Association of life's essential 8 with chronic cardiovascular-kidney disorder: a prospective cohort study.

BACKGROUND: The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association's Life's Essential 8 (LE8), and CCV-KD. METHODS: We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (< 50 points), intermediate (50 to < 80 points), and high (≥ 80 points), with a higher score indicating better CVH health. Adjusted Cox proportional hazard models were conducted to explore the association of CVH with the risk of CCV-KD. The adjusted proportion of population attributable risk (PAR%) was used to calculate the population-level risk caused by low or intermediate CVH. RESULTS: During a median follow-up of 12.5 years, 1,054 participants (0.8%) had incident CCV-KD. Participants with intermediate and high CVH had 54% (HR = 0.46, 95% CI: 0.40-0.54, P < 0.001) and 75% (HR = 0.25, 95% CI: 0.18-0.34, P < 0.001) lower risks of incident CCV-KD compared with those in low CVH group. There was an approximately dose-response linear relationship between the overall LE8 score and incident CCV-KD. The risk of incident CCV-KD decreased by 30% (HR = 0.70, 95% CI: 0.67-0.74, P < 0.001) for a 10-point increment of LE8 score. The adjusted PAR% of lower overall CVH was 47.4% (95% CI: 31.6%-59.8%). CONCLUSIONS: Better CVH, assessed by using LE8 score, was strongly associated with decreased risk of incident CCV-KD. These findings imply optimizing CVH may be a preventive strategy to reduce the burden of CCV-KD.

Highly specific GSH-triggered bifunctional molecules to enable precise imaging and targeted therapy of cancer.

The utilization of diagnostic-integrated molecules can enable targeted delivery and controlled release to significantly enhance therapeutic effectiveness and minimize toxic effects. Herein, we developed a novel class of glutathione (GSH)-activated bifunctional molecules that respond to elevated levels of GSH in tumor microenvironment. These bifunctional molecules retained the pharmacodynamic effects of parent molecules and mitigated cytotoxicity. Meanwhile, controlled release was monitored using fluorescent signals, enabling detection of drug distribution and accumulation in situ and in real time. Moreover, the correlation between GSH levels and fluorescence intensity offers the possibility of monitoring the effectiveness of responsive drugs. In conclusion, bifunctional molecules, as novel diagnostic-integrated molecules with both fluorescence imaging and therapeutic effects, exhibited potential applications in cancer therapy and imaging.

Prediction of the treatment effect of FLASH radiotherapy with synchrotron radiation from the Circular Electron-Positron Collider (CEPC).

The Circular Electron-Positron Collider (CEPC) in China can also work as an excellent powerful synchrotron light source, which can generate high-quality synchrotron radiation. This synchrotron radiation has potential advantages in the medical field as it has a broad spectrum, with energies ranging from visible light to X-rays used in conventional radiotherapy, up to several megaelectronvolts. FLASH radiotherapy is one of the most advanced radiotherapy modalities. It is a radiotherapy method that uses ultra-high dose rate irradiation to achieve the treatment dose in an instant; the ultra-high dose rate used is generally greater than 40 Gy s-1, and this type of radiotherapy can protect normal tissues well. In this paper, the treatment effect of CEPC synchrotron radiation for FLASH radiotherapy was evaluated by simulation. First, a Geant4 simulation was used to build a synchrotron radiation radiotherapy beamline station, and then the dose rate that the CEPC can produce was calculated. A physicochemical model of radiotherapy response kinetics was then established, and a large number of radiotherapy experimental data were comprehensively used to fit and determine the functional relationship between the treatment effect, dose rate and dose. Finally, the macroscopic treatment effect of FLASH radiotherapy was predicted using CEPC synchrotron radiation through the dose rate and the above-mentioned functional relationship. The results show that the synchrotron radiation beam from the CEPC is one of the best beams for FLASH radiotherapy.

Targeted therapy for leukemia based on nanomaterials.

