Case report: A case of recurrent cervical cancer with bronchial and esophageal metastases presenting with hemoptysis and dysphagia.

Background: The treatment outcomes and prognosis for recurrent cervical cancer are generally poor, with a 5-year survival rate of only 10%-20%. Case presentation: In this case, the patient is a young woman who experienced a recurrence 5 years after the initial treatment of cervical cancer. Her primary symptoms were hemoptysis and dysphagia, indicative of hilar and mediastinal lymph node metastases, with further involvement of the bronchus and esophagus. Additionally, the patient also presented with tumor-associated dermatomyositis. Following combined treatment with albumin-bound paclitaxel, carboplatin, bevacizumab, and cadonilimab, the patient's tumor was effectively controlled.

The Association of Micro-RNA 21 and Hypertension: A Meta-Analysis.

Hypertension is a multifactorial, complex disease with high morbidity and mortality rates. Studies have found that micro-RNA 21 (miR-21) levels are significantly increased in patients with hypertension. However, other studies have reported opposite results. Therefore, the relationship between miR-21 expression and hypertension remains controversial. This meta-analysis was conducted to statistically evaluate the miR-21 levels of patients with hypertension. A literature research was conducted using Web of Science, Embase, PubMed, and CNKI. To search for titles or abstracts, 'hypertension' in combination with the terms 'miR-21,' 'microRNA-21,' or 'miRNA-21' were used as keywords. Standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were determined from the results of the meta-analysis. In total, 12 articles were included in this meta-analysis, involving 546 cases and 436 controls. The results of the meta-analysis showed that miR-21 levels in patients with hypertension were significantly higher than those in the controls (SMD: 1.22; 95% CI [0.35, 2.09]). This meta-analysis is the first to evaluate miR-21 in patients with hypertension. MiR-21 may be a new target for the prediction and treatment of hypertension. Further high-quality studies are needed to better support the association between miR-21 and hypertension.

Cascaded *CO-*COH Intermediates on a Nonmetallic Plasmonic Photocatalyst for CO2-to-C2H6 with 90.6% Selectivity.

Oxygen vacancies (OV) in nonmetallic plasmonic photocatalysts can decrease the energy barrier for CO2 reduction, boosting C1 intermediate production for potential C2 formation. However, their susceptibility to oxidation weakens C1 intermediate adsorption. Herein we proposed a "photoelectron injection" strategy to safeguard OV in W18O49 by creating a W18O49/ZIS (W/Z) plasmonic photocatalyst. Moreover, photoelectrons contribute to the local multi-electron environment of W18O49, enhancing the intrinsic excitation of its hot electrons with extended lifetimes, as confirmed by in-situ XPS and femtosecond transient absorption analysis. Density functional theory calculations revealed that W/Z with Ov enhances CO2 adsorption, activating *CO production, while reducing the energy barrier for *COH production (0.054 eV) and subsequent *CO-COH coupling (0.574 eV). Successive hydrogenation revealed that the free energy for *CH2CH2 hydrogenation (0.108 eV) was lower than that for *CH2CH2 desorption for C2H4 production (0.277 eV), favouring C2H6 production. Consequently, W/Z achieves an efficient C2H6 activity of 653.6 µmol g-1 h-1 under visible light, with an exceptionally high selectivity of 90.6%. This work offers a new strategy for the rational design of plasmonic photocatalysts with high selectivity for C2+ products.

An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy.

Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.

Sintilimab combined with anlotinib as first-line treatment for advanced sarcomatoid carcinoma of head and neck: a case report and literature review.

Sarcomatoid carcinoma (SC) is a rare, complex, aggressive tumor that spreads rapidly, is highly malignant, and has metastasized. Surgical resection is the primary treatment, and it usually occurs in the lungs and kidneys but rarely in the neck. Patients with advanced sarcomatoid carcinoma (SC) of the head and neck (HN) have a poor progonsis. In recent years, immune checkpoint inhibitors (ICIs) have been established as treatments for many solid tumors; however, the effectiveness of ICIs in treating SC of HN is still little recognized. We report a case study of a middle-aged woman with primary sarcomatoid carcinoma of the neck. She developed sarcomatoid carcinoma of the contralateral neck 7 months after the first surgical treatment. Subsequently, disease recurrence and metastasis occurred 8 months after the second surgery. The patient did not receive any treatment after both surgeries. The tumor showed high programmed death-ligand 1 (PD-L1) expression, with a combined positive score (CPS): 95. The patient's response to treatment was assessed as partial remission (PR) after 2 cycles of anlotinib combined with sintilimab. The patient has survived for over 2 years and remains in PR status, despite experiencing grade 2 hypothyroidism as an adverse event during treatment. The case highlights the efficacy and safety of anlotinib and sintilimab as a first-line treatment.

