Acupuncture modulation of chronic neuropathic pain and its association with brain functional properties.

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture group or sham acupuncture group and received 10 sessions of treatment during 4 weeks. The Visual Analog Scale (VAS) for leg pain, Oswestry Disability Index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression (SVR) analyses were performed. Compared to sham acupuncture, acupuncture significantly improved symptoms, including VAS for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus (PoCG). Furthermore, the actual 4-week ODI values were positively correlated with the SVR predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right PoCG may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain.

Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage: A case report.

BACKGROUND: Programmed cell death 1 (PD-1) inhibitors are immune checkpoint inhibitors (ICI) that have demonstrated significant efficacy in treating various advanced malignant tumors. While most patients tolerate treatment well, several adverse drug reactions, such as fatigue, myelosuppression, and ICI-associated colitis, have been reported. CASE SUMMARY: This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab (a PD-1 inhibitor) for six months. The treatment led to repeated life-threatening lower gastrointestinal hemorrhage. The patient received infliximab, vedolizumab, and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal bleeding. Currently, postoperative gastrointestinal bleeding has stopped, the patient's stool has turned yellow, and his full blood cell count has returned to normal. CONCLUSION: This case highlights the necessity of early identification, timely and adequate treatment of ICI-related colitis, and rapid escalation to achieve the goal of improving prognosis.

The characteristic pattern of functional connectivity density influenced by postmenopausal females in the preclinical stage of dementia.

Subjective cognitive decline (SCD) is considered an early indicator of Alzheimer's disease. Previous evidence suggests that postmenopausal females are at heightened risk for developing dementia. However, the potential effects of gender (i.e. postmenopausal female) on functional connectivity density (FCD) in individuals with SCD are not well understood. A total of 56 healthy controls and 57 subjects with SCD were included. The short-range and long-range FCD (srFCD and lrFCD) mapping of each participant was calculated. The interactive effect of gender × diagnosis on the FCD was explored by two-way analysis of variance. The interaction effect of gender × diagnosis on lrFCD was primarily in the right middle frontal gyrus (MFG). The older males with SCD exhibited significantly enhanced lrFCD in the right MFG relative to other subgroups. The lrFCD of the right MFG was positively associated with cognitive performance in older females with SCD. Cognition-related functional terms were significantly related to the right MFG. Decreased lrFCD of the right MFG in cognitively normal older women may explain why postmenopausal females have a higher risk for progression to dementia than men. Furthermore, this altered pattern could be applied to identify individuals with a high risk for dementia.

Recent trends in Tuina for chronic pain management: A bibliometric analysis and literature review.

BACKGROUND: The utilization of Tuina as a therapeutic intervention for the management of chronic pain has experienced a gradually increase in its popularity, and the purpose of this bibliometric analysis is to offer a comprehensive understanding of the current state and frontier trends, as well as to provide recommendations for future research directions. METHODS: Publications on Tuina for chronic pain published between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC). Microsoft Excel, CiteSpace, VOSViewer, and the R package "bibliometrix" were used to quantitatively analyse the annual publication volume, countries/regions, journals, institutions, cited references, authors, and keywords. RESULTS: A total of 287 publications were retrieved. The number of annual publications on the use of Tuina for treating chronic pain has gradually increased. Most publications were published in China and the United States. Notably, the most productive institution and author were identified as Shanghai University of Traditional Chinese Medicine and Min Fang, respectively. Medicine ranked first as the most influential affiliate and most productive journal. These publications came from 1,650 authors, among whom Edzard Ernst had the most co-citations. Keyword analysis revealed that the new research frontier was low back pain. CONCLUSION: The utilization of Tuina for the treatment of chronic pain has been gaining increasing recognition. Acupuncture, randomised controlled trials, systematic reviews, etc. were the main research subjects. Furthermore, low back pain is the new research frontier. This study provides an in-depth perspective on Tuina for chronic pain, which provides valuable reference material for clinicians with insights of therapeutic strategy, educators with valuable topics, and researchers with new research directions.

Efficacy and safety of multiple external therapies in patients with insomnia: a systematic review and network meta-analysis.

