Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration.

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

Analysis of pollutant dispersion patterns in rivers under different rainfall based on an integrated water-land model.

In the context of rapid urban expansion, the interaction between humanity and nature has become more prominent. Urban land and rivers often exist as distinct entities with limited material exchange. However, during rainfall, these two systems interconnect, resulting in the transfer of land-derived pollutants into rivers. Such transfer significantly increases river pollutant levels, adversely affecting water quality. Therefore, developing a water quality simulation and prediction model is crucial. This model should effectively illustrate pollutant movement and dispersion during rain events. This study proposes a comprehensive model that merges the Storm Water Management Model (SWMM) with the Environmental Fluid Dynamics Code (EFDC). This integrated model assesses the spread and dispersion of pollutants, including Ammonia Nitrogen (NH3-N), Total Phosphorus (TP), Total Nitrogen (TN), and Chemical Oxygen Demand (COD), within urban water cycles for various rainfall conditions, thus offering critical theoretical support for managing the water environment. The application of this model under different rainfall intensities (light, moderate and heavy) provides vital insights. During light rainfall, the river's natural purification process can sustain surface water quality at Class IV. Moderate rainfall causes accumulation of pollutants, reducing water quality to Class V. Conversely, heavy rainfall rapidly increases pollutant concentrations due to higher inflow, pushing the river to a degraded Class V status, which is beyond its natural purification capacity, necessitating engineering solutions to reattain Class IV quality. Furthermore, pollutant accumulation in downstream river sections is more influenced by flow rate than by rainfall intensity. In summary, the SWMM-EFDC integrated model proves highly effective in predicting river water quality, thereby significantly aiding urban water pollution control.

Phonon promoted charge density wave in topological kagome metal ScV6Sn6.

Charge density wave (CDW) orders in vanadium-based kagome metals have recently received tremendous attention, yet their origin remains a topic of debate. The discovery of ScV6Sn6, a bilayer kagome metal featuring an intriguing [Formula: see text] CDW order, offers a novel platform to explore the underlying mechanism behind the unconventional CDW. Here, we combine high-resolution angle-resolved photoemission spectroscopy, Raman scattering and density functional theory to investigate the electronic structure and phonon modes of ScV6Sn6. We identify topologically nontrivial surface states and multiple van Hove singularities (VHSs) in the vicinity of the Fermi level, with one VHS aligning with the in-plane component of the CDW vector near the [Formula: see text] point. Additionally, Raman measurements indicate a strong electron-phonon coupling, as evidenced by a two-phonon mode and new emergent modes. Our findings highlight the fundamental role of lattice degrees of freedom in promoting the CDW in ScV6Sn6.

Application of a Magnetic Resonance Imaging-Based Lumbar Vertebral Bone Quality Scoring System in Patients with Degenerative Lumbar Scoliosis.

BACKGROUND: Although dual-energy X-ray absorptiometry is still the gold standard for diagnosing osteoporosis, it can lead to inaccurate bone mineral density measurements due to lumbar degeneration and scoliosis. Many researchers have investigated diagnostic methods for osteoporosis in patients with degenerative lumbar scoliosis (DLS). This study aimed to investigate the differences between conventional vertebral bone quality (VBQ) scores and modified VBQ scores in patients with DLS and the influence of lumbar scoliosis on VBQ scores. METHODS: We retrospectively collected the clinical and radiological data of 68 patients with DLS admitted to Sun Yat-sen Memorial Hospital from July 2018 to April 2023. The patients were classified into one of 2 groups based on the T score of the left femoral neck. VBQ scores relative to cerebrospinal fluid at different levels, VBQ scores on different planes and single-level VBQ scores were compared. Receiver operating characteristic analysis was also performed. Different modified VBQ scores were compared between the moderate scoliosis group (10°

Multilayer nanodrug delivery system with spatiotemporal drug release improves tumor microenvironment for synergistic anticancer therapy.

