Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

High-enhancement photoluminescence of monolayer MoS2 in hybrid plasmonic systems.

Monolayer molybdenum disulfide (M o S 2) has a weak light-matter interaction due to ultrathin thickness, which limits its potential application in lasing action. In this study, we propose a hybrid structure consisting of a nanocavity and Au nanoparticles to enhance the photon emission efficiency of monolayer M o S 2. Numerical simulations show that photoluminescence (PL) emission is significantly enhanced by introducing localized surface plasmon resonance (LSPR) to the proposed structure. Furthermore, an exciton energy band system is proposed to elucidate the physical mechanism of the PL process. By optimizing the spacer thickness, a high Purcell enhancement factor of 95 can be achieved. The results provided by this work pave the way to improve the PL efficiency of two-dimensional (2D) material, which constitutes a significant step towards the development of nanodevices such as nanolasers and sensors.

Co-occurring EGFR p.E709X mutation Mediates Primary Resistance to the Third-generation EGFR-TKIs in EGFR p.G719X-mutant Patients with Advanced NSCLC.

PURPOSE: Current NCCN guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in the absence of head-to-head trials comparing afatinib with osimertinib in EGFR p.G719X mutant patients, it is unclear which regimen is the preferred treatment option. EXPERIMENTAL DESIGN: A large cohort of 4228 treatment-naïve patients with lung cancer who underwent targeted NGS testing was screened for EGFR p.G719X mutation. A multicenter cohort involving 68 EGFR p.G719X-mutant patients with advanced NSCLC and NGS profiling was retrospectively enrolled to evaluate clinical responses to afatinib(n=37) and the third-generation EGFR-TKIs(n=31). Ba/F3 cells stably expressing the EGFR p.G719A mutation were created to investigate the response to EGFR-TKIs in vitro. RESULTS: Concurrent EGFR p.E709X mutations, being the most frequent co-occurring EGFR mutation in EGFR p.G719X-mutant NSCLC(~30%), exerted a detrimental effect on outcomes in patients treated with third-generation EGFR-TKI(G719X/E709X vs. G719X; ORR:0.00% vs. 47.62%, P<0.001; mPFS:7.18 vs. 14.2 months, P=0.04; respectively). Conversely, no significant difference was found in the treatment efficacy of afatinib between EGFR p.G719X/E709X and EGFR p.G719X patients(G719X/E709X vs. G719X; ORR:71.43% vs. 56.67%, P=0.99; mPFS:14.7 vs. 15.8 months, P=0.69; respectively). In vitro experiments elucidated a resistant drug sensitivity and poor inhibition of EGFR phosphorylation in Ba/F3 cells expressing EGFR p.G719A/E709K mutation upon the third-generation EGFR-TKIs treatment. CONCLUSION: Co-occurring EGFR p.E709X mutation mediates primary resistance to the third-generation EGFR-TKIs in EGFR p.G719X-mutant patients but remained sensitive to afatinib. A personalized treatment strategy should be undertaken based on the co-existing EGFR p.E709X mutation status.

Androgen loss weakens anti-tumor immunity and accelerates brain tumor growth.

Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity. Here, we show that androgens drive anti-tumor immunity in brain tumors, in contrast to its effect in other tumor types. Upon castration, tumor growth was accelerated with attenuated T cell function in GBM and brain tumor models, but the opposite was observed when tumors were located outside the brain. Activity of the hypothalamus-pituitary-adrenal gland (HPA) axis was increased in castrated mice, particularly in those with brain tumors. Blockade of glucocorticoid receptors reversed the accelerated tumor growth in castrated mice, indicating that the effect of castration was mediated by elevated glucocorticoid signaling. Furthermore, this mechanism was not GBM specific, but brain specific, as hyperactivation of the HPA axis was observed with intracranial implantation of non-GBM tumors in the brain. Together, our findings establish that brain tumors drive distinct endocrine-mediated mechanisms in the androgen-deprived setting and highlight the importance of organ-specific effects on anti-tumor immunity.

Clinical characteristics and prognostic implications of immune-related hepatitis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a retrospective study.

