Pristine/magnesium-loaded biochar and ZVI affect rice grain arsenic speciation and cadmium accumulation through different pathways in an alkaline paddy soil.

Cadmium (Cd) and arsenic (As) co-contamination has threatened rice production and food safety. It is challenging to mitigate Cd and As contamination in rice simultaneously due to their opposite geochemical behaviors. Mg-loaded biochar with outstanding adsorption capacity for As and Cd was used for the first time to remediate Cd/As contaminated paddy soils. In addition, the effect of zero-valent iron (ZVI) on grain As speciation accumulation in alkaline paddy soils was first investigated. The effect of rice straw biochar (SC), magnesium-loaded rice straw biochar (Mg/SC), and ZVI on concentrations of Cd and As speciation in soil porewater and their accumulation in rice tissues was investigated in a pot experiment. Addition of SC, Mg/SC and ZVI to soil reduced Cd concentrations in rice grain by 46.1%, 90.3% and 100%, and inorganic As (iAs) by 35.4%, 33.1% and 29.1%, respectively, and reduced Cd concentrations in porewater by 74.3%, 96.5% and 96.2%, respectively. Reductions of 51.6% and 87.7% in porewater iAs concentrations were observed with Mg/SC and ZVI amendments, but not with SC. Dimethylarsinic acid (DMA) concentrations in porewater and grain increased by a factor of 4.9 and 3.3, respectively, with ZVI amendment. The three amendments affected grain concentrations of iAs, DMA and Cd mainly by modulating their translocation within plant and the levels of As(III), silicon, dissolved organic carbon, iron or Cd in porewater. All three amendments (SC, Mg/SC and ZVI) have the potential to simultaneously mitigate Cd and iAs accumulation in rice grain, although the pathways are different.

Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals.

Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

A nomogram-based predictive model for tooth survival in Chinese patients with periodontitis: An 11-year retrospective cohort study.

AIM: To develop a nomogram-based predictive model of tooth survival by comprehensively analysing clinical and radiographic risk factors of tooth loss (TL). MATERIALS AND METHODS: In this study, 3447 teeth of 131 subjects who underwent non-surgical periodontal treatment were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. A nomogram-based predictive model was developed, and its validation and discriminatory ability were analysed. RESULTS: In all, 313 teeth were lost in 94 patients in this study (overall tooth loss [OTL] 9.08%; 0.21 teeth/patient/year). Male, heavy smoking, molar teeth, probing depth (PD), attachment loss (AL), tooth mobility and radiographic bone loss were significantly associated with TL (p < .05). A gradient effect of tooth mobility on TL increased from degree I to III versus none (p < .0001). The area under the curve (AUC) of the model was 0.865. Calibration curve and decision curve analysis demonstrated good performance and high net benefit, respectively. CONCLUSIONS: Adopting a specific nomogram could facilitate the prediction of tooth survival and the development of tailored treatment plans in Chinese patients with advanced periodontitis.

Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

Novel diagnostic and prognostic approach for rapidly progressive dementias: Indicators based on amyloid/tau/neurodegeneration (ATN) framework.

AIMS: Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs). METHODS: CSF and serum biomarkers of Alzheimer's disease (AD) common neuropathology including Aß42, Aß40, p-Tau, and t-Tau were measured in cognitively normal (CN) controls (n = 33) and three RPD groups with rapidly progressive AD (rpAD, n = 23), autoimmune encephalitis (AE, n = 25), and Creutzfeldt-Jakob disease (CJD, n = 28). Logistic regression and multiple linear regression were used for producing combined indicators and prognostic assessment, respectively, including A&T, A&N, T&N, A&T&N, etc. RESULTS: Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square = 0.16, p = 0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square = 0.273, p = 0.014). CONCLUSION: Combined indicators based on the ATN framework provide a novel perspective for establishing biomarkers for early recognition of RPDs due to treatment-responsive causes.

Identifying modifiable factors and their joint effect on brain health: an exposome-wide association study.

Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.

Whole exome sequencing analyses reveal novel genes in telomere length and their biomedical implications.

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes.

Successful treatment of nasopalatine duct cyst after maxillary anterior implant surgery: a case report.

BACKGROUND: Sporadic studies have reported the occurrence of nasopalatine duct cysts after maxillary anterior implant surgery, and the treatment methods still have clinical uncertainty. PURPOSE: We report a potential therapy method that successfully treated a nasopalatine duct cyst that developed and expanded one year after maxillary anterior implant placement following periodontally hopeless teeth extraction. MATERIALS AND METHODS: The nasopalatine cyst was treated surgically without removing implants. During flap surgery, the cyst was removed intact, and the exposed implant's surface was debrided thoroughly by hydrogen peroxide (H2O2) rinsing, glycine air polishing, and saline rinsing. To deal with the significant bone defect caused by the cyst, a bovine porous bone mineral injected platelet-rich fibrin (BPBM-i-PRF) complex was applied to fill the defect, following a resorbable collagen membrane to cover. RESULTS: 7 years after surgery, no cyst recurrence was observed, and bone regeneration in the bone graft area was stable. The implants functioned well without mobility. CONCLUSIONS: For nasopalatine duct cysts associated with dental implant placement, complete surgical debridement and longitudinal stable bone regeneration are possibly accessible by regenerative surgery without implant removal.

The modeling method for vibration characteristics analysis of composite laminated rotationally stiffened shell.

The composite laminated rotationally stiffened shell is widely applied in aviation, aerospace, ship, machinery and other fields. To investigate the vibration characteristics of composite laminated rotationally stiffened shells with varying elastic boundary conditions, a modeling method of composite laminated rotationally stiffened shells is established. Firstly, the first-order shear deformation theory (FSDT) and the modified Fourier series method are effectively applied to establish the allowable displacement function of the composite laminated rotationally stiffened shell. Secondly, the energy function of composite laminated rotationally stiffened shell is established, and the simulation of complex elastic boundary and coupling boundary is realized by using artificial virtual spring technology. Thirdly, the Rayleigh-Ritz method is used to solve the energy function. Finally, the vibration characteristics of composite laminated rotationally stiffened shells are obtained and analyzed. In the analysis of numerical results, the fast and uniform convergence of analysis modeling and the accuracy of the calculated results are verified. On this basis, the effect of some important parameters such as thickness-to-radius ratio and length-to-radius ratio of shell, boundary spring stiffness values, cone apex angle, thickness and width of laminated beams, number of stiffeners on the vibration characteristics of composite laminated rotationally stiffened shell is studied. In theory, it makes up for the vibration characteristics analysis of composite laminated rotationally stiffened shells. In practical application, it guides the noise reduction design of related structures.

Enhancing Electrocatalytic Kinetics via Synergy of Co Nanoparticles and Co/Ni-N4-C- and N-Doped Porous Carbon.

Transition-metal species embedded in carbon have sparked intense interest in the fields of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). However, improvement of the electrocatalytic kinetics remains a challenge caused by the synergistic assembly. Here, we propose a biochemical strategy to fabricate the Co nanoparticles (NPs) and Co/Ni-N4-C co-embedded N-doped porous carbon (CoNPs&Co/Ni-N4-C@NC) catalysts via constructing the zeolitic imidazolate framework (ZIF)@yeast precursor. The rich amino groups provide the possibility for the anchorage of Co2+/Ni2+ ions as well as the construction of Co/Ni-ZIF@yeast through the yeast cell biomineralization effect. The functional design induces the formation of CoNPs and Co/Ni-N4-C sites in N-doped carbon as well as regulates the porosity for exposing such sites. Synergy of CoNPs, Co/Ni-N4-C, and porous N-doped carbon delivered excellent electrocatalytic kinetics (the ORR Tafel slope of 76.3 mV dec-1 and the OER Tafel slope of 80.4 mV dec-1) and a high voltage of 1.15 V at 10 mA cm-2 for the discharge process in zinc air batteries. It provides an effective strategy to fabricate high-performance catalysts.

Deep insight into regulation mechanism of band distribution in phase junction CdS for enhanced photocatalytic H2 production.

An in-depth understanding of structure-activity relationship between the phase constitution and solar-to-hydrogen (STH) conversion efficiency is conducive to guiding the optimization route of targeted photocatalyst candidates, further establishing advanced photocatalytic systems. Herein, based on the concept of phase engineering, we encompassed the crystalline phase of CdS and achieved precise regulation of phase proportion as well as phase boundary width in the phase junction for the first time. The above cooperative effect not only modifies energy band distribution for sufficient redox potentials, but also guarantees the reverse migration orientation of photogenerated carriers in phase junction, thereby endowing photocarriers with a prolonged lifetime. Compared to pure cubic or hexagonal phase (72.6 or 101.1 µmol h-1 g-1), this CdS system with optimized phase junction demonstrates an improved photocatalytic hydrogen evolution activity of 1.04 mmol h-1 g-1 and favorable stability without cocatalyst assistance, which mainly stems from an efficient protons reduction process interacting with long-lived photogenerated electrons. This research explores the mechanism behind phase regulation and its relationship with junction capability, providing a powerful strategy to manipulate crystal phase distribution and paving a feasible avenue for other phase-dependent photocatalysts towards rational design of heterostructures based on different phases in solar energy conversion field.