Leukemia is a kind of hematopoietic stem cell malignant clonal disease. Drug therapy is the core treatment strategy for leukemia, but the current therapeutic drugs have defects such as low bioavailability, large adverse reactions and inconvenient intravenous administration. Targeted therapy can combine drugs with specific carcinogenic sites on cells to kill cancer cells and avoid damage to normal cells, which has gradually become the mainstream method of leukemia treatment. In addition, nanomedicine delivery systems can significantly improve drug efficacy through controlled size and targeted optimization of drug delivery by modification strategies. Therefore, the targeted treatment of leukemia based on nanomaterials has great research value and application prospect. This paper gives an overview of the current therapeutic strategies for leukemia, and then reviews the cutting-edge targeted therapeutic nanomaterials for leukemia, including organic nanomaterials (mainly carbon-based nanomaterials, lipid materials, polymers, etc.) and inorganic nanomaterials (mainly noble metal nanoparticles, magnetic nanoparticles, hollow mesoporous materials, etc.). The challenges and prospects for the future development of targeted nanomaterials in the treatment of leukemia are also briefly reviewed.

Electroacupuncture protects against cerebral ischemia-reperfusion injury through mitochondrial dynamics.

Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury. Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining. Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury. Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.

Generation of Anti-Mastitis Gene-Edited Dairy Goats with Enhancing Lysozyme Expression by Inflammatory Regulatory Sequence using ISDra2-TnpB System.

Gene-editing technology has become a transformative tool for the precise manipulation of biological genomes and holds great significance in the field of animal disease-resistant breeding. Mastitis, a prevalent disease in animal husbandry, imposes a substantial economic burden on the global dairy industry. In this study, a regulatory sequence gene editing breeding strategy for the successful creation of a gene-edited dairy (GED) goats with enhanced mastitis resistance using the ISDra2-TnpB system and dairy goats as the model animal is proposed. This included the targeted integration of an innate inflammatory regulatory sequence (IRS) into the promoter region of the lysozyme (LYZ) gene. Upon Escherichia Coli (E. coli) mammary gland infection, GED goats exhibited increased LYZ expression, showing robust anti-mastitis capabilities, mitigating PANoptosis activation, and alleviating blood-milk-barrier (BMB) damage. Notably, LYZ is highly expressed only in E. coli infection. This study marks the advent of anti-mastitis gene-edited animals with exogenous-free gene expression and demonstrates the feasibility of the gene-editing strategy proposed in this study. In addition, it provides a novel gene-editing blueprint for developing disease-resistant strains, focusing on disease specificity and biosafety while providing a research basis for the widespread application of the ISDra2-TnpB system.

Comparison of one-year outcomes and quality of life between radiofrequency ablation and microwave ablation in the treatment of lower extremity varicose veins: A retrospective cohort study.

OBJECTIVE: This study compared the outcomes of radiofrequency ablation (RFA) and microwave ablation (EMA) for treating lower limb varicose veins. METHODS: Patients who underwent RFA (n = 240) or EMA (n = 209) at our institute from December 2020 to August 2022 were included in this retrospective investigation. Follow-up outcomes included active vein occlusion rate, Venous Clinical Severity Score (VCSS), the Aberdeen Varicose Vein Questionnaire (AVVQ), and Chronic Insufficiency Venous Quality of Life questionnaire-14 (CIVIQ-14)score. RESULTS: There was no significant difference in the active vein occlusion rate between the two groups after the operation (p > .05). Compared to pre-surgery scores, both groups showed substantial improvement in VCSS, AVVQ, and CIVIQ-14 scores(p < .05), there was no significant difference in these scores in either group (p > .05). CONCLUSION: Intravenous radiofrequency and microwave ablation effectively improve the quality of life for patients with lower limb varicose veins, with low post-operative complication and recurrence rates.

Oncology stewardship practice in the United States: A Hematology/Oncology Pharmacy Association national survey.