Background: With the widespread use of immune checkpoint inhibitors (ICIs), patients inevitably experience immune-related adverse events (irAEs). Therefore, the study was conducted on the clinical characteristics and outcomes of patients with non-small cell lung cancer (NSCLC) with immune-related hepatitis (ir-hepatitis). Methods: We identified patients with advanced NSCLC who developed ir-hepatitis after immunotherapy between June 2016 and December 2022. Their irAEs were categorized according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE 4.03). Kaplan-Meier curves and log-rank tests were used to analyze survival. Results: A total of 35 patients were enrolled in the study. The numbers of mild (grade 1-2) and severe (grade 3-4) ir-hepatitis cases were 13 (grade 1, 3; grade 2, 10) and 22 (grade 3, 17; grade 4, 5), respectively. The median onset time of ir-hepatitis was 1.6 months. The median progression-free survival (mPFS) was 8.3 months. PFS differed between patients with early ir-hepatitis developing within two treatment cycles and those with ir-hepatitis developing more than two treatment cycles (5.5 vs. 12.7 months, P=0.004). Patients with severe rather than mild ir-hepatitis tended to poorer PFS survival (5.8 vs. 11.2 months, P=0.130). The appearance of ir-hepatitis within two treatment cycles (P=0.002) and higher severity grades of ir-hepatitis (P=0.005) were independent risk factors for PFS. Conclusions: Early and severe ir-hepatitis are associated with worse survival benefits, which still required more basic and perspective studies.

Exploration of efficacy of different therapy regimens for advanced NSCLC patients with KRAS mutation in the first-line treatment.

PURPOSE: The treatment of the advanced non-small cell lung cancer (NSCLC) with KRAS mutation has been closely paid more attention. The aim of this study is to investigate the efficacy of different first-line regimens in advanced KRAS-mutated non-small cell lung cancer. METHODS: In our retrospective study, we collected patients with advanced NSCLC with KRAS mutation in Zhejiang Cancer Hospital between January 2015 and May 2023. We analyzed the benefit of different first-line therapy according to theraputic methods and the differential effect of the same treatment method among KRAS-mutated subtypes. We divided the patients into group A (A1, chemotherapy alone; A2, immunotherapy alone) and group B (B1, chemotherapy plus immunotherapy; B2, chemotherapy combined with antiangiogenic therapy; B3, chemotherapy combined with immunotherapy plus antiangiogenic therapy). The Kaplan-Meier survival curve was used to reflect the PFS and OS of different methods. The objective response rate (ORR) and the disease control rate (DCR) were used to evaluated the response. RESULTS: We enrolled 227 patients including eighty-two with KRAS G12C mutation. The ORR and DCR of first-line treatment in the overall population were 32.2% and 80.6% respectively. The median PFS was 6.7 months and the median OS was 17.4 months for the overall population. The PFS of the Group B was significantly better than that of the Group A (7.7 months vs 5.4 months, P = 0.003), while no significant difference in OS was observed (19.4 months vs 15.0 months, P = 0.077). In the Group B, chemotherapy combined immunotherapy with antiangiogenic therapy showed better PFS than chemotherapy plus immunotherapy (14.1 months vs 7.7 months, P = 0.049), and OS also showed that tendency of difference (31.9 months vs 19.3 months, P = 0.158). There was no statistically significant difference between KRAS G12C and non-G12C mutation according to first-line treatment methods, whereas patients with TP53 co-mutation showed a better survival benefit (OS, 23.7 vs 12.5 months, P = 0.023). CONCLUSION: In the first-line treatment, combination regimen has advantages over single regimen. Among them, chemotherapy combined with immunotherapy plus antiangiogenic therapy can achieve significant efficacy benefits.

Photosensitized 1,2-Difunctionalization of Alkenes to Access ß-Amino Sulfonamides.

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse ß-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of ß-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

Usefulness of KIT mutant transcript levels for monitoring measurable residual disease in t (8;21) acute myeloid leukemia.

In addition to RUNX1::RUNX1T1 transcript levels, measurable residual disease monitoring using KIT mutant (KITmut ) DNA level is reportedly predictive of relapse in t (8; 21) acute myeloid leukemia (AML). However, the usefulness of KITmut transcript levels remains unknown. A total of 202 bone marrow samples collected at diagnosis and during treatment from 52 t (8; 21) AML patients with KITmut (D816V/H/Y or N822K) were tested for KITmut transcript levels using digital polymerase chain reaction. The individual optimal cutoff values of KITmut were identified by performing receiver operating characteristics curve analysis for relapse at each of the following time points: at diagnosis, after achieving complete remission (CR), and after Course 1 and 2 consolidations. The cutoff values were used to divide the patients into the KITmut -high (KIT_H) group and the KITmut -low (KIT_L) group. The KIT_H patients showed significantly lower relapse-free survival (RFS) and overall survival (OS) rates than the KIT_L patients after Course 1 consolidation (p = 0.0040 and 0.021, respectively) and Course 2 consolidation (p = 0.018 and 0.011, respectively) but not at diagnosis and CR. The <3-log reduction in the RUNX1::RUNX1T1 transcript levels after Course 2 consolidation was an independent adverse prognostic factor for RFS and OS. After Course 2 consolidation, the KIT_H patients with >3-log reduction in the RUNX1::RUNX1T1 transcript levels (11/45; 24.4%) had similar RFS as that of patients with <3-log reduction in the RUNX1::RUNX1T1 transcript levels. The combination of KITmut and RUNX1::RUNX1T1 transcript levels after Course 2 consolidation may improve risk stratification in t (8; 21) AML patient with KIT mutation.

