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1.
Int J Biol Macromol ; 190: 463-473, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34506859

RESUMO

Xanthine oxidase (XO) plays a vital role in inducing hyperuricemia and increasing the level of superoxide free radicals in blood, and is proved as an important target for gout. Chrysoeriol (CHE) is a natural flavone with potent XO inhibitory activity (IC50 = 2.487 ± 0.213 µM), however, the mechanism of interaction is still unclear. Therefore, a comprehensive analysis of the interaction between CHE and XO was accomplished by enzyme kinetics, isothermal titration calorimetry (ITC), multi-spectroscopic methods, molecular simulation and ADMET. The results showed that CHE acted as a rapid reversible and competitive-type XO inhibitor and its binding to XO was driven by hydrogen bonding and hydrophobic interaction. Moreover, CHE exhibited a strong fluorescence quenching effect through a static quenching procedure and induced conformational changes of XO. Its binding pattern with XO was revealed by docking study and the binding affinity to XO was enhanced by the interactions with key amino acid residues in the active pocket of XO. Further, CHE showed good stability and pharmacokinetic behavior properties in molecule dynamic simulation and ADMET prediction. Overall, this study shed some light on the mechanism of interaction between CHE and XO, also provided some valuable information concerning the future therapeutic application of CHE as natural XO inhibitor.

2.
Sci Total Environ ; 804: 149965, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34508937

RESUMO

Ammonium removal in wastewater treatment plants demands large quantities energy input, such as aeration for wastewater and the addition of organics for nitrate reduction. Anaerobic ammonium oxidation coupled to Fe(III) reduction, called Feammox process play a crucial role in natural nitrogen cycle, which has been rarely investigated in the field of wastewater treatment. Besides, Iron-reducing bacteria (FeRB) as function bacteria of Feammox could transfer electrons to iron oxide by oxidizing organics. The possibility of anaerobic ammonium removal coupled with organics should be investigated to assess the potential of Feammox process for conventional wastewater treatment. In this study, five Fe(III) compounds, Fe2O3, Fe3O4, Fe(OH)3, Citrate-Fe and pyrite were supplemented to investigate the effect of iron oxides on ammonium removal in serum bottles with working volume of 100 mL. It was found that ammonium removal efficiency of the Fe2O3 group was the highest. To simulate wastewater treatment process in sewage treatment plant, three Up-flow anaerobic sludge blanket reactors with volume of 250 mL adding Fe2O3 were applied with influent of ammonium and carbon sources. It was found that the organics significantly inhibited the ammonium removal by Feammox process. This was attributed to that carbon sources and ammonium could be used as electron donors for Fe(III) reduction. In addition, this nitrogen removal was also likely related with the iron cycle, i.e., Fe(III) reduction with ammonium oxidation and Fe(II) oxidation with nitrate/nitrite reduction. This study provides a promising alternative technology for anaerobic ammonium removal in wastewater treatment. Optimizing nitrogen removal and carbon sources applied in conventional wastewater plants are required in future.

3.
Int J Med Sci ; 18(15): 3533-3543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522180

RESUMO

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.

4.
J Hazard Mater ; 423(Pt A): 127104, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523482

RESUMO

Soils contamination with Cd result in detriment to the environmental quality. In-situ immobilization methods by applying clay minerals have been gaining prominence. The effects on sepiolite of thermal activation at different temperatures (300-750 °C), for removing Cd from aqueous solutions were evaluated, in order to consider their further application for soil remediation. The influence of activation temperature was investigated using XRD, SEM, and N2 adsorption-desorption measurements. The S-600 exhibited the maximum adsorption capacity (21.28 mg/g), despite its lower SSA, and Langmuir model described the adsorption isotherms better than the Freundlich equation. TCLP was used to quantify the remediation effects of thermal-activated sepiolite on simulated soils artificially polluted with Cd. The results indicated that the mobility of Cd in soil was effectively reduced after treating with thermal-activated sepiolite and the use of S-600 was the most efficient, reducing the TCLP-Cd by approximately 73% compared with the control test. The main remediation mechanism was considered as the cation exchange of Cd by Mg at the edges of octahedral sheet. This study showed that thermal-activated sepiolite could be promising amendments for remediation of Cd-contaminated soil.