INTRODUCTION: The treatment of cancer is associated with high risk for toxicity and high cost. Strategies to enhance the value, quality, and safety of cancer care are often managed independently of one another. Oncology stewardship is a potential framework to unify these efforts and enhance outcomes. This landscape survey establishes baseline information on oncology stewardship in the United States. METHODS: The Hematology/Oncology Pharmacy Association (HOPA) distributed a 38-item survey composed of demographic, institutional, clinical decision-making, support staff, metrics, and technology sections to 675 HOPA members between 9 September 2022 and 9 October 2022. RESULTS: Most organizations (78%) have adopted general pharmacy stewardship practices; however, only 31% reported having established a formalized oncology stewardship team. More than 70% of respondents reported implementation of biosimilars, formulary management, and dose rounding as oncology stewardship initiatives in both inpatient and outpatient settings. Frequently cited barriers to oncology stewardship included lack of clinical pharmacist availability (74%), lack of oncology stewardship training (62%), lack of physician/provider buy-in (32%), and lack of cost-saving metrics (33%). Only 6.6% of survey respondents reported their organization had defined "value in oncology." Lack of a formalized stewardship program was most often cited (77%) as the rationale for not defining value. CONCLUSIONS: Less than one-third of respondents have established oncology stewardship programs; however, most are providing oncology stewardship practices. This manuscript serves as a call to action for stakeholders to work together to formalize oncology stewardship programs that optimize value, quality, and safety for patients with cancer.

Coupling High-Entropy Core with Rh Shell for Efficient pH-Universal Hydrogen Evolution.

Constructing high-entropy alloys (HEAs) with core-shell (CS) nanostructure is efficient for enhancing catalytic activity. However, it is extremely challenging to incorporate the CS structure with HEAs. Herein, PtCoNiMoRh@Rh CS nanoparticles (PtCoNiMoRh@Rh) with ∼5.7 nm for pH-universal hydrogen evolution reaction (HER) are reported for the first time. The PtCoNiMoRh@Rh just require 9.1, 24.9, and 17.1 mV to achieve -10 mA cm-2 in acid, neutral, and alkaline electrolyte, and the corresponding mass activity are 5.8, 2.79, and 91.8 times higher than that of Rh/C. Comparing to PtCoNiMoRh nanoparticles, the PtCoNiMoRh@Rh exhibit excellent HER activity attributed to the decrease of Rh 4d especially 4d5/2 unoccupied state induced by the multi-active sites in HEA, as well as the synergistic effect in Rh shell and HEA core. Theorical calculation exhibits that Rh-dyz, dx2, and dxz orbitals experience a negative shift with shell thickness increasing. The HEAs with CS structure would facilitate the rational design of high-performance HEAs catalysts.

Novel Loss-of-Function SYCP2 Variants in Infertile Males Upgrade the Gene-Disease Clinical Validity Classification for SYCP2 and Male Infertility to Strong.

Male infertility affects approximately 7% of the male population, and about 15% of these cases are predicted to have a genetic etiology. One gene implicated in autosomal dominant male infertility, SYCP2, encodes a protein critical for the synapsis of homologous chromosomes during meiosis I, resulting in impaired spermatogenesis. However, the clinical validity of the gene-disease pair was previously categorized as on the border of limited and moderate due to few reported cases. This study investigates the genetic cause of infertility for three unrelated Chinese patients with oligoasthenozoospermia. Whole exome sequencing (WES) and subsequent Sanger sequencing revealed novel heterozygous loss-of-function (LOF) variants in SYCP2 (c.89dup, c.946_947del, and c.4378_4379del). These cases, combined with the previously reported cases, provide strong genetic evidence supporting an autosomal dominant inheritance pattern. The experimental evidence also demonstrates a critical role for SYCP2 in spermatogenesis. Collectively, this updated assessment of the genetic and experimental evidence upgrades the gene-disease association strength of SYCP2 and autosomal dominant male infertility from on the border of limited and moderate to strong. The reclassification improves SYCP2 variant interpretation and qualifies it for the inclusion on diagnostic male infertility gene panels and prioritization in whole exome or genome studies for related phenotypes. These findings therefore improve the clinical interpretation of SYCP2 LOF variants.

[Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure].

This study aimed to investigate the therapeutic effect of Shenfu Injection on mice with chronic heart failure(CHF) and its effect on macrophage polarization. C57BL/6J mice were randomly assigned to the normal and model groups. The CHF model was established by intraperitoneal injection of isoproterenol(ISO, 7.5 mg·kg~(-1), 28 d). The successful modeling was determined by asses-sing the cardiac function and N-terminal pro-brain natriuretic peptide(NT-proBNP). The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days. Cardiac function was evaluated using echocardiography. Hematoxylin-eosin(HE) staining was used to detect the pathomorphology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the values of serum NT-proBNP, interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), IL-10, and arginase 1(Arg-1). Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. Quantitative polymerase chain reaction(qPCR) and Western blot were used to detect the changes in the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway-related mRNA and protein expressions. Compared with the normal group, mice in the model group had lower values of left ventricular ejection fraction(LVEF) and left ventricular fractional shorte-ning(LVFS), higher values of left ventricular internal diastolic end-diastolic(LVIDd), left ventricular internal diastolic end-systolic(LVIDs), NT-proBNP, TNF-α, and IL-6(P<0.01); the number of macrophages increased in cardiac tissues(P<0.05), and the values of M1-F4/80~+CD86~+ were increased(P<0.01), while the values of M2-F4/80~+CD163~+ decreased(P<0.05); the mRNA and protein expressions of TLR4, myeloid differentiation factor 88(MyD88), IκB kinase α(IKKα), and NF-κB p65 in myocardial tissues were significantly elevated(P<0.05, P<0.01). Compared with the model group, mice in the Shenfu Injection and TAK-242 groups showed elevated LVEF, LVFS, IL-10, and Arg-1 levels, and decreased LVIDd, LVIDs, NT-proBNP, TNF-α, and IL-6 levels(P<0.05, P<0.01); the cardiac F4/80~+CD11b~+(macrophage) and M1-F4/80~+ CD86~+ values were significantly down-regulated, while M2-F4/80~+CD163~+ values were increased(P<0.05, P<0.01); and the mRNA and protein expressions of TLR4, MyD88, IKKα, and NF-κB p65 in myocardial tissues were notably decreased(P<0.05, P<0.01). CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.

Monoallelic missense variants in MAB21L1 cause a novel autosomal dominant microphthalmia.

PURPOSE: The biallelic variant of MAB21L1 has previously been documented in conjunction with the autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG). The purpose of this study was to investigate the gene-disease association of MAB21L1 and the newly discovered autosomal dominant (AD) microphthalmia. METHODS: We report the presence of an exceptionally rare missense variant in a single allele of the Arg51 codon of MAB21L1 among four individuals from a single family diagnosed with microphthalmia, which suggesting an autosomal dominant inheritance pattern. Subsequently, based on comprehensive literature review, we identified another 13 families that have reported cases of autosomal dominant microphthalmos. RESULTS: Genotype-phenotype analysis revealed that patients with a single allele missense variant in MAB21L1 exhibited solely eye abnormalities. This starkly diverged from the clinical presentation of COFG, typified by the concurrent occurrence of ocular and extraocular symptoms stemming from the biallelic variant in MAB21L1. Our findings revealed that the heterozygous pathogenic variant in MAB21L1 resulted in the emergence of autosomal dominant microphthalmia. By combining these genetic and experimental evidence, the clinical validity of MAB21L1 and the emerging autosomal dominant microphthalmia can be regarded as moderate. CONCLUSION: In summary, there is sufficient convincing evidence to prove that MAB21L1 is a novel pathogenic gene responsible for autosomal dominant microphthalmia, thus offering valuable insights for precise diagnosis and targeted therapeutic interventions in cases of microphthalmia.

A review of factors affecting the soil microbial community structure in wetlands.

Microbial community in wetland soils is crucial for maintaining the stability of the wetland ecosystem. Nevertheless, the soil microbial community is sensitive to the environmental stress in wetlands. This leads to the possibility that the microbial community structure may be influenced by environmental factors. To gain an in-depth understanding in the response of microbial community structure in wetland soils under different environmental factors, this review comprehensively explores the factors of natural conditions (e.g., different types of wetland, soil physical and chemical properties, climate conditions), biological factors (e.g., plants, soil animals), and human activities (e.g., land use, soil pollution, grazing). Those factors can affect microbial community structure and activities in wetland soils through different ways such as (i) affecting the wetland soil environment in which soil microorganisms survived in, (ii) influencing the available nutrients (e.g., carbon, nitrogen) required for microbial activity, and (iii) the direct effects on soil microorganisms (toxicity or promotion of resistant species). This review can provide references for the conservation of microbial diversity in wetland soils, the maintenance of wetland ecosystem balance, and the wetland ecological restoration.

Adjustments in energy metabolism of brown adipose tissue in heat-acclimated Kunming mice.