The inflammatory response is one of the general symptoms that accompany tumorigenesis, the pro-inflammatory factors cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin-2 (PGE-2) in the inflammatory environment surrounding tumors possess promoting tumor development, metastasis and angiogenesis effects. In addition, the hypoxic environment of tumors severely limits the effectiveness of photodynamic therapy (PDT). In this study, a universal extracellular-intracellular 'on-demand' release nanomedicine DOX@PDA-ICG@MnO2@GN-CEL was developed for the combined fight against malignant tumors using a spatiotemporal controlled gelatin coated polydopamine (PDA@GN) as the carrier and loaded with the chemotherapeutic drug doxorubicin (DOX), the photosensitizer indocyanine green (ICG), the PDT enhancer MnO2and the anti-inflammatory drug celecoxib (CEL) individually. Our results showed that DOX@PDA-ICG@MnO2@GN-CEL could release CEL extracellularly by matrix metalloproteinase-2 response and inhibit the COX-2/PGE-2 pathway, reduce chemotherapy resistance and attenuate the concurrent inflammation. After entering the tumor cells, the remaining DOX@PDA-ICG@MnO2released DOX, ICG and MnO2intracellularly through PDA acid response. MnO2promoted the degradation of endogenous H2O2to generate oxygen under acidic conditions to alleviate the tumor hypoxic environment, enhance PDT triggered by ICG. PDA and ICG exhibited photothermal therapy synergistically, and DOX exerted chemotherapy with reduced chemotherapy resistance. The dual responsive drug release switch enabled the chemotherapeutic, photothermal, photodynamic and anti-inflammatory drugs precisely acted on different sites of tumor tissues and realized a promising multimodal combination therapy.

Construction of Fall Prevention Exercise Training Scheme for Elderly Discharged Patients Using Self-Efficacy Theory Framework.

Objective: We conducted this study to help older discharged patients recover better, reduce the risk of falls, and improve quality of life through self-efficacy intervention and the Otago exercise program. The purpose of this study was to address specific challenges in rehabilitation and quality of life in older patients. Methods: 60 elderly patients discharged from January 1 to June 10, 2022, were selected as the study subjects and randomly divided into the experimental group (n = 30) and the controls (n = 30). We studied the impact of a self-efficacy intervention combined with the Otago Exercise Program (OEP) in older discharged patients. We included patients aged 65 and above who understood the study protocol and randomly divided them into two groups: one group received a combined self-efficacy intervention and OEP, and the other group received only OEP treatment. The intervention period is 12 weeks, 3 times a week, 30-45 minutes each time. We focused on the exercise capacity, fall risk, quality of life, and well-being of patients in both groups after the intervention. The aim of the study was to determine whether this combined intervention could improve recovery and quality of life in older discharged patients. Results: Comparison of clinical data between the two groups: there were no differences in gender, age, ethnicity, education, residence, family income, complications, and chronic diseases (P > .05). Self-efficacy increased significantly between the two groups after the intervention, but there was no difference before the intervention (P > .05). The self-efficacy of the experimental group was higher than that of the control group on days 15, 30, 45, and 60 (P < .05). Berg balance scale, TUG, PSMS, IADL, ADL, and total fall risk scores were significantly improved, but there was no difference before intervention (P > .05). All indicators of the experimental group were better than those of the control group on days 15, 30, 45, and 60 (P < .05). EAQ scores were significantly improved, but there was no difference between the two groups before intervention (P > .05). The EAQ of the experimental group was higher than that of the control group on days 15, 30, 45, and 60 (P < .05). Conclusions: This study found that a self-efficacy-based intervention combined with the Otago Exercise Program (OEP) was of value to older discharged patients. This comprehensive intervention approach can improve patients' self-efficacy, balance, walking speed, daily functioning, reduce fall risk, and improve quality of life. For healthcare providers and institutions, this means that this approach could be considered to improve the care of older discharged patients. By enhancing patients' self-efficacy and physical function, it can promote better recovery and independent living, reduce the risk of readmissions, and thus reduce the burden on the healthcare system. This study provides important practical guidance for improving the recovery and quality of life of older discharged patients.