Background: The annual incidence of insomnia continues to increase owing to changes in lifestyle habits, increased work pressure, and increased environmental pollution. In recent years, an increasing number of external therapies have been proven effective in treating insomnia and have been widely used. However, the relative benefits and harms of external therapies remain uncertain, and an optimal treatment strategy has not yet been determined. Objectives: A network meta-analysis was performed to evaluate and compare the efficacy and safety of multiple external therapies for patients with insomnia. Methods: Eight electronic databases were comprehensively searched from their inception to June 2023 for relevant literature. We also searched the grey literature and reviewed the reference lists of related systematic reviews. Two independent reviewers performed the study selection, data extraction, and bias assessment of the included randomized controlled trials (RCTs) using the Cochrane Reviewers' Handbook, and a network meta-analysis was conducted using Stata and RevMan software. Results: In total, 14,826 studies were identified. Of these, 83 studies, including 9 external therapies and 6,100 patients, were deemed eligible for the present network meta-analysis. Except for the SL outcome, each external therapy was better than conventional medicine and the sham intervention (SI) in improving sleep quality. In terms of improving the psychological state indices of insomnia patients, each external therapy was superior to the SI; each external therapy had a better effect on the regulation of monoamine neurotransmitters. Tuina may be the most effective intervention in improving the total effective rate, Pittsburgh sleep quality index score, and SL. Repetitive transcranial magnetic stimulation (rTMS) perhaps resulted in the best improvement in total sleep time and awakening time (surface under the cumulative ranking curve [SUCRA] = 78.3 and 75.4%, respectively); and moxibustion (MB) and hyperbaric oxygen (HBO) were the most effective in reducing Self-rating Anxiety Scale and Self-rating Depression Scale scores. In terms of improving the monoamine neurotransmitters 5-hydroxytryptamine, norepinephrine, and dopamine, the best interventions were acupoint catgut embedding, electroacupuncture, and Tuina (SUCRA = 82.0, 69.9 and 90.3%, respectively). Safety results showed that the three safest interventions were the SI, Tuina, and foot bath. No serious adverse events were reported across the studies, and the most common minor adverse events included drowsiness, pain, excessive thirst, and hematoma. Conclusion: Both Tuina and rTMS have significant effects on improving sleep quality, but the safety of rTMS is low. Therefore, Tuina can be recommended as the first line of treatment to improve sleep quality. If a patient's anxiety and depression symptoms are evident, MB or HBO can be selected for treatment based on the actual situation. External therapy to improve sleep quality may be related to the regulation of monoamine neurotransmitters, which may be a potential mechanism of action. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=440882.

Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacy.

Type I interferons have been well recognized for their roles in various types of immune cells during tumor immunotherapy. However, their direct effects on tumor cells are less understood. Oxidative phosphorylation is typically latent in tumor cells. Whether oxidative phosphorylation can be targeted for immunotherapy remains unclear. Here, we find that tumor cell responsiveness to type I, but not type II interferons, is essential for CD47-SIRPα blockade immunotherapy in female mice. Mechanistically, type I interferons directly reprogram tumor cell metabolism by activating oxidative phosphorylation for ATP production in an ISG15-dependent manner. ATP extracellular release is also promoted by type I interferons due to enhanced secretory autophagy. Functionally, tumor cells with genetic deficiency in oxidative phosphorylation or autophagy are resistant to CD47-SIRPα blockade. ATP released upon CD47-SIRPα blockade is required for antitumor T cell response induction via P2X7 receptor-mediated dendritic cell activation. Based on this mechanism, combinations with inhibitors of ATP-degrading ectoenzymes, CD39 and CD73, are designed and show synergistic antitumor effects with CD47-SIRPα blockade. Together, these data reveal an important role of type I interferons on tumor cell metabolic reprograming for tumor immunotherapy and provide rational strategies harnessing this mechanism for enhanced efficacy of CD47-SIRPα blockade.

The association between different levels of depression and overactive bladder: A cross-sectional study of the 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND: There is growing evidence of a possible correlation between depression and overactive bladder (OAB). However, few studies have classified depression according to its severity. Whether there is an association between different levels of depression and OAB symptoms remains unclear. METHODS: Participants with complete information about depression, OAB, and covariates in the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included in this study. Depression symptoms were assessed by the Patient Health Questionnaire-9. OAB symptoms were evaluated by the Overactive Bladder Symptom Score. Weighted multivariate logistic regression models were applied to analyze the relationship between depression and OAB. RESULTS: A total of 30 359 participants were included in this study, consisting of 6245 OAB patients and 24 114 non-OAB participants. The multivariate logistic regression suggested depression independently correlated with OAB (odds ratio [OR] = 2.764, 95% confidence interval [CI] = 2.429-3.146, p < 0.001). Further, mild (OR = 2.355, 95% CI = 2.111-2.627, p < 0.001), moderate (OR = 3.262, 95% CI = 2.770-3.841, p < 0.001), and moderately severe to severe depression (OR = 3.927, 95% CI = 3.246-4.752, p < 0.001) were all associated with OAB. Additionally, depression was also correlated with urgency urinary incontinence (OR = 2.249, 95% CI = 1.986-2.548, p < 0.001) and nocturia (OR = 2.166, 95% CI = 1.919-2.446, p < 0.001). CONCLUSION: This study indicated different levels of depression, even mild depression, were independent risk factors for OAB. Given the frequent coexistence and potential interactions between depression and OAB, clinicians should be aware of the importance of assessing both physical and psychological symptoms in these patients. Early diagnosis and holistic treatment may improve the treatment outcomes, particularly for those suffering from both conditions.

Epidermal growth factor receptor­targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-ß1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1ß) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Over 18.2% efficiency of layer-by-layer all-polymer solar cells enabled by homoleptic iridium(III) carbene complex as solid additive.

The vertical phase distribution of active layers plays a vital role in balancing exciton dissociation and charge transport for achieving efficient polymer solar cells (PSCs). The layer-by-layer (LbL) PSCs are commonly prepared by using sequential spin-coating method from donor and acceptor solutions with distinct solvents and solvent additives. The enhanced exciton dissociation is expected in the LbL PSCs with efficient charge transport in the relatively neat donor or acceptor layers. In this work, a series of LbL all-polymer solar cells (APSCs) were fabricated with PM6 as donor and PY-DT as acceptor, and triplet material m-Ir(CPmPB)3 is deliberately incorporated into PY-DT layer to prolong exciton lifetimes of active layers. The power conversion efficiency (PCE) of LbL APSCs is improved to 18.24% from 17.32% by incorporating 0.3 wt% m-Ir(CPmPB)3 in PY-DT layer, benefiting from the simultaneously enhanced short-circuit current density (JSC) of 25.17 mA cm-2 and fill factor (FF) of 74.70%. The enhancement of PCE is attributed to the efficient energy transfer of m-Ir(CPmPB)3 to PM6 and PY-DT, resulting in the prolonged exciton lifetime in the active layer and the increased exciton diffusion distance. The efficient energy transfer from m-Ir(CPmPB)3 to PM6 and PY-DT layer can be confirmed by the increased photoluminescence (PL) intensity and the prolonged PL lifetime of PM6 and PY-DT in PM6 + m-Ir(CPmPB)3 and PY-DT + m-Ir(CPmPB)3 films. This study indicates that the triplet material as solid additive has great potential in fabricating efficient LbL APSCs by prolonging exciton lifetimes in active layers.

Exploring the Mechanism of Shen Qi Gui Oral Liquid against Chemotherapy-Induced Myelosuppression in Cancer Patients Based on Network Pharmacology and Molecular Docking.

BACKGROUND: Shen Qi Gui oral liquid (SQG) may be beneficial for chemotherapyinduced myelosuppression (CIM). However, the underlying mechanism of CIM treated with SQG is still lacking. METHODS: A total of 27 blood samples from cancer patients were selected to perform RNA-seq to obtain the Differentially Expressed Genes (DEGs). Then, the active components and target genes of SQG were acquired. Next, the drug targets and DEGs were intersected to obtain the intersection genes, followed by functional enrichment analysis and construction of a drug-compoundgene- disease network. Subsequently, core genes were selected. Then, immune cell infiltration, molecular docking, pharmacokinetic and toxicity prediction, and RT-qPCR were performed. RESULTS: A total of 1,341 DEGs, 51 active compounds, and 264 target genes were identified. Then, 30 intersection genes were acquired. Next, a drug-compound-gene-disease network was constructed, and 7 core genes were acquired. Immune infiltration analysis exhibited that only T follicular helper cells were significantly increased in the CIM group, which was significantly negatively correlated with MAPK1, MAPK14, MCL1, PTEN, and PTGS2. The luteolin, quercetin, and beta-sitosterol showed better affinity with core genes. Luteolin and quercetin, which satisfied Lipinski's rule of five, were likely absorbed by the gastrointestinal system. Toxicity predictions showed that neither luteolin nor quercetin exhibited carcinogenicity or hepatotoxicity. CONCLUSION: PTEN, PTGS2, CCL2, FOS, MCL1, MAPK1, and MAPK14 were identified as the core genes in CIM patients, which were involved in the MAPK and PI3K-Akt signaling pathways. Luteolin and quercetin may be the promising drugs against CIM.

