Deep Learning Analysis for Predicting Tumor Spread through Air Space in Early-Stage Lung Adenocarcinoma Pathology Images.

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

Optimization of Ultrasound-Assisted Deep Eutectic Solvent Extraction, Characterization, and Bioactivities of Polysaccharide from Pericarpium Citri Reticulatae.

The ultrasonic-assisted deep eutectic solvent method was used to extract the polysaccharides of Pericarpium Citri Reticulatae (PCRP), and the ultrasound-assisted DES extraction process was optimized by Box-Behnken response surface test using the extraction rate of the PCRP as an index; the in vitro activities of purified the PCRP(PCRPs-1) were investigated by determining the scavenging rate of DPPH• and ABTS•+ as well as by enzyme inhibition assay. The monosaccharide composition was analyzed by HPLC. The best process conditions for response surface optimization were a material-liquid ratio of 1:37 g/mL, water content of 44%, time of 89 min, and power of 320 W. The polysaccharide extraction rate was measured to be 5.41%, which was well optimized when compared with that of the ordinary aqueous extraction method of 3.92%. By α-glucosidase and α-amylase inhibition activity test, it showed that the PCRPs-1 had hypoglycemic activity. The DPPH radical scavenging activity test and ABTS + scavenging activity test indicated that the PCRPs-1 had good biological activity. Analysis of the monosaccharide fractions showed that the PCRPs-1 consisted of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose, and arabinose, with molar ratios of 1:39.24:4.41:8.91:7.83:86.00:1.02:9.17. The activity studies showed that PCRPs-1 possessed certain hypoglycaemic and antioxidant activities.

Van der Waals Epitaxial Growth of Ultrathin Indium Antimonide on Arbitrary Substrates through Low-Thermal Budget.

III-V semiconductors possess high mobility, high frequency response, and detection sensitivity, making them potentially attractive for beyond-silicon electronics applications. However, the traditional heteroepitaxy of III-V semiconductors is impeded by a significant lattice mismatch and the necessity for extreme vacuum and high temperature conditions, thereby impeding their in situ compatibility with flexible substrates and silicon-based circuits. In this study, a novel approach is presented for fabricating ultrathin InSb single-crystal nanosheets on arbitrary substrates with a thickness as thin as 2.4 nm using low-thermal-budget van der Waals (vdW) epitaxy through chemical vapor deposition (CVD). In particular, in situ growth has been successfully achieved on both silicon-based substrates and flexible polyimide (PI) substrates. Notably, the growth temperature required for InSb nanosheets (240 °C) is significantly lower than that employed in back-end-of-line processes (400 °C). The field effect transistor devices based on fabricated ultrathin InSb nanosheets exhibit ultra-high on-off ratio exceeding 108 and demonstrate minimal gate leakage currents. Furthermore, these ultrathin InSb nanosheets display p-type characteristics with hole mobilities reaching up to 203 cm2 V-1 s-1 at room temperatures. This study paves the way for achieving heterogeneous integration of III-V semiconductors and facilitating their application in flexible electronics.

Empyema associated with peritoneal dialysis peritonitis.

A 65-year-old woman on peritoneal dialysis (PD) was admitted due to abdominal pain with cloudy PD effluent. The white blood cell count in PD effluent was 5860/µL with 85% polymorphonuclear neutrophils. Therefore, she was clinically diagnosed with peritonitis. The cultures of PD effluent were negative. Initial abdominal computed tomography did not find suggest any intraabdominal pathology. The patient was treated with empirical intraperitoneal antibiotics. Because abdominal pain with cloudy PD effluent persisted, the PD catheter was removed eventually. The culture of the removed PD catheter grew Klebsiella pneumoniae. However, intermittent fever was noted over the following days and empyema developed approximately 2 weeks after PD catheter removal. The culture of pleural fluid also grew K. pneumoniae. Another computed tomography revealed multiple intraabdominal abscesses that was assumed to come from a complication of PD-associated peritonitis. We postulate that the empyema might be caused by transdiaphragmatic extension of the intraabdominal abscesses into the pleural space.

Rare Orbital Involvement Originating from Extranodal Marginal Zone Lymphoma.

Ocular adnexa region (OAR) primary lymphomas are uncommon, accounting for 1-2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Extranodal marginal zone lymphoma (EMZL) originates from several epithelial tissues, including the stomach, salivary gland, lung, small intestine, thyroid gland, and ocular adnexa region. Here, we report a 66-year-old female patient who was diagnosed with EMZL of OAR. In consideration of the possible side effect of radiotherapy, such as conjunctivitis, visual acuity impairment, and even retinal complications, she received six cycles of triweekly targeted chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) without radiotherapy. Then, she remained in complete remission up to the present day.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Two-Dimensional Semiconductors and Transistors for Future Integrated Circuits.