5.
J Vasc Access ; : 11297298211045505, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524025

RESUMO

BACKGROUND: Quantitative physical examination (PE) indicators, including palpable pulsatility length and outflow scores, can be used to quantify stenosis severity at hemodialysis vascular access sites. It is known that the risk of high-shear-related thrombosis is increased when the minimal luminal diameter (MLD) of stenosis decreases. At present, MLD is measured using sonography or angiography. This study sought to determine the relationship between quantitative PE indicators and MLD and report their diagnostic performance in detecting patients with stenosis at a high risk of thrombosis. METHODS: We performed a retrospective case-control study using routinely collected data. We used the post-stenosis palpable pulsatility length (sPPL) and pulse-and-thrill based outflow score to assess the severity of AVF inflow and outflow stenosis, respectively. We recorded paired quantitative PE indicators and MLD before and after angioplasty in patients enrolled over a 4-month period. RESULTS: A total of 249 paired PE indicators and MLD measurements were obtained from 163 patients. A receiver operating characteristic curve analysis showed that an MLD cutoff value of <1.55 mm and an MLD of <1.95 mm discriminated sPPL = 0 and PESOS (physical examination significant outflow stenosis)/1- of the outflow score, respectively, from all other measurements, with the area under the curve values of 0.8922 and 0.9618, respectively. With sPPL = 0 and PESOS/1- of the outflow score as diagnostic tools to detect inflow stenosis with an MLD of ⩽1.5 mm and outflow stenosis with an MLD of ⩽1.9 mm at vascular access sites, sensitivity = 86.00% and 88.46%; specificity = 97.67% and 92.11%; positive predictive values of 97.73% and 92.00% and negative predictive values of 85.71% and 88.61%, respectively, were observed. CONCLUSIONS: Our preliminary results showed that physical examination can potentially be a diagnostic tool in detecting patients with stenosis who are at a high risk of thrombosis at hemodialysis vascular access sites with high diagnostic accuracy.

6.
Int J Nanomedicine ; 16: 6129-6140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511910

RESUMO

Purpose: With the development of nanomedicine, microwave ablation enhanced by multifunctional nanoplatforms has been widely studied for synergistic cancer therapy. Though scientists have got a lot of significant achievements in this field, the detailed molecular mechanisms and potential targets of microwave ablation enhanced by multifunctional nanoplatforms still need further exploration. In this study, we found that a kind of magnetite Fe3O4 nanoparticles (Fe3O4 NPs) could induce severe endoplasmic reticulum stress and activate cancer apoptosis under the irradiation of mild microwave. Methods: In this study, plenty of studies including cell immunofluorescence, mitochondrial membrane potential, electron microscopy, atomic force microscopy and microwave ablation in vivo were conducted to explore the molecular mechanisms and potential targets of microwave ablation enhanced by the Fe3O4 NPs. Results: The IRE1-ASK1-JNK pathway was strongly activated in A375 cells treated with both Fe3O4 NPs and mild microwave. The endoplasmic reticulum of the A375 cells was significantly dilated and exhibited ballooning degeneration. By investigating the mitochondrial membrane potential (ΔΨm), we found that the mitochondria of cancer cells had been significantly damaged under microwave treatment coupled with Fe3O4 NPs. In addition, melanoma of B16F10-bearing mice had also been effectively inhibited after being treated with Fe3O4 NPs and microwave. Conclusion: In this study, we found that a kind of magnetite Fe3O4 nanoparticles could induce severe ER stress and activate cancer apoptosis under mild microwave irradiation. Apparent apoptosis had been observed in the A375 cells under a scanning electron microscope and transmission electron microscope. Moreover, melanoma had also been inhibited effectively in vivo. As a result, the endoplasmic reticulum stress is a promising target with clinical potential in nanomedicine and cancer therapy.

7.
Chem Biodivers ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519420

RESUMO

Two new oleanane-triterpenoid saponins, clinograsaponins A ( 1 ) and B ( 2 ), together with twelve known ones ( 3-14 ), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF- κ B).

8.
Artigo em Inglês | MEDLINE | ID: mdl-34501846

RESUMO

BACKGROUND: Cervical elongation is commonly associated with pelvic organ prolapse (POP). It was an identified risk for recurrent prolapse after hysteropexy, requiring additional surgeries. The aim of the study is to investigate the risk factors for uterine cervical elongation among women with POP. METHODS: In this single-center retrospective cohort study, women who underwent vaginal total hysterectomy for POP between 2014 and 2016 were collected. The cervical and total uterine lengths were measured by pathologists, while the ratio of cervical length to total uterine length were calculated. The cervical elongation is defined as corpus/cervix ratio ≤ 1.5. RESULTS: A total of 133 patients were enrolled in this study. Among these patients, 43 women had cervical elongation and 90 women had normal length of uterine cervix. We found that age > 65 years old (67.4% vs. 42.2%, p = 0.007), total vaginal length ≥ 9.5 cm (65.1% vs. 45.6%, p = 0.035), uterine weight < 51 gm (72.1% vs. 52.2%, p = 0.03), and Pelvic Organ Prolapse Distress Inventory 6 (POPDI-6) ≥ 12 (30.2% vs. 14.4%, p = 0.032) were associated with the risk of cervical elongation. There were no significant differences on preoperative urodynamic parameters in the two groups. CONCLUSION: The patient age > 65 years old, the total vaginal length of POP-Q system ≥ 9.5 cm, uterine weight < 51 g, and POPDI-6 ≥ 12 are independent risk factors of cervical elongation in women with POP. For women scheduled for pelvic reconstructive hysteropexy, concomitant cervical amputation should be considered.

9.
PLoS One ; 16(9): e0251937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34506505

RESUMO

Pine wilt disease (PWD) is a devastating disease affecting trees belonging to the genus Pinus. To control the spread of PWD in the Masson pine forest in China, PWD resistant Masson pine clones have been selected by the Anhui Academy of Forestry. However, because Masson pine is a difficult-to-root species, producing seedlings is challenging, especially from trees older than 5 years of age, which impedes the application of PWD resistant clones. In this study, we investigated the factors affecting rooting of PWD resistant clones and established a cheap, reliable, and simple method that promotes rooting. We tested the effects of three management methods, four substrates, two cutting materials, two cutting treatments, and three collection times on the rooting of cuttings obtained from 9-year-old PWD resistant clones. Rooting was observed only in stem cuttings treated with the full-light automatic spray management method. Additionally, stem cuttings showed a significantly higher rooting rate and root quality than needles cuttings. Compared with other substrates, stem cuttings planted in perlite produced the longest adventitious root and the highest total root length and lateral root number. Moreover, stem cuttings of PWD resistant clones collected in May showed a significantly higher rooting rate and root quality than those collected in June and July. Moreover, stem cuttings prepared with a horizontal cut while retaining the needles showed significantly higher rooting rate and root quality than those prepared with a diagonal cut while partly removing the needles. This study promotes the reproduction of seedlings of PWD-resistant Masson pine clones which helps control the spread of PWD, meanwhile, provides a technical reference for the propagation of mature pine trees via cuttings.

10.
Chin J Traumatol ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34509352

RESUMO

Intertrochanteric fractures have become a severe public health problem in elderly patients. Proximal femoral nail anti-rotation (PFNA) is a commonly used intramedullary fixation device for unstable intertrochanteric fractures. Pelvic perforation by cephalic screw is a rare complication. We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture. The patient underwent surgery with PFNA as the intramedullary fixation device. Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation. We performed a cemented total hip arthroplasty as the savage procedure. At the latest follow-up 12 months after total hip arthroplasty, the patient had no pain or loosening of the prosthesis in the left hip. Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device, especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation. The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.

11.
J Org Chem ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514788

RESUMO

In this study we found that 2,6-dimethanolpyridine displays good complementarity toward di(ethylene glycol) for the complexation of Na+ ions, allowing us to use this recognition system for the efficient synthesis of hetero[2]catenanes; indeed, it allowed us to attach multiple copies of [2]catenanes to branched systems presenting multiple isophthalaldehyde units. When we attempted to form a catenane from a preformed macrocycle featuring only a single di(ethylene glycol) unit, reacting it with a di(ethylene glycol) derivative presenting two amino termini, isophthalaldehyde, and templating Na+ ions [i.e., with the aim of using di(ethylene glycol)·Na+·di(ethylene glycol) recognition to template the formation of the interlocked imino macrocycle], the yields of the hetero[2]catenane and homo[2]catenane, comprising two imino macrocyclic units, were both poor (14% and 7%, respectively). In contrast, when one or two 2,6-dimethanolpyridine units were present in the preformed macrocycles, their reactions with the same diamine, dialdehyde, and Na+ ions provided the hetero[2]catenanes with high selectivity and efficiency (44% and 64% yields, respectively), with minimal formation of the competing homo[2]catenane. The high complementary of the 2,6-dimethanolpyridine·Na+·di(ethylene glycol) ligand pair allowed us to synthesize [2]catenane dimers and trimers directly from corresponding isophthalaldehyde-presenting cores, with yields, after subsequent reduction and methylation, of 42% and 31%, respectively.

12.
Exp Biol Med (Maywood) ; : 15353702211038511, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514884

RESUMO

In breast cancer, tumor-associated macrophages with activated phenotypes promote tumor invasion and metastasis. The more aggressive mesenchymal-like breast cancer cells have a selective advantage, skewing macrophages toward the more immunosuppressive subtype. However, the mechanism underlying this shift is poorly understood. Cyclin D1b is a highly oncogenic variant of cyclin D1. Our previous study showed that non-metastatic epithelial-like breast cancer cells were highly metastatic in vivo when cyclin D1b was overexpressed. The present study determined whether cyclin D1b contributed to the interaction between breast cancer cells and macrophages. The results showed that cyclin D1b promoted the invasion of breast cancer cells in vitro. Specifically, through overexpression of cyclin D1b, breast cancer cells regulated the differentiation of macrophages into a more immunosuppressive M2 phenotype. Notably, tumor cells overexpressing cyclin D1b activated macrophages and induced migration of breast cancer cells. Further investigations indicated that SDF-1 mediated macrophage activation through breast cancer cells overexpressing cyclin D1b. These results revealed a previously unknown link between aggressive breast cancer cells and Tumor-associated macrophages, and highlighted the importance of cyclin D1b activity in the breast cancer microenvironment.

13.
Drug Des Devel Ther ; 15: 3697-3708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465981

RESUMO

Purpose: Puerarin (PR), a Chinese medicine rich in natural components, has been reported to display anti-fibrotic, antioxidant, anti-inflammatory and immunomodulatory properties. However, the protective mechanism of PR against unilateral ureteral obstruction (UUO)-mediated renal injury is not fully clarified. Therefore, the aim of this study was to investigate the effects of PR on UUO mice and its possible mechanisms. Methods: A total of 32 C57BL/6 mice were divided randomly into four groups (n=8): i) sham-operated group (Sham); ii) UUO group (UUO); iii) UUO + PR 50 mg/kg/day (UUO + PRL); and iv) UUO + PR 100 mg/kg/day (UUO + PRH). Continuous gavage administration for 14 days starting one week postoperatively, while the mice in Sham and UUO groups were given equal amounts of vehicle by the same means. All mice were then sacrificed and serum, 24-hour urine and tissue specimens were collected for renal function, histopathology, Western blot, immunohistochemistry. Results: Renal function and histopathology revealed that PR improved UUO-mediated renal dysfunction and partially reversed tubular injury and tubulointerstitial fibrosis. Additionally, according to the results of Western blot and immunohistochemistry, PR inhibited the expression of inflammatory factors including IL-1ß, IL-6, MCP-1 and ECM-related proteins including α-SMA, COL I and VIM. More importantly, the expression of fibrotic pathways TGF-ß1, Smad3, p-Smad3 and inflammatory pathways NF-κB p65, NF-κB p-p65, STAT3, p-STAT3 were inhibited to various extents under the PR treatment, while Smad7 was upregulated. Conclusion: These findings indicate that PR may inhibit the recruitment of inflammatory factors and extracellular matrix (ECM) deposition through the regulation of the NF-κB p65/STAT3 and TGFß1/Smads pathways, which alleviates the UUO-induced inflammatory and fibrotic response, thereby reversing renal injury.

14.
Eur J Pharm Sci ; : 105986, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474119

RESUMO

BACKGROUND: Efavirenz is a vital component used to treat HIV-1 infection. Nevertheless, it shows large between-subject variability, which affects both its therapeutic response and adverse effects. OBJECTIVE: To investigate the impact of gene polymorphisms and non-genetic factors on the variability of efavirenz pharmacokinetics and to propose the optimal dose regimens. METHODS: A total of 769 plasma samples from 376 HIV-infected Han Chinese outpatients were collected to develop a population pharmacokinetic model using NONMEM software. The impact of patient demographics, laboratory tests, concomitant medication, and genetic polymorphisms of CYP2B6 and ABCB1 on efavirenz pharmacokinetics were explored. According to the final model, the model-informed dose optimization was conducted. RESULTS: The pharmacokinetics of efavirenz was characterized by a one-compartment model with first-order absorption and elimination. The typical values of the estimated apparent oral clearance, volume of distribution, and absorption rate constant in the final model were 9.44 L/h, 200 L, and 0.727 h-1, respectively. Efavirenz clearance was significantly influenced by CYP2B6 variants, including rs2099361, rs3745274, and rs2279343, along with albumin and weight. The volume of distribution was affected by albumin and weight. Based on the CYP2B6 polymorphisms of patients, the recommended daily doses of efavirenz were 100 mg for CYP2B6 slow metabolizers, 400 or 600 mg for intermediate metabolizers, and 800 or 1000 mg for extensive metabolizers. CONCLUSIONS: Polymorphisms of CYP2B6, along with albumin and weight, resulted as the predictors of efavirenz pharmacokinetic variability, which could be used in prescribing optimal efavirenz doses.

16.
Small ; : e2102470, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480417

RESUMO

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.

17.
Neurol Sci ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480640

RESUMO

Susac syndrome is a rare disease presenting with a classic triad of symptoms. These are sensorineural hearing loss, encephalopathy, and branch retinal artery occlusions. Initial presentation is usually headache and symptoms of encephalopathy. Hearing loss is unusual in the early stages but, when it does present, can often lead to a misdiagnosis of sudden sensorineural hearing loss. Hence, neurological and retinal examinations are essential to an accurate diagnosis. In this study, we aimed to raise awareness of Susac syndrome among physicians and facilitate recognition of its manifestation, especially in those patients presenting with hearing loss alone. Identifying Susac syndrome that presents as sudden sensorineural hearing loss can be challenging but a number of case reviews have been reported in recent years and treatment guidelines are available.

19.
Int J Biol Macromol ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487782

RESUMO

In this work, binding interaction between molybdenum disulfide quantum dots (MoS2 QDs) and human serum albumin (HSA) was researched deeply to dissect the conformational variation and fibrillation of HSA affected by MoS2 QDs. The results revealed that MoS2 QDs bound strongly with HSA with molar ratio of 1:1 under the joint actions of hydrogen bond and van der Waals force, leading to the static fluorescence quenching of HSA. MoS2 QDs caused the secondary structure transition of HSA from α-helix stepwise to ß-turn, ß-sheet, and random coil gradually. MoS2 QDs reduced both the molar enthalpy change and the melting temperature of HSA, reducing the thermal stability of HSA significantly. It is worth noting that MoS2 QDs inhibited the fibrillation process of HSA according to the reduced hydrophobic environment and the disturbance of disulfide bonds in HSA network structure. These results reveal the precise binding mechanism of MoS2 QDs with HSA at molecular level, providing indispensable information for the potential application of MoS2 QDs in biological fields.

20.
J Med Internet Res ; 23(9): e27098, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491204

RESUMO

BACKGROUND: Hemodialysis (HD) therapy is an indispensable tool used in critical care management. Patients undergoing HD are at risk for intradialytic adverse events, ranging from muscle cramps to cardiac arrest. So far, there is no effective HD device-integrated algorithm to assist medical staff in response to these adverse events a step earlier during HD. OBJECTIVE: We aimed to develop machine learning algorithms to predict intradialytic adverse events in an unbiased manner. METHODS: Three-month dialysis and physiological time-series data were collected from all patients who underwent maintenance HD therapy at a tertiary care referral center. Dialysis data were collected automatically by HD devices, and physiological data were recorded by medical staff. Intradialytic adverse events were documented by medical staff according to patient complaints. Features extracted from the time series data sets by linear and differential analyses were used for machine learning to predict adverse events during HD. RESULTS: Time series dialysis data were collected during the 4-hour HD session in 108 patients who underwent maintenance HD therapy. There were a total of 4221 HD sessions, 406 of which involved at least one intradialytic adverse event. Models were built by classification algorithms and evaluated by four-fold cross-validation. The developed algorithm predicted overall intradialytic adverse events, with an area under the curve (AUC) of 0.83, sensitivity of 0.53, and specificity of 0.96. The algorithm also predicted muscle cramps, with an AUC of 0.85, and blood pressure elevation, with an AUC of 0.93. In addition, the model built based on ultrafiltration-unrelated features predicted all types of adverse events, with an AUC of 0.81, indicating that ultrafiltration-unrelated factors also contribute to the onset of adverse events. CONCLUSIONS: Our results demonstrated that algorithms combining linear and differential analyses with two-class classification machine learning can predict intradialytic adverse events in quasi-real time with high AUCs. Such a methodology implemented with local cloud computation and real-time optimization by personalized HD data could warn clinicians to take timely actions in advance.

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