Physical exercise, social relationships, and bullying perpetration among school adolescents in China.

Despite contradictory empirical evidence, some suggest that physical exercise is directly related to bullying perpetration. Moreover, the quality of social relationships between adolescents and their parents, peers, and teachers has been proposed as a crucial mediator in the relationship between physical exercise and bullying perpetration. However, few empirical studies have examined such hypotheses. This study used data obtained from the 2014-2015 China Education Panel Survey to examine the direct association between physical exercise and bullying behaviors, as well as the indirect pathways from physical exercise to bullying that are mediated by teenagers' social relationship quality. The results showed no significant direct relationship between physical exercise and bullying behaviors. However, physical exercise has indirect associations with bullying behaviors mediated through social relationship quality, with peer relationships having the strongest mediating effect. The findings indicate that social relationships could mediate the association between physical exercise and bullying behaviors. The study suggests that future prevention and intervention programs should promote adolescents' participation in physical exercise and their social interactions with parents, peers, and teachers to reduce bullying perpetration.

Highly Efficient Organic Solar Cells with the Highly Crystalline Third Component as a Morphology Regulator.

The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules.

A comparison of different intensified upstream processes highlighting the advantage of WuXi Biologics' Ultra-high Productivity platform (WuXiUPTM) in improved product quality and purification yield.

WuXiUPTM, WuXi Biologics' Ultra-high Productivity platform, is an intensified and integrated continuous bioprocess platform developed for production of various biologics including monoclonal antibodies, fusion proteins, and bispecific antibodies. This process technology platform has manifested its remarkable capability in boosting the volumetric productivity of various biologics and has been implemented for large-scale clinical material productions. In this paper, case studies of the production of different pharmaceutical proteins using two high-producing and intensified culture modes of WuXiUPTM and the concentrated fed-batch (CFB), as well as the traditional fed-batch (TFB) are discussed from the perspectives of cell growth, productivity, and protein quality. Both WuXiUPTM and CFB outperformed TFB regarding volumetric productivity. Additionally, distinctive advantages in product quality profiles in the WuXiUPTM process, such as reduced acidic charge variants and fragmentation, are revealed. Therefore, a simplified downstream purification process with only two chromatographic steps can be developed to deliver the target product at a satisfactory purity and an extremely-high yield.

An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H2-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H2-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

Development and validation of a multi-parameter nomogram for venous thromboembolism in gastric cancer patients: a retrospective analysis.

Objective: Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra cost. However, up to now, there is not a high-quality VTE model to steadily predict the risk for VTE in China. Consequently, setting up a prediction model to predict the VTE risk is imperative. Methods: Data from 3,092 patients from December 15, 2017, to December 31, 2022, were retrospectively analyzed. Multiple logistic regression analysis was performed to assess risk factors for GC, and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot was created to evaluate the accuracy of the nomogram. Results: The risk factors of suffering from VTE were older age (OR = 1.02, 95% CI [1.00-1.04]), Karnofsky Performance Status (KPS) ≥ 70 (OR = 0.45, 95% CI [0.25-0.83]), Blood transfusion (OR = 2.37, 95% CI [1.47-3.84]), advanced clinical stage (OR = 3.98, 95% CI [1.59-9.99]), central venous catheterization (CVC) (OR = 4.27, 95% CI [2.03-8.99]), operation (OR = 2.72, 95% CI [1.55-4.77]), fibrinogen degradation product (FDP) >5 µg/mL (OR = 1.92, 95% CI [1.13-3.25]), and D-dimer > 0.5 mg/L (OR = 2.50, 95% CI [1.19-5.28]). The area under the ROC curve (AUC) was 0.82 in the training set and 0.85 in the validation set. Conclusion: Our prediction model can accurately predict the risk of the appearance of VTE in gastric cancer patients and can be used as a robust and efficient tool for evaluating the possibility of VTE.

Dysrhythmic saliva microbiota in mobile phone addicts with sleep disorders and restored by acupuncture.

Background: Mobile phone addiction (MPA) greatly affects the biological clock and sleep quality and is emerging as a behavioral disorder. The saliva microbiota has been linked to circadian rhythms, and our previous research revealed dysrhythmic saliva metabolites in MPA subjects with sleep disorders (MPASD). In addition, acupuncture had positive effects. However, the dysbiotic saliva microbiota in MPASD patients and the restorative effects of acupuncture are unclear. Objectives: To probe the circadian dysrhythmic characteristics of the saliva microbiota and acupunctural restoration in MPASD patients. Methods: MPASD patients and healthy volunteers were recruited by the Mobile Phone Addiction Tendency Scale (MPATS) and the Pittsburgh Sleep Quality Index (PSQI). Saliva samples were collected every 4 h for 72 h. After saliva sampling, six MPDSD subjects (group M) were acupuncturally treated (group T), and subsequent saliva sampling was conducted posttreatment. Finally, all the samples were subjected to 16S rRNA gene sequencing and bioinformatic analysis. Results: Significantly increased MPATS and PSQI scores were observed in MPDSD patients (p< 0.01), but these scores decreased (p<0.001) after acupuncture intervention. Compared with those in healthy controls, the diversity and structure of the saliva microbiota in MPASD patients were markedly disrupted. Six genera with circadian rhythms were detected in all groups, including Sulfurovum, Peptostreptococcus, Porphyromonas and Prevotella. There were five genera with circadian rhythmicity in healthy people, of which the rhythmicities of the genera Rothia and Lautropia disappeared in MPASD patients but effectively resumed after acupuncture intervention. Conclusions: This work revealed dysrhythmic salivary microbes in MPASD patients, and acupuncture, as a potential intervention, could be effective in mitigating this ever-rising behavioral epidemic.

Straw removal reduces Cd availability and rice Cd accumulation in Cd-contaminated paddy soil: Cd fraction, soil microorganism structure and porewater DOC and Cd.

The impacts of straw removal on rice Cd absorption, behaviour of Cd and microbial community in rhizosphere soil were investigated in paddy fields over two consecutive seasons. The results of the experiments in two fields revealed that straw removal promoted the transformation of soil Cd from acid-extractable and oxidisable fraction to residual fraction and reduced soil DTPA-Cd content with the reduction in DOC and Cd ions in soil porewater, thereby decreasing Cd content in rice. Specifically, the Cd content in brown rice of early rice was below 0.2 mg·kg-1 when all rice straw and roots were removed in the slightly Cd-contaminated soils. The α-diversity of soil microbial communities was less influenced by continuous straw removal, ß-diversity was altered and the relative abundances of Anaeromyxobacter, Methylocystis and Mycobacterium microbes were increased. Redundancy analysis and network analysis exhibited that soil pH predominantly influenced the microbial community. Path analysis revealed that the Cd content in brown rice could be directly influenced by the soil Total-Cd and DTPA-Cd, as well as soil pH and OM. Straw removal, including roots removal, is an economical and effective technique to reduce Cd accumulation in rice plants.

Establishment of a semi-continuous scale-down clone screening model for intensified perfusion culture.

PURPOSE: Perfusion cultures have been extensively used in the biotechnology industry to achieve high yields of recombinant products, especially those with stability issue. The WuXiUP™ platform represents a novel intensified perfusion that can achieve ultra-high productivity. This study describes a representative scale-down 24-deep well plate (24-DWP) cell culture model for intensified perfusion clone screening. METHODS: Clonal cell lines were expanded and evaluated in 24-DWP semi-continuous culture. Cell were sampled and counted daily with the aid of an automated liquid handler and high-throughput cell counter. To mimic perfusion culture, 24-DWP plates were spun down and resuspended with fresh medium daily. Top clones were ranked based on growth profiles and productivities. The best performing clones were evaluated on bioreactors. RESULTS: The selected clones achieved volumetric productivity (Pv) up to 5 g/L/day when expressing a monoclonal antibody, with the accumulative harvest Pv exceeding 60 g/L in a 21-day cell culture. Product quality attributes of clones cultured in 24-DWP were comparable with those from bioreactors. A high seeding strategy further shortened the clone screening timeline. CONCLUSION: In this study, a 24-DWP semi-continuous scale-down model was successfully developed to screen for cell lines suitable for intensified perfusion culture.