Silicon transistors are approaching their physical limit, calling for the emergence of a technological revolution. As the acknowledged ultimate version of transistor channels, 2D semiconductors are of interest for the development of post-Moore electronics due to their useful properties and all-in-one potentials. Here, the promise and current status of 2D semiconductors and transistors are reviewed, from materials and devices to integrated applications. First, we outline the evolution and challenges of silicon-based integrated circuits, followed by a detailed discussion on the properties and preparation strategies of 2D semiconductors and van der Waals heterostructures. Subsequently, the significant progress of 2D transistors, including device optimization, large-scale integration, and unconventional devices, are presented. We also examine 2D semiconductors for advanced heterogeneous and multifunctional integration beyond CMOS. Finally, the key technical challenges and potential strategies for 2D transistors and integrated circuits are also discussed. We envision that the field of 2D semiconductors and transistors could yield substantial progress in the upcoming years and hope this review will trigger the interest of scientists planning their next experiment.

Spontaneous Skyrmion Bubbles in an Iron-Silicon Alloy with Uniaxial Magnetic Anisotropy.

The magnetic skyrmions exhibit intriguing topological behaviors, holding promise for future applications in the realm of spintronic devices. Despite recent advancements, achieving spontaneous magnetic skyrmions and topological transitions in magnets featuring uniaxial magnetic anisotropy, particularly at elevated temperatures (>100 K), remains a challenging endeavor. Here, single-crystal Fe5Si3 nanorods with the central symmetry and uniaxial magnetic anisotropy were successfully synthesized on a mica substrate through chemical vapor deposition, which exhibit a high Curie temperature (TC) of about 372 K. The real-time observation, facilitated by Lorentz transmission electron microscopy, revealed the spontaneous formation of magnetic skyrmions and evolution of domains in focused ion beam-prepared Fe5Si3 thin foils. Moreover, Fe5Si3 device transport measurements expose notable magnetoresistance (MR) effects, enabling the interchange between positive and negative MR across specific temperature settings. These results offer various potential avenues for exploring diverse topological spin textures and their formation mechanisms, indicating inventive applications for iron-silicon alloy in the realm of spintronics.

Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

van der Waals Epitaxial Growth of One-Unit-Cell-Thick Ferroelectric CuCrS2 Nanosheets.

Ferroelectric two-dimensional (2D) materials with a high transition temperature are highly desirable for new physics and next-generation memory electronics. However, the long-range polar order of ferroelectrics will barely persist when the thickness reaches the nanoscale. In this work, we synthesized 2D CuCrS2 nanosheets with thicknesses down to one unit cell via van der Waals epitaxy in a chemical vapor deposition system. A combination of transmission electron microscopy, second-harmonic generation, and Raman spectroscopy measurements confirms the R3m space group and noncentrosymmetric structure. Switchable ferroelectric domains and obvious ferroelectric hysteresis loops were created and visualized by piezoresponse force microscopy. Theoretical calculation helps us understand the mechanism of ferroelectric switching in CuCrS2 nanosheets. Finally, we fabricated a ferroelectric memory device that achieves an on/off ratio of ∼102 and remains stable after 2000 s, indicating its applicability in novel nanoelectronics. Overall, 2D CuCrS2 nanosheets exhibit excellent ferroelectric properties at the nanoscale, showing great promise for next-generation devices.

Periodically tunable multimode soliton pulsation in a spatiotemporal mode-locked fiber laser.

Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.

Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Relationship between anion gap and in-hospital mortality in intensive care patients with liver failure: a retrospective propensity score matching analysis.

OBJECTIVES: To elucidate the association between anion gap (AG) and in-hospital mortality in intensive care patients with liver failure. METHODS: Demographic and clinical characteristics of intensive care patients with liver failure in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database were collected, and binomial logistic and Cox regression was conducted to investigate the association between AG and in-hospital mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was conducted to characterize the performance of AG in predicting in-hospital mortality, and was compared with the albumin corrected anion gap (ACAG) and the End-Stage Liver Disease (MELD) score. The Kaplan-Meier curve was plotted for in-hospital survival analysis of AG and patients with liver failure. The propensity score matching (PSM) analysis was performed to mitigate selection bias. RESULTS: AG was an independent risk factor for in-hospital mortality in intensive care patients with liver failure. Before PSM, the AUCs of AG, ACAG, and MELD were 0.666, 0.682, and 0.653, respectively. After PSM, the AUCs of AG, ACAG, and MELD scores were 0.645, 0.657, and 0.645, respectively, and there is no difference in the predictive performance of the three indicators upon comparison. Compared with the low-AG (≤20 mmol/L) group, the hazard ratio (HR) for in-hospital death of the high-AG (>20 mmol/L) group was determined to be 2.1472 (before PSM)/1.8890 (after PSM). CONCLUSIONS: AG is associated with in-hospital mortality in intensive care patients with liver failure and demonstrates a moderate predictive value, which is comparable to the predictive power of the MELD score. AG may serve as an indirect marker of in-hospital mortality of patients with liver failure by reflecting the degree of metabolic acidosis.