Efficacy of traditional Chinese medicine external therapy on sleep quality in patients with cancer: A systematic review and network meta-analysis.

Objective: This network meta-analysis aims to assess and compare the effectiveness of various external therapies from traditional Chinese medicine (TCM) in enhancing sleep quality among patients with cancer. Methods: We systematically searched nine electronic databases, encompassing five English and four Chinese databases, for randomized controlled trials (RCTs) from their inception up to August 10, 2023. The random effects model was utilized for effect size analysis, and the standardized mean difference (SMD) along with its corresponding 95% confidence interval (CI) were computed. Network meta-analysis and comparative effects ranking were executed utilizing STATA 14.0. Results: We included thirty-four RCTs involving seven distinct external TCM therapies. Among these, Chinese medicine pillow (SMD = -3.27; 95% CI: -6.03 to -0.51), auricular acupressure (SMD = -2.33; 95% CI: -3.36 to -1.29), moxibustion (SMD = -2.28; 95% CI: -3.63 to -0.94), acupressure (SMD = -1.67; 95% CI: -2.64 to -0.70), and acupuncture (SMD = -1.43; 95% CI: -2.65 to -0.21) demonstrated significant effects in improving sleep quality when compared to usual care or waitlist. The cumulative ranking curve values revealed that the Chinese medicine pillow exhibited the highest potential for effectively enhancing sleep quality in patients with cancer, followed by auricular acupressure, moxibustion, acupressure, acupuncture, Tuina, and electroacupuncture. Conclusions: Our study highlights the Chinese medicine pillow as an optimal external TCM therapy for ameliorating sleep quality in cancer patients, but more RCTs are needed to validate this conclusion. These findings serve as valuable support for future clinical trials and research endeavors. Systematic review registration: CRD42022381370.

The neuroprotective effects of Liuwei Dihuang medicine in the APP/PS1 mouse model are dependent on the PI3K/Akt signaling pathway.

Alzheimer's disease (AD) is an age-related neurodegenerative disease that progressively impairs cognitive function and memory. The occurrence and development of Alzheimer's disease involves many processes. In response to the complex pathogenesis of AD, the Traditional Chinese medicine formula Liuwei Dihuang Pill (LWD) has been shown to improve the cognitive function of AD animal models. However, the active ingredients and mechanism of action of LWD have not been fully elucidated. In this study, network pharmacological analysis predicted 40 candidate compounds in LWD, acting on 227 potential targets, of which 185 were associated with AD. Through network pharmacological analysis, the mechanism of action of LWD therapy AD is related to the inhibition of inflammatory response, regulation of neuronal state, and autophagy. In this experiment, LWD was detected in the APP/PS1 transgenic mouse model. The objective was to observe the effects of LWD on hippocampal learning and memory ability, Aß clearance, autophagy and inflammatory response in APP/PS1 mice. The results showed that LWD improved long-term memory and working memory in APP/PS1 mice compared with the WT group. At the same time, LWD can increase the expression of hippocampal autophagy biomarkers, reduce the precipitation of Aß, and the activation of microglia and astrocytes. Its mechanism may be related to the regulation of the PI3K/Akt signaling pathway. Thus, we demonstrate for the first time that LWD has a neuroprotective effect on APP/PS1 mice and provide theoretical foundation for the development of a new clinical treatment for AD.

Associations between maternal stressful life events experiences and risk of neural tube defects in offspring: a systematic review and meta-analysis.

OBJECTIVES: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring. METHODS: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. RESULTS: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively. CONCLUSIONS: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

Enhancement for phonon-mediated superconductivity up to 37 K in few-hydrogen metal-bonded layered magnesium hydride under atmospheric pressure.