Targeting the intracellular neurexin interactome by in vivo proximity ligation.

In a recent study, Profes, Tiroumalechetty, and colleagues used the in vivo proximity ligation technique TurboID to scrupulously characterize the interactome of the intracellular domain (ICD) of neurexin, revealing that this domain may be involved in presynaptic actin assembly by interacting with actin-associated proteins.

Bosea beijingensis sp. nov., Telluria beijingensis sp. nov. and Agrococcus beijingensis sp. nov., isolated from baijiu mash.

The baijiu fermentation environment hosts a variety of micro-organisms, some of which still remain uncultured and uncharacterized. In this study, the isolation, cultivation and characterization of three novel aerobic bacterial strains are described. The cells of strain REN20T were Gram-negative, strictly aerobic, motile and grew at 26-37 °C, at pH 6.0-9.0 and in the presence of 0-5.0   % (w/v) NaCl. The cells of strain REN29T were Gram-negative, strictly aerobic, motile and grew at 15-30 °C, at pH 6.0-9.0 and in the presence of 0-10.0   % (w/v) NaCl. The cells of strain REN33T were Gram-positive, strictly aerobic, motile and grew at 15-37 °C, at pH 5.0-10.0 and in the presence of 0-7.0   % (w/v) NaCl. The digital DNA-DNA hybridization and average nucleotide identity by orthology values between type strains in related genera and REN20T (20.3-36.8 % and 79.8-89.9  %), REN29T (20.3-36.8  % and 74.5-88.5  %) and REN33T (22.6-48.6  % and 75.8-84.2  %) were below the standard cut-off criteria for the delineation of bacterial species, respectively. Based on polyphasic taxonomy analysis, we propose three new species, Bosea beijingensis sp. nov. (=REN20T=GDMCC 1.2894T=JCM 35118T), Telluria beijingensis sp. nov. (=REN29T=GDMCC 1.2896T=JCM 35119T) and Agrococcus beijingensis sp. nov. (=REN33T=GDMCC 1.2898T=JCM 35164T), which were recovered during cultivation and isolation from baijiu mash.

Tunable double notch filter on a thin-film lithium niobate platform.

Tunable optical filters at the chip scale play a crucial role in fulfilling the need for reconfigurability in channel routing, optical switching, and wavelength division multiplexing systems. In this Letter, we propose a tunable double notch filter on thin-film lithium niobate using dual microring architecture. This unique integrated filter is essential for complex photonic integrated circuits, along with multiple channels and various frequency spacing. With only one loaded voltage, the device demonstrates a wide frequency spacing tunability from 16.1 to 89.9 GHz by reversely tuning the resonances of the two microrings while the center wavelength between the two resonances remains unaltered. Moreover, by utilizing the pronounced electro-optic properties of lithium niobate associated with the tight light confined nanophotonic waveguides, the device demonstrates a spacing tunability of 0.82 GHz/V and a contrast of 10-16 dB. In addition, the device has an ultracompact footprint of 0.0248 mm2.

CyanoStrainChip: A Novel DNA Microarray Tool for High-Throughput Detection of Environmental Cyanobacteria at the Strain Level.

Detecting cyanobacteria in environments is an important concern due to their crucial roles in ecosystems, and they can form blooms with the potential to harm humans and nonhuman entities. However, the most widely used methods for high-throughput detection of environmental cyanobacteria, such as 16S rRNA sequencing, typically provide above-species-level resolution, thereby disregarding intraspecific variation. To address this, we developed a novel DNA microarray tool, termed the CyanoStrainChip, that enables strain-level comprehensive profiling of environmental cyanobacteria. The CyanoStrainChip was designed to target 1277 strains; nearly all major groups of cyanobacteria are included by implementing 43,666 genome-wide, strain-specific probes. It demonstrated strong specificity by in vitro mock community experiments. The high correlation (Pearson's R > 0.97) between probe fluorescence intensities and the corresponding DNA amounts (ranging from 1-100 ng) indicated excellent quantitative capability. Consistent cyanobacterial profiles of field samples were observed by both the CyanoStrainChip and next-generation sequencing methods. Furthermore, CyanoStrainChip analysis of surface water samples in Lake Chaohu uncovered a high intraspecific variation of abundance change within the genus Microcystis between different severity levels of cyanobacterial blooms, highlighting two toxic Microcystis strains that are of critical concern for Lake Chaohu harmful blooms suppression. Overall, these results suggest a potential for CyanoStrainChip as a valuable tool for cyanobacterial ecological research and harmful bloom monitoring to supplement existing techniques.