Ce-based three-dimensional mesoporous microspheres with Mn homogeneous incorporation for toluene oxidation.

Ce-based three-dimensional (3D) mesoporous microspheres with Mn homogeneous incorporation were synthesized. The CeMn-0.4, characterized by a Ce/Mn molar ratio of 6:4, demonstrated exceptional catalytic activity and stability. The formation of CeMn solid solution strengthened the Ce-Mn interaction, yielding higher concentrations of Ce3+ and Mn4+. Mn4+ initiated toluene preliminary activation owing to its robust oxidative properties, while Ce3+ contributed to oxygen vacancy generation, enhancing the activation of gaseous oxygen and lattice oxygen mobility. Integrating experiments and Density Functional Theory (DFT) calculations elucidated the oxygen reaction mechanisms. A portion of oxygen was converted into surface reactive oxygen species (Oads) that directly oxidized toluene. Additionally, the presence of oxygen vacancies promoted the participation of oxygen in toluene oxidation by converting it into lattice oxygen, which was crucial for the deep oxidation of toluene. Diffuse Reflectance Fourier Transform Infrared Spectroscopy (DRIFTS) indicated the accumulation of benzene-ring intermediates on the catalyst surface hindered continuous toluene oxidation. Thus, the abundant oxygen vacancies in CeMn-0.4 played a pivotal role in sustaining the oxidation process by bolstering the activation of gaseous oxygen and the mobility of lattice oxygen.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.

Discovery of Photoexcited 2-Chloro-3,5-Dinitrobenzoic Acid as a Chemical Deprenylase of i6A RNA.

RNA modifications play crucial roles in regulating gene expression and cellular homeostasis.  Modulating RNA modifications, particularly by targeting the enzymes responsible for their catalysis, has emerged as a promising therapeutic strategy.  However, limitations, such as the lack of identified modifying enzymes and compensatory mechanisms, hinder targeted interventions.  Chemical approaches independent of enzymatic activity offer an alternative strategy for RNA modification modulation.  Here, we present the identification of 2-chloro-3,5-dinitrobenzoic acid as a highly effective photochemical deprenylase of i6A RNA.  This method demonstrates exceptional selectivity towards i6A, converting its substituent into a "N-doped" ozonide, which upon hydrolysis releases natural adenine.  We believe that this chemical approach will pave the way for a better understanding of RNA modification biology and the development of novel therapeutic modalities.

Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis.

BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

JWA binding to NCOA4 alleviates degeneration in dopaminergic neurons through suppression of ferritinophagy in Parkinson's disease.

Parkinson's disease (PD) poses a significant challenge in neurodegenerative disorders, characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). The intricate mechanisms orchestrating DA neurodegeneration in PD are not fully understood, necessitating the exploration of innovative therapeutic approaches. Recent studies have implicated ferroptosis as a major contributor to the loss of DA neurons, revealing a complex interplay between iron accumulation and neurodegeneration. However, the sophisticated nature of this process challenges the conventional belief that mere iron removal could effectively prevent DA neuronal ferroptosis. Here, we report JWA, alternatively referred to as ARL6IP5, as a negative regulator of ferroptosis, capable of ameliorating DA neuronal loss in the context of PD. In this study, synchronized expression patterns of JWA and tyrosine hydroxylase (TH) in PD patients and mice were observed, underscoring the importance of JWA for DA neuronal survival. Screening of ferroptosis-related genes unraveled the engagement of iron metabolism in the JWA-dependent inhibition of DA neuronal ferroptosis. Genetic manipulation of JWA provided compelling evidence linking its neuroprotective effects to the attenuation of NCOA4-mediated ferritinophagy. Molecular docking, co-immunoprecipitation, and immunofluorescence studies confirmed that JWA mitigated DA neuronal ferroptosis by occupying the ferritin binding site of NCOA4. Moreover, the JWA-activating compound, JAC4, demonstrated promising neuroprotective effects in cellular and animal PD models by elevating JWA expression, offering a potential avenue for neuroprotection in PD. Collectively, our work establishes JWA as a novel regulator of ferritinophagy, presenting a promising therapeutic target for addressing DA neuronal ferroptosis in PD.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level.

The gut commensal bacteria Christensenellaceae species are negatively associated with many metabolic diseases, and have been seen as promising next-generation probiotics. However, the cultured Christensenellaceae strain resources were limited, and their beneficial mechanisms for improving metabolic diseases have yet to be explored. In this study, we developed a method that enabled the enrichment and cultivation of Christensenellaceae strains from fecal samples. Using this method, a collection of Christensenellaceae Gut Microbial Biobank (ChrisGMB) was established, composed of 87 strains and genomes that represent 14 species of 8 genera. Seven species were first described and the cultured Christensenellaceae resources have been significantly expanded at species and strain levels. Christensenella strains exerted different abilities in utilization of various complex polysaccharides and other carbon sources, exhibited host-adaptation capabilities such as acid tolerance and bile tolerance, produced a wide range of volatile probiotic metabolites and secondary bile acids. Cohort analyses demonstrated that Christensenellaceae and Christensenella were prevalent in various cohorts and the abundances were significantly reduced in T2D and OB cohorts. At species level, Christensenellaceae showed different changes among healthy and disease cohorts. C. faecalis, F. tenuis, L. tenuis, and Guo. tenuis significantly reduced in all the metabolic disease cohorts. The relative abundances of C. minuta, C. hongkongensis and C. massiliensis showed no significant change in NAFLD and ACVD. and C. tenuis and C. acetigenes showed no significant change in ACVD, and Q. tenuis and Geh. tenuis showed no significant change in NAFLD, when compared with the HC cohort. So far as we know, this is the largest collection of cultured resource and first exploration of Christensenellaceae prevalences and abundances at species level.

Construction of cryomicroneedles loaded with milk-derived exosomes encapsulated TNF-α siRNA and efficacy of percutaneous acupoint administration in rheumatoid arthritis.

Inhibiting the expression of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine widely distributed in the serum and synovial fluid, is important for managing rheumatoid arthritis (RA). Despite the good therapeutic effects of TNF-α small interfering RNA (TNF-α siRNA) in RA animal models, safe and efficient siRNA delivery systems that retain stability are lacking. We introduced a novel therapy using milk-derived exosomes(mEXOs)-encapsulated TNF-α siRNA-coated cryomicroneedle (cryoMN) patch and evaluated its efficacy via local transdermal administration through acupoints in RA treatment. The loading of TNF-α siRNAs into mEXOs was achieved by sonication, the loading rate, stability, and in vitro release of mEXOs-TNF-α siRNA were determined. The cryoMNs were prepared by micromolding, morphology, drug loading, and mechanical strength of the cryoMN array were analyzed. The loading efficiency of TNF-α siRNA was up to 21% and each cryoMN contained 39.6 ± 1.29 µg of TNF-α siRNA. Frozen sections penetrated 523 ± 63 µm deep. In vitro experiments have shown that mEXOs-TNF-α siRNA cryoMNs have good biocompatibility and inhibit the proliferation of HFLS-RA cells. In vivo pharmacodynamics studies found that general conditions, changes in microcirculation indexes, synovial histopathological changes, and expression of related proteins in the synovial tissue in RA rabbits were effectively alleviated by mEXOs-TNF-α siRNA cryoMNs. Improvement of each index at acupoints was greater than that at non-acupoints. Our findings facilitate the development of cryoMNs combined with exosomes and acupoints drug delivery for the treatment of RA. The combination of exosomes and cryoMNs will enable the development of new-generation microneedle-based treatments.

DCTPep, the data of cancer therapy peptides.

With the discovery of the therapeutic activity of peptides, they have emerged as a promising class of anti-cancer agents due to their specific targeting, low toxicity, and potential for high selectivity. In particular, as peptide-drug conjugates enter clinical, the coupling of targeted peptides with traditional chemotherapy drugs or cytotoxic agents will become a new direction in cancer treatment. To facilitate the drug development of cancer therapy peptides, we have constructed DCTPep, a novel, open, and comprehensive database for cancer therapy peptides. In addition to traditional anticancer peptides (ACPs), the peptide library also includes peptides related to cancer therapy. These data were collected manually from published research articles, patents, and other protein or peptide databases. Data on drug library include clinically investigated and/or approved peptide drugs related to cancer therapy, which mainly come from the portal websites of drug regulatory authorities and organisations in different countries and regions. DCTPep has a total of 6214 entries, we believe that DCTPep will contribute to the design and screening of future cancer therapy peptides.