The discovery of superconductivity in layered MgB2 has renewed interest in the search for high-temperature conventional superconductors, leading to the synthesis of numerous hydrogen-dominated materials with high critical temperatures (Tc) under high pressures. However, achieving a high-Tc superconductor under ambient pressure remains a challenging goal. In this study, we propose a novel approach to realize a high-temperature superconductor under ambient pressure by introducing a hexagonal H monolayer into the hexagonal close-packed magnesium lattice, resulting in a new and stable few-hydrogen metal-bonded layered magnesium hydride (Mg4)2H1. This compound exhibits superior ductility compared to multi-hydrogen, cuprate, and iron-based superconductors due to its metallic bonding. Our unconventional strategy diverges from the conventional design principles used in hydrogen-dominated covalent high-temperature superconductors. Using anisotropic Migdal-Eliashberg equations, we demonstrate that the stable (Mg4)2H1 compound is a typical phonon-mediated superconductor, characterized by strong electron-phonon coupling and an excellent Tc of 37 K under ambient conditions, comparable to that of MgB2. Our findings not only present a new pathway for exploring high-temperature superconductors but also provide valuable insights for future experimental synthesis endeavors.

Efficacy of mind-body therapies for sleep disturbance in patients with early-stage cancer: A systematic review and network meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy of different mind-body therapies (MBTs) for sleep disturbance in patients with early-stage cancer. METHODS: Randomised controlled trials that included patients (aged ≥18 years) with early stage cancer who underwent MBTs (mindfulness, hypnosis, relaxation, yoga, and qigong) were searched in the CINAHL via the EBSCO Host, Cochrane Library, Embase, MEDLINE, PsycINFO, PubMed, and Scopus databases, from the date of database inception to October 2022. The outcomes were subjective sleep disturbance and objective sleep efficiency. Network meta-analysis (NMA) and comparative effects ranking were performed using STATA (v14.0; STATACorp, College Station, TX, USA). RESULTS: Forty-seven studies investigating five MBTs were included in the NMA. For cancer patients receiving active treatment, mindfulness demonstrated the largest effect size in reducing subjective sleep disturbance (standardised mean difference [SMD]: 0.85; 95% confidence intervals [CI]: 0.20-1.50; Grading of Recommendations Assessment, Development, and Evaluation assessment: moderate), and had the highest cumulative probability compared to usual care or waitlist. For cancer patients who had completed active treatment, qigong demonstrated the largest effect size in reducing subjective sleep disturbance (SMD: 0.99; 95% CI: 0.35-1.63; GRADE: low), followed by hypnosis (SMD: 0.87; 95% CI: 0.32-1.42; GRADE: moderate), and mindfulness (SMD: 0.42; 95% CI: 0.24-0.59; GRADE: moderate). Qigong also demonstrated the largest effect size in improving objective sleep efficiency (weighted mean differences: 10.76; 95% CI: 2.01-19.50; GRADE: low); however, the effect of qigong was tested in only one study in this NMA. Among the eight different treatment conditions, cognitive behavioral therapy (CBT) showed the highest cumulative probability (surface under the cumulative ranking curve: 96.3%) in reducing subjective sleep disturbance and the second highest cumulative probability (SUCRA: 83.3%) in improving objective sleep efficiency. CONCLUSION: There is no evidence supporting the use of MBTs to replace or be comparable to CBT. Mindfulness can be recommended as an optional treatment for reducing sleep disturbance in patients with early-stage cancer. Some support was observed for qigong and hypnosis in reducing sleep disturbances in patients with early-stage cancer who had completed active treatment. More rigorous trials are warranted to confirm whether different forms of MBTs have different effects on sleep in patients with cancer.

Oridonin employs interleukin 1 receptor type 2 to treat noise-induced hearing loss by blocking inner ear inflammation.

