Weight-adjusted waist index is an independent predictor of all-cause and cause-specific mortality in patients with asthma.

BACKGROUND: There is a close relationship between obesity and the occurrence of asthma.The weight-adjusted waist index (WWI) is a relatively novel anthropometric parameter that reflects obesity. OBJECTIVE: We aimed to explore the association between WWI and mortality in the asthma population. METHODS: We included adult with asthma from NHANES 1999-2018. WWI = Waist circumference (cm)/square root of body weight (kg). Current asthma was determined by the participant's responses in standardized questionnaires. All-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality information was obtained by prospectively matching these data to the National Death Index. Multivariate-adjusted Cox proportional hazards regression analyses, Kaplan Meier survival analyses, restricted cubic spline (RCS) analyses, stratified analyses, and sensitivity analyses were used to clarify these associations. RESULTS: A total of 101,316 participants were included in the study, and 3223 were diagnosed with asthma.WWI was independently and positively associated with all-cause and all factor-specific mortality in asthma. In fully adjusted models, each unit increase in WWI was associated with 43 % (hazard ratio [HR] and 95 % confidence interval [CI] = 1.43 [1.25,1.64], p < 0.0001), 58 % (1.58 [1.25, 1.99], p < 0.001), 50 % (1.50 [1.19, 1.90], p < 0.001), and 79 % (1.79 [1.34, 2.39], p < 0.0001) increased all-cause, CVD, cancer, and respiratory disease mortality, respectively. RCS analyses showed largely linear associations between WWI and all mortality risks. Stratified analyses indicated that these associations were influenced by multiple factors, and that age was consistently the effect modifier across all associations. CONCLUSIONS: WWI is an independent predictor of all-cause, CVD, cancer, and respiratory-related mortality in the adult asthma population. These findings highlight that WWI may have novel prognostic value as a simple and easily accessible obesity parameter in asthma patients.

L-shaped association between serum chloride levels with 90-day and 365-day all-cause mortality in critically ill patients with COPD: a retrospective cohort study.

This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P < 0.05), accompanied by lower 90-day and 365-day mortality (P < 0.05). Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile after adjusting for confounders (90-day HR = 0.54, 365-day HR = 0.52, both P < 0.05). An L-shape relationship was observed, with risks of death decreasing as serum chloride levels increased, although the magnitude decreased when levels reached 102 mmol/L. This study demonstrated an independent L-shaped association between serum chloride levels and all-cause mortality in critically ill patients with COPD. This finding helps us to understand the prognostic value of serum chloride levels in critically ill patients with COPD.

The oral microbiome and oral and upper gastrointestinal diseases.

Background: Microbiomes are essential components of the human body, and their populations are substantial. Under normal circumstances, microbiomes coexist harmoniously with the human body, but disturbances in this equilibrium can lead to various diseases. The oral microbiome is involved in the occurrence and development of many oral and gastrointestinal diseases. This review focuses on the relationship between oral microbiomes and oral and upper gastrointestinal diseases, and therapeutic strategies aiming to provide valuable insights for clinical prevention and treatment. Methods: To identify relevant studies, we conducted searches in PubMed, Google Scholar, and Web of Science using keywords such as "oral microbiome," "oral flora, " "gastrointestinal disease, " without any date restrictions. Subsequently, the retrieved publications were subject to a narrative review. Results: In this review, we found that oral microbiomes are closely related to oral and gastrointestinal diseases such as periodontitis, dental caries, reflux esophagitis, gastritis, and upper gastrointestinal tumors (mainly the malignant ones). Oral samples like saliva and buccal mucosa are not only easy to collect, but also display superior sample stability compared to gastrointestinal tissues. Consequently, analysis of the oral microbiome could potentially serve as an efficient preliminary screening method for high-risk groups before undergoing endoscopic examination. Besides, treatments based on the oral microbiomes could aid early diagnosis and treatment of these diseases. Conclusions: Oral microbiomes are essential to oral and gastrointestinal diseases. Therapies centered on the oral microbiomes could facilitate the early detection and management of these conditions.

1. Various microbiomes exist in the oral cavity. 2. Under normal circumstances, oral microbes and human health coexist in harmony, once this balance is broken, it may cause a variety of diseases. 3. Oral microbiota are associated with upper digestive diseases, which are expected to be an effective triage for high-risk population before endoscopic screening.

Qufeng tongluo decoction decreased proteinuria in diabetic mice by protecting podocytes via promoting autophagy.

Background: Diabetic kidney disease (DKD) is one of diabetic complications, which has become the leading cause of end-stage kidney disease. In addition to angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker(ACEI/ARB) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), traditional Chinese medicine (TCM) is an effective alternative treatment for DKD. In this study, the effect of Qufeng Tongluo (QFTL) decoction in decreasing proteinuria has been observed and its mechanism has been explored based on autophagy regulation in podocyte. Methods: In vivo study, db/db mice were used as diabetes model and db/m mice as blank control. Db/db mice were treated with QFTL decoction, rapamycin, QFTL + 3-Methyladenine (3-MA), trehalose, chloroquine (CQ) and QFTL + CQ. Mice urinary albumin/creatinine (UACR), nephrin and autophagy related proteins (LC3 and p62) in kidney tissue were detected after intervention of 9 weeks. Transcriptomics was operated with the kidney tissue from model group and QFTL group. In vitro study, mouse podocyte clone-5 (MPC-5) cells were stimulated with hyperglycemic media (30 mmol/L glucose) or cultured with normal media. High-glucose-stimulated MPC-5 cells were treated with QFTL freeze-drying powder, rapamycin, CQ, trehalose, QFTL+3-MA and QFTL + CQ. Cytoskeletal actin, nephrin, ATG-5, ATG-7, Beclin-1, cathepsin L and cathepsin B were assessed. mRFP-GFP-LC3 was established by stubRFP-sensGFP-LC3 lentivirus transfection. Results: QFTL decoction decreased the UACR and increased the nephrin level in kidney tissue and high-glucose-stimulated podocytes. Autophagy inhibitors, including 3-MA and chloroquine blocked the effects of QFTL decoction. Further study showed that QFTL decoction increased the LC3 expression and relieved p62 accumulation in podocytes of db/db mice. In high-glucose-stimulated MPC-5 cells, QFTL decoction rescued the inhibited LC3 and promoted the expression of ATG-5, ATG-7, and Beclin-1, while had no effect on the activity of cathepsin L and cathepsin B. Results of transcriptomics also showed that 51 autophagy related genes were regulated by QFTL decoction, including the genes of ATG10, SCOC, ATG4C, AMPK catalytic subunit, PI3K catalytic subunit, ATG3 and DRAM2. Conclusion: QFTL decoction decreased proteinuria and protected podocytes in db/db mice by regulating autophagy.

Exploiting biochemical data to improve osteosarcoma diagnosis with deep learning.

Early and accurate diagnosis of osteosarcomas (OS) is of great clinical significance, and machine learning (ML) based methods are increasingly adopted. However, current ML-based methods for osteosarcoma diagnosis consider only X-ray images, usually fail to generalize to new cases, and lack explainability. In this paper, we seek to explore the capability of deep learning models in diagnosing primary OS, with higher accuracy, explainability, and generality. Concretely, we analyze the added value of integrating the biochemical data, i.e., alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and design a model that incorporates the numerical features of ALP and LDH and the visual features of X-ray imaging through a late fusion approach in the feature space. We evaluate this model on real-world clinic data with 848 patients aged from 4 to 81. The experimental results reveal the effectiveness of incorporating ALP and LDH simultaneously in a late fusion approach, with the accuracy of the considered 2608 cases increased to 97.17%, compared to 94.35% in the baseline. Grad-CAM visualizations consistent with orthopedic specialists further justified the model's explainability.

Multiscale Structural Engineering Boosts Piezoelectricity in Na0.5Bi2.5Nb2O9-Based High-Temperature Piezoceramics.

High-temperature piezoelectric materials, which enable the accurate and reliable sensing of physical parameters to guarantee the functional operation of various systems under harsh conditions, are highly demanded. To this end, both large piezoelectricity and high Curie temperature are pivotal figures of merit (FOMs) for high-temperature piezoceramics. Unfortunately, despite intensive pursuits, it remains a formidable challenge to unravel the inverse correlation between these FOMs. Herein, a conceptual material paradigm of multiscale structural engineering was proposed to address this dilemma. The synergistic effects of phase structure reminiscent of a polymorphic phase boundary and refined domain morphology simultaneously contribute to a large piezoelectric coefficient d33 of 30.3 pC/N and a high Curie temperature TC of 740 °C in (LiCeNd) codoped Na0.5Bi2.5Nb2O9 (NBN-LCN) ceramics. More encouragingly, the system has exceptional thermal stability and is nonsusceptible to mechanical loading. This study not only demonstrates that the high-performance and robust NBN-LCN high-temperature piezoceramics hold great potential for implements under harsh conditions but also opens an avenue for integrating antagonistic properties for the enhancement of the collective performance in functional materials.

Evolution of groundwater system in the Pearl River Delta and its adjacent shelf since the late Pleistocene.

Our extensive field studies demonstrate that saline groundwater inland and freshened groundwater offshore coexist in the same aquifer system in the Pearl River delta and its adjacent shelf. This counterintuitive phenomenon challenges the commonly held assumption that onshore groundwater is typically fresh, while offshore groundwater is saline. To address this knowledge gap, we conduct a series of sophisticated paleo-hydrogeological models to explore the formation mechanism and evolution process of the groundwater system in the inland-shelf systems. Our findings indicate that shelf freshened groundwater has formed during the lowstands since late Pleistocene, while onshore saline groundwater is generated by paleo-seawater intrusion during the Holocene transgression. This reveals that terrestrial and offshore groundwater systems have undergone alternating changes on a geological timescale. The groundwater system exhibits hysteresis responding to paleoclimate changes, with a lag of 7 to 8 thousand years, suggesting that paleoclimatic forcings exert a significantly residual influence on the present-day groundwater system.

Association between dietary inflammation index and asthma COPD overlap.

There are few studies on the relationship between dietary habits and asthma-COPD overlap (ACO). In this study, we aimed to investigate the association between dietary inflammation index (DII) score and ACO. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. The DII score was first calculated and the demographic characteristics of the grouping based on the DII quartile were assessed. The weighted logistic regression model was used to study the relationship between DII and ACO. Subgroup analysis was used to further explore the differences in different subgroups. Restricted cubic spline (RCS) plot was used to show the general trend of DII score and disease risk, and threshold effect analysis was used to determine the inflection point. In a comparison of baseline characteristics, the highest ACO prevalence was found in the fourth quartile array of people in DII. An adjusted weighted logistic regression model showed that DII was positively correlated with the incidence of ACO. Subgroup analysis showed that the association was more pronounced in women, non-Hispanics, people with cardiovascular disease, and people without diabetes. The RCS graph shows that overall, the risk of ACO increases with the increase of DII score. Threshold effect analysis showed that the inflection point was 3.779, and the risk was more significant after the DII score was greater than the inflection point value (OR 2.001, 95% CI 1.334-3.001, P < 0.001). Higher DII scores were positively associated with ACO risk. These results further support diet as an intervention strategy for ACO prevention and treatment.

Enhancement of autophagy can alleviate oxidative stress, inflammation, and apoptosis induced by ammonia stress in yellow catfish Pelteobagrus fulvidraco.

Ammonia in aquatic environments is toxic to fish, directly impacting their growth performance and development. Activation of autophagy can facilitate intracellular component renewal and enhance an organism's adaptability to adverse environments. Therefore, this study investigates the impact of autophagy on the yellow catfish under acute ammonia stress. In this study, the yellow catfish intraperitoneally injected with 0.9 % sodium chloride were placed with 0 (CON group) and 125 (HA group) mg/L T-AN (Total ammonia nitrogen) dechlorinated water. The yellow catfish intraperitoneally injected with 30 mg/kg fish CQ (Chloroquine, HA + CQ group) and 1.5 mg/kg fish RAPA (rapamycin, HA + RAPA group) were placed in dechlorinated water containing 125 mg/L T-AN. The results showed that activation of autophagy by injecting with RAPA can alleviate oxidative stress (catalase, superoxide dismutase, total antioxidant capacity significantly increased, H2O2 content significantly decreased), and inflammatory response (pro-inflammatory factors TNF-α, MyD88, IL 1-ß gene expression decreased significantly), apoptosis (baxa, Bcl2, Tgf-ß, Smad2, Caspase3, Caspase 9 gene expression decreased significantly) induced by ammonia stress. In addition, activation of autophagy in yellow catfish can enhance ammonia detoxification by promoting the urea cycle and synthesis of glutamine (the mRNA level of CPS Ⅰ, ARG, OTC, ASS, ASL, and GS increased in the HA + RAPA group). The data above demonstrates that activating autophagy can alleviate oxidative stress, inflammatory responses, and cell apoptosis induced by ammonia stress. Therefore, enhancing autophagy is proposed as a potential strategy to mitigate the detrimental impacts of ammonia stress on yellow catfish.

Contribution of irreversible non-180° domain to performance for multiphase coexisted potassium sodium niobate ceramics.

Despite the dominance of lead-based piezoelectric materials with ultrahigh electric-field-induced strain in actuating applications, seeking eco-friendly substitutes with an equivalent performance remains an urgent demand. Here, a strategy of regulating the irreversible non-180° domain via phase engineering is introduced to optimize the available strain (the difference between the maximum strain and the remnant strain in a unipolar strain curve) in the lead-free potassium-sodium niobate-based piezoelectric ceramics. In situ synchrotron X-ray diffraction and Rayleigh analysis reveal the contribution of the non-180° domain to available strain in the tetragonal-orthorhombic-rhombohedral phase boundary. The reducing orthorhombic phase and increasing rhombohedral/tetragonal phase accompanied by the reduced irreversible non-180° domain are obtained with increasing doping of Sb5+, resulting in an enlarged available strain due to the significantly lowered remnant strain. This optimization is mainly attributed to the reduced irreversible non-180° domain wall motion and the increased lattice distortion, which are beneficial to decrease extrinsic contribution and enhance intrinsic contribution. The mesoscopic structure of miniaturized nanosized domain with facilitated domain switching also contributes to the enhancement of available strain due to the improved random field and decreased energy barrier. The study will shed light on the design of lead-free high-performance piezoelectric ceramics for actuator applications.

Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR-II Fluorescence Imaging.

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

Ultraflexible, High-Performance Transistors and Logic Circuits on Biocompatible Polylactic Acid (PLA) Substrate.

Wearable and implantable devices have gained significant popularity, playing a crucial role in smart healthcare and human-machine interfaces, which necessitates the development of more complex electronic devices and circuits on biocompatible flexible materials. Polylactic acid (PLA) stands out due to its biodegradability, cost-effectiveness, and low immunogenicity. In this study, we utilize a solution-based spin-coating method to produce high-quality PLA thin films, serving as substrates for the fabrication of thin-film transistors (TFTs) in which the dielectric layer material is silicon dioxide, the channel layer material is IGZO, and the gate, drain, and source material is ITO at low temperatures (<40 °C) through a shadow masking technique. The resulting PLA-TFT devices exhibited remarkable flexibility, biocompatibility, and impressive electrical characteristics, including a charge carrier mobility of 27.81 cm2/(V s), a subthreshold swing of 162.8 mV/decade, and an ON/OFF current ratio of up to 1 × 106, and maintained performance under various deformations. We successfully constructed fundamental logic gate circuits using PLA-TFTs, including AND, OR, and NOT gates, which effectively performed logical functions and demonstrated stability under diverse bending conditions. These research findings provide valuable support for future endeavors in fabricating intricate logic circuits and realizing advanced functionalities on biocompatible flexible materials.

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).

Textured Potassium Sodium Niobate Lead-Free Ceramics with High d33 and Qm for Meeting High-Power Applications.

Potassium sodium niobate (KNN) lead-free piezoceramics have garnered significant attention for their environmentally friendly attributes, desired piezoelectric activity (d33), and high Curie temperature (Tc). However, the limited applicability of most KNN systems in high-power apparatus, including ultrasonic motors, transformers, and resonators, persists due to the inherent low mechanical quality factor (Qm). Herein, we proposed an innovative strategy for achieving high Qm accompanied by desirable d33 via synergistic chemical doping and texturing in KNN piezoceramics. Comprehensive electrical measurements along with quantitative structural characterization at multilength scales reveal that the excellent electromechanical properties (kp = 0.58, d33 ∼ 134 pC·N-1, Qm = 582, and Tc ∼ 415 °C) originate from the high <001> texturing degree, nanodomain, as well as acceptor hardening. Our findings provide an insight and guidance for achieving high-power performance in lead-free KNN-based piezoceramics, which were expected to be used in advanced transducer technology.

Few-Shot Medical Image Segmentation via Generating Multiple Representative Descriptors.

Automatic medical image segmentation has witnessed significant development with the success of large models on massive datasets. However, acquiring and annotating vast medical image datasets often proves to be impractical due to the time consumption, specialized expertise requirements, and compliance with patient privacy standards, etc. As a result, Few-shot Medical Image Segmentation (FSMIS) has become an increasingly compelling research direction. Conventional FSMIS methods usually learn prototypes from support images and apply nearest-neighbor searching to segment the query images. However, only a single prototype cannot well represent the distribution of each class, thus leading to restricted performance. To address this problem, we propose to Generate Multiple Representative Descriptors (GMRD), which can comprehensively represent the commonality within the corresponding class distribution. In addition, we design a Multiple Affinity Maps based Prediction (MAMP) module to fuse the multiple affinity maps generated by the aforementioned descriptors. Furthermore, to address intra-class variation and enhance the representativeness of descriptors, we introduce two novel losses. Notably, our model is structured as a dual-path design to achieve a balance between foreground and background differences in medical images. Extensive experiments on four publicly available medical image datasets demonstrate that our method outperforms the state-of-the-art methods, and the detailed analysis also verifies the effectiveness of our designed module.

Association between dietary antioxidant intakes and chronic respiratory diseases in adults.

Background: Chronic respiratory diseases (CRDs) pose a significant global health burden. Antioxidant-rich diets have been associated with improved lung health, but the specific relationship with CRDs remains unclear. Methods: This study examined the relationship between dietary antioxidant intakes and CRDs using data from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). Information on dietary antioxidant intakes, including vitamins A, C, and E, zinc, selenium, and carotenoid, were collected from the 2 24-h recall interviews to calculate composite dietary antioxidant index (CDAI). CRDs were determined based on self-reported physician diagnoses. To examine the relationship between CDAI and CRDs, multivariate logistic regression was used. To study potential non-linear correlations within these associations, restricted cubic spline (RCS) regression was performed. Results: The study involved 40 557 individuals. The median CDAI was -0.09 (-2.05, 2.25). We discovered those who were in the fourth quartile of CDAI scores had a 19% lower prevalence than those in the first quartile (OR = 0.81 [0.72-0.91], Ptrend < 0.01) after adjusting for all relevant covariates. The fourth quartile of CDAI was linked with a lower prevalence of emphysema (OR = 0.57 [0.40-0.81], Ptrend < 0.01) and chronic bronchitis (OR = 0.74 [0.62-0.88], Ptrend < 0.01). RCS regression showed that CDAI was non-linearly related to the prevalence of CRDs, with inflection points of 3.20 (P for non-linearity <0.01). The stratified analysis did not identify variables that significantly affected the results. Conclusion: Higher dietary antioxidant intakes were related with a lower prevalence of CRDs (particularly emphysema and chronic bronchitis) in general adults.

A Prospective, Multicentered, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Keluoxin Capsules in the Treatment of Microalbuminuria in Patients with Type 2 Early Diabetic Kidney Disease.

Background: To evaluate the efficacy and safety of Keluoxin (KLX) capsules and provide validated evidence for the application of KLX in the treatment of diabetic kidney disease (DKD). Methods: A multicenter, randomized, double-blind, placebo-controlled trial design was used to screen 129 patients with DKD (urinary albumin-to-creatinine ratio [UACR]: male, 2.5-30 mg/mmol; female, 3.5-30 mg/mmol) and with Qi and Yin deficiency and blood stasis symptoms. Written informed consent was obtained from all patients. The patients were randomly divided into KLX and control groups. The KLX group was orally administered KLX (6 g/day) and irbesartan tablets (150 mg/day), whereas the control group was administered KLX placebo (6 g/day) and irbesartan tablets (150 mg/day). Patients were observed for 24 weeks to evaluate the natural logarithm of the UACR (log-UACR), the odds ratio (OR) for a sustained increase in the UACR of at least 30% and 40%, estimated glomerular filtration rate (eGFR), changes in symptoms and quality-of-life scores, and adverse events. Results: The changes of the natural log-UACR during the 24 weeks compared with baseline in the KLX group were better than those in the control group (LS mean ± standard error, -0.26 ± 0.10 vs. 0.01 ± 0.09, p = 0.0292). The incidence of a sustained increase in the UACR of at least 30% and 40% was found to be significantly lower in the KLX group (OR, 0.26; 95% confidence interval [CI], 0.09-0.75; OR, 0.29; 95% CI, 0.10-0.82). Changes in symptoms and quality-of-life scores in the KLX group were better than those in the control group. There was no statistically significant difference in eGFR or the incidence of adverse events between the groups. Conclusions: Overall, these results suggest that KLX capsules combined with irbesartan can reduce microalbuminuria, relieve the symptoms, and improve the quality of life for patients with type 2 early DKD compared with the use of irbesartan alone. Trial registration: Chinese Clinical Trial Registry, registration number: ChiCTR2100052764.

Helicobacter pylori promotes gastric fibroblast proliferation and migration by expulsing exosomal miR-124-3p.

Gastric fibroblasts (GFs) are direct targets of Helicobacter pylori (H. pylori). GFs infected with H. pylori exhibit marked changes in their morphology and biological behavior. However, the molecular mechanisms by which H. pylori regulates GFs remain unknown. In this study, we cocultured GFs with H. pylori for 48 h. As a result, GFs exhibited an elongated and spindle-shaped morphology. Further, cancer-associated fibroblast (CAF) biomarkers were increased, and related behaviors were significantly enhanced in H. pylori-activated GFs. The number of extracellular vesicles (EVs) secreted by H. pylori-activated GFs remarkably increased. The miR-124-3p level was increased in secreted EVs but decreased in the cytoplasm of H. pylori-activated GFs. Overexpression of miRNA-124-3p in the original GFs significantly suppressed their proliferation and migration. In addition, the migration-promoting effects of H. pylori-activated GFs were suppressed by miR-124-3p and GW4869, which blocked EV generation. Finally, pull-down and luciferase assays revealed that SNAI2 is a target of miR-124-3p. The migration-inhibitory effects of GFs treated with miR-124-3p were eliminated by the overexpression of SNAI2, and the upregulation of SNAI2 in H. pylori-activated GFs was partially alleviated by miR-124-3p or GW4869. Overall, H. pylori infection promotes the proliferation and migration of GFs by accelerating the expulsion of EVs carrying miRNA-124-3p, a SNAI2 inhibitor.