that possesses CD44 receptor targeting ability, which largely enhanced the PTT effect of both MWNT and ICG-NH2. To realize the synergistic therapeutic effect of chemotherapy and phototherapy, doxorubicin (DOX) was attached on the wall of MWNT via π-π interaction to obtain the final MWNT-HA-ICG/DOX nanocomplexes. Both in vitro and in vivo experiments verified the great therapeutic efficacy of MWNT-HA-ICG/DOX nanocomplexes, which was characterized by improved photothermal performance, strengthened cytotoxicity, and elevated tumor growth inhibition based on MCF-7 tumor models. Therefore, this synergistic strategy we report here might offer a new idea with promising application prospect for cancer treatment.