NOD-like receptor protein 3 (NLRP3) inflammasomes trigger the inflammatory cascades and participate in various inflammatory diseases, including noise-induced hearing loss (NIHL) caused by oxidative stress. Recently, the anti-inflammatory traditional medicine oridonin (Ori) has been reported to provide hearing protection in mice after noise exposure by blocking the NLRP3-never in mitosis gene A-related kinase 7 (NEK7)-inflammasome complex assembly. Using RNA sequencing analysis, we further elucidated that interleukin 1 receptor type 2 (IL1R2) may be another crucial factor regulated by Ori to protect NIHL. We observed that IL1R2 expression was localized in spiral ganglion neurons, inner and outer hair cells, in Ori-treated mouse cochleae. Additionally, we confirmed that ectopic overexpression of IL1R2 in the inner ears of healthy mice using an adeno-associated virus delivery system significantly reduced noise-induced ribbon synapse lesions and hearing loss by blocking the "cytokine storm" in the inner ear. This study provides a novel theoretical foundation for guiding the clinical treatment of NIHL.

A Double-Chamber "Dandelion" Appearance Sequential Drug Delivery System for Synergistic Treatment of Malignant Tumors.

Introduction: During the combined treatment of tumors, the non-interfering transportation of drugs with different solubilities and the controllable sequential release are the main challenges. Here, we reported a double-chamber "Dandelion" -like sequential drug delivery system to realize the sequential release of different drugs for treating malignant tumors synergistically. Methods: After synthesizing mesoporous silica nanoparticles (MSN) by template method, a hydrophilic chemotherapy drug doxorubicin (DOX) was loaded into the channels of mesoporous silica (MSN) and locked with polydopamine (PDA) coating. Next, ß-cyclodextrin (ß-CDs) was decorated on PDA by Michael addition reaction, and the hydrophobic photosensitizer chlorin e6 (Ce6) was encapsulated into the hydrophobic chambers of ß-CDs. Finally, AS1411 was modified on the surface of PDA and obtained DOX@MSN@PDA-ß-CD/Ce6-AS1411 nanoparticles (DMPCCA) through which orthogonal loading and effective controlled release of different drugs were realized. Results: Under the sequential irradiations of 808 nm and 660 nm near-infrared (NIR) laser, PDA promoted the extensive release of Ce6 firstly while playing the effect of photothermal therapy (PTT), further to achieve the effect of photodynamic therapy (PDT) of Ce6. Meanwhile, the rapid release of DOX loaded in MSN channels showed a time lag of about 5 h after Ce6 release, through which it maximized the chemotherapeutic effect. Besides, the present drug loading nano-platform combined passive tumor-targeting effect given by EPR and active tumor-targeting effect endowed by AS1411 realized PTT-PDT-chemotherapy triple mode synergistic combination. Conclusion: We offer a general solution to address the key limitations for the delivery and sequential release of different drugs with different solubilities.

Aptamer-functionalized quercetin thermosensitive liposomes for targeting drug delivery and antitumor therapy.

Chemo-thermotherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. In this study, a novel aptamer functionalized thermosensitive liposome encapsulating hydrophobic drug quercetin was fabricated as an efficient drug delivery system. This aptamer-functionalized quercetin thermosensitive liposomes (AQTSL) combined the merits of high-loading yield, sustained drug release, long-term circulation in the body of PEGylated liposomes, passive targeting provided by 100-200 nm nanoparticles, active targeting and improved internalization effects offered by AS1411 aptamer, and temperature-responsive of quercetin release. In addition, AQTSL tail vein injection combined with 42 °C water bath heating on tumor site (AQTSL + 42 °C)treatment inhibited the tumor growth significantly compared with the normal saline administration (p< 0.01), and the inhibition rate reached 75%. Furthermore, AQTSL + 42 °C treatment also slowed down the tumor growth significantly compared with QTSL combined with 42 °C administration (p< 0.05), confirming that AS1411 decoration on QTSL increased the active targeting and internalization effects of the drug delivery system, and AS1411 aptamer itself might also contribute to the tumor inhibition. These data indicate that AQTSL is a potential carrier candidate for different hydrophobic drugs and tumor targeting delivery, and this kind of targeted drug delivery system combined with temperature responsive drug release mode is expected to achieve an ideal tumor therapy effect.

Stem Cell Theory of Cancer: Implications for Translational Research from Bedside to Bench.

A stem cell theory of cancer considers genetic makeup in the proper cellular context. It is a unified theory of cancer that unites the genome with the epigenome, links the intracellular with the extracellular, and connects the cellular constituents and compartments with the microenvironment. Although it allies with genomic medicine, it is better aligned with integrated medicine. In this perspective, we focus on translational research in cancer care. We expose some intrinsic fallacies in translational research when it relates to the basic principles of the scientific method in the care of patients with genomic medicine versus integrated medicine. We postulate that genomic medicine may be at the root of many failed efforts in drug development and data reproducibility. We propose an alternate heuristic approach that may expedite the development of safe and effective treatments and minimize the generation of unproductive pharmaceutical products and nonreproducible experimental results. Importantly, a heuristic approach emphasizes the role of a pertinent scientific theory and distinguishes therapy development from drug development, such that we discover not only useful drugs but also better ways to use them in order to optimize patient care and maximize clinical outcomes.

[Chiropractic plus plum-blossom needling combined with flexibility training on attention deficit in mentally-retarded adolescents].

OBJECTIVE: To observe the clinical efficacy of chiropractic plus plum-blossom needling combined with flexibility training for attention deficit in mentally-retarded adolescents. METHODS: Thirty adolescents with mild mental retardation were randomly divided into a medical rehabilitation plus flexibility training group (10 cases, 2 cases dropped off), a flexibility training group (10 cases, 1 case dropped off) and a control group (10 cases). The patients in the flexibility training group received flexibility training, once every other day, 3 times a week for 12 weeks. The patients in the medical rehabilitation plus flexibility training group received chiropractic and plum-blossom needling at Baihui (GV 20) and Sishencong (EX-HN 1) on the basis of the treatment in the flexibility training group, once every other day, 3 times a week for 12 weeks. The patients in the control group did not receive any targeted physical training and medical rehabilitation. Tobii Pro Spectrum eye movement instrument was used to test the attention concentration (T), attention span (M), attention transfer (γ%) and attention distribution (η). RESULTS: Compared before treatment, T and M in the medical rehabilitation plus flexibility training group and the flexibility training group were increased after treatment (P<0.01, P<0.05), and γ% in the medical rehabilitation plus flexibility training group was increased after treatment (P<0.05). The increasing range of T, M and γ% in the medical rehabilitation plus flexibility training group and the flexibility training group was greater than that in the control group (P<0.01), and the increasing range of T and γ% in the medical rehabilitation plus flexibility training group was greater than that in the flexibility training group (P<0.05). CONCLUSION: The chiropractic plus plum blossom needling combined with flexibility training can improve the attention deficit in mentally-retarded adolescents.

[Preparation and effect against cervical cancer invasion in vitro of harmine-loaded photosensitive liposomes].

Despite the development of HPV vaccines and screening programs, cervical cancer is still a serious threat to women's health. Early-stage cervical cancer is mainly treated by surgery. However, considering the serious complications after surgery, hyperthermia is recommended to enhance the effect of chemotherapy, retain the integrity of cervix, improve the treatment effect, which provides a therapeutic basis for the early treatment of cervical cancer. The photosensitive liposomes containing harmine and dye IR-780 were prepared by thin-film dispersion method and separated by Sephadex G-50 dextran gel column. The preparation conditions were optimized as the mass ratio of phospholipid to cholesterol membrane material being 8∶1 and that of drug to lipid being 1∶20. The results of HPLC showed that the encapsulation efficiency of harmine was 55.6%±0.18%. The prepared photosensitive liposomes were round and evenly distributed under transmission electron microscope, with the particle size of(125.2±0.62) nm determined by Marvin particle size analyzer and the Zeta potential of(-2.55±0.76) mV. Additionally, the photosensitive liposomes had the photothermal conversion efficiency, an important property of photothermal agent, of 27.1%±0.86%. The photosensitive liposomes stored at 4 ℃ showed stable encapsulation efficiency in the first 14 days without flocculation. The sulforhodamine B(SRB) assay was employed to determine the inhibitory effect of the liposomes on the proliferation of HeLa cells under near-infrared(NIR) irradiation or not, which showcased stronger inhibitory effect under NIR irradiation. The results of Transwell assay indicated that the prepared liposomes significantly inhibited the invasion and migration of HeLa cells in vitro. The findings of this study provide a basis for the treatment of cervical cancer with harmine.