Large-scale whole-exome sequencing of neuropsychiatric diseases and traits in 350,770 adults.

While numerous genomic loci have been identified for neuropsychiatric conditions, the contribution of protein-coding variants has yet to be determined. Here we conducted a large-scale whole-exome-sequencing study to interrogate the impact of protein-coding variants on 46 neuropsychiatric diseases and 23 traits in 350,770 adults from the UK Biobank. Twenty new genes were associated with neuropsychiatric diseases through coding variants, among which 16 genes had impacts on the longitudinal risks of diseases. Thirty new genes were associated with neuropsychiatric traits, with SYNGAP1 showing pleiotropic effects across cognitive function domains. Pairwise estimation of genetic correlations at the coding-variant level highlighted shared genetic associations among pairs of neurodegenerative diseases and mental disorders. Lastly, a comprehensive multi-omics analysis suggested that alterations in brain structures, blood proteins and inflammation potentially contribute to the gene-phenotype linkages. Overall, our findings characterized a compendium of protein-coding variants for future research on the biology and therapeutics of neuropsychiatric phenotypes.

Assessment of Left Ventricular Longitudinal Systolic Function Using Global Tissue Motion Annular Displacement in Patients with Chronic Severe Aortic Regurgitation.

Background: In patients with chronic aortic regurgitation (AR), the left ventricle (LV) develops compensatory mechanisms to sustain its function. LV global longitudinal strain (GLS) is a key means to detect subclinical LV dysfunction, even when LV ejection fraction (LVEF) remains within the normal range. Compared to GLS, Tissue motion annular displacement (TMAD) is a simpler strain-based method to assess LV systolic function. This study investigated the correlation among TMAD parameters, LVEF, and GLS, and determined the diagnostic value and threshold of TMAD parameters for left ventricular systolic dysfunction. Methods: A prospective study was conducted at a single center. The case and control groups consisted of patients with chronic severe AR and healthy volunteers, respectively. Speckle-tracking echocardiography (STE) was used to assess the GLS and TMAD parameters in the apical 4-chamber and apical 2-chamber. Subsets of participants were analyzed for inter- and intra-observer variability and analysis time. A correlation analysis was performed among the TMAD parameters, LVEF, and GLS. Receiver operating characteristic curves and the area under the curves (AUCs) were used to evaluate the predictive value of the TMAD parameters for LVEF <50% and GLS > -18%. Results: This study involved 96 patients with severe chronic AR and 45 healthy volunteers. Compared to GLS, TMAD demonstrated superior intra- and inter-observer consistency and shorter average analysis time. Biplane global Midpt% showed the highest correlation with GLS and LVEF among all the TMAD parameters, with r values of 0.81 and 0.74, respectively. Furthermore, global Midpt% had AUCs of 0.89 and 0.92 for predicting LVEF< 50% and GLS > -18%, respectively. Conclusion: The TMAD global Midpt% has the potential to replace GLS in clinical practice and find wide applications.

[Seasonal dynamics in photosynthetic characteristics and growth of Cunninghamia lanceolata saplings and their response to soil warming]. / æ‰æœ¨å¹¼æ ‘å ‰åˆç‰¹æ€§ä¸Žç”Ÿé•¿çš„å­£èŠ‚å˜åŒ–åŠå ¶å¯¹åœŸå£¤å¢žæ¸©çš„å“åº”.

In order to understand the response and adaptation mechanisms of photosynthetic characteristics and growth for Cunninghamia lanceolata saplings in the subtropical region to global warming, we conducted the root-box warming experiment (ambient, ambient+4 ℃) at the Sanming Forest Ecosystem National Observation and Research Station in Fujian Province to investigate the effects of soil warming on the photosynthetic characteristics and growth of C. lanceolata saplings in different seasons. The results showed that the net photosynthetic rate (Pn) and stomatal conductance (gs) of C. lanceolata significantly decreased in summer compared with in spring and autumn. Soil warming had no effect on the Pn and gs of C. lanceolata. However, the interaction between warming and season significantly impacted the leaf water use efficiency (WUE). The tree height and ground diameter growth of C. lanceolata significantly increased in spring compared with in summer and autumn. Warming significantly reduced ground diameter growth, and it diminished the net diameter growth by 48.1% in autumn. However, warming had no impact on the tree height growth of C. lanceolata in each season. The specific leaf area, soluble sugar, and non-structural carbohydrates contents of C. lanceolata significantly improved in summer and autumn compared with in spring. Warming had rarely influence on leaf functional traits in each season. In conclusion, the response of photosynthesis for C. lanceolata to soil warming was insignificant. The photosynthesis of C. lanceolata exhibited significant seasonal dynamics, primarily controlled by gs. C. lanceolata adapted to soil warming by adjusting WUE, and it adjusted to high temperatures and drought stress in summer by increasing soluble sugar content and specific leaf area. The effect of warming on ground diameter growth of C. lanceolata was primarily driven by soil moisture. The seasonal difference in the growth of C. lanceolata was influenced by the photosynthesis of C. lanceolata and the trade-off between the utilization and storage of photosynthetic products.

Study of Sintering Behavior of Methane Hydrate Particles on the Wall Surface.

The sintering of hydrate aggregates on the pipe wall is a major form of hydrate deposition. Understanding the sintering behavior of hydrates on the wall is crucial for promoting hydrate safety management and preventing pipeline blockage. However, limited research currently exists on this topic. In this study, the cohesive force strength of hydrate particles on the wall surface under different conditions was directly measured using a high-pressure micromechanical force device (HP-MMF). Subsequently, the effects of subcooling and glycine on the cohesive force were investigated. The results indicate that the cohesive force is influenced by different growth states during the process of free water on the wall surface gradually growing into hydrate. Three states with larger measured values during the growth process were selected for research. Observation showed that increased subcooling strengthened sintering by accelerating the growth rate of the hydrate film, resulting in a significant increase in cohesive force. The role of glycine in the methane hydrate system was then evaluated. Glycine was found to reduce the degree of sintering by reducing the growth rate of the hydrate film, thereby decreasing the cohesive force. The optimal concentration in the system was determined to be 0.25 wt %. Moreover, compared with low subcooling (1 °C), glycine had a better effect at high subcooling (5 °C). At 5 °C subcooling and the optimal concentration, the cohesive force in the wall droplet state decreases from 677.38 to 489.02 mN/m, the cohesive force at the low-saturation state decreases from 951.79 to 543.32 mN/m, and the cohesive force at the high-saturation state decreases from 1194.95 to 641.76 mN/m. These findings contribute to a better understanding of the cohesive force behavior of gas hydrate on the inner wall of the pipeline and provide basic data for reducing the risk of hydrate blockage.

Three­dimensional finite element analysis: Anatomical splint fixation for Colles fractures.

With the rapid development of digital research in clinical orthopedics, the efficacy and safety of splint fixation can be better evaluated through biomechanical analysis based on a three-dimensional (3D) finite element model. It is essential to address the current gap in understanding the biomechanical implications of anatomical splint fixation for Colles fractures. By employing advanced 3D finite element analysis, the present study aimed to provide a comprehensive evaluation, offering valuable insights that can contribute to enhancing the effectiveness of anatomical splint fixation in the clinical management of Colles fractures. The 3D finite element models of the forearm and hand were constructed using Mimics 15.0 according to data from computed tomography of a patient with a Colles fracture. After the validity of the model was verified, the corresponding material properties of the models were adjusted to simulate a Colles fracture. Subsequently, the reduction functions, such as radial inclination and ulnar deviation, of the simulated fracture were completed and the mechanical changes of the tissues surrounding the fracture were calculated. Anatomical splints were then placed on the surfaces of the 3D finite element models of Colles fractures at various positions to analyze the changes in the stress cloud diagram, such as for the soft tissue and anatomical splints. In the present study, the constructed 3D finite element models were accurate and valid. The maximum stress of the anatomical splints and soft tissues was 2.346 and 0.106 MPa in pronation, 1.780 and 0.069 MPa in median rotation and 3.045 and 0.057 MPa in supination, respectively. Splint stress reached the highest level in supination and soft tissue stress achieved the highest level in pronation. The peak of splint stress occurred during supination, which contrasts to the peak of soft tissue stress observed in pronation, suggesting splint fixation median rotation can effectively avoid compression of the local soft tissue.

Rheumatoid Arthritis Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).