Gustatory Receptor 206 Participates in the Foraging Behavior of Larvae of Polyphagous Pest Spodoptera litura.

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.

Preclinical Evaluation of JAB-2485, a Potent AURKA Inhibitor with High Selectivity and Favorable Pharmacokinetic Properties.

As a critical mitotic regulator, Aurora kinase A (AURKA) is aberrantly activated in a wide range of cancers. Therapeutic targeting of AUKRA is a promising strategy for the treatment of solid tumors. In this study, we evaluated the preclinical characteristics of JAB-2485, a small-molecule inhibitor of AURKA currently in Phase I/IIa clinical trial in the US (NCT05490472). Biochemical studies demonstrated that JAB-2485 is potent and highly selective on AURKA, with subnanomolar IC50 and around 1500-fold selectivity over AURKB or AURKC. In addition, JAB-2485 exhibited favorable pharmacokinetic properties featured by low clearance and good bioavailability, strong dose-response relationship, as well as low risk for hematotoxicity and off-target liability. As a single agent, JAB-2485 effectively induced G2/M cell cycle arrest and apoptosis and inhibited the proliferation of small cell lung cancer, triple-negative breast cancer, and neuroblastoma cells. Furthermore, JAB-2485 exhibited robust in vivo antitumor activity both as monotherapy and in combination with chemotherapies or the bromodomain inhibitor JAB-8263 in xenograft models of various cancer types. Together, these encouraging preclinical data provide a strong basis for safety and efficacy evaluations of JAB-2485 in the clinical setting.

Construction of an Immunogenic Cell Death-Related Gene Signature and Genetic Subtypes for Predicting Prognosis, Immune Microenvironments, and Drug Sensitivity in Hepatocellular Carcinoma.

Purpose: Immunogenic cell death (ICD) is a type of regulated cell death that modifies the immune response by releasing DAMPs or danger signals. Herein, we aimed to develop an ICD-related predictive model for patients with hepatocellular carcinoma (HCC) and investigate its applicability for predicting prognostic outcomes and immunotherapeutic responses. Methods: Differentially expressed genes of ICD were identified in the HCC and normal liver samples. A prognostic risk model and a nomogram containing clinicopathological features were created. To validate the effectiveness of the model, an external dataset was used. Clinical characteristics, prognosis, tumor mutation burden, immune microenvironments, biological function and chemotherapeutic drug sensitivity were evaluated for different genetic subtypes and risk groups. Results: A total of 35 ICD-related genes (ICDRGs) were identified between HCC and normal samples, 11 of which were significantly associated with overall survival (OS) in HCC patients. Four different genetic subtypes were formed and eight ICDRGs were selected to develop a risk prognostic model. The risk scores were shown to be an independent prognostic factor for HCC and positively correlated with pathological severity. Patients in the high-risk group had a higher frequency of TP53 mutations, increased expression of immune checkpoints and human leukocyte antigen genes. The inhibitory concentrations of chemotherapeutic drugs differed in different populations. Conclusion: In this study, we developed an ICDRG risk model and demonstrated its applicability in predicting survival outcomes, immune and chemotherapeutic responses in HCC patients. ICDRGs are expected to be used as novel biomarkers in the medical decision-making of HCC.

Effects of movement training based on rhythmic auditory stimulation in cognitive impairment: a meta-analysis of randomized controlled clinical trial.

Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.

A new substrate equalization method for optimizing the influent conditions and fluid flow patterns of a multifed upflow anaerobic sludge blanket reactor with mature anammox granules.

To improve nitrogen removal efficiency (NRE) and achieve homogenous distribution of anammox sludge and substrate, a new substrate equalization theory and a cumulative overload index was proposed for multifed upflow anaerobic sludge bed (MUASB) reactors with mature anammox granules. The performance and flow patterns of MUASB reactors were investigated under various influent conditions. The results showed that the nitrogen removal performance and stability of MUASB reactors could be optimized by minimizing the cumulative load. The NRE gradually increased from 83.3 ± 2.2 %, 86.8 ± 4.2 % to 89.3 ± 4.1 % and 89.7 ± 1.6 % in feeding flow tests and feeding port tests, respectively. Furthermore, the flow patterns were compared based on residence time distribution and computational fluid dynamics, indicating that a better equilibrium distribution of microorganisms and substrates could be achieved in the MUASB reactors under the lowest cumulative load. Therefore, substrate equalization theory can be used to optimize the nitrogen removal performance of MUASB reactors with low-carbon footprints.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.