Respiratory adverse effects in patients treated with immune checkpoint inhibitors in combination with radiotherapy: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. METHODS: We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. RESULTS: Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1-5 cough, 0.176 (95%CI: 0.113-0.274, I2 = 92.36%); grades 1-5 pneumonitis, 0.118 (95%CI: 0.067-0.198, I2 = 88.64%); grades 1-5 upper respiratory tract infection, 0.064 (95%CI: 0.049-0.080, I2 = 0.98%); grades 3-5 cough, 0.050 (95%CI: 0.012-0.204, I2 = 8.90%); grades 3-5 pneumonitis, 0.052 (95%CI: 0.031-0.078, I2 = 83.86%); grades 3-5 upper respiratory tract infection, 0.040 (95%CI: 0.007-0.249, I2 = 45.31%). CONCLUSIONS: Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Exploring the MRI and Clinical Features of P53-Mutated Hepatocellular Carcinoma.

Purpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients. Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student's t test, χ2 test, and multivariable regression analysis. Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson-Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC. Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.

Critical role of apoptosis in MeCP2-mediated epithelial-mesenchymal transition of ARPE-19 cells.

Proliferative vitreoretinopathy (PVR) is a complex disease that significantly contributes to recurrent retinal detachment. Its development is notably affected by epithelial-mesenchymal transition (EMT), where apoptosis plays a crucial role as a regulator of EMT. However, the function of MeCP2 in governing apoptosis and EMT in retinal pigment epithelial (RPE) cells and its implications for PVR development have remained inadequately understood. Thus, we investigated the impact of MeCP2 on proliferation, migration, apoptosis and EMT in ARPE-19 cells to provide a fresh perspective on the etiology of PVR. The morphological changes in ARPE-19 cells induced by recombinant human MeCP2 protein and MeCP2 knockdown were observed. Wound healing assay were performed to verify the effects of recombinant human MeCP2 protein and MeCP2 knockdown on ARPE-19 cell migration. Furthermore, cell proliferation was assessed using the CCK-8 assay and flow cytometry. Western blot analysis, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and immunofluorescence analysis were conducted to measure the protein levels associated with apoptosis, cell cycle and EMT. Western blot analysis and immunofluorescence assays confirmed that MeCP2 promoted EMT formation in ARPE-19 cells. The CCK-8 assay revealed that MeCP2 treatment enhanced the proliferation of ARPE-19 cells, whereas MeCP2 knockdown inhibited ARPE-19 cell proliferation. Treatment with recombinant human MeCP2 protein and MeCP2 knockdown altered the morphology of ARPE-19 cells. Wound healing assay demonstrated that MeCP2 knockdown inhibited ARPE-19 cell migration, and MeCP2 treatment promoted ARPE-19 cell migration. MeCP2 knockdown induced a G0/G1 phase block, inhibiting cell growth, and qRT-PCR data indicated reduced expression of cell cycle-related genes. Increased apoptosis was observed after MeCP2 knockdown in ARPE-19 cells. Overall, MeCP2 treatment stimulates cell proliferation, migration and EMT formation; conversely, MeCP2 knockdown inhibits EMT, cell proliferation, migration and cell cycle G1/S phase transition, and induces apoptosis.

Global-local aware Heterogeneous Graph Contrastive Learning for multifaceted association prediction in miRNA-gene-disease networks.

Unraveling the intricate network of associations among microRNAs (miRNAs), genes, and diseases is pivotal for deciphering molecular mechanisms, refining disease diagnosis, and crafting targeted therapies. Computational strategies, leveraging link prediction within biological graphs, present a cost-efficient alternative to high-cost empirical assays. However, while plenty of methods excel at predicting specific associations, such as miRNA-disease associations (MDAs), miRNA-target interactions (MTIs), and disease-gene associations (DGAs), a holistic approach harnessing diverse data sources for multifaceted association prediction remains largely unexplored. The limited availability of high-quality data, as vitro experiments to comprehensively confirm associations are often expensive and time-consuming, results in a sparse and noisy heterogeneous graph, hindering an accurate prediction of these complex associations. To address this challenge, we propose a novel framework called Global-local aware Heterogeneous Graph Contrastive Learning (GlaHGCL). GlaHGCL combines global and local contrastive learning to improve node embeddings in the heterogeneous graph. In particular, global contrastive learning enhances the robustness of node embeddings against noise by aligning global representations of the original graph and its augmented counterpart. Local contrastive learning enforces representation consistency between functionally similar or connected nodes across diverse data sources, effectively leveraging data heterogeneity and mitigating the issue of data scarcity. The refined node representations are applied to downstream tasks, such as MDA, MTI, and DGA prediction. Experiments show GlaHGCL outperforming state-of-the-art methods, and case studies further demonstrate its ability to accurately uncover new associations among miRNAs, genes, and diseases. We have made the datasets and source code publicly available at https://github.com/Sue-syx/GlaHGCL.

The mrp-3 gene is involved in haem efflux and detoxification in a blood-feeding nematode.

BACKGROUND: Haem is essential but toxic for metazoan organisms. Auxotrophic nematodes can acquire sufficient haem from the environment or their hosts in the meanwhile eliminate or detoxify excessive haem through tightly controlled machinery. In previous work, we reported a role of the unique transporter protein HRG-1 in the haem acquisition and homeostasis of parasitic nematodes. However, little is known about the haem efflux and detoxification via ABC transporters, particularly the multiple drug resistance proteins (MRPs). RESULTS: Here, we further elucidate that a member of the mrp family (mrp-3) is involved in haem efflux and detoxification in a blood-feeding model gastrointestinal parasite, Haemonchus contortus. This gene is haem-responsive and dominantly expressed in the intestine and inner membrane of the hypodermis of this parasite. RNA interference of mrp-3 resulted in a disturbance of genes (e.g. hrg-1, hrg-2 and gst-1) that are known to be involved in haem homeostasis and an increased formation of haemozoin in the treated larvae and lethality in vitro, particularly when exposed to exogenous haem. Notably, the nuclear hormone receptor NHR-14 appears to be associated the regulation of mrp-3 expression for haem homeostasis and detoxification. Gene knockdown of nhr-14 and/or mrp-3 increases the sensitivity of treated larvae to exogenous haem and consequently a high death rate (> 80%). CONCLUSIONS: These findings demonstrate that MRP-3 and the associated molecules are essential for haematophagous nematodes, suggesting novel intervention targets for these pathogens in humans and animals.

Stimulation of cytochrome c oxidase activity by detergents.

Cytochrome c oxidase (CytcO) is an integral membrane protein, which catalyzes four-electron reduction of oxygen linked to proton uptake and pumping. Amphipathic molecules bind in sites near the so-called K proton pathway of CytcO to reversibly modulate its activity. However, purification of CytcO for mechanistic studies typically involves the use of detergents, which may interfere with binding of these regulatory molecules. Here, we investigated the CytcO enzymatic activity as well as intramolecular electron transfer linked to proton transfer upon addition of different detergents to bovine heart mitoplasts. The CytcO activity increased upon addition of alkyl glucosides (DDM and DM) and the steroid analog GDN. The maximum stimulating effect was observed for DDM and DM, and the half-stimulating effect correlated with their CMC values. With GDN the stimulation effect was smaller and occurred at a concentration higher than CMC. A kinetic analysis suggests that the stimulation of activity is due to removal of a ligand bound near the K proton pathway, which indicates that in the native membrane this site is occupied to yield a lower than maximal possible CytcO activity. Possible functional consequences are discussed.

Corrigendum: Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease.

[This corrects the article DOI: 10.3389/fphar.2024.1346168.].

BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma.

BACKGROUND: Chimeric antigen receptor (CAR)-T cell has revolutionary efficacy against relapsed/refractory multiple myeloma (R/R MM). However, current CAR-T cell therapy has several limitations including long vein-to-vein time and limited viability. METHODS: A 4-1BB-costimulated B-cell maturation antigen (BCMA) CAR-T integrating an independently-expressed OX40 (BCMA-BBZ-OX40) was designed and generated by a traditional manufacturing process (TraditionCART) or instant manufacturing platform (named InstanCART). The tumor-killing efficiency, differentiation, exhaustion, and expansion level were investigated in vitro and in tumor-bearing mice. An investigator-initiated clinical trial was performed in patients with R/R MM to evaluate the outcomes of both TraditionCART and InstanCART. The primary objective was safety within 1 month after CAR-T cell infusion. The secondary objective was the best overall response rate. RESULTS: Preclinical studies revealed that integrated OX40 conferred BCMA CAR-T cells with superior cytotoxicity and reduced exhaustion levels. InstanCART process further enhanced the proliferation and T-cell stemness of BCMA-BBZ-OX40 CAR-T cells. BCMA-BBZ-OX40 CAR-T cells were successfully administered in 22 patients with R/R MM, including 15 patients with TraditionCART and 7 patients with InstanCART. Up to 50% (11/22) patients had a high-risk cytogenetic profile and 36% (8/22) had extramedullary disease. CAR-T therapy caused grade 1-2 cytokine release syndrome in 19/22 (80%) patients, grade 1 neurotoxicity in 2/22 (9%) patients and led to ≥grade 3 adverse events including neutropenia (20/22, 91%), thrombocytopenia (15/22, 68%), anemia (12/22, 55%), creatinine increased (1/22, 5%), hepatic enzymes increased (5/22, 23%), and sepsis (1/22, 5%). The best overall response rate was 100%, and 64% (14/22) of the patients had a complete response or better. The median manufacturing time was shorter for InstanCART therapy (3 days) than for TraditionCART therapy (10 days). Expansion and duration were dramatically higher for InstanCART cells than for TraditionCART cells. CONCLUSIONS: BCMA-BBZ-OX40 CAR-T cells were well tolerated and exhibited potent responses in patients with R/R MM. InstanCART shortened the manufacturing period compared to TraditionCART, and improved the cellular kinetics. Our results demonstrated the potency and feasibility of OX40-modified BCMA CAR-T cells using InstanCART technology for R/R MM therapy. TRIAL REGISTRATION NUMBER: This trial was registered at www. CLINICALTRIALS: gov as #NCT04537442.

Electron transfer in the respiratory chain at low salinity.

Recent studies have established that cellular electrostatic interactions are more influential than assumed previously. Here, we use cryo-EM and perform steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III2-IV supercomplex from Saccharomyces cerevisiae at low salinity. The kinetic studies show a sharp transition with a Hill coefficient ≥2, which together with the cryo-EM data at 2.4 Å resolution indicate multiple cyt. c molecules bound along the supercomplex surface. Negatively charged loops of CIII2 subunits Qcr6 and Qcr9 become structured to interact with cyt. c. In addition, the higher resolution allows us to identify water molecules in proton pathways of CIV and, to the best of our knowledge, previously unresolved cardiolipin molecules. In conclusion, the lowered electrostatic screening renders engagement of multiple cyt. c molecules that are directed by electrostatically structured CIII2 loops to conduct electron transfer between CIII2 and CIV.

A case of human diarrhea caused by Gallibacterium anatis: a case report.

Gallibacterium anatis (G. anatis) is an opportunistic pathogen previously associated with deaths in poultry and is also a pathogen that rarely causes human diseases. G. anatis has only been reported twice as the causative agent of a human disease (both in France). Here, we report a 62-year-old male patient with hypertension and type 2 diabetes who suffered from acute watery diarrhea caused by this bacterium which was identified by MALDI-TOF MS and 16 S rRNA sequencing. Despite human diarrhea caused by G.anatis is rare, with the continuous emergence of multidrug-resistant isolates of G. anatis in recent years, this case report will inform clinicians that G. anatis especially drug-resistant G. anatis may be a possible infectious source of human diarrhea in immune-suppressed populations.

[Prediction of color simulation prescription for traditional Chinese medicine placebo solution based on whale algorithm-optimized back propagation neural network].

Traditional Chinese medicine(TCM) placebos are simulated preparations for specific objects and the color simulation in the development of TCM placebos is both crucial and challenging. Traditionally, the prescription screening and pattern exploration process involves extensive experimentation, which is both time-consuming and labor-intensive. Therefore, accurate prediction of color simulation prescriptions holds the key to the development of TCM placebos. In this study, we efficiently and precisely predict the color simulation prescriptions of placebos using an image-based approach combined with Matlab software. Firstly, images of TCM placebo solutions are captured, and 13 chromaticity space values such as the L* a* b*, RGB, HSV, and CMYK values are extracted using Photoshop software. Correlation analysis and normalization are then performed on these extracted values to construct a 13×9×3 back propagation(BP) neural network model. Subsequently, the whale optimization algorithm(WOA) is employed to optimize the initial weights and thresholds of the BP neural network. Finally, the optimized WOA-BP neural network is validated using three representative instances. The training and prediction results indicate that, compared to the BP neural network, the WOA-BP neural network demonstrates superior performance in predicting the pigment ratios of placebos. The correlation coefficients for training, validation,testing, and the overall dataset are 0. 95, 0. 87, 0. 95, and 0. 95, respectively, approaching unity. Furthermore, all error values are reduced, with the maximum reduction reaching 99. 83%. The color difference(ΔE) values for the three validation instances are all less than 3, further confirming the accuracy and practicality of the WOA-BP neural network approach.

SNPs Give LACTB Oncogene-Like Functions and Prompt Tumor Progression via Dual-Regulating p53.

LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTBM5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene-like functions to LACTB. Mechanistically, LACTBM5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53R156P protein from lysosomal degradation, which suggesting LACTBM5L+R469K is a dual-regulator for wt-p53 and mutant p53, and derive oncogene-like functions. More importantly, clavulanate potassium, a bacterial ß-lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTBM5L+R469K. These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene-like functions to LACTB. Inhibiting LACTBM5L+R469K can suppress the progression of osteosarcoma harbouring wild-type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTBM5L+R469K-p53 pathway for the treatment of osteosarcoma patients.

Pilot Study of Intelligent Office Blood Pressure Measurement Model in Shanghai, China, 2022.

Introduction: An intelligent office blood pressure measurement (IOBPM) model for community-based hypertension management was piloted in Shanghai, China, to overcome the conventional blood pressure management (CBPM) model's deficiencies. Methods: We selected adults aged 35-89 years who were being treated and managed for hypertension in two community health centers for the IOBPM and CBPM models. The IOBPM model consisted of two or three consecutive blood pressure (BP) measurements using a pre-programmed and validated automatic device. The BP data for the CBPM model were obtained from the routine follow-up records of hypertensive patients and derived from the Shanghai Non-communicable Diseases Management Information System. Subjects in the IOBPM model were selected by a simple random sampling method, and propensity score matching was used to select a comparable control population from the CBPM model based on important covariables. The BP levels, end-digit preferences, frequency distribution, and BP control were compared between the two models. Results: We selected 2,909 patients for the IOBPM model and 5,744 for the CBPM model. The systolic BP in the CBPM model was 12.3 mmHg lower than in the IOBPM model. In the CBPM model, there were statistically significant end-digit preferences (P < 0.001), with zero being the most reported end-digit (23.3% for systolic BP and 27.7% for diastolic BP). There was no significant end-digit preference in the IOBPM model. Certain BP values below 140/90 mmHg in the CBPM model were more frequent, while the IOBPM model showed a normal distribution. The BP control in the CBPM model was significantly higher than the IOBPM model (P < 0.001). Conclusion: The IOBPM model appears to overcome the deficiencies of the CBPM model, leading to more accurate and reliable BP measurements.

DGA-grafting pyridine for ultra-selective and prior extraction of 99TcO4- from simulated spent nuclear fuel.

Selective and prior extraction of 99TcO4- ahead of uranium and plutonium separation is a beneficial strategy for the modern nuclear fuel cycle. Herein, a novel DGA-grafting pyridine ligand BisDODGA-DAPy (L1) was tailored for the efficient separation of TcO4- from simulated spent nuclear fuel based on the selectivity of pyridine and synergistic effect of diglycolamide (DGA) group. Compared to the ligands BisDOSCA-DAPy (L2) and BisDODGA-MPDA (L3) with similar structure, BisDODGA-DAPy (L1) demonstrated the better separation performance including good extraction efficiency, reusability, and high loading capacity for TcO4- under high acidic medium. The interactions of the ligands with Tc(VII)/Re(VII) have been investigated in detail using FT-IR, 1H NMR titration, UV-Vis spectrophotometric titration, ESI-HRMS and DFT simulations. The extraction mechanism affected by the protonation of ligand was elucidated under different acidity. BisDODGA-DAPy (L1) demonstrated the ultra-selective extraction ability for TcO4- from simulated spent nuclear fuel. The maximum SFTc/U and SFTc/Pu values were up to 1.29 × 104 and 5.08 × 103, respectively. In the presence of 9 × 104-fold excess of NO3-, the extraction of TcO4- was almost unaffected. Moreover, the good radiolytic stability further highlights the promising potential of this ligand for 99Tc separation. DFT calculation revealed the dominant role of DAPy and DODGA in TcO4- extraction, providing the theoretical evidence for BisDODGA-DAPy (L1) to selectively bind TcO4- over NO3-.

The control rate of hypertension across months of year and hours of day in a large real-world database.

We investigated the control rate of hypertension across months of year and hours of day in a real-world database. The study participants were hypertensive patients from 142 community health centers across 16 districts in Shanghai, China, who measured their blood pressure with an automatic office blood pressure measurement platform between 2018 and 2023. The 343,400 hypertensive patients included 53.7% of women, and had average age of 70.2 (±8.1) years (range 50-90 years). For months of year, the control rate of hypertension was lowest in February and highest in August (51.9% vs 71.8%). For hours of day, the control rate of hypertension was lowest at 7:00 AM and highest at 12:00 PM (52.1% vs 76.0%). When the months of year and hour of day were considered together, the control rate was lowest at 7 AM in February (42.1%), and highest at 12 PM in July (86.8%). In 8516 patients who had uncontrolled blood pressure in the early morning and had their blood pressure also measured around noon, 45.7% had masked uncontrolled morning hypertension, with higher rates in spring and summer, and in women, those aged 50-69 years, and non-diabetic patients. The control rate of hypertension varies greatly across months of year and hours of day, suggesting that the evaluation of blood pressure control has to take into full consideration the measurement time in terms of months and hours.

Individuality and generality of intratumoral microbiome in the three most prevalent gynecological malignancies: an observational study.

Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.

A scoping review of social determinants of health's impact on substance use disorders over the life course.

BACKGROUND: Substance use is a public crisis in the U.S. Substance use can be understood as a series of events in the life course, from initiation to mortality. Social Determinants of Health (SDoH) have increasingly been recognized as essential contributors to individuals' health. This scoping review aims to examine available evidence of SDoH impact on the life course of substance use disorder (SUD). METHODS: This study identified peer-reviewed articles that reported longitudinal studies with SDoH factors as independent variables and substance use and disorders as dependent variables from PubMed, Embase, and Web of Science. The reported associations between SDoH and substance use stages over the life course were narratively and graphically summarized. RESULTS: Among the 50 studies identified, ten revealed parental monitoring/support and early childhood education as protective factors, while negative peer influences and neighborhood instability were risk factors of substance use initiation. Nineteen articles reported factors associated with escalation in substance use, including unemployment, neighborhood vulnerability, negative peer influence, violence/trauma, and criminal justice system (CJS) involvement. Ten articles suggested that employment, social support, urban living, and low-barrier medication treatment facilitated treatment participation, while stigma and CJS involvement had negative impact on treatment trajectory. Social support and employment could foster progress in recovery and CJS involvement and unstable housing deterred recovery. Four studies suggested that unemployment, unstable housing, CJS involvement, and lack of social support were associated with overdose and mortality. CONCLUSIONS: This review underscores the influence of social networks and early life experiences on the life course of SUD. Future SDoH research should investigate overdose and mortality and the impact of broader upstream SDoH on SUD. Interventions addressing these social factors are needed to mitigate their detrimental effects on the trajectories of SUD over the life course.

Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease.

Objective: To investigate the effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease. Methods: In the study conducted at Heping Hospital of Changzhi Medical College from March 2021 to December 2022, 30 cases of patients diagnosed with diabetic nephropathy were meticulously selected as study subjects. Employing a double-blind randomized table method, these patients were randomly allocated into three groups: the control group (n = 10), the Bifidobacterium bifidum tetragonum tablets group (n = 10), and the Jin Gui Ren Qi Pill group (n = 10). The control group received standard western medical treatments for diabetic nephropathy, including serum glucose, blood lipids, blood pressure management, and other conventional therapies. In addition to the standard treatments, the Bifidobacterium bifidum tetragonum tablets group received Bifidobacterium bifidum tetragonum tablets, while the Jin Gui Ren Qi Pill group received Jin Gui Ren Qi Pill. Before and after a 4-week treatment period, various baseline parameters were assessed, including fasting blood glucose, 2-h postprandial blood glucose, triglycerides, serum total cholesterol, serum low-density lipoprotein cholesterol, serum high-density lipoprotein cholesterol, random urine microalbumin/creatinine ratio (ACR), blood creatinine (SCr), and traditional Chinese medicine evidence scores. Stool specimens were collected from all three groups before and after treatment for 16S rDNA high-throughput sequencing, followed by comprehensive analyses including OUT clustering, Alpha diversity, Beta diversity, species composition analysis, LEfSe analysis, and KEGG function prediction. Spearman correlation analysis was employed to explore the relationship between intestinal flora and clinical indicators. Furthermore, fasting peripheral venous blood was collected from patients in the Bifidobacterium tetrapunctate tablets group and the control group before and after intervention to measure the optical density values of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) using the Beijing Biolite ELISA kit. This study was conducted with the approval of the Ethics Committee of Changzhi Medical College. Results: 1. The 2hPBG, total cholesterol and LDL levels were observed among patients with diabetic kidney disease (DKD) across all groups: the Jin Gui Ren Qi Pill group, the Bifidobacterium bifidum tetragonum tablets group, and the control group (p < 0.05). 2. The Jin Gui Ren Qi Pill demonstrated superior efficacy in alleviating TCM symptoms and reducing the ACR compared to both the Bifidobacterium bifidum tetragonum tablets group and the control group. Conversely, Bifidobacterium bifidum tetragonum tablets exhibited a more pronounced reduction in TC levels compared to both the Jin Gui Ren Qi Pill and control groups. Notably, Bifidobacterium bifidum tetragonum tablets effectively decreased (IL-2) levels in patients with DKD. 3. Bifidobacterium bifidum tetragonum tablets also demonstrated efficacy in reducing IL-2 levels in DKD patients. 4. Analysis of intestinal microorganism abundance and diversity before and after the intervention, as well as among the three groups, revealed no significant alterations. Similarly, comparisons of ACE, Chao, Simpson, and Shannon indices showed no statistically significant differences (p > 0.05). 5. Qualitative analysis of intestinal microorganisms before and after intervention, as well as among the three groups, indicated no significant differences. Anosim test results also did not reveal qualitative distinctions (Anosim test R = 0.021, p = 0.215). 6. LEfSe analysis unveiled a noteworthy increase in Prevotella_7 abundance within the Jin Gui Ren Qi Pill group post-intervention (p < 0.05). 7. Furthermore, Chinese medicine evidence scores, body mass index, TC, and LDL levels correlated positively with the relative abundance of Tyzzerella_3 bacterial flora. Conversely, age, disease duration, and 2hPBG correlated positively with the relative abundance of Christensenellaceae_R_7 flora, while TC and LDL levels displayed a negative correlation with the relative abundance of Christensenellaceae_R_7 flora. Conclusion: The combination of Jin Gui Ren Qi Pill with western medical treatment exhibited superior efficacy in ameliorating clinical symptoms and reducing the ACR in patients with DKD compared to western medical treatment alone. Furthermore, this combination therapy led to an increase in the abundance of Prevotella_7 within the intestinal flora of patients, suggesting a potential enhancement in carbohydrate metabolism by the intestinal microbiota. On the other hand, Bifidobacterium bifidum tetragonum tablets bacterial tablets combined with western medical treatment demonstrated enhanced efficacy in reducing TC levels in DKD patients compared to western medical treatment alone. Additionally, this combination therapy effectively reduced the levels of IL-2 in DKD patients, thus mitigating inflammation in these individuals.