The thermogenic capacity of brown adipose tissue (BAT) in rodents decreases with prolonged heat exposure. However, the underlying mechanisms are not well understood. In this study, Kunming mice were acclimated at 23 ± 1 °C and 33 ± 1 °C for four weeks each to examine the body heat balance and BAT alterations. Results showed that heat-acclimated Kunming mice exhibited reduced body mass and elevated body temperature. Additionally, they displayed lower resting metabolic rates, diminished non-shivering thermogenesis, and reduced BAT thermogenic function. Metabolically, there was a significant reduction in several key metabolites involved in energy metabolism in BAT, including thiamine pyrophosphate, citric acid, cis-Aconitate, isocitric acid, oxoglutaric acid, succinate, fumarate, L-Malic acid, oxaloacetate, flavin mononucleotide, nicotinamide adenine dinucleotide, and adenosine 5'-triphosphate. These findings suggest that BAT adapts to heat acclimation by regulating pathways related to pyruvate oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, which may help maintain thermal homeostasis in Kunming mice.

Development and validation of rapid screening of 192 veterinary drug residues in aquatic products using HPLC-HRMS coupled with QuEChERS.

The presence of veterinary drug residues in aquatic products represents a significant challenge to food safety. The current detection methods, limited in both scope and sensitivity, underscore the urgent need for more advanced techniques. This research introduces a swift and potent screening technique using high-performance liquid chromatography-high-resolution mass spectrometry (HPLC-HRMS) and a refined QuEChERS protocol, allowing simultaneous qualitative and semi-quantitative analysis of 192 residues. A comprehensive database, employing full scan mode and data-dependent secondary mass spectroscopy, enhances screening accuracy. The method involves efficient extraction using 90% acetonitrile, dehydration with Na2SO4, and acetic acid, followed by cleanup using dispersive solid-phase extract sorbent primary secondary amine. It is suitable for samples with varying fat content, offering detection limits ranging from 0.5 to 10 µg/kg, high recovery rates (60-120%), and low relative standard deviations (<20%). Practical application has validated its effectiveness for multi-residue screening, marking a significant advancement in food safety evaluation.

[Tongdu Tiaoshen acupuncture for subjective tinnitus:a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of Tongdu Tiaoshen acupuncture (acupuncture for promoting the circulation of the governor vessel and regulating the spirit) for subjective tinnitus, and explore its potential mechanism. METHODS: A total of 92 patients with subjective tinnitus were randomly divided into an acupuncture group (46 cases, 5 cases dropped out) and a medication group (46 cases, 2 cases dropped out). The acupuncture group received Tongdu Tiaoshen acupuncture at Shuigou (GV 26), Yintang (GV 24+), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14) and Zhongzhu (TE 3), Tinghui (GB 2), Yifeng (TE 17) on the affected side, 30 min each time, once every other day, 3 times a week. The medication group was orally administered ginkgo biloba leaves tablets (40 mg each time) and mecobalamin tablets (0.5 mg each time), 3 times a day. Both groups were treated for 4 weeks. The scores of tinnitus severity, tinnitus loudness visual analogue scale (VAS) and depression anxiety stress scale-21(DASS-21) before and after treatment were observed in the two groups, serum level of brain-derived neurotrophic factor (BDNF) before and after treatment in the two groups was detected, and the clinical effect was evaluated in the two groups. RESULTS: After treatment，the scores of tinnitus severity, tinnitus loudness VAS and DASS-21 were decreased compared with those before treatment in the two groups (P<0.01), and the scores in the acupuncture group were lower than those in the medication group (P<0.05). After treatment, the serum level of BDNF was decreased compared with that before treatment in the two groups (P<0.01), and the serum level of BDNF in the acupuncture group was lower than that in the medication group (P<0.05). The total effective rate of the acupuncture group was 82.9% (34/41), which was higher than 70.5% (31/44) in the medication group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture could improve the severity of tinnitus, tinnitus loudness and negative emotion in patients with subjective tinnitus. Its mechanism may be related to the regulation of serum level of BDNF and thus affect auditory central plasticity.

Improvement of Post-Surgery Constipation in Patients with Fractures by Lactobacillus rhamnosus JYLR-127: A Single-Blind Randomized Controlled Trial.