Stem Cell Theory of Cancer: Implications for Drug Resistance and Chemosensitivity in Cancer Care.

When it concerns cancer care and cancer therapy, drug resistance is more than an obstacle to successful treatment; it is a major cause of frustration in our attempts to optimize drug development versus therapy development. Importantly, overcoming the challenges of drug resistance may provide invaluable clues about the origin and nature of cancer. From this perspective, we discuss how chemoresistance and chemosensitivity in cancer therapy could be directly linked to the stem cell origin of cancer. A stem cell theory of cancer stipulates that both normal stem cells and cancer stem cells are similarly endowed with robust efflux pumps, potent antiapoptotic mechanisms, redundant DNA repair systems, and abundant antioxidation reserves. Cancer stem cells, like their normal stem cell counterparts, are equipped with the same drug resistance phenotypes (e.g., ABC transporters, anti-apoptotic pathways, and DNA repair mechanisms). Drug resistance, like other cancer hallmarks (e.g., tumor heterogeneity and cancer dormancy), could be intrinsically ingrained and innately embedded within malignancy. We elaborate that cellular context and the microenvironment may attenuate the effects of cancer treatments. We examine the role of circadian rhythms and the value of chronotherapy to maximize efficacy and minimize toxicity. We propose that a stem cell theory of drug resistance and drug sensitivity will ultimately empower us to enhance drug development and enable us to improve therapy development in patient care.

GALNT14 genotype-guided chemoembolization plus sorafenib therapy in hepatocellular carcinoma: a randomized trial.

BACKGROUND: GALNT14-rs9679162 "TT" genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 "non-TT" unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy. METHODS: Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with "TT" genotype received only TACE, labeled as TT (TACE) group. Patients with "non-TT" genotype ("GG" or "GT") were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE. RESULTS: From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p < 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p < 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, < 0.001, respectively). CONCLUSION: Combination of sorafenib and TACE for "non-TT" patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT02504983.

Chiropractic plus plum-blossom needling combined with flexibility training on attention deficit in mentally-retarded adolescents / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of chiropractic plus plum-blossom needling combined with flexibility training for attention deficit in mentally-retarded adolescents.@*METHODS@#Thirty adolescents with mild mental retardation were randomly divided into a medical rehabilitation plus flexibility training group (10 cases, 2 cases dropped off), a flexibility training group (10 cases, 1 case dropped off) and a control group (10 cases). The patients in the flexibility training group received flexibility training, once every other day, 3 times a week for 12 weeks. The patients in the medical rehabilitation plus flexibility training group received chiropractic and plum-blossom needling at Baihui (GV 20) and Sishencong (EX-HN 1) on the basis of the treatment in the flexibility training group, once every other day, 3 times a week for 12 weeks. The patients in the control group did not receive any targeted physical training and medical rehabilitation. Tobii Pro Spectrum eye movement instrument was used to test the attention concentration (T), attention span (M), attention transfer (γ%) and attention distribution (η).@*RESULTS@#Compared before treatment, T and M in the medical rehabilitation plus flexibility training group and the flexibility training group were increased after treatment (P<0.01, P<0.05), and γ% in the medical rehabilitation plus flexibility training group was increased after treatment (P<0.05). The increasing range of T, M and γ% in the medical rehabilitation plus flexibility training group and the flexibility training group was greater than that in the control group (P<0.01), and the increasing range of T and γ% in the medical rehabilitation plus flexibility training group was greater than that in the flexibility training group (P<0.05).@*CONCLUSION@#The chiropractic plus plum blossom needling combined with flexibility training can improve the attention deficit in mentally-retarded adolescents.