Dual inhibitors of DNMT and HDAC induce viral mimicry to induce antitumour immunity in breast cancer.

The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo. Mechanistically, 15a induces a viral mimicry response by promoting the expression of endogenous retroviral elements in breast cancer cells, thus increasing the intracellular level of double-stranded RNA to activate the RIG-I-MAVS pathway. This in turn promotes the production of interferons and chemokines and augments the expression of interferon-stimulated genes and PD-L1. The combination of 15a and an anti-PD-L1 antibody had an additive effect in vivo. These findings indicate that this DNMT/HDACi has immunomodulatory functions and enhances the effectiveness of immune checkpoint blockade therapy. A novel dual DNMT and HDAC inhibitor induces viral mimicry, which induces the accumulation of dsRNA to activate tumoral IFN signalling and cytokine production to enhance the immune response in breast cancer.

Capacitive Pressure Sensor Combining Dual Dielectric Layers with Integrated Composite Electrode for Wearable Healthcare Monitoring.

Foot activity can reflect numerous physiological abnormalities in the human body, making gait a valuable metric in health monitoring. Research on flexible sensors for gait monitoring has focused on high sensitivity, wide working range, fast response, and low detection limit, but challenges remain in areas such as elasticity, antibacterial activity, user-friendliness, and long-term stability. In this study, we have developed a novel capacitive pressure sensor that offers an ultralow detection limit of 1 Pa, wide detection ranges from 1 Pa to 2 MPa, a high sensitivity of 0.091 kPa-1, a fast response time of 71 ms, and exceptional stability over 6000 cycles. This sensor not only has the ability of accurately discriminating mechanical stimuli but also meets the requirements of elasticity, antibacterial activity, wearable comfort, and long-term stability for gait monitoring. The fabrication method of a dual dielectric layer and integrated composite electrode is simple, cost-effective, stable, and amenable to mass production. Thereinto, the introduction of a dual dielectric layer, based on an optimized electrospinning network and micropillar array, has significantly improved the sensitivity, detection range, elasticity, and antibacterial performance of the sensor. The integrated flexible electrodes are made by template method using composite materials of carbon nanotubes (CNTs), two-dimensional titanium carbide Ti3C2Tx (MXene), and polydimethylsiloxane (PDMS), offering synergistic advantages in terms of conductivity, stability, sensitivity, and practicality. Additionally, we designed a smart insole that integrates the as-prepared sensors with a miniature instrument as a wearable platform for gait monitoring and disease warning. The developed sensor and wearable platform offer a cutting-edge solution for monitoring human activity and detecting diseases in a noninvasive manner, paving the way for future wearable devices and personalized healthcare technologies.

Progress of studies on natural products for glioblastoma therapy.

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.

Surgical management of chronic Achilles tendon rupture: evidence-based guidelines.

BACKGROUND: Chronic Achilles tendon ruptures (CATR) often require surgical intervention to restore function. Despite numerous treatment modalities available, the optimal management strategy remains controversial given the limited high-quality evidence available. This article aims to provide evidence-based guidelines for the surgical management of CATR through a comprehensive systematic review of the available data. The consensus reached by synthesizing the findings will assist clinicians in making informed decisions and improving patient outcomes. METHODS: A group of 9 foot surgeons in three continents was consulted to gather their expertise on guidelines regarding the surgical management of CATR. Following the proposal of 9 clinical topics, a thorough and comprehensive search of relevant literature published since 1980 was conducted for each topic using electronic databases, including PubMed, MEDLINE, and Cochrane Library, to identify relevant studies published until 1 October 2023. All authors collaborated in drafting, discussing, and finalizing the recommendations and statements. The recommendations were then categorized into two grades: grade a (strong) and grade b (weak), following the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) concept. Additionally, feedback from 21 external specialists, who were independent from the authors, was taken into account to further refine and finalize the clinical guidelines. RESULTS: Nine statements and guidelines were completed regarding surgical indications, surgical strategies, and postoperative rehabilitation protocol. CONCLUSION: Based on the findings of the systematic review, this guideline provides recommendations for the surgical management of CATR. We are confident that this guideline will serve as a valuable resource for physicians when making decisions regarding the surgical treatment of patients with CATR.

A noncoding role of coding mRNA in monogenic olfactory receptor choice.

In a recent study, Pourmorady and colleagues uncovered a noncoding role for olfactory receptor (OR)-coding mRNA in mediating nuclear architecture and singular OR choice. The OR mRNAs reinforce the prevailing enhancer hub and inhibit other competitors, facilitating transition from polygenic to singular OR expression.

Comparison of the efficacy and safety of anlotinib monotherapy or anlotinib plus immune checkpoint inhibitor for advanced small cell lung cancer with brain metastases.

BACKGROUND: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. METHOD: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. RESULTS: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy. CONCLUSION: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.

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).