[Research on bitter taste and efficacy of Ginkgo biloba extract based on UPLC-Q-TOF-MS~E integrated with molecular docking].

Based on high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) and molecular docking technique, bitter compounds of Ginkgo biloba extract(GBE) were characterized, and their relationship with bitter efficacy was investigated. Firstly, UPLC-Q-TOF-MS~E was used for qualitative analysis of GBE components, and 60 chemical components were identified. These chemical components were molecular-docked with bitter receptors, and 26 bitter substances were selected, mainly flavonoids. Secondly, sensory and electronic tongue bitterness evaluation techniques were used to verify that total flavones of GBE were the main bitter substances, which was consistent with the molecular docking results. Finally, network pharmacology was used to predict and analyze bitter substances. The relationship between the target of bitter substance and bitter effect was explored. The key targets of bitter substances are CYP2B6, ALOX15, and PTGS2, etc., and bitter substances may exert a bitter efficacy by ac-ting on related disease targets, indicating that bitter substances of GBE are the material basis of the bitter effect. In summary, the study indicated that the molecular docking technique had a guiding effect on the screening of bitter substances in traditianal Chinese medicine(TCM), and bitter substances of GBE had a bitter efficacy. It provides ideas and references for the study of the "taste-efficacy relationship" of TCM in the future.

The Relationship Between Voluntary Participation Status and Health Promotion Lifestyle Among Middle-Aged and Older Adults in the Community.

The purpose of this study was to understand the relationship between the characteristics, health status, and health-promoting lifestyles of volunteer workers who participate in the community among middle-aged and older adults. A cross-sectional study was conducted to collect data from 173 middle-aged and older adults volunteers from 2 communities in North Taiwan. Data were collected using a structured questionnaire that included Demographic Characteristics Form, Self-Rated Health Status Scale, and Health Promotion Lifestyle Scale. Most of the volunteers were female, with an average age of 60.41 (±9.30) years. The average item score for the health promotion lifestyle was 74.07 (SD = 19.27). Participants scored highest on the social support subscales and lowest on the exercise subscales, followed by health responsibility subscales. Multiple regression analysis revealed that an average of 6 to 8 hours of volunteer services per week, diversity of volunteer services, and self-rated health status were each significantly associated with a greater health promotion lifestyle. Community health care workers should strengthen community volunteer support networks and motivate volunteers to attend health-related classes. Various community activities can remind each volunteer of their health responsibilities and awareness of a healthy promotion lifestyle.