Wearable Sensor Based on a Tough Conductive Gel for Real-Time and Remote Human Motion Monitoring.

The usage of a conductive hydrogel in wearable sensors has been thoroughly researched recently. Nonetheless, hydrogel-based sensors cannot simultaneously have excellent mechanical property, high sensitivity, comfortable wearability, and rapid self-healing performance, which result in poor durability and reusability. Herein, a robust conductive hydrogel derived from one-pot polymerization and subsequent solvent replacement is developed as a wearable sensor. Owing to the reversible hydrogen bonds cross-linked between polymer chains and clay nanosheets, the resulting conductive hydrogel-based sensor exhibits outstanding flexibility, self-repairing, and fatigue resistance performances. The embedding of graphene oxide nanosheets offers an enhanced hydrogel network and easy release of wearable sensor from the target position through remote irradiation, while Li+ ions incorporated by solvent replacement endow the wearable sensor with low detection limit (sensing strain: 1%), high conductivity (4.3 S m-1) and sensitivity (gauge factor: 3.04), good freezing resistance, and water retention. Therefore, the fabricated wearable sensor is suitable to monitor small and large human motions on the site and remotely under subzero (-54 °C) or room temperature, indicating lots of promising applications in human-motion monitoring, information encryption and identification, and electronic skins.

Two-Dimensional Oxide Crystals for Device Applications: Challenges and Opportunities.

Atomically thin two-dimensional (2D) oxide crystals have garnered considerable attention because of their remarkable physical properties and potential for versatile applications. In recent years, significant advancements have been made in the design, preparation, and application of ultrathin 2D oxides, providing many opportunities for new-generation advanced technologies. This review focuses on the controllable preparation of 2D oxide crystals and their applications in electronic and optoelectronic devices. Based on their bonding nature, the various types of 2D oxide crystals are first summarized, including both layered and nonlayered crystals, as well as their current top-down and bottom-up synthetic approaches. Subsequently, in terms of the unique physical and electrical properties of 2D oxides, recent advances in device applications are emphasized, including photodetectors, field-effect transistors, dielectric layers, magnetic and ferroelectric devices, memories, and gas sensors. Finally, conclusions and future prospects of 2D oxide crystals are presented. It is hoped that this review will provide comprehensive and insightful guidance for the development of 2D oxide crystals and their device applications.

Palmoplantar pustulosis with psoriatic arthritis ineffective to interleukin-17 inhibitors: two patients successfully treated with upadacitinib.

Palmoplantar pustulosis (PPP) is a rare chronic pustular disease. Psoriatic arthritis (PsA) is one of the common manifestations of arthritis in PPP associated with a high burden of disease. The treatment of PPP is difficult and still in the exploratory stage. Only a few cases show that PPP complicated with arthritis have been successfully treated with janus kinase inhibition, interleukin (IL)-6 inhibitors, IL-12/23 inhibitors and tumor necrosis factor inhibitors. Here we reported that two patients were diagnosed as PPP with PsA and initially treated with IL-17 inhibitors. One case was only partially relieved, and the other case had severe paradoxical reaction in the trunk. The joint and skin condition of two patients had been significantly improved without reported adverse reactions after 18 weeks treatment with upadacitinib, which support upadacitinib may be a potential option for patients with PPP combined PsA.

Average current mode controller for bridgeless PFC SEPIC converter with second-order model reduction operated in continuous conduction mode.

This paper proposes an average current mode controller (ACMC) for a single-phase bridgeless power factor correction (PFC) circuit using a single ended primary inductor converter (SEPIC) via second-order model reduction. The superiority of the proposed controller is PFC accomplished at power up to 350 W with high efficiency via the second-order model reduction. The design and implementation of ACMC on the converter operated with continuous conduction mode (CCM) is explained in detail. ACMC forces input current to follow sinusoidal current reference at different power levels and sustain high power factor (PF). The proposed controller is designed based on the theoretical analysis operation of the circuit. For verification, MATLAB/Simulink simulations are carried out and validation through an experiment test rig for 110-220 Vrms input, 100 Vdc/ 350 W output prototype at 20 kHz switching frequency. It is proven that the proposed controller strategy accomplishes high PF, high efficiency and conformity with the simulation.