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.

Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase: A case report.

BACKGROUND: High-grade B-cell lymphoma (HGBL) is an unusual malignancy that includes myelocytomatosis viral oncogene (MYC), B-cell lymphoma-2 (BCL-2), and/or BCL-6 rearrangements, termed double-hit or triple-hit lymphomas, and HGBL-not otherwise specific (HGBL-NOS), which are morphologically characteristic of HGBL but lack MYC, BCL-2, or BCL-6 rearrangements. HGBL is partially transformed by follicular lymphoma and other indolent lymphoma, with few cases of marginal zone lymphoma (MZL) transformation. HGBL often has a poor prognosis and intensive therapy is currently mainly advocated, but there is no good treatment for these patients who cannot tolerate chemotherapy. CASE SUMMARY: We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression. Gene analysis revealed the gene expression profile was identical in the pre- and post-transformed tissues, suggesting that the two diseases are homologous, not secondary tumors. The chemotherapy was ineffective and the side effect was severe, so we tried combination therapy including venetoclax and obinutuzumab. The patient tolerated treatment well, and reached partial response. The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure. He survived for 12 months after diagnosis. CONCLUSION: Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients, who are unsuitable for chemotherapy.

Elesclomol-copper synergizes with imidazole ketone erastin by promoting cuproptosis and ferroptosis in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) encompass a collection of clonal hematopoietic malignancies distinguished by the depletion of peripheral blood cells. The treatment of MDS is hindered by the advanced age of patients, with a restricted repertoire of drugs currently accessible for therapeutic intervention. In this study, we found that ES-Cu strongly inhibited the viability of MDS cell lines and activated cuproptosis in a copper-dependent manner. Importantly, ferroptosis inducer IKE synergistically enhanced ES-Cu-mediated cytotoxicity both in vitro and in vivo. Of note, the combination of IKE and ES-Cu intensively impaired mitochondrial homeostasis with increased mitochondrial ROS, MMP hyperpolarized, down-regulated iron-sulfur proteins and declined oxygen consumption rate. Additionally, ES-Cu/IKE treatment could enhance the lipoylation-dependent oligomerization of the DLAT. To elucidate the specific order of events in the synergistic cell death, inhibitors of ferroptosis and cuproptosis were utilized to further characterize the basis of cell death. Cell viability assays showed that the glutathione and its precursor N-acetylcysteine could significantly rescue the cell death under either mono or combination treatment, demonstrating that GSH acts at the crossing point in the regulation network of cuproptosis and ferroptosis. Significantly, the reconstitution of xCT expression and knockdown of FDX1 cells have been found to contribute to the tolerance of mono treatment but have little recovery impact on the combined treatment. Collectively, these findings suggest that a synergistic interaction leading to the induction of multiple programmed cell death pathways could be a promising approach to enhance the effectiveness of therapy for MDS.

The relationship between anxiety symptoms and disturbances in biological rhythms in patients with depression.

BACKGROUND: Biological rhythms denote the cyclical patterns of life activities anchored to a 24-hour cycle. Research shows that depression exhibits disturbances in biological rhythms. Yet, the relationship between these biological rhythms and concomitant anxiety symptoms is insufficiently investigated in structured clinical assessments. METHODS: This multicenter study, carried out in four Chinese hospitals, comprehensively examined the relationship between anxiety and disruptions in biological rhythms among patients with depression. The study encompassed 218 patients diagnosed with depression and 205 matched healthy controls. The Chinese version of the Biological Rhythms Interview of Assessment in Neuropsychiatry was utilized to evaluate the participants' biological rhythms, focusing on four dimensions: sleep, activity, social, and diet. RESULTS: In patients with depression, there is a significant positive correlation between the severity of anxiety symptoms and the disturbances in biological rhythms. The severity of anxiety and depression, along with the quality of life, are independently associated with disruptions in biological rhythms. The mediation model reveals that anxiety symptoms mediate the relationship between depressive symptoms and biological rhythms. CONCLUSION: This research highlights the role of anxiety within the spectrum of depressive disorders and the associated disturbances in biological rhythms. Our findings shed light on potential pathways towards more targeted preventive strategies and therapeutic interventions for individuals battling depression and anxiety.