[Qianliexin Capsules for carrageenin-induced chronic nonbacterial prostatitis: A metabolomics study].

OBJECTIVE: To explore the regulating mechanism of the Chinese medicinal compound Qianliexin Capsules (QLX) in the treatment of chronic nonbacterial prostatitis (CNP). METHODS: We randomly divided 18 SPF SD male rats into a normal control (n = 6), a model control (n = 6) and a QLX group (n = 6). After successful establishment of a CNP model in the latter two groups by injecting 50 µl 1% carrageenan bilaterally into the prostate, we treated the rats in the QLX group by intragastrical administration of QLX at 4 g/kg, tid, and those in the normal and model control groups with the same volume of pure water, all for 45 days. Then, we examined the possible lower urinary tract symptoms (LUTS) of CNP by detecting the prostate indexes, expression of the tissue inflammatory factor IL-1 ß, 24-hour urine volume and pain threshold reaction (PTR) time, and conducted a metabonomics analysis of the urine and plasma samples. RESULTS: Compared with the normal controls, the CNP model rats showed dramatically increased prostate coefficient (ï¼»0.75 ± 0.09ï¼½ ‰ vs ï¼»1.60 ± 0.35ï¼½ ‰, P < 0.01) and the expression of IL-1ß (ï¼»22.61 ± 2.77ï¼½ vs ï¼»55.12 ± 4.94ï¼½ ng/ml, P < 0.01), which were both decreased in the QLX group (ï¼»0.97 ± 0.10ï¼½ ‰ and ï¼»36.64 ± 7.25ï¼½ ng/ml) in comparison with those in the model controls (P < 0.01). The urine volume was remarkably reduced in the model control group compared with that in the normal controls (4 ml vs 16.38 ml, P < 0.01), and so was the PTR time (ï¼»13.83 ± 5.67ï¼½ vs ï¼»23.73 ± 2.52ï¼½ s, P < 0.01), while the levels of urea nitrogen (ï¼»23.06 ± 3.71ï¼½ vs ï¼»17.92 ± 1.41ï¼½ mg/dL, P < 0.01), creatinine (ï¼»48.08 ± 9.31ï¼½ vs ï¼»40.31 ± 3.53ï¼½ µmol/L, P < 0.01) and uric acid (ï¼»181.36 ± 64.06ï¼½ vs ï¼»84.33 ± 21.40ï¼½ µmol/L, P < 0.01) increased significantly. The animals in the QLX group exhibited significant improvement in the urine volume (ï¼»13.44 ± 2.26ï¼½ ml), PTR time (ï¼»31.45 ± 2.96ï¼½ s), urea nitrogen (ï¼»16.49 ± 1.86ï¼½ mg/dL), creatinine (ï¼»36.88 ± 7.98ï¼½ µmol/L) and uric acid (ï¼»117.47 ± 40.09ï¼½ µmol/L) in comparison with the model controls (P < 0.01). Metabonomics analysis revealed a reversing effect of QLX on the carrageenin-induced alteration in a variety of metabolites in the urine and serum, restoring the ratios of such metabolites as glycine, cysteine, ketoimine quinolinic acid, aminobutyraldehyde and triphosphate to almost normal. Pathway enrichment analysis showed that the main metabolic pathways were aspartate and glutamate pathways. The ratios of such metabolites as neuroside, adipic acid, diacylglycerol, choline lecithin and so on in the plasma sample were dramatically improved in the QLX group compared with those in the model controls (P < 0.01). CONCLUSION: QLX significantly improves the symptoms of CNP and has a definite effect on amino acids, phosphatidyl and other biomarkers through the tricarboxylic acid cycle, amino acid metabolism, lipid metabolism and other related pathways.

Engineering Atomic-Scale Patterning and Resistive Switching in 2D Crystals and Application in Image Processing.

The ultrathin thickness of 2D layered materials affords the control of their properties through defects, surface modification, and electrostatic fields more efficiently compared with bulk architecture. In particular, patterning design, such as moiré superlattice patterns and spatially periodic dielectric structures, are demonstrated to possess the ability to precisely control the local atomic and electronic environment at large scale, thus providing extra degrees of freedom to realize tailored material properties and device functionality. Here, the scalable atomic-scale patterning in superionic cuprous telluride by using the bonding difference at nonequivalent copper sites is reported. Moreover, benefitting from the natural coupling of ordered and disordered sublattices, controllable piezoelectricity-like multilevel switching and bipolar switching with the designed crystal structure and electrical contact is realized, and their application in image enhancement is demonstrated. This work extends the known classes of patternable crystals and atomic switching devices, and ushers in a frontier for image processing with memristors.

Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function.

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations. Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized. Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h-